Sample records for tansa koseido mt

  1. Mt, St. Helens, Mt. Adams, and Mt. Rainier, WA, USA

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This view of Mt. St. Helens (46.5N, 122.0W), taken 12 years after the volcanic eruption on 18 May 1980, in which the top 1300 ft. of the 9,677 ft. mountain was blown away, shows the rapid vegetation recovery within the blast area. Many fir trees have grown to heights of 20 ft. within the 150 square mile devastated area. Mt. Adams, an extinct volcano is just to the west and Mt. Rainier is to the north. Checkerboard logging can be seen throughout.

  2. 2. BUILDING MT76A AND MT76B FROM STREET, BUILDING MT76A IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. BUILDING MT-76-A AND MT-76-B FROM STREET, BUILDING MT-76-A IN FOREGROUND - Fort Keogh, Livestock & Range Research Station, 3 miles west of Miles City on U.S. Highway 10, Miles City, Custer County, MT

  3. Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function

    PubMed Central

    Baba, Kenkichi; Benleulmi-Chaachoua, Abla; Journé, Anne-Sophie; Kamal, Maud; Guillaume, Jean-Luc; Dussaud, Sébastien; Gbahou, Florence; Yettou, Katia; Liu, Cuimei; Contreras-Alcantara, Susana; Jockers, Ralf; Tosini, Gianluca

    2013-01-01

    The formation of G protein-coupled receptor (GPCR) heteromers elicits signaling diversification and holds great promise for improved drug selectivity. Most studies have been conducted in heterologous expression systems; however, in vivo validation is missing from most cases thus questioning the physiological significance of GPCR heteromerization. Melatonin MT1 and MT2 receptors have been shown to exist as homo- and heteromers in vitro. We show here that the effect of melatonin on rod photoreceptor light sensitivity is mediated by melatonin MT1/MT2 receptor heteromers. This effect involves activation of the heteromer-specific PLC/PKC pathway and is abolished in MT1−/− and MT2−/− mice as well as in mice overexpressing a non-functional MT2 receptor mutant that competes with the formation of functional MT1/MT2 heteromers in photoreceptor cells. This study establishes the essential role of melatonin receptor heteromers in retinal function and supports the physiological importance of GPCR heteromerization. Finally, our work may have important therapeutic implications, as the heteromer complex may provide a unique pharmacological target to improve photoreceptor functioning and to extend the viability of photoreceptors during aging. PMID:24106342

  4. Pharmacological characterization of human recombinant melatonin mt1 and MT2 receptors

    PubMed Central

    Browning, Christopher; Beresford, Isabel; Fraser, Neil; Giles, Heather

    2000-01-01

    We have pharmacologically characterized recombinant human mt1 and MT2 receptors, stably expressed in Chinese hamster ovary cells (CHO-mt1 and CHO-MT2), by measurement of [3H]-melatonin binding and forskolin-stimulated cyclic AMP (cAMP) production. [3H]-melatonin bound to mt1 and MT2 receptors with pKD values of 9.89 and 9.56 and Bmax values of 1.20 and 0.82 pmol mg−1 protein, respectively. Whilst most melatonin receptor agonists had similar affinities for mt1 and MT2 receptors, a number of putative antagonists had substantially higher affinities for MT2 receptors, including luzindole (11 fold), GR128107 (23 fold) and 4-P-PDOT (61 fold). In both CHO-mt1 and CHO-MT2 cells, melatonin inhibited forskolin-stimulated accumulation of cyclic AMP in a concentration-dependent manner (pIC50 9.53 and 9.74, respectively) causing 83 and 64% inhibition of cyclic AMP production at 100 nM, respectively. The potencies of a range of melatonin receptor agonists were determined. At MT2 receptors, melatonin, 2-iodomelatonin and 6-chloromelatonin were essentially equipotent, whilst at the mt1 receptor these agonists gave the rank order of potency of 2-iodomelatonin>melatonin>6-chloromelatonin. In both CHO-mt1 and CHO-MT2 cells, melatonin-induced inhibition of forskolin-stimulated cyclic AMP production was antagonized in a concentration-dependent manner by the melatonin receptor antagonist luzindole, with pA2 values of 5.75 and 7.64, respectively. Melatonin-mediated responses were abolished by pre-treatment of cells with pertussis toxin, consistent with activation of Gi/Go G-proteins. This is the first report of the use of [3H]-melatonin for the characterization of recombinant mt1 and MT2 receptors. Our results demonstrate that these receptor subtypes have distinct pharmacological profiles. PMID:10696085

  5. MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective

    PubMed Central

    Liu, Jiabei; Clough, Shannon J.; Hutchinson, Anthony J.; Adamah-Biassi, Ekue B.; Popovska-Gorevski, Marina; Dubocovich, Margarita L.

    2016-01-01

    Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein–coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents. PMID:26514204

  6. Genome sequence of two members of the chloroaromatic-degrading MT community: Pseudomonas reinekei MT1 and Achromobacter xylosoxidans MT3.

    PubMed

    Gutierrez-Urrutia, Izabook; Miossec, Matthieu J; Valenzuela, Sandro L; Meneses, Claudio; Dos Santos, Vitor A P Martins; Castro-Nallar, Eduardo; Poblete-Castro, Ignacio

    2018-06-10

    We describe the genome sequence of Pseudomonas reinekei MT1 and Achromobacter xylosoxidans MT3, the most abundant members of a bacterial community capable of degrading chloroaromatic compounds. The MT1 genome contains open reading frames encoding enzymes responsible for the catabolism of chlorosalicylate, methylsalicylate, chlorophenols, phenol, benzoate, p-coumarate, phenylalanine, and phenylacetate. On the other hand, the MT3 strain genome possesses no ORFs to metabolize chlorosalicylates; instead the bacterium is capable of metabolizing nitro-phenolic and phenolic compounds, which can be used as the only carbon and energy source by MT3. We also confirmed that MT3 displays the genetic machinery for the metabolism of chlorocathecols and chloromuconates, where the latter are toxic compounds secreted by MT1 when degrading chlorosalicylates. Altogether, this work will advance our fundamental understanding of bacterial interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Snow cover correlation between Mt. Villarrica and Mt. Lliama in Chile

    NASA Astrophysics Data System (ADS)

    Kim, Jeong-Cheol; Park, Sung-Hwan; Jung, Hyung-Sup

    2014-11-01

    The Southern Volcanic Zone (SVZ) of Chile consists of many volcanoes, and all of the volcanoes are covered with snow at the top of mountain. Monitoring snow cover variations in these regions can give us a key parameter in order to understand the mechanisms of volcanic activity. In this study, we investigate on the volcanic activity and snow cover interaction from snow cover area mapping, snow-line extraction. The study areas cover Mt. Villarrica and Mt. Llaima, Chile. Both of them are most active volcanos in SVZ. Sixty Landsat TM and Landsat ETM+ images are used for observing snow cover variations of Mt. Villarrica and Mt. Llaima, spanning the 25 years from September 1986 to February 2011. Results show that snow cover area between volcanic activity and non-activity are largely changed from 42.84 km2 to 13.41 km2, temporarily decreased 79% at the Mt. Villarrica and from 28.98 km2 to 3.82 km2, temporarily decreased 87% at the Mt. Villarrica. The snow line elevation of snow cover retreated by approximately 260 m from 1,606m to 1,871 m at the Mt. Villarrica, approximately 266m from 1,741m to 2,007m at the Mt. Llaima. The results show that there are definitely correlations between snow cover and volcanic activity.

  8. Pathogenic role of mtDNA duplications in mitochondrial diseases associated with mtDNA deletions.

    PubMed

    Odoardi, Francesca; Rana, Michele; Broccolini, Aldobrando; Mirabella, Massimiliano; Modoni, Anna; D'Amico, Adele; Papacci, Manuela; Tonali, Pietro; Servidei, Serenella; Silvestri, Gabriella

    2003-04-30

    We estimated the frequency of multiple mtDNA rearrangements by Southern blot in 32 patients affected by mitochondrial disorders associated with single deletions in order to assess genotype-phenotype correlations and elucidate the pathogenic significance of mtDNA duplications. Muscle in situ hybridization studies were performed in patients showing mtDNA duplications at Southern blot. We found multiple rearrangements in 12/32 (37.5%) patients; in particular, mtDNA duplications were detected in 4/4 Kearns-Sayre syndrome (KSS), in 1 Pearson's syndrome, in 1/3 encephalomyopathies with progressive external ophthalmoplegia (PEO), and in 2/23 PEO. In situ studies documented an exclusive accumulation of deleted mtDNAs in cytochrome c oxidase negative fibers of patients with mtDNA duplications. The presence of mtDNA duplications significantly correlated with onset of symptoms before age 15 and occurrence of clinical multisystem involvement. Analysis of biochemical data documented a predominant reduction of complex III in patients without duplications compared to patients with mtDNA duplications. Our data indicate that multiple mtDNA rearrangements are detectable in a considerable proportion of patients with single deletions and that mtDNA duplications do not cause any oxidative impairment. They more likely play a pathogenic role in the determination of clinical expression of mitochondrial diseases associated with single mtDNA deletions, possibly generating deleted mtDNAs in embryonic tissues by homologous recombination. Copyright 2003 Wiley-Liss, Inc.

  9. The MtDMI2-MtPUB2 Negative Feedback Loop Plays a Role in Nodulation Homeostasis1[OPEN

    PubMed Central

    Deng, Jie; Zhu, Fugui; Lu, Zheng

    2018-01-01

    DOES NOT MAKE INFECTION 2 (MtDMI2) is a Leu rich repeat-type receptor kinase required for signal transduction in the Medicago truncatula/Sinorhizobium meliloti symbiosis pathway. However, the mechanisms through which MtDMI2 participates in nodulation homeostasis are poorly understood. In this study, we identified MtPUB2—a novel plant U-box (PUB)–type E3 ligase—and showed that it interacts with MtDMI2. MtDMI2 and MtPUB2 accumulation were shown to be similar in various tissues. Roots of plants in which MtPUB2 was silenced by RNAi (MtPUB2-RNAi plants) exhibited impaired infection threads, fewer nodules, and shorter primary root lengths compared to those of control plants transformed with empty vector. Using liquid chromatography-tandem mass spectrometry, we showed that MtDMI2 phosphorylates MtPUB2 at Ser-316, Ser-421, and Thr-488 residues. When MtPUB2-RNAi plants were transformed with MtPUB2S421D, which mimics the phosphorylated state, MtDMI2 was persistently ubiquitinated and degraded by MtPUB2S421D, resulting in fewer nodules than observed in MtPUB2/MtPUB2-RNAi-complemented plants. However, MtPUB2S421A/MtPUB2-RNAi-complemented plants showed no MtPUB2 ubiquitination activity, and their nodulation phenotype was similar to that of MtPUB2-RNAi plants transformed with empty vector. Further studies demonstrated that these proteins form a negative feedback loop of the prey (MtDMI2)-predator (MtPUB2) type. Our results suggest that the MtDMI2-MtPUB2 negative feedback loop, which displays crosstalk with the long-distance autoregulation of nodulation via MtNIN, plays an important role in nodulation homeostasis. PMID:29440269

  10. 75 FR 43556 - TA-W-73,381, MT Rail Link, Inc., Missoula, MT; TA-W-73,381A, Billings, MT; TA-W-73,381B, Laurel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... DEPARTMENT OF LABOR Employment and Training Administration TA-W-73,381, MT Rail Link, Inc., Missoula, MT; TA-W-73,381A, Billings, MT; TA-W-73,381B, Laurel, MT; TA-W-73,381C, Livingston, MT; TA-W-73... Helena, Montana. The amended notice applicable to TA-W-73,381 is hereby issued as follows: All workers of...

  11. Contrasting expression of membrane metalloproteinases, MT1-MMP and MT3-MMP, suggests distinct functions in skeletal development.

    PubMed

    Yang, Maozhou; Zhang, Bingbing; Zhang, Liang; Gibson, Gary

    2008-07-01

    Membrane-type 1 matrix metalloproteinase (MT1-MMP) is the most ubiquitous and widely studied of the membrane-type metalloproteinases (MT-MMPs). It was thus surprising to find no published data on chicken MT1-MMP. We report here the characterization of the chicken gene. Its low sequence identity with the MT1-MMP genes of other species, high GC content, and divergent catalytic domain explains the absence of data and our difficulties in characterizing the gene. The absence of structural features in the chicken gene that have been suggested to be critical for the activation of MMP-2 by MT1-MMP; for the effect of MT1-MMP on cell migration and for the recycling of MT1-MMP suggest these features are either not essential or that MT1-MMP does not perform these functions in chickens. Comparison of the expression of chicken MT1-MMP with MT3-MMP and with MMP-2 and MMP-13 has confirmed the previously recognized co-expression of MT1-MMP with MMP-2 and MMP-13 in fibrous and vascular tissues, particularly those surrounding the developing long bones in other species. By contrast, MT3-MMP expression differs markedly from that of MT1-MMP and of both MMP-2 and MMP-13. MT3-MMP is expressed by chondrocytes of the developing articular surface. Similar expression patterns of this group of MT-MMPs and MMPs have been observed in mouse embryos and suggest distinct and specific functions for MT1-MMP and MT3-MMP in skeletal development.

  12. Interface Symbiotic Membrane Formation in Root Nodules of Medicago truncatula: the Role of Synaptotagmins MtSyt1, MtSyt2 and MtSyt3

    PubMed Central

    Gavrin, Aleksandr; Kulikova, Olga; Bisseling, Ton; Fedorova, Elena E.

    2017-01-01

    Symbiotic bacteria (rhizobia) are maintained and conditioned to fix atmospheric nitrogen in infected cells of legume root nodules. Rhizobia are confined to the asymmetrical protrusions of plasma membrane (PM): infection threads (IT), cell wall-free unwalled droplets and symbiosomes. These compartments rapidly increase in surface and volume due to the microsymbiont expansion, and remarkably, the membrane resources of the host cells are targeted to interface membrane quite precisely. We hypothesized that the change in the membrane tension around the expanding microsymbionts creates a vector for membrane traffic toward the symbiotic interface. To test this hypothesis, we selected calcium sensors from the group of synaptotagmins: MtSyt1, Medicago truncatula homolog of AtSYT1 from Arabidopsis thaliana known to be involved in membrane repair, and two other homologs expressed in root nodules: MtSyt2 and MtSyt3. Here we show that MtSyt1, MtSyt2, and MtSyt3 are expressed in the expanding cells of the meristem, zone of infection and proximal cell layers of zone of nitrogen fixation (MtSyt1, MtSyt3). All three GFP-tagged proteins delineate the interface membrane of IT and unwalled droplets and create a subcompartments of PM surrounding these structures. The localization of MtSyt1 by EM immunogold labeling has shown the signal on symbiosome membrane and endoplasmic reticulum (ER). To specify the role of synaptotagmins in interface membrane formation, we compared the localization of MtSyt1, MtSyt3 and exocyst subunit EXO70i, involved in the tethering of post-Golgi secretory vesicles and operational in tip growth. The localization of EXO70i in root nodules and arbusculated roots was strictly associated with the tips of IT and the tips of arbuscular fine branches, but the distribution of synaptotagmins on membrane subcompartments was broader and includes lateral parts of IT, the membrane of unwalled droplets as well as the symbiosomes. The double silencing of synaptotagmins

  13. mtDNA recombination in a natural population.

    PubMed

    Saville, B J; Kohli, Y; Anderson, J B

    1998-02-03

    Variation in mtDNA has been used extensively to draw inferences in phylogenetics and population biology. In the majority of eukaryotes investigated, transmission of mtDNA is uniparental and clonal, with genotypic diversity arising from mutation alone. In other eukaryotes, the transmission of mtDNA is biparental or primarily uniparental with the possibility of "leakage" from the minority parent. In these cases, heteroplasmy carries the potential for recombination between mtDNAs of different descent. In fungi, such mtDNA recombination has long been documented but only in laboratory experiments and only under conditions in which heteroplasmy is ensured. Despite this experimental evidence, mtDNA recombination has not been to our knowledge documented in a natural population. Because evidence from natural populations is prerequisite to understanding the evolutionary impact of mtDNA recombination, we investigated the possibility of mtDNA recombination in an organism with the demonstrated potential for heteroplasmy in laboratory matings. Using nucleotide sequence data, we report here that the genotypic structure of mtDNA in a natural population of the basidiomycete fungus Armillaria gallica is inconsistent with purely clonal mtDNA evolution and is fully consistent with mtDNA recombination.

  14. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease

    PubMed Central

    Nicholls, Thomas J.; Zsurka, Gábor; Peeva, Viktoriya; Schöler, Susanne; Szczesny, Roman J.; Cysewski, Dominik; Reyes, Aurelio; Kornblum, Cornelia; Sciacco, Monica; Moggio, Maurizio; Dziembowski, Andrzej; Kunz, Wolfram S.; Minczuk, Michal

    2014-01-01

    MGME1, also known as Ddk1 or C20orf72, is a mitochondrial exonuclease found to be involved in the processing of mitochondrial DNA (mtDNA) during replication. Here, we present detailed insights on the role of MGME1 in mtDNA maintenance. Upon loss of MGME1, elongated 7S DNA species accumulate owing to incomplete processing of 5′ ends. Moreover, an 11-kb linear mtDNA fragment spanning the entire major arc of the mitochondrial genome is generated. In contrast to control cells, where linear mtDNA molecules are detectable only after nuclease S1 treatment, the 11-kb fragment persists in MGME1-deficient cells. In parallel, we observed characteristic mtDNA duplications in the absence of MGME1. The fact that the breakpoints of these mtDNA rearrangements do not correspond to either classical deletions or the ends of the linear 11-kb fragment points to a role of MGME1 in processing mtDNA ends, possibly enabling their repair by homologous recombination. In agreement with its functional involvement in mtDNA maintenance, we show that MGME1 interacts with the mitochondrial replicase PolgA, suggesting that it is a constituent of the mitochondrial replisome, to which it provides an additional exonuclease activity. Thus, our results support the viewpoint that MGME1-mediated mtDNA processing is essential for faithful mitochondrial genome replication and might be required for intramolecular recombination of mtDNA. PMID:24986917

  15. Earthworm Lumbricus rubellus MT-2: Metal Binding and Protein Folding of a True Cadmium-MT.

    PubMed

    Kowald, Gregory R; Stürzenbaum, Stephen R; Blindauer, Claudia A

    2016-01-05

    Earthworms express, as most animals, metallothioneins (MTs)-small, cysteine-rich proteins that bind d(10) metal ions (Zn(II), Cd(II), or Cu(I)) in clusters. Three MT homologues are known for Lumbricus rubellus, the common red earthworm, one of which, wMT-2, is strongly induced by exposure of worms to cadmium. This study concerns composition, metal binding affinity and metal-dependent protein folding of wMT-2 expressed recombinantly and purified in the presence of Cd(II) and Zn(II). Crucially, whilst a single Cd₇wMT-2 species was isolated from wMT-2-expressing E. coli cultures supplemented with Cd(II), expressions in the presence of Zn(II) yielded mixtures. The average affinities of wMT-2 determined for either Cd(II) or Zn(II) are both within normal ranges for MTs; hence, differential behaviour cannot be explained on the basis of overall affinity. Therefore, the protein folding properties of Cd- and Zn-wMT-2 were compared by ¹H NMR spectroscopy. This comparison revealed that the protein fold is better defined in the presence of cadmium than in the presence of zinc. These differences in folding and dynamics may be at the root of the differential behaviour of the cadmium- and zinc-bound protein in vitro, and may ultimately also help in distinguishing zinc and cadmium in the earthworm in vivo.

  16. Nonconscious memory for motion activates MT+.

    PubMed

    Thakral, Preston P; Slotnick, Scott D

    2014-11-12

    Extrastriate region MT+ is widely thought to reflect conscious motion processing. The primary aim of the present functional MRI study was to assess whether MT+ is activated during nonconscious memory for motion. During the encoding phase, moving and stationary abstract shapes were presented to the left or right of fixation. During the retrieval phase, the same shapes were presented at fixation and participants classified each shape as 'moving-left', 'moving-right', 'stationary-left', or 'stationary-right'. The contrast of moving>stationary shapes at encoding was used to identify the location of MT+. Event-related activity was then extracted from MT+ within each hemisphere. MT+ activity was significantly greater for moving-misses than for stationary-misses, which indicates that nonconscious memory for motion activates MT+. Furthermore, nonconscious memory activity (moving-misses) had an earlier temporal onset than conscious memory activity (moving-hits). The present results are the first, to our knowledge, to demonstrate that MT+ is associated with nonconscious motion processing. Therefore, activity in this region or in other visual-sensory regions should not be assumed to reflect conscious processing.

  17. mtDNA lineage analysis of mouse L-cell lines reveals the accumulation of multiple mtDNA mutants and intermolecular recombination

    PubMed Central

    Fan, Weiwei; Lin, Chun Shi; Potluri, Prasanth; Procaccio, Vincent; Wallace, Douglas C.

    2012-01-01

    The role of mitochondrial DNA (mtDNA) mutations and mtDNA recombination in cancer cell proliferation and developmental biology remains controversial. While analyzing the mtDNAs of several mouse L cell lines, we discovered that every cell line harbored multiple mtDNA mutants. These included four missense mutations, two frameshift mutations, and one tRNA homopolymer expansion. The LA9 cell lines lacked wild-type mtDNAs but harbored a heteroplasmic mixture of mtDNAs, each with a different combination of these variants. We isolated each of the mtDNAs in a separate cybrid cell line. This permitted determination of the linkage phase of each mtDNA and its physiological characteristics. All of the polypeptide mutations inhibited their oxidative phosphorylation (OXPHOS) complexes. However, they also increased mitochondrial reactive oxygen species (ROS) production, and the level of ROS production was proportional to the cellular proliferation rate. By comparing the mtDNA haplotypes of the different cell lines, we were able to reconstruct the mtDNA mutational history of the L–L929 cell line. This revealed that every heteroplasmic L-cell line harbored a mtDNA that had been generated by intracellular mtDNA homologous recombination. Therefore, deleterious mtDNA mutations that increase ROS production can provide a proliferative advantage to cancer or stem cells, and optimal combinations of mutant loci can be generated through recombination. PMID:22345519

  18. Barley metallothioneins: MT3 and MT4 are localized in the grain aleurone layer and show differential zinc binding.

    PubMed

    Hegelund, Josefine Nymark; Schiller, Michaela; Kichey, Thomas; Hansen, Thomas Hesselhøj; Pedas, Pai; Husted, Søren; Schjoerring, Jan Kofod

    2012-07-01

    Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins believed to play a role in cytosolic zinc (Zn) and copper (Cu) homeostasis. However, evidence for the functional properties of MTs has been hampered by methodological problems in the isolation and characterization of the proteins. Here, we document that barley (Hordeum vulgare) MT3 and MT4 proteins exist in planta and that they differ in tissue localization as well as in metal coordination chemistry. Combined transcriptional and histological analyses showed temporal and spatial correlations between transcript levels and protein abundance during grain development. MT3 was present in tissues of both maternal and filial origin throughout grain filling. In contrast, MT4 was confined to the embryo and aleurone layer, where it appeared during tissue specialization and remained until maturity. Using state-of-the-art speciation analysis by size-exclusion chromatography inductively coupled plasma mass spectrometry and electrospray ionization time-of-flight mass spectrometry on recombinant MT3 and MT4, their specificity and capacity for metal ion binding were quantified, showing a strong preferential Zn binding relative to Cu and cadmium (Cd) in MT4, which was not the case for MT3. When complementary DNAs from barley MTs were expressed in Cu- or Cd-sensitive yeast mutants, MT3 provided a much stronger complementation than did MT4. We conclude that MT3 may play a housekeeping role in metal homeostasis, while MT4 may function in Zn storage in developing and mature grains. The localization of MT4 and its discrimination against Cd make it an ideal candidate for future biofortification strategies directed toward increasing food and feed Zn concentrations.

  19. Analysis of European mtDNAs for recombination.

    PubMed

    Elson, J L; Andrews, R M; Chinnery, P F; Lightowlers, R N; Turnbull, D M; Howell, N

    2001-01-01

    The standard paradigm postulates that the human mitochondrial genome (mtDNA) is strictly maternally inherited and that, consequently, mtDNA lineages are clonal. As a result of mtDNA clonality, phylogenetic and population genetic analyses should therefore be free of the complexities imposed by biparental recombination. The use of mtDNA in analyses of human molecular evolution is contingent, in fact, on clonality, which is also a condition that is critical both for forensic studies and for understanding the transmission of pathogenic mtDNA mutations within families. This paradigm, however, has been challenged recently by Eyre-Walker and colleagues. Using two different tests, they have concluded that recombination has contributed to the distribution of mtDNA polymorphisms within the human population. We have assembled a database that comprises the complete sequences of 64 European and 2 African mtDNAs. When this set of sequences was analyzed using any of three measures of linkage disequilibrium, one of the tests of Eyre-Walker and colleagues, there was no evidence for mtDNA recombination. When their test for excess homoplasies was applied to our set of sequences, only a slight excess of homoplasies was observed. We discuss possible reasons that our results differ from those of Eyre-Walker and colleagues. When we take the various results together, our conclusion is that mtDNA recombination has not been sufficiently frequent during human evolution to overturn the standard paradigm.

  20. Phylogenetic Network for European mtDNA

    PubMed Central

    Finnilä, Saara; Lehtonen, Mervi S.; Majamaa, Kari

    2001-01-01

    The sequence in the first hypervariable segment (HVS-I) of the control region has been used as a source of evolutionary information in most phylogenetic analyses of mtDNA. Population genetic inference would benefit from a better understanding of the variation in the mtDNA coding region, but, thus far, complete mtDNA sequences have been rare. We determined the nucleotide sequence in the coding region of mtDNA from 121 Finns, by conformation-sensitive gel electrophoresis and subsequent sequencing and by direct sequencing of the D loop. Furthermore, 71 sequences from our previous reports were included, so that the samples represented all the mtDNA haplogroups present in the Finnish population. We found a total of 297 variable sites in the coding region, which allowed the compilation of unambiguous phylogenetic networks. The D loop harbored 104 variable sites, and, in most cases, these could be localized within the coding-region networks, without discrepancies. Interestingly, many homoplasies were detected in the coding region. Nucleotide variation in the rRNA and tRNA genes was 6%, and that in the third nucleotide positions of structural genes amounted to 22% of that in the HVS-I. The complete networks enabled the relationships between the mtDNA haplogroups to be analyzed. Phylogenetic networks based on the entire coding-region sequence in mtDNA provide a rich source for further population genetic studies, and complete sequences make it easier to differentiate between disease-causing mutations and rare polymorphisms. PMID:11349229

  1. METHYLATION OF ARSENIC BY RECOMBINANT HUMAN AS3MT/287M AND AS3MT/287T POLYMORPHS

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). AS3MT polymorphism is, in part, responsible for interindividual differences in iAs metabolism. AS3MT/M287T polymorphism that is found in ~ 10% of C...

  2. Keeping mtDNA in Shape between Generations

    PubMed Central

    Stewart, James B.; Larsson, Nils-Göran

    2014-01-01

    Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing. PMID:25299061

  3. Widespread recombination in published animal mtDNA sequences.

    PubMed

    Tsaousis, A D; Martin, D P; Ladoukakis, E D; Posada, D; Zouros, E

    2005-04-01

    Mitochondrial DNA (mtDNA) recombination has been observed in several animal species, but there are doubts as to whether it is common or only occurs under special circumstances. Animal mtDNA sequences retrieved from public databases were unambiguously aligned and rigorously tested for evidence of recombination. At least 30 recombination events were detected among 186 alignments examined. Recombinant sequences were found in invertebrates and vertebrates, including primates. It appears that mtDNA recombination may occur regularly in the animal cell but rarely produces new haplotypes because of homoplasmy. Common animal mtDNA recombination would necessitate a reexamination of phylogenetic and biohistorical inference based on the assumption of clonal mtDNA transmission. Recombination may also have an important role in producing and purging mtDNA mutations and thus in mtDNA-based diseases and senescence.

  4. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

  5. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

  6. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

  7. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

  8. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

  9. Patterns in Seismicity at Mt St Helens and Mt Unzen

    NASA Astrophysics Data System (ADS)

    Lamb, Oliver; De Angelis, Silvio; Lavallee, Yan

    2014-05-01

    Cyclic behaviour on a range of timescales is a well-documented feature of many dome-forming volcanoes. Previous work on Soufrière Hills volcano (Montserrat) and Volcán de Colima (Mexico) revealed broad-scale similarities in behaviour implying the potential to develop general physical models of sub-surface processes [1]. Using volcano-seismic data from Mt St Helens (USA) and Mt Unzen (Japan) this study explores parallels in long-term behaviour of seismicity at two dome-forming systems. Within the last twenty years both systems underwent extended dome-forming episodes accompanied by large Vulcanian explosions or dome collapses. This study uses a suite of quantitative and analytical techniques which can highlight differences or similarities in volcano seismic behaviour, and compare the behaviour to changes in activity during the eruptive episodes. Seismic events were automatically detected and characterized on a single short-period seismometer station located 1.5km from the 2004-2008 vent at Mt St Helens. A total of 714 826 individual events were identified from continuous recording of seismic data from 22 October 2004 to 28 February 2006 (average 60.2 events per hour) using a short-term/long-term average algorithm. An equivalent count will be produced from seismometer recordings over the later stages of the 1991-1995 eruption at MT Unzen. The event count time-series from Mt St Helens is then analysed using Multi-taper Method and the Short-Term Fourier Transform to explore temporal variations in activity. Preliminary analysis of seismicity from Mt St Helens suggests cyclic behaviour of subannual timescale, similar to that described at Volcán de Colima and Soufrière Hills volcano [1]. Frequency Index and waveform correlation tools will be implemented to analyse changes in the frequency content of the seismicity and to explore their relations to different phases of activity at the volcano. A single station approach is used to gain a fine-scale view of variations in

  10. Coso MT Site Locations

    DOE Data Explorer

    Doug Blankenship

    2011-05-04

    This data includes the locations of the MT data collected in and around the Coso Geothermal field that covered the West Flank area. These are the data that the 3D MT models were created from that were discussed in Phase 1 of the West Flank FORGE project. The projected coordinate system is NAD 1927 State Plane California IV FIPS 0404 and the Projection is Lambert Conformal Conic. Units are in feet.

  11. Barley Metallothioneins: MT3 and MT4 Are Localized in the Grain Aleurone Layer and Show Differential Zinc Binding1[W][OA

    PubMed Central

    Hegelund, Josefine Nymark; Schiller, Michaela; Kichey, Thomas; Hansen, Thomas Hesselhøj; Pedas, Pai; Husted, Søren; Schjoerring, Jan Kofod

    2012-01-01

    Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins believed to play a role in cytosolic zinc (Zn) and copper (Cu) homeostasis. However, evidence for the functional properties of MTs has been hampered by methodological problems in the isolation and characterization of the proteins. Here, we document that barley (Hordeum vulgare) MT3 and MT4 proteins exist in planta and that they differ in tissue localization as well as in metal coordination chemistry. Combined transcriptional and histological analyses showed temporal and spatial correlations between transcript levels and protein abundance during grain development. MT3 was present in tissues of both maternal and filial origin throughout grain filling. In contrast, MT4 was confined to the embryo and aleurone layer, where it appeared during tissue specialization and remained until maturity. Using state-of-the-art speciation analysis by size-exclusion chromatography inductively coupled plasma mass spectrometry and electrospray ionization time-of-flight mass spectrometry on recombinant MT3 and MT4, their specificity and capacity for metal ion binding were quantified, showing a strong preferential Zn binding relative to Cu and cadmium (Cd) in MT4, which was not the case for MT3. When complementary DNAs from barley MTs were expressed in Cu- or Cd-sensitive yeast mutants, MT3 provided a much stronger complementation than did MT4. We conclude that MT3 may play a housekeeping role in metal homeostasis, while MT4 may function in Zn storage in developing and mature grains. The localization of MT4 and its discrimination against Cd make it an ideal candidate for future biofortification strategies directed toward increasing food and feed Zn concentrations. PMID:22582132

  12. Application of remote sensing analysis and MT method for identification geothermal prospect zone in Mt. Endut

    NASA Astrophysics Data System (ADS)

    Akbar, A. M.; Permadi, A. N.; Wildan, D.; Sobirin, R.; Supriyanto

    2017-07-01

    Mount Endut is located at Banten Province, 40 km southward Rangkasbitung City, with geographic UTM position between 9261000-9274000 N and 639000-652000 E. Preliminary survey at Mt. Endut was geological and geochemical survey in 2006, resistivity survey and MT survey in 2007 with 27 measurement point. All survey conducted by Pusat Sumber Daya Geologi (PSDG). According to result of premilinary survey, Mt. Endut is dominated by quartenary volcanic rock produced by Mt. Endut, which breakthrough tertiary sediment layer. NE to SW normal fault produced surface manifestation, namely Cikawah (CKW) hot spring and Handeleum (HDL) hot spring. According to SiO2 and NaK geothermometer, subsurface temperature of Mt Endut is ranging from 162 to 180 °C. Apparent resistivity maps show that thermal manifestation areas coincide with pronounced high anomaly due to resistive intrusion bodies contrast to conductive sedimentary basements. In order to delineate permeability zone, fracture fault density (FFD) analysis from remote sensing image is carry out. FFD analysis from lansdat 7 image shows the area on westward flank of Mt. Endut have high fracture fault density (162-276 m/km2), higher than it's surrounding area and can be assume that area is weak zone and have high permeability. That's structure density anomaly coincide with low resistivity from Magnetotelluric data. Resistivity structure from Magnetotelluric data shows western flank have low permeability layer (14-27 Ohmm) with average thickness 250 m. Below this layer there is layer with higher resistivity (37-100 Ohmm) with ±1000 m depth and interpreted as shallow reservoir. Massive resistif intrusive bodies act controlled the surface manifestation, and act as boundary and bounded the geothermal system in western part of Mt. Endut.

  13. Rainwater chemistry at a high-altitude station, Mt. Lulin, Taiwan: Comparison with a background station, Mt. Fuji

    NASA Astrophysics Data System (ADS)

    Wai, Ka Ming; Lin, Neng-Huei; Wang, Sheng-Hsiang; Dokiya, Yukiko

    2008-03-01

    Samples of rainwater were collected at a high-altitude site in east Asia between April 2003 and May 2005. The volume weighted mean pH value for the whole sampling period was 5.12, approaching that of typical natural water. Non-sea-salt (nss) SO42- and NH4+ were the most abundant anion and cation, respectively, both existing mostly in the form of (NH4)2SO4. Chloride was excessive in most of the samples. The signature of biomass burning in south and Southeast Asia was evident in the Mt. Lulin samples. Concentrations of chemical species were found to be elevated in the spring months, owing to the emissions from south/Southeast Asia and peak biomass burning activities and frequent dust storms (in the Indian Thar Desert). In the summer and fall seasons our samples are mainly influenced by marine air masses. The episodic species concentrations measured at the summit of Mt. Fuji during the spring were due to the influence of volcanic emissions from Miyake-Jima. Tropical cyclones (TC) over the western Pacific region and deep convections play important roles in the transport of boundary layer pollutants to the free troposphere, although their influence is not frequently detected at Mt. Lulin and Mt. Fuji. The rainwater chemistry at Mt. Lulin and Mt. Fuji were examined together with the aerosol chemistry obtained from the TRACE-P and ACE-Asia campaigns. The analysis of the Mt. Lulin data set demonstrates its background characteristics of the rainwater chemistry in east Asia.

  14. Day/night expression of MT1 and MT2 receptors in hypothalamic nuclei of the primate Sapajus apella.

    PubMed

    Pinato, Luciana; Ramos, Dayane; Hataka, Alessandre; Rossignoli, Patricia S; Granado, Marcos Donisete; Mazzetto, Marina Cardoso; Campos, Leila M G

    2017-04-01

    Melatonin is involved in the temporal organization of several physiological and behavioral events, controlled by hypothalamic nuclei, like sleep, feeding, reproduction and metabolic modulation and acts through two types of high-affinity G protein-coupled membrane receptors: MT 1 and MT 2 . This study aimed to investigate the expression of MT 1 and MT 2 receptors proteins in four hypothalamic nuclei, i.e., SCN, supraoptic (SON), paraventricular (PVN) and anteroventral periventricular nuclei (AVPV), of the diurnal primate Sapajus apella using immunohistochemistry. Since these areas are involved in the expression of biological rhythms, they are candidates to have variations in their neurochemistry, so the MT 1 and MT 2 expression has been analyzed at a point in light and another in the dark phase. Both receptors were found to have day/night differences in the four hypothalamic nuclei with an apparent inverse expression in the SCN compared with the other areas. These differences could be related to the idea that the individual should be prepared to respond by different ways to melatonin signal within the several processes and can contribute to the efficacy of melatonin ligands or melatonin in therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. MT3DMS: Model use, calibration, and validation

    USGS Publications Warehouse

    Zheng, C.; Hill, Mary C.; Cao, G.; Ma, R.

    2012-01-01

    MT3DMS is a three-dimensional multi-species solute transport model for solving advection, dispersion, and chemical reactions of contaminants in saturated groundwater flow systems. MT3DMS interfaces directly with the U.S. Geological Survey finite-difference groundwater flow model MODFLOW for the flow solution and supports the hydrologic and discretization features of MODFLOW. MT3DMS contains multiple transport solution techniques in one code, which can often be important, including in model calibration. Since its first release in 1990 as MT3D for single-species mass transport modeling, MT3DMS has been widely used in research projects and practical field applications. This article provides a brief introduction to MT3DMS and presents recommendations about calibration and validation procedures for field applications of MT3DMS. The examples presented suggest the need to consider alternative processes as models are calibrated and suggest opportunities and difficulties associated with using groundwater age in transport model calibration.

  16. Mt. Everest

    NASA Image and Video Library

    1994-09-30

    STS068-259-009 (30 September-11 October 1994) --- This south-looking, summer-time view of Mt. Everest (center) - with strong sense of three dimension because of reduced amount of snow - and neighboring peaks of the Himalayas. Clouds cover lower slopes in India.

  17. mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt).

    PubMed

    Kenny, Timothy C; Germain, Doris

    2017-01-01

    While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPR mt ) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR mt has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPR mt may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPR mt do not. This review aims at offering an overview of the confusing literature on mtDNA mutations and metastasis and the more recent work on the UPR mt in this setting.

  18. Mt. Etna, Italy

    NASA Image and Video Library

    2002-11-07

    On Sunday, November 3, 2002, Mt. Etna's ash-laden plume was imaged by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. The plume is seen blowing toward the south-southeast, over the city and airport of Catania, Sicily. The previous day, the plume was blowing toward the northwest, and posed no hazard to Catania. The current eruption of Mt. Etna, Europe's most active volcano, began on October 27. These sorts of observations from space may help civil defense authorities mitigate hazards from active eruptions. Space data may also help scientists evaluate the behavior and effects volcanic eruptions have on our global climate system. http://photojournal.jpl.nasa.gov/catalog/PIA03881

  19. Zinc metallothionein (MT) induction by parenteral iron and endotoxin: A temporal analysis of hepatic MT mRNA changes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McCormick, C.C.

    The present study was undertaken to compare the temporal characteristics of iron-induced hepatic MT mRNA accumulation to that effected by endotoxin. Young chicks were given (ip) either endotoxin, ferrous gluconate or an equivalent volume of saline. At various times following injections, liver was obtained from 5 chicks per treatment for total RNA extraction. Equal amounts of total hepatic RNA from each chick were pooled and 10 {mu}g separated by denaturing agarose gel electrophoresis. Hepatic MT mRNA and albumin mRNA were analyzed by Northern blot analysis using synthetic oligonucleotides. The results indicated little temporal difference in the accumulation of hepatic MTmore » mRNA as affected by either endotoxin or iron. In both treatments, MT mRNA was minimally affected at 3 hours post-injection. Maximum accumulation was achieved during a 6 h period from 6 to 12 hours post-injection. At 24 hours, MT mRNA was considerably higher in liver of endotoxin-injected chicks when compared to that of iron-injection chicks. Albumin expression appeared not to be substantially affected by either treatment. The results suggest that the induction of hepatic MT by iron injection is not substantially different than that observed following endotoxin administration. It would be speculative to suggest that the processes by which MT is induced under these conditions are also similar.« less

  20. Genetic diversities of MT-ND1 and MT-ND2 genes are associated with high-altitude adaptation in yak.

    PubMed

    Shi, Yu; Hu, Yongsong; Wang, Jie; Elzo, Mauricio A; Yang, Xue; Lai, Songjia

    2018-04-01

    Tibetan yak (Bos grunniens) inhabiting the Qinghai-Tibet Plateau (QTP) where the average altitude is 4000 m, is specially adapted to live at these altitudes. Conversely, cattle (B. taurus) has been found to suffer from high-altitude hypertension or heart failure when exposed to these high altitudes. Two mitochondrial genes, MT-ND1 and MT-ND2, encode two subunits of NADH dehydrogenase play an essential role in the electron transport chain of oxidative phosphorylation (OXPHOS). We sequenced these two mitochondrial genes in two bovine groups (70 Tibetan yaks and 70 Xuanhan cattle) and downloaded 300 sequences of B. taurus (cattle), 93 sequences of B. grunniens (domestic yak), and 2 sequences of B. mutus (wild yak) from NCBI to increase our understanding of the mechanisms of adaptability to hypoxia at high altitudes in yaks compared to cattle. MT-ND1 SNP m.3907 C > T, present in all Tibetan yaks, was positively associated with high-altitude adaptation (p < .0006). Specially, mutation m.3638 A > G present in all cattle, resulting in the termination of transcription, was negatively associated with high-altitude adaptation (p < .0006). Additionally, MT-ND2 SNPs m.4351 G > A and m.5218 C > T also showed positive associations with high-altitude adaptation (p < .0004). MT-ND1 haplotypes H2, H3, H4, H6, and H7 showed positive associations but haplotype H20 had a negative association with high-altitude adaptation (p < .0008). Similarly, MT-ND2 haplotypes Ha1 Ha8, Ha10, and Ha11 were positively associated whereas haplotype Ha2 was negatively associated with adaptability to high-altitudes (p < .0008). Thus, MT-ND1 and MT-ND2 can be considered as candidate genes associated with adaptation to high-altitude environments.

  1. Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

    PubMed

    Liao, Dezhong Joshua; Wang, Yong; Wu, Jiusheng; Adsay, Nazmi Volkan; Grignon, David; Khanani, Fayyaz; Sarkar, Fazlul H

    2006-07-05

    In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgf alpha-ES lines, TGF alpha transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2-7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al 1. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgf alpha-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgf alpha/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.

  2. 27 CFR 9.123 - Mt. Veeder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Mt. Veeder. 9.123 Section 9.123 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.123 Mt. Veeder. (a) Name. The name of the viticultural are...

  3. 27 CFR 9.123 - Mt. Veeder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Mt. Veeder. 9.123 Section 9.123 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.123 Mt. Veeder. (a) Name. The name of the viticultural are...

  4. 27 CFR 9.123 - Mt. Veeder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Mt. Veeder. 9.123 Section 9.123 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.123 Mt. Veeder. (a) Name. The name of the viticultural are...

  5. 27 CFR 9.123 - Mt. Veeder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Mt. Veeder. 9.123 Section 9.123 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.123 Mt. Veeder. (a) Name. The name of the viticultural are...

  6. 27 CFR 9.123 - Mt. Veeder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Mt. Veeder. 9.123 Section 9.123 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL AMERICAN VITICULTURAL AREAS Approved American Viticultural Areas § 9.123 Mt. Veeder. (a) Name. The name of the viticultural are...

  7. Identifying Water on Mt. Baker and Mt. St. Helens, WA with Geophysics: Implications for Volcanic Landslide Hazards

    NASA Astrophysics Data System (ADS)

    Finn, C.; Bedrosian, P.; Wisniewski, M.; Deszcz-Pan, M.

    2015-12-01

    Groundwater position, abundance, and flow rates within a volcano affect the transmission of fluid pressure, transport of mass and heat and formation of mechanically weak hydrothermal alteration influencing the stability of volcanoes. In addition, eruptions can shatter volcanic rocks, weakening the edifice. Helicopter magnetic and electromagnetic (HEM) data collected over Mt. Baker and Mt. St. Helens volcanoes reveal the distribution of water, shattered volcanic rocks and hydrothermal alteration essential to evaluating volcanic landslide hazards. These data, combined with geological mapping and rock property measurements, indicate the presence of localized <100 m thick zones of water-saturated hydrothermally altered rock beneath Sherman Crater and the Dorr Fumarole Fields at Mt. Baker. Nuclear magnetic resonance data indicate that the hydrothermal clays contain ~50% bound water with no evidence for free water ponded beneath the ice. The HEM data suggest water-saturated fresh volcanic rocks from the surface to the detection limit (~100 m) over the entire summit of Mt. Baker (below the ice). A 50-100 m thick high resistivity layer (>1500 ohm-m) corresponding to domes, debris avalanche, volcanic rocks and glaciers mantles the crater at Mt. St. Helens. Shallow low resistivity layers corresponding to fresh, cold water and hot brines are observed below the high resistivity surface in EM data. Shallow ground water mainly concentrates in shattered dome material in the crater of Mt. St. Helens. Aeromagnetic data indicate the location of basalts sandwiched between debris avalanche deposits and shattered dome material. The combination of the EM and magnetic data help map the location of the shattered dome material that is considered to be the failure surface for the 1980 debris avalanche. The EM data image the regional groundwater table near the base of the volcano. The geophysical identification of groundwater and weak layers constrain landslide hazards assessments.

  8. Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism.

    PubMed

    Engström, Karin; Vahter, Marie; Mlakar, Simona Jurkovic; Concha, Gabriela; Nermell, Barbro; Raqib, Rubhana; Cardozo, Alejandro; Broberg, Karin

    2011-02-01

    Arsenic (As) occurs as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in humans, and the methylation pattern demonstrates large interindividual differences. The fraction of urinary MMA is a marker for susceptibility to As-related diseases. We evaluated the impact of polymorphisms in five methyltransferase genes on As metabolism in two populations, one in South America and one in Southeast Asia. The methyltransferase genes were arsenic(+III oxidation state) methyltransferase (AS3MT), DNA-methyltransferase 1a and 3b (DNMT1a and DNMT3b, respectively), phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood. Subjects were women exposed to As in drinking water in the Argentinean Andes [n = 172; median total urinary As (U-As), 200 µg/L] and in rural Bangladesh (n = 361; U-As, 100 µg/L; all in early pregnancy). Urinary As metabolites were measured by high-pressure liquid chromatography/inductively coupled plasma mass spectrometry. Polymorphisms (n = 22) were genotyped with Sequenom, and AS3MT expression was measured by quantitative real-time polymerase chain reaction using TaqMan expression assays. Six AS3MT polymorphisms were significantly associated with As metabolite patterns in both populations (p ≤ 0.01). The most frequent AS3MT haplotype in Bangladesh was associated with a higher percentage of MMA (%MMA), and the most frequent haplotype in Argentina was associated with a lower %MMA and a higher percentage of DMA. Four polymorphisms in the DNMT genes were associated with metabolite patterns in Bangladesh. Noncoding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altered levels of gene expression. Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations, suggesting that AS3MT may have an impact on As metabolite

  9. Polymorphisms in Arsenic(+III Oxidation State) Methyltransferase (AS3MT) Predict Gene Expression of AS3MT as Well as Arsenic Metabolism

    PubMed Central

    Engström, Karin; Vahter, Marie; Mlakar, Simona Jurkovic; Concha, Gabriela; Nermell, Barbro; Raqib, Rubhana; Cardozo, Alejandro; Broberg, Karin

    2011-01-01

    Background Arsenic (As) occurs as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in humans, and the methylation pattern demonstrates large interindividual differences. The fraction of urinary MMA is a marker for susceptibility to As-related diseases. Objectives We evaluated the impact of polymorphisms in five methyltransferase genes on As metabolism in two populations, one in South America and one in Southeast Asia. The methyltransferase genes were arsenic(+III oxidation state) methyltransferase (AS3MT), DNA-methyltransferase 1a and 3b (DNMT1a and DNMT3b, respectively), phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood. Methods Subjects were women exposed to As in drinking water in the Argentinean Andes [n = 172; median total urinary As (U-As), 200 μg/L] and in rural Bangladesh (n = 361; U-As, 100 μg/L; all in early pregnancy). Urinary As metabolites were measured by high-pressure liquid chromatography/inductively coupled plasma mass spectrometry. Polymorphisms (n = 22) were genotyped with Sequenom, and AS3MT expression was measured by quantitative real-time polymerase chain reaction using TaqMan expression assays. Results Six AS3MT polymorphisms were significantly associated with As metabolite patterns in both populations (p ≤ 0.01). The most frequent AS3MT haplotype in Bangladesh was associated with a higher percentage of MMA (%MMA), and the most frequent haplotype in Argentina was associated with a lower %MMA and a higher percentage of DMA. Four polymorphisms in the DNMT genes were associated with metabolite patterns in Bangladesh. Noncoding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altered levels of gene expression. Conclusions Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations

  10. Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

    PubMed

    Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

    2016-01-01

    Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

  11. Decay spectroscopy of element 115 daughters: Rg 280 → Mt 276 and Mt 276 → Bh 272

    DOE PAGES

    Gates, J. M.; Gregorich, K. E.; Gothe, O. R.; ...

    2015-08-03

    In this study, forty-six decay chains, assigned to the decay of 288115, were produced using the 243Am ( 48Ca, 3n) 288115 reaction at the Lawrence Berkeley National Laboratory 88-in. cyclotron. The resulting series of α decays were studied using α-photon and α-x-ray spectroscopies. Multiple α-photon coincidences were observed in the element 115 decay chain members, particularly in the third- and fourth-generation decays (presumed to be 280Rg and 276Mt, respectively). Upon combining these data with those from 22 288115 decay chains observed in a similar experiment, updated level schemes in 276Mt and 272Bh (populated by the α decay of 280Rg andmore » 276Mt, respectively) are proposed. Additionally, photons were observed in the energy range expected for K x rays coincident with the α decay of both 280Rg and 276Mt. However, Compton scattering of higher-energy γ rays and discrete transitions are present in the K x-ray region preventing a definitive Z identification to be made based on observation of characteristic K x-ray energies.« less

  12. Italy: Mt. Etna

    Atmospheric Science Data Center

    2013-04-17

    article title:  Eruption of Mt. Etna     View ... repeated caldera collapse, and partially buried by younger volcanic structures. Eruptions are related to a complex tectonic situation, ... available at JPL . July 22, 2001 - Eruption of the volcano in true-color and stereo. project:  ...

  13. Pharmacology of Ramelteon, a Selective MT1/MT2 Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders

    PubMed Central

    Miyamoto, Masaomi

    2009-01-01

    An estimated one-third of the general population is affected by insomnia, and this number is increasing due to more stressful working conditions and the progressive aging of society. However, current treatment of insomnia with hypnotics, gamma-aminobutyric acid A (GABAA) receptor modulators, induces various side effects, including cognitive impairment, motor disturbance, dependence, tolerance, hangover, and rebound insomnia. Ramelteon (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT1/MT2 receptor agonist. Unlike the sedative hypnotics that target GABAA receptor complexes, ramelteon is a chronohypnotic that acts on the melatonin MT1 and MT2 receptors, which are primarily located in the suprachiasmatic nucleus, the body's “master clock.” As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades. Ramelteon has demonstrated sleep-promoting effects in clinical trials, and coupled with its favorable safety profile and lack of abuse potential or dependence, this chronohypnotic provides an important treatment option for insomnia. PMID:19228178

  14. Subsurface Structure Interpretation Beneath of Mt. Pandan Based on Gravity Data

    NASA Astrophysics Data System (ADS)

    Santoso, D.; Wahyudi, E. J.; Alawiyah, S.; Nugraha, A. D.; Widiyantoro, S.; Kadir, W. G. A.; Supendi, P.; Wiyono, S.; Zulkafriza

    2017-04-01

    Mt. Pandan is one of the volcano that state as dormant volcano. On the other hand, Smyth et al. (2008) defined that Mt. Pandan is an active volcano. This volcano is apart a volcanic chain in Java island which is trending east-west along the island. This volcanic chain known as present day volcanic arc. Mt. Wilis is located in the south and it relatively much bigger compare to Mt. Pandan. There were earthquakes activity experienced in the surrounding Mt. Pandan area in the past several years. This event is interesting, because Mt. Pandan is not classify as the active volcano according to the list of volcanoes in Indonesia. On the otherhand Smyth et. al. (2008) mentioned that G. Pandan as modern volcanic which is located in Kendeng Zone of East Java. Gravity measurement around Mt. Pandan area was done in order to understand subsurface structure of Mt. Pandan. Gravity interpretation results shows that there is a low density structure beneath Mt. Pandan. It could be interpreted as existing of magma body below the surface. Some indication of submagmatic activities were found as hot spring and warm ground. Therefore it could be concluded that there is a possibility of magmatic activity below the Mt. Pandan.

  15. α -decay chains of superheavy Mt-279265 isotopes

    NASA Astrophysics Data System (ADS)

    Santhosh, K. P.; Nithya, C.

    2017-10-01

    The α -decay chains of the isotopes Mt-279265 are predicted by comparing the α half-lives calculated within the Coulomb and proximity potential model for deformed nuclei of Santhosh et al. [Nucl. Phys. A 850, 34 (2011)], 10.1016/j.nuclphysa.2010.12.002 with the spontaneous fission half-lives using the shell-effect-dependent formula of Santhosh and Nithya [Phys. Rev. C 94, 054621 (2016)], 10.1103/PhysRevC.94.054621. α half-lives also are calculated using different theoretical formalisms for comparison. The predicted half-lives and decay modes match well with the experimental results. The use of four different mass tables for calculating the α - decay energies indicates that the mass table of Wang et al. [Chin. Phys. C 41, 030003 (2017)], 10.1088/1674-1137/41/3/030003, which is based on the AME2016 atomic mass evaluation, is in better agreement with experimental results. The paper predicts long α chains from 265,267-269,271-273MT with half-lives within experimental limits. The isotopes 274-276,278Mt exhibit 2α chains followed by spontaneous fission. The 2α chain of 266Mt and the 4α chain of 270Mt end with electron capture. The isotopes Mt,279277 decay via spontaneous fission. We hope that the paper will open up new areas in this field.

  16. The Formation and Erosion History of Mt. Sharp

    NASA Technical Reports Server (NTRS)

    Allen, Carlton C.; Dapremont, Angela M.

    2014-01-01

    The Curiosity rover is exploring 155 km diameter Gale crater and Mt. Sharp, Gale's 5 km high central mound (Fig. 1). This study addresses the formation and erosion history of Mt. Sharp. Gale lies on the topographic dichotomy between the southern highlands and the northern plains - a drop of over 2 km [1,2]. Altitude differences between the north and south rim reflect this regional slope, as do altitude differences between the deep annulus north of Mt. Sharp and the southern crater floor. Orbiter and rover images demonstrate that most exposed areas on Mt. Sharp consist of thin, sub-parallel units interpreted as sedimentary layers [3]. Gale is typical of the 50 large martian craters that have been totally or partially filled with such layers [4,5]. In many craters these sediments have been deeply eroded. Central Peak and Peak Ring: The highest point on Mt. Sharp, near the crater's center, is interpreted as a central peak [6]. The peak has a massive lower portion and a thin, smooth capping deposit (Fig. 2). Gale's size is transitional between martian craters with single central peaks and craters with peak rings approximately half the crater's diameter [2,6]. The boundaries of Mt. Sharp, as well as an arc of hills to the southeast of the mountain, closely match a circle approximately 80 km in diameter (Fig. 3). This morphology suggests that the Gale impact may have formed both a central peak and a partial peak ring, which is covered by the sediments of Mt. Sharp in the north and possibly exposed in the arc of eroded hills in the southeast quadrant (Figs. 3,4).

  17. First Results from SERPENT Marine MT Study

    NASA Astrophysics Data System (ADS)

    Naif, S.; Key, K. W.; Constable, S.; Evans, R. L.

    2010-12-01

    In April 2010 we conducted a controlled source electromagnetic (CSEM) and magnetotelluric (MT) survey over the Middle Americas subduction zone offshore Nicaragua. Seismic and heat flow studies have been conducted in the region to explore the role water plays at convergent margins, yet the quantity of water entering the downgoing slab remains poorly constrained. Electrical conductivity, however, is highly sensitive to the amount and distribution of water in the crust, and possibly mantle. Our broadband marine MT receivers recorded electric and magnetic field variations at the seafloor in water depths ranging from 60-5100 m. A total of 54 receiver deployments along a 300 km profile resulted in the largest MT dataset ever collected over an active subduction zone, all recorded in a single 28 day cruise aboard the R/V Melville. Spectrograms of the raw data show strong signal, including a significant magnetic storm from 5/2 to 5/3. Robust multiple station processing of the MT data produced high quality apparent resistivity and phase estimates for periods of roughly 10-20,000 s. Impedance polar diagrams and skew estimates display an evolution of 1D structure on the abyssal plain, 2D structure at the outer rise, 3D structure on/near the trench, and 1D-2D structure along the continental shelf. The MT responses generally lack the severe anisotropy usually associated with the ocean-side coast effect in near-shore MT studies. However, large distortions are evident at a few sites on the prism side of the trench, where extremely high skews are strongly localized in both space and frequency; these are spatially correlated with cusps in apparent resistivity and negative phase wrapping of the TE mode. We suspect this is caused by a combination of severe bathymetric effects and local variations in conductivity structure. Initial modeling results will be presented.

  18. Construct validity of the MMPI-2 College Maladjustment (Mt) Scale.

    PubMed

    Barthlow, Deanna L; Graham, John R; Ben-Porath, Yossef S; McNulty, John L

    2004-09-01

    The construct validity of the MMPI-2 (Minnesota Multiphasic Personality Inventory-2) College Maladjustment (Mt) Scale was examined using 376 student clients at a university psychological clinic. A principal components analysis and correlations of Mt scale scores with clients' and therapists' ratings of symptoms and functioning showed that the Mt scale identifies the presence of maladjustment as defined in terms of depressive and anxious symptoms. There is no evidence to show that the scale is specific to college students or that it is sensitive to severe psychological disturbance. The Mt scale does not inform the clinician as to why a person is distressed. In addition, there is no evidence from this study to suggest the superiority of the Mt scale over other MMPI-2 maladjustment measures. Therapists should use the entire MMPI-2 profile, not just the Mt scale, to gain the most comprehensive and specific understanding of clients.

  19. Metabolic rescue in pluripotent cells from patients with mtDNA disease.

    PubMed

    Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

    2015-08-13

    Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

  20. The expression characteristics of mt-ND2 gene in chicken.

    PubMed

    Zhang, Wenwen; Hou, Lingling; Wang, Ting; Lu, Weiwei; Tao, Yafei; Chen, Wen; Du, Xiaohui; Huang, Yanqun

    2016-09-01

    Subunit 2 of NADH dehydrogenase (ND2) is encoded by the mt-ND2 gene and plays a critical role in controlling the production of the mitochondrial reactive oxygen species. Our study focused on exploring the mt-ND2 tissue expression patterns and the effects of energy restriction and dietary fat (linseed oil, corn oil, sesame oil or lard) level (2.5% and 5%) on its expression in chicken. The results showed that mt-ND2 gene was expressed in the 15 tissues of hybrid chickens with the highest level in heart and lowest level in pancreas tissue; 30% energy restriction did not significantly affect mt-ND2 mRNA level in chicken liver tissue. Both the mt-ND2 mRNA levels in chicken pectoralis (p < 0.05) and hepatic tissues (p < 0.05) at 42 d-old were affected by the type of dietary fats in 5% level, while not in abdominal fat tissues. The expression of mt-ND2 in hepatic tissues was down-regulated with chicken age (p < 0.01). The interactive effect of dietary fat types with chicken age (p < 0.05) was significant on mt-ND2 mRNA level. The study demonstrated that mt-ND2 gene was extensively expressed in tissues, and the expression was affected by dietary fat types and chicken age.

  1. SignMT: An Alternative Language Learning Tool

    ERIC Educational Resources Information Center

    Ditcharoen, Nadh; Naruedomkul, Kanlaya; Cercone, Nick

    2010-01-01

    Learning a second language is very difficult, especially, for the disabled; the disability may be a barrier to learn and to utilize information written in text form. We present the SignMT, Thai sign to Thai machine translation system, which is able to translate from Thai sign language into Thai text. In the translation process, SignMT takes into…

  2. Food-induced reinforcement is abrogated by the genetic deletion of the MT1 or MT2 melatonin receptor in C3H/HeN mice.

    PubMed

    Clough, Shannon J; Hudson, Randall L; Dubocovich, Margarita L

    2018-05-02

    Palatable food is known for its ability to enhance reinforcing responses. Studies have suggested a circadian variation in both drug and natural reinforcement, with each following its own time course. The goal of this study was to determine the role of the MT 1 and MT 2 melatonin receptors in palatable snack food-induced reinforcement, as measured by the conditioned place preference (CPP) paradigm during the light and dark phases. C3H/HeN wild-type mice were trained for snack food-induced CPP at either ZT 6 - 8 (ZT: Zeitgeber time; ZT 0 = lights on), when endogenous melatonin levels are low, or ZT 19 - 21, when melatonin levels are high. These time points also correspond to the high and low points for expression of the circadian gene Period1, respectively. The amount of snack food (chow, Cheetos®, Froot Loops® and Oreos®) consumed was of similar magnitude at both times, however only C3H/HeN mice conditioned to snack food at ZT 6 - 8 developed a place preference. C3H/HeN mice with a genetic deletion of either the MT 1 (MT 1 KO) or MT 2 (MT 2 KO) receptor tested at ZT 6 - 8 did not develop a place preference for snack food. Although the MT 2 KO mice showed a similar amount of snack food consumed when compared to wild-type mice, the MT 1 KO mice consumed significantly less than either genotype. We conclude that in our mouse model snack food-induced CPP is dependent on time of day and the presence of the MT 1 or MT 2 receptors, suggesting a role for melatonin and its receptors in snack food-induced reinforcement. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Mitochondrial DNA copy number threshold in mtDNA depletion myopathy.

    PubMed

    Durham, S E; Bonilla, E; Samuels, D C; DiMauro, S; Chinnery, P F

    2005-08-09

    The authors measured the absolute amount of mitochondrial DNA (mtDNA) within single muscle fibers from two patients with thymidine kinase 2 (TK2) deficiency and two healthy controls. TK2 deficient fibers containing more than 0.01 mtDNA/microm3 had residual cytochrome c oxidase (COX) activity. This defines the minimum amount of wild-type mtDNA molecules required to maintain COX activity in skeletal muscle and provides an explanation for the mosaic histochemical pattern seen in patients with mtDNA depletion syndrome.

  4. MT Ser, a binary blue subdwarf

    NASA Astrophysics Data System (ADS)

    Shimanskii, V. V.; Borisov, N. V.; Sakhibullin, N. A.; Sheveleva, D. V.

    2008-06-01

    We have classified and determined the parameters of the evolved close binary MT Ser. Our moderate-resolution spectra covering various phases of the orbital period were taken with the 6-m telescope of the Special Astrophysical Observatory. The spectra of MT Ser freed from the contribution of the surrounding nebula Abell 41 contained no emission lines due to the reflection effect. The radial velocities measured from lines of different elements showed them to be constant on a time scale corresponding to the orbital period. At the same time, we find effects of broadening for the HeII absorption lines, due to the orbital motion of two hot stars of similar types. As a result, we classify MT Ser as a system with two blue subdwarfs after the common-envelope stage. We estimate the component masses and the distance to the object from the Doppler broadening of the HeII lines. We demonstrate that the age of the ambient nebula, Abell 41, is about 35 000 years.

  5. Distant Mt. Fuji, Island of Honshu Japan

    NASA Image and Video Library

    1992-11-01

    This distant view of Mt. Fuji, on the main home island of Honshu, Japan (34.0N, 139.0E) was taken from about 450 miles to the south. Evan at that great distance, the majestic and inspiring Mt. Fuji is still plainly visible and easily recognized as a world renowned symbol of Japan. The snow capped extinct volcano lies just a few miles south of Tokyo.

  6. Leber Hereditary Optic Neuropathy: Exemplar of an mtDNA Disease.

    PubMed

    Wallace, Douglas C; Lott, Marie T

    2017-01-01

    The report in 1988 that Leber Hereditary Optic Neuropathy (LHON) was the product of mitochondrial DNA (mtDNA) mutations provided the first demonstration of the clinical relevance of inherited mtDNA variation. From LHON studies, the medical importance was demonstrated for the mtDNA showing its coding for the most important energy genes, its maternal inheritance, its high mutation rate, its presence in hundreds to thousands of copies per cell, its quantitatively segregation of biallelic genotypes during both mitosis and meiosis, its preferential effect on the most energetic tissues including the eye and brain, its wide range of functional polymorphisms that predispose to common diseases, and its accumulation of mutations within somatic tissues providing the aging clock. These features of mtDNA genetics, in combination with the genetics of the 1-2000 nuclear DNA (nDNA) coded mitochondrial genes, is not only explaining the genetics of LHON but also providing a model for understanding the complexity of many common diseases. With the maturation of LHON biology and genetics, novel animal models for complex disease have been developed and new therapeutic targets and strategies envisioned, both pharmacological and genetic. Multiple somatic gene therapy approaches are being developed for LHON which are applicable to other mtDNA diseases. Moreover, the unique cytoplasmic genetics of the mtDNA has permitted the first successful human germline gene therapy via spindle nDNA transfer from mtDNA mutant oocytes to enucleated normal mtDNA oocytes. Such LHON lessons are actively being applied to common ophthalmological diseases like glaucoma and neurological diseases like Parkinsonism.

  7. Mt. Etna: rationale and implementation of a Supersite

    NASA Astrophysics Data System (ADS)

    Puglisi, Giuseppe

    2017-04-01

    Mt. Etna is one of the most active volcanoes on Earth and, in the past few decades, has erupted virtually every year. The volcanism of Mt. Etna results from the interaction between magma ascent in the rather complex plumbing feeding system and the local tectonic regime controlled by the volcano edifice's eastern flank instability, whose driving conditions (e.g., structural setting, tectonic forces) and cause-effect relationships are not yet completely understood. At the surface, the combination of the two factors produces eruptions that might consist of either strongly explosive (e.g., 2002; 2011) and produce volcanic ash plumes likely to disrupt air traffic for hours to weeks (e.g., 5 January 2012), including powerful summit paroxysms in the 2012-2013 time span or lava flows capable of invading the populated sectors, that can threat human property and vital infrastructures. Mt. Etna presents many characteristics that make it prone to be a Geohazard Supersite. The volcano consists of an open-vent system characterised by continuous degassing from the volcano summit craters and frequent eruptive summit and flank eruptions. Eruptions can be of different kinds passing from violent short-lasting explosive events to long-lasting lava output, thus producing different kinds of impacts on the surrounding environment, and especially on the large number of people living around the volcano foot. Over time, the frequency and variety of Mt. Etna's eruptive activity have made the volcano one of the most well-studied and monitored worldwide. At Mt. Etna volcanic activity produces a wide spectrum of signals, spanning from seismic and geodetic to geochemical and radiometric signals, which are tracked in continuous and in real-and quasi-real time by the automatic multi-disciplinary monitoring systems deployed by INGV. The huge amount of ground-based collected data sets enforces the vision of Mt. Etna supersite as a Geohazard Supersite where applying the overarching criteria of the

  8. High-quality mtDNA control region sequences from 680 individuals sampled across the Netherlands to establish a national forensic mtDNA reference database.

    PubMed

    Chaitanya, Lakshmi; van Oven, Mannis; Brauer, Silke; Zimmermann, Bettina; Huber, Gabriela; Xavier, Catarina; Parson, Walther; de Knijff, Peter; Kayser, Manfred

    2016-03-01

    The use of mitochondrial DNA (mtDNA) for maternal lineage identification often marks the last resort when investigating forensic and missing-person cases involving highly degraded biological materials. As with all comparative DNA testing, a match between evidence and reference sample requires a statistical interpretation, for which high-quality mtDNA population frequency data are crucial. Here, we determined, under high quality standards, the complete mtDNA control-region sequences of 680 individuals from across the Netherlands sampled at 54 sites, covering the entire country with 10 geographic sub-regions. The complete mtDNA control region (nucleotide positions 16,024-16,569 and 1-576) was amplified with two PCR primers and sequenced with ten different sequencing primers using the EMPOP protocol. Haplotype diversity of the entire sample set was very high at 99.63% and, accordingly, the random-match probability was 0.37%. No population substructure within the Netherlands was detected with our dataset. Phylogenetic analyses were performed to determine mtDNA haplogroups. Inclusion of these high-quality data in the EMPOP database (accession number: EMP00666) will improve its overall data content and geographic coverage in the interest of all EMPOP users worldwide. Moreover, this dataset will serve as (the start of) a national reference database for mtDNA applications in forensic and missing person casework in the Netherlands. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Petrographic and geochemical investigation of magma chamber processes beneath small Quaternary volcanic centers between Mt. Jefferson and Mt. Hood volcanoes, Cascade Range Volcanic Arc

    NASA Astrophysics Data System (ADS)

    Cunningham, E.; Cribb, J. W.

    2017-12-01

    The northern Oregon Cascade Range has been dominated by andesite to rhyodacite lavas at both Mt. Jefferson (Conrey, 1991) and at Mt. Hood (Cribb and Barton, 1996) during the Quaternary period. Eruptive sequences at both Mt. Hood and Mt. Jefferson have been attributed to open-system mama mixing (Kent et al., 2010) (Ferrell et al., 2015), and the narrow range of lavas erupted at both centers has been derived from repeated cycles of magma mixing-fractionation (Cribb and Barton, 1996). This research examines major and trace element geochemistry as well as the petrographic characteristics of Clear Lake Butte (CLB), Pinhead Butte (PB), and Olallie Butte (OB), all of which are located between Mt. Hood and Mt. Jefferson, and have ben active in the Quaternary period. The research investigates whether the same type of open-system magma mixing known to have occurred at Mt. Hood and Mt. Jefferson has also occurred at CLB, PB, or OB, or whether those systems were closed to mixing and dominated by fractional crystallization. One of the main goals of this project is to highlight the similarities and differences exhibited by neighboring magmatic systems of similar age, but different scale. Disequilibrium textures observed in thin sections from CLB, OB, and PB suggest open-system magma mixing is likely occurring beneath all three buttes. This petrographic evidence includes plagioclase and pyroxene zoning, embayed margins, sieving, and reaction rims. Major element oxide trends at all three buttes are consistent with fractional crystallization, but show narrow concentrations and non-overlapping compositions between PB, CLB, and OB. All three buttes are characterized by narrow ranges of incompatible and compatible trace element concentrations. CLB, PB, and OB all exhibit LREE enrichment and lack significant HFSE depletions, with PB exhibiting greatest enrichment in REE.

  10. Optimized mtDNA Control Region Primer Extension Capture Analysis for Forensically Relevant Samples and Highly Compromised mtDNA of Different Age and Origin

    PubMed Central

    Eduardoff, Mayra; Xavier, Catarina; Strobl, Christina; Casas-Vargas, Andrea; Parson, Walther

    2017-01-01

    The analysis of mitochondrial DNA (mtDNA) has proven useful in forensic genetics and ancient DNA (aDNA) studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR) is commonly sequenced using established Sanger-type Sequencing (STS) protocols involving fragment sizes down to approximately 150 base pairs (bp). Recent developments include Massively Parallel Sequencing (MPS) of (multiplex) PCR-generated libraries using the same amplicon sizes. Molecular genetic studies on archaeological remains that harbor more degraded aDNA have pioneered alternative approaches to target mtDNA, such as capture hybridization and primer extension capture (PEC) methods followed by MPS. These assays target smaller mtDNA fragment sizes (down to 50 bp or less), and have proven to be substantially more successful in obtaining useful mtDNA sequences from these samples compared to electrophoretic methods. Here, we present the modification and optimization of a PEC method, earlier developed for sequencing the Neanderthal mitochondrial genome, with forensic applications in mind. Our approach was designed for a more sensitive enrichment of the mtDNA CR in a single tube assay and short laboratory turnaround times, thus complying with forensic practices. We characterized the method using sheared, high quantity mtDNA (six samples), and tested challenging forensic samples (n = 2) as well as compromised solid tissue samples (n = 15) up to 8 kyrs of age. The PEC MPS method produced reliable and plausible mtDNA haplotypes that were useful in the forensic context. It yielded plausible data in samples that did not provide results with STS and other MPS techniques. We addressed the issue of contamination by including four generations of negative controls, and discuss the results in the forensic context. We finally offer perspectives for future research to enable the validation and accreditation of the PEC MPS method for

  11. 77 FR 64714 - Modification of Class E Airspace; Wolf Point, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ...-0569; Airspace Docket No. 12-ANM-17] Modification of Class E Airspace; Wolf Point, MT AGENCY: Federal... Wolf Point, MT. Controlled airspace is necessary to accommodate aircraft using Nondirectional Radio Beacon (NDB) standard instrument approach procedures at L M Clayton Airport, Wolf Point, MT. This...

  12. MT-4 suppresses resistant ovarian cancer growth through targeting tubulin and HSP27.

    PubMed

    Pai, Hui Chen; Kumar, Sunil; Shen, Chien-Chang; Liou, Jing Ping; Pan, Shiow Lin; Teng, Che Ming

    2015-01-01

    In this study, the anticancer mechanisms of MT-4 were examined in A2780 and multidrug-resistant NCI-ADR/res human ovarian cancer cell lines. To evaluate the activity of MT-4, we performed in vitro cell viability and cell cycle assays and in vivo xenograft assays. Immunoblotting analysis was carried out to evaluate the effect of MT-4 on ovarian cancer. Tubulin polymerization was determined using a tubulin binding assay. MT-4 (2-Methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-phenol), a derivative of moscatilin, can inhibit both sensitive A2780 and multidrug-resistant NCI-ADR/res cell growth and viability. MT-4 inhibited tubulin polymerization to induce G2/M arrest followed by caspase-mediated apoptosis. Further studies indicated that MT-4 is not a substrate of P-glycoprotein (p-gp). MT-4 also caused G2/M cell cycle arrest, accompanied by the upregulation of cyclin B, p-Thr161 Cdc2/p34, polo-like kinase 1 (PLK1), Aurora kinase B, and phospho-Ser10-histone H3 protein levels. In addition, we found that p38 MAPK pathway activation was involved in MT-4-induced apoptosis. Most importantly, MT-4 also decreased heat shock protein 27 expression and reduced its interaction with caspase-3, which inured cancer cells to chemotherapy resistance. Treatment of cells with SB203580 or overexpression of dominant negative (DN)-p38 or wild-type HSP27 reduced PARP cleavage caused by MT-4. MT-4 induced apoptosis through regulation of p38 and HSP27. Our xenograft models also show the in vivo efficacy of MT-4. MT-4 inhibited both A2780 and NCI-ADR/res cell growth in vitro and in vivo. These findings indicate that MT-4 could be a potential lead compound for the treatment of multidrug-resistant ovarian cancer.

  13. 76 FR 57633 - Amendment of Class E Airspace; Miles City, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-16

    ...-0515; Airspace Docket No. 11-ANM-11] Amendment of Class E Airspace; Miles City, MT AGENCY: Federal... Miles City, MT, to accommodate aircraft using a new Area Navigation (RNAV) Global Positioning System... proposed rulemaking to modify controlled airspace at Miles City, MT (76 FR 41725). Interested parties were...

  14. Mt. St. Helens Memories.

    ERIC Educational Resources Information Center

    Sharp, Len

    1992-01-01

    Provides a personal account of one science teacher's participation in a teacher workshop in which teachers learned about volcanic development, types of eruption, geomorphology, plate tectonics, volcano monitoring, and hazards created by volcanoes by examining Mt. St. Helens. Provides a graphic identifying volcanoes active since 1975. (MDH)

  15. Mt Agung (Bali) Eruption Plumes

    Atmospheric Science Data Center

    2018-05-23

    article title:  Mt Agung (Bali) Eruption Plumes     View larger image ... 2017 (left) and calculated plume heights (right)   Volcanic eruptions can generate a significant amount of atmospheric aerosols ...

  16. The Nitrate Transporter MtNPF6.8 (MtNRT1.3) Transports Abscisic Acid and Mediates Nitrate Regulation of Primary Root Growth in Medicago truncatula1[W

    PubMed Central

    Pellizzaro, Anthoni; Clochard, Thibault; Cukier, Caroline; Bourdin, Céline; Juchaux, Marjorie; Montrichard, Françoise; Thany, Steeve; Raymond, Valérie; Planchet, Elisabeth; Morère-Le Paven, Marie-Christine

    2014-01-01

    Elongation of the primary root during postgermination of Medicago truncatula seedlings is a multigenic trait that is responsive to exogenous nitrate. A quantitative genetic approach suggested the involvement of the nitrate transporter MtNPF6.8 (for Medicago truncatula NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER Family6.8) in the inhibition of primary root elongation by high exogenous nitrate. In this study, the inhibitory effect of nitrate on primary root elongation, via inhibition of elongation of root cortical cells, was abolished in npf6.8 knockdown lines. Accordingly, we propose that MtNPF6.8 mediates nitrate inhibitory effects on primary root growth in M. truncatula. pMtNPF6.8:GUS promoter-reporter gene fusion in Agrobacterium rhizogenes-generated transgenic roots showed the expression of MtNPF6.8 in the pericycle region of primary roots and lateral roots, and in lateral root primordia and tips. MtNPF6.8 expression was insensitive to auxin and was stimulated by abscisic acid (ABA), which restored the inhibitory effect of nitrate in npf6.8 knockdown lines. It is then proposed that ABA acts downstream of MtNPF6.8 in this nitrate signaling pathway. Furthermore, MtNPF6.8 was shown to transport ABA in Xenopus spp. oocytes, suggesting an additional role of MtNPF6.8 in ABA root-to-shoot translocation. 15NO3−-influx experiments showed that only the inducible component of the low-affinity transport system was affected in npf6.8 knockdown lines. This indicates that MtNPF6.8 is a major contributor to the inducible component of the low-affinity transport system. The short-term induction by nitrate of the expression of Nitrate Reductase1 (NR1) and NR2 (genes that encode two nitrate reductase isoforms) was greatly reduced in the npf6.8 knockdown lines, supporting a role of MtNPF6.8 in the primary nitrate response in M. truncatula. PMID:25367858

  17. Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts.

    PubMed

    Hurtado-Roca, Yamilee; Ledesma, Marta; Gonzalez-Lazaro, Monica; Moreno-Loshuertos, Raquel; Fernandez-Silva, Patricio; Enriquez, Jose Antonio; Laclaustra, Martin

    2016-01-01

    Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.

  18. Ethidium bromide as a marker of mtDNA replication in living cells

    NASA Astrophysics Data System (ADS)

    Villa, Anna Maria; Fusi, Paola; Pastori, Valentina; Amicarelli, Giulia; Pozzi, Chiara; Adlerstein, Daniel; Doglia, Silvia Maria

    2012-04-01

    Mitochondrial DNA (mtDNA) in tumor cells was found to play an important role in maintaining the malignant phenotype. Using laser scanning confocal fluorescence microscopy (LSCFM) in a recent work, we reported a variable fluorescence intensity of ethidium bromide (EB) in mitochondria nucleoids of living carcinoma cells. Since when EB is bound to nucleic acids its fluorescence is intensified; a higher EB fluorescence intensity could reflect a higher DNA accessibility to EB, suggesting a higher mtDNA replication activity. To prove this hypothesis, in the present work we studied, by LSCFM, the EB fluorescence in mitochondria nucleoids of living neuroblastoma cells, a model system in which differentiation affects the level of mtDNA replication. A drastic decrease of fluorescence was observed after differentiation. To correlate EB fluorescence intensity to the mtDNA replication state, we evaluated the mtDNA nascent strands content by ligation-mediated real-time PCR, and we found a halved amount of replicating mtDNA molecules in differentiating cells. A similar result was obtained by BrdU incorporation. These results indicate that the low EB fluorescence of nucleoids in differentiated cells is correlated to a low content of replicating mtDNA, suggesting that EB may be used as a marker of mtDNA replication in living cells.

  19. Inattention blindness to motion in area MT

    PubMed Central

    Harrison, Ian T.; Weiner, Katherine F.; Ghose, Geoffrey M.

    2013-01-01

    Subjects naturally form and use expectations to solve familiar tasks, but the accuracy of these expectations, and the neuronal mechanisms by which these expectations enhance behavior, are unclear. We trained animals (Macaca mulatta) in a challenging perceptual task in which the likelihood of a very brief pulse of motion was consistently modulated over time and space. Pulse likelihood had dramatic effects on behavior: unexpected pulses were nearly invisible to the animals. To examine the neuronal basis of such inattention blindness, we recorded from single neurons in the middle temporal (MT) area, an area related to motion perception. Fluctuations in how reliably MT neurons both signaled stimulus events and predicted behavioral choices were highly correlated with changes in performance over the course of individual trials. A simple neuronal pooling model reveals the dramatic behavioral effects of attention in this task can be completely explained by changes in the reliability of a small number of MT neurons. PMID:23658178

  20. Modeling the Geologic History of Mt. Sharp

    NASA Technical Reports Server (NTRS)

    Pascuzzo, A.; Allen, C.

    2015-01-01

    Gale is an approximately 155 km diameter crater located on the martian dichotomy boundary (5 deg S 138 deg E). Gale is estimated to have formed 3.8 - 3.5 Gya, in the late Noachian or early Hesperian. Mt. Sharp, at the center of Gale Crater, is a crescent shaped sedimentary mound that rises 5.2 km above the crater floor. Gale is one of the few craters that has a peak reaching higher than the rim of the crater wall. The Curiosity rover is currently fighting to find its way across a dune field at the northwest base of the mound searching for evidence of habitability. This study used orbital images and topographic data to refine models for the geologic history of Mt. Sharp by analyzing its morphological features. In addition, it assessed the possibility of a peak ring in Gale. The presence of a peak ring can offer important information to how Mt. Sharp was formed and eroded early in Gale's history.

  1. [MT-45--a dangerous and potentially ototoxic internet drug].

    PubMed

    Lindeman, Erik; Bäckberg, Matilda; Personne, Mark; Helander, Anders

    2014-09-11

    During the last years several synthetic opioids have been introduced on Internet sites selling new psychoactive substances (NPS). One of these, called MT-45, a piperazine derivative originally synthesized as a therapeutic drug candidate in the 1970s, has recently been detected in 21 deaths, according to unpublished data from the Swedish National Board of Forensic Medicine. We present clinical data from 12 analytically confirmed hospital cases of MT-45 poisoning. The cases demonstrate that MT-45, like other opioids, can induce potentially life threatening respiratory depression and loss of consciousness in users and that symptoms are usually reversed by standard doses of the opioid receptor antagonist naloxone. Significant auditory symptoms with transient tinnitus and hearing loss occurred in two cases and a pronounced sensorineural hearing loss still present at two weeks follow-up in one case. This indicates that MT-45 may be an ototoxic substance, illustrating the ubiquitous risk of unintended adverse effects NPSs pose to users.

  2. Mt. St. Helens

    NASA Image and Video Library

    2001-10-22

    This 3-D anaglyph image of Mt. St. Helens volcano combines the nadir-looking and back-looking band 3 images of ASTER. To view the image in stereo, you will need blue-red glasses. Make sure to look through the red lens with your left eye. This ASTER image of Mt. St. Helens volcano in Washington was acquired on August 8, 2000 and covers an area of 37 by 51 km. Mount Saint Helens, a volcano in the Cascade Range of southwestern Washington that had been dormant since 1857, began to show signs of renewed activity in early 1980. On 18 May 1980, it erupted with such violence that the top of the mountain was blown off, spewing a cloud of ash and gases that rose to an altitude of 19 kilometers. The blast killed about 60 people and destroyed all life in an area of some 180 square kilometers (some 70 square miles), while a much larger area was covered with ash and debris. It continues to spit forth ash and steam intermittently. As a result of the eruption, the mountain's elevation decreased from 2,950 meters to 2,549 meters. The image is centered at 46.2 degrees north latitude, 122.2 degrees west longitude. http://photojournal.jpl.nasa.gov/catalog/PIA11160

  3. Full-wave Ambient Noise Tomography of Mt Rainier volcano, USA

    NASA Astrophysics Data System (ADS)

    Flinders, Ashton; Shen, Yang

    2015-04-01

    Mount Rainier towers over the landscape of western Washington (USA), ranking with Fuji-yama in Japan, Mt Pinatubo in the Philippines, and Mt Vesuvius in Italy, as one of the great stratovolcanoes of the world. Notwithstanding its picturesque stature, Mt Rainier is potentially the most devastating stratovolcano in North America, with more than 3.5 million people living beneath is shadow in the Seattle-Tacoma area. The primary hazard posed by the volcano is in the form of highly destructive debris flows (lahars). These lahars form when water and/or melted ice erode away and entrain preexisting volcanic sediment. At Mt Rainier these flows are often initiated by sector collapse of the volcano's hydrothermally rotten flanks and compounded by Mt Rainier's extensive snow and glacial ice coverage. It is therefore imperative to ascertain the extent of the volcano's summit hydrothermal alteration, and determine areas prone to collapse. Despite being one of the sixteen volcanoes globally designated by the International Association of Volcanology and Chemistry of the Earth's Interior as warranting detailed and focused study, Mt Rainier remains enigmatic both in terms of the shallow internal structure and the degree of summit hydrothermal alteration. We image this shallow internal structure and areas of possible summit alteration using ambient noise tomography. Our full waveform forward modeling includes high-resolution topography allowing us to accuratly account for the effects of topography on the propagation of short-period Rayleigh waves. Empirical Green's functions were extracted from 80 stations within 200 km of Mt Rainier, and compared with synthetic greens functions over multiple frequency bands from 2-28 seconds.

  4. Myopathic mtDNA Depletion Syndrome Due to Mutation in TK2 Gene.

    PubMed

    Martín-Hernández, Elena; García-Silva, María Teresa; Quijada-Fraile, Pilar; Rodríguez-García, María Elena; Rivera, Henry; Hernández-Laín, Aurelio; Coca-Robinot, David; Fernández-Toral, Joaquín; Arenas, Joaquín; Martín, Miguel A; Martínez-Azorín, Francisco

    2017-01-01

    Whole-exome sequencing was used to identify the disease gene(s) in a Spanish girl with failure to thrive, muscle weakness, mild facial weakness, elevated creatine kinase, deficiency of mitochondrial complex III and depletion of mtDNA. With whole-exome sequencing data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The analysis of whole exome uncovered a homozygous pathogenic mutation in thymidine kinase 2 gene ( TK2; NM_004614.4:c.323 C>T, p.T108M). TK2 mutations have been identified mainly in patients with the myopathic form of mtDNA depletion syndromes. This patient presents an atypical TK2-related myopathic form of mtDNA depletion syndromes, because despite having a very low content of mtDNA (<20%), she presents a slower and less severe evolution of the disease. In conclusion, our data confirm the role of TK2 gene in mtDNA depletion syndromes and expanded the phenotypic spectrum.

  5. MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

    PubMed Central

    Li, Xiaoran; Zhong, Yali; Lu, Jie; Axcrona, Karol; Eide, Lars; Syljuåsen, Randi G.; Peng, Qian; Wang, Junbai; Zhang, Hongquan; Goscinski, Mariusz Adam; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features. PMID:27248169

  6. A reduced number of mtSNPs saturates mitochondrial DNA haplotype diversity of worldwide population groups.

    PubMed

    Salas, Antonio; Amigo, Jorge

    2010-05-03

    The high levels of variation characterising the mitochondrial DNA (mtDNA) molecule are due ultimately to its high average mutation rate; moreover, mtDNA variation is deeply structured in different populations and ethnic groups. There is growing interest in selecting a reduced number of mtDNA single nucleotide polymorphisms (mtSNPs) that account for the maximum level of discrimination power in a given population. Applications of the selected mtSNP panel range from anthropologic and medical studies to forensic genetic casework. This study proposes a new simulation-based method that explores the ability of different mtSNP panels to yield the maximum levels of discrimination power. The method explores subsets of mtSNPs of different sizes randomly chosen from a preselected panel of mtSNPs based on frequency. More than 2,000 complete genomes representing three main continental human population groups (Africa, Europe, and Asia) and two admixed populations ("African-Americans" and "Hispanics") were collected from GenBank and the literature, and were used as training sets. Haplotype diversity was measured for each combination of mtSNP and compared with existing mtSNP panels available in the literature. The data indicates that only a reduced number of mtSNPs ranging from six to 22 are needed to account for 95% of the maximum haplotype diversity of a given population sample. However, only a small proportion of the best mtSNPs are shared between populations, indicating that there is not a perfect set of "universal" mtSNPs suitable for all population contexts. The discrimination power provided by these mtSNPs is much higher than the power of the mtSNP panels proposed in the literature to date. Some mtSNP combinations also yield high diversity values in admixed populations. The proposed computational approach for exploring combinations of mtSNPs that optimise the discrimination power of a given set of mtSNPs is more efficient than previous empirical approaches. In contrast to

  7. A Reduced Number of mtSNPs Saturates Mitochondrial DNA Haplotype Diversity of Worldwide Population Groups

    PubMed Central

    Salas, Antonio; Amigo, Jorge

    2010-01-01

    Background The high levels of variation characterising the mitochondrial DNA (mtDNA) molecule are due ultimately to its high average mutation rate; moreover, mtDNA variation is deeply structured in different populations and ethnic groups. There is growing interest in selecting a reduced number of mtDNA single nucleotide polymorphisms (mtSNPs) that account for the maximum level of discrimination power in a given population. Applications of the selected mtSNP panel range from anthropologic and medical studies to forensic genetic casework. Methodology/Principal Findings This study proposes a new simulation-based method that explores the ability of different mtSNP panels to yield the maximum levels of discrimination power. The method explores subsets of mtSNPs of different sizes randomly chosen from a preselected panel of mtSNPs based on frequency. More than 2,000 complete genomes representing three main continental human population groups (Africa, Europe, and Asia) and two admixed populations (“African-Americans” and “Hispanics”) were collected from GenBank and the literature, and were used as training sets. Haplotype diversity was measured for each combination of mtSNP and compared with existing mtSNP panels available in the literature. The data indicates that only a reduced number of mtSNPs ranging from six to 22 are needed to account for 95% of the maximum haplotype diversity of a given population sample. However, only a small proportion of the best mtSNPs are shared between populations, indicating that there is not a perfect set of “universal” mtSNPs suitable for all population contexts. The discrimination power provided by these mtSNPs is much higher than the power of the mtSNP panels proposed in the literature to date. Some mtSNP combinations also yield high diversity values in admixed populations. Conclusions/Significance The proposed computational approach for exploring combinations of mtSNPs that optimise the discrimination power of a given set of

  8. Extensive paternal mtDNA leakage in natural populations of Drosophila melanogaster.

    PubMed

    Nunes, Maria D S; Dolezal, Marlies; Schlötterer, Christian

    2013-04-01

    Strict maternal inheritance is considered a hallmark of animal mtDNA. Although recent reports suggest that paternal leakage occurs in a broad range of species, it is still considered an exceptionally rare event. To evaluate the impact of paternal leakage on the evolution of mtDNA, it is essential to reliably estimate the frequency of paternal leakage in natural populations. Using allele-specific real-time quantitative PCR (RT-qPCR), we show that heteroplasmy is common in natural populations with at least 14% of the individuals carrying multiple mitochondrial haplotypes. However, the average frequency of the minor mtDNA haplotype is low (0.8%), which suggests that this pervasive heteroplasmy has not been noticed before due to a lack of power in sequencing surveys. Based on the distribution of mtDNA haplotypes in the offspring of heteroplasmic mothers, we found no evidence for strong selection against one of the haplotypes. We estimated that the rate of paternal leakage is 6% and that at least 100 generations are required for complete sorting of mtDNA haplotypes. Despite the high proportion of heteroplasmic individuals in natural populations, we found no evidence for recombination between mtDNA molecules, suggesting that either recombination is rare or recombinant haplotypes are counter-selected. Our results indicate that evolutionary studies using mtDNA as a marker might be biased by paternal leakage in this species. © 2013 Blackwell Publishing Ltd.

  9. 77 FR 41939 - Proposed Establishment of Class E Airspace; Deer Lodge, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-17

    ...-0379; Airspace Docket No. 12-ANM-7 Proposed Establishment of Class E Airspace; Deer Lodge, MT AGENCY... action proposes to establish Class E airspace at Deer Lodge-City-County Airport, Deer Lodge, MT... System (GPS) standard instrument approach procedures at Deer Lodge-City-County Airport, Deer Lodge, MT...

  10. Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.

    PubMed

    Sharan, Kunal; Lewis, Kirsty; Furukawa, Takahisa; Yadav, Vijay K

    2017-09-01

    Tryptophan, an essential amino acid through a series of enzymatic reactions gives rise to various metabolites, viz. serotonin and melatonin, that regulate distinct biological functions. We show here that tryptophan metabolism in the pineal gland favors bone mass accrual through production of melatonin, a pineal-derived neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes the first step in the melatonin biosynthesis lead to a decrease in melatonin levels and a low bone mass due to an isolated decrease in bone formation while bone resorption parameters remained unaffected. Skeletal analysis of the mice deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/- and MT2-/- mice showed a cell intrinsic defect in the proliferation, differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT counterparts, and the mutant cells did not respond to melatonin addition. Finally, we demonstrate that daily oral administration of melatonin can increase bone accrual during growth and can cure ovariectomy-induced structural and functional degeneration of bone by specifically increasing bone formation. By identifying pineal-derived melatonin as a regulator of bone mass through MT2 receptors, this study expands the role played by tryptophan derivatives in the regulation of bone mass and underscores its therapeutic relevance in postmenopausal osteoporosis. © 2017 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd.

  11. mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Chengye; Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091; Graduate University of the Chinese Academy of Sciences, Beijing 100039

    2006-09-22

    Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To testmore » this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL.« less

  12. 78 FR 52112 - Proposed Amendment of Class E Airspace; Cut Bank, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ...-0664; Airspace Docket No. 13-ANM-22] Proposed Amendment of Class E Airspace; Cut Bank, MT AGENCY... action proposes to modify Class E airspace at Cut Bank Municipal Airport, Cut Bank, MT. Controlled... from 700/1,200 feet above the surface at Cut Bank Municipal Airport, Cut Bank, MT. Controlled airspace...

  13. [Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

    PubMed

    Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

    2012-10-01

    The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

  14. mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences

    PubMed Central

    Zapico, Sara C.; Ubelaker, Douglas H.

    2013-01-01

    Mitochondria are independent organelles with their own DNA. As a primary function, mitochondria produce the energy for the cell through Oxidative Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic products of this process is Reactive Oxygen Species (ROS), which can induce oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear DNA (nDNA), and as such is more exposed to oxidative, mutation-inducing damage. This review analyzes the causes and consequences of mtDNA mutations and their relationship with the aging process. Neurodegenerative diseases, related with the aging, are consequences of mtDNA mutations resulting in a decrease in mitochondrial function. Also described are “mitochondrial diseases”, pathologies produced by mtDNA mutations and whose symptoms are related with mitochondrial dysfunction. Finally, mtDNA haplogroups are defined in this review; these groups are important for determination of geographical origin of an individual. Additionally, different haplogroups exhibit variably longevity and risk of certain diseases. mtDNA mutations in aging and haplogroups are of special interest to forensic science research. Therefore this review will help to clarify the key role of mtDNA mutations in these processes and support further research in this area. PMID:24307969

  15. Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice.

    PubMed

    Safdar, Adeel; Khrapko, Konstantin; Flynn, James M; Saleem, Ayesha; De Lisio, Michael; Johnston, Adam P W; Kratysberg, Yevgenya; Samjoo, Imtiaz A; Kitaoka, Yu; Ogborn, Daniel I; Little, Jonathan P; Raha, Sandeep; Parise, Gianni; Akhtar, Mahmood; Hettinga, Bart P; Rowe, Glenn C; Arany, Zoltan; Prolla, Tomas A; Tarnopolsky, Mark A

    2016-01-01

    Human genetic disorders and transgenic mouse models have shown that mitochondrial DNA (mtDNA) mutations and telomere dysfunction instigate the aging process. Epidemiologically, exercise is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of exercise are well established, the molecular mechanisms instigating these observations remain unclear. Endurance exercise reduces mtDNA mutation burden, alleviates multisystem pathology, and increases lifespan of the mutator mice, with proofreading deficient mitochondrial polymerase gamma (POLG1). We report evidence for a POLG1-independent mtDNA repair pathway mediated by exercise, a surprising notion as POLG1 is canonically considered to be the sole mtDNA repair enzyme. Here, we show that the tumor suppressor protein p53 translocates to mitochondria and facilitates mtDNA mutation repair and mitochondrial biogenesis in response to endurance exercise. Indeed, in mutator mice with muscle-specific deletion of p53, exercise failed to prevent mtDNA mutations, induce mitochondrial biogenesis, preserve mitochondrial morphology, reverse sarcopenia, or mitigate premature mortality. Our data establish a new role for p53 in exercise-mediated maintenance of the mtDNA genome and present mitochondrially targeted p53 as a novel therapeutic modality for diseases of mitochondrial etiology.

  16. MtSWEET11, a Nodule-Specific Sucrose Transporter of Medicago truncatula

    DOE PAGES

    Kryvoruchko, Igor S.; Sinharoy, Senjuti; Torres-Jerez, Ivone; ...

    2016-03-28

    Optimization of nitrogen fixation by rhizobia in legumes is a key area of research for sustainable agriculture. Symbiotic nitrogen fixation (SNF) occurs in specialized organs called nodules and depends on a steady supply of carbon to both plant and bacterial cells. Here we report the functional characterization of a nodule-specific Suc transporter, MtSWEET11 from Medicago truncatula. MtSWEET11 belongs to a clade of plant SWEET proteins that are capable of transporting Suc and play critical roles in pathogen susceptibility. When expressed in mammalian cells, MtSWEET11 transported sucrose (Suc) but not glucose (Glc). The MtSWEET11 gene was found to be expressed inmore » infected root hair cells, and in the meristem, invasion zone, and vasculature of nodules. Expression of an MtSWEET11-GFP fusion protein in nodules resulted in green fluorescence associated with the plasma membrane of uninfected cells and infection thread and symbiosome membranes of infected cells. Two independent Tnt1-insertion sweet11 mutants were uncompromised in SNF. Furthermore, although MtSWEET11 appears to be involved in Suc distribution within nodules, it is not crucial for SNF, probably because other Suc transporters can fulfill its role(s).« less

  17. 75 FR 30367 - North Mt. Baker-Snoqualmie Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ... DEPARTMENT OF AGRICULTURE Forest Service North Mt. Baker-Snoqualmie Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The North Mt. Baker-Snoqualmie (MBS... meeting to: (1) Provide an orientation about Title II and the Federal Resource Advisory Committee; (2...

  18. Development of forensic-quality full mtGenome haplotypes: success rates with low template specimens.

    PubMed

    Just, Rebecca S; Scheible, Melissa K; Fast, Spence A; Sturk-Andreaggi, Kimberly; Higginbotham, Jennifer L; Lyons, Elizabeth A; Bush, Jocelyn M; Peck, Michelle A; Ring, Joseph D; Diegoli, Toni M; Röck, Alexander W; Huber, Gabriela E; Nagl, Simone; Strobl, Christina; Zimmermann, Bettina; Parson, Walther; Irwin, Jodi A

    2014-05-01

    Forensic mitochondrial DNA (mtDNA) testing requires appropriate, high quality reference population data for estimating the rarity of questioned haplotypes and, in turn, the strength of the mtDNA evidence. Available reference databases (SWGDAM, EMPOP) currently include information from the mtDNA control region; however, novel methods that quickly and easily recover mtDNA coding region data are becoming increasingly available. Though these assays promise to both facilitate the acquisition of mitochondrial genome (mtGenome) data and maximize the general utility of mtDNA testing in forensics, the appropriate reference data and database tools required for their routine application in forensic casework are lacking. To address this deficiency, we have undertaken an effort to: (1) increase the large-scale availability of high-quality entire mtGenome reference population data, and (2) improve the information technology infrastructure required to access/search mtGenome data and employ them in forensic casework. Here, we describe the application of a data generation and analysis workflow to the development of more than 400 complete, forensic-quality mtGenomes from low DNA quantity blood serum specimens as part of a U.S. National Institute of Justice funded reference population databasing initiative. We discuss the minor modifications made to a published mtGenome Sanger sequencing protocol to maintain a high rate of throughput while minimizing manual reprocessing with these low template samples. The successful use of this semi-automated strategy on forensic-like samples provides practical insight into the feasibility of producing complete mtGenome data in a routine casework environment, and demonstrates that large (>2kb) mtDNA fragments can regularly be recovered from high quality but very low DNA quantity specimens. Further, the detailed empirical data we provide on the amplification success rates across a range of DNA input quantities will be useful moving forward as PCR

  19. Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

    PubMed Central

    Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

    2015-01-01

    The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

  20. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.

    PubMed

    Lewis, Samantha C; Uchiyama, Lauren F; Nunnari, Jodi

    2016-07-15

    Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria. Copyright © 2016, American Association for the Advancement of Science.

  1. Re-examining overlap between tactile and visual motion responses within hMT+ and STS

    PubMed Central

    Jiang, Fang; Beauchamp, Michael S.; Fine, Ione

    2015-01-01

    Here we examine overlap between tactile and visual motion BOLD responses within the human MT+ complex. Although several studies have reported tactile responses overlapping with hMT+, many used group average analyses, leaving it unclear whether these responses were restricted to sub-regions of hMT+. Moreover, previous studies either employed a tactile task or passive stimulation, leaving it unclear whether or not tactile responses in hMT+ are simply the consequence of visual imagery. Here we carried out a replication of one of the classic papers finding tactile responses in hMT+ (Hagen et al. 2002). We mapped MT and MST in individual subjects using visual field localizers. We then examined responses to tactile motion on the arm, either presented passively or in the presence of a visual task performed at fixation designed to minimize visualization of the concurrent tactile stimulation. To our surprise, without a visual task, we found only weak tactile motion responses in MT (6% of voxels showing tactile responses) and MST (2% of voxels). With an unrelated visual task designed to withdraw attention from the tactile modality, responses in MST reduced to almost nothing (<1% regions). Consistent with previous results, we did observe tactile responses in STS regions superior and anterior to hMT+. Despite the lack of individual overlap, group averaged responses produced strong spurious overlap between tactile and visual motion responses within hMT+ that resembled those observed in previous studies. The weak nature of tactile responses in hMT+ (and their abolition by withdrawal of attention) suggests that hMT+ may not serve as a supramodal motion processing module. PMID:26123373

  2. mtDNA sequence diversity of Hazara ethnic group from Pakistan.

    PubMed

    Rakha, Allah; Fatima; Peng, Min-Sheng; Adan, Atif; Bi, Rui; Yasmin, Memona; Yao, Yong-Gang

    2017-09-01

    The present study was undertaken to investigate mitochondrial DNA (mtDNA) control region sequences of Hazaras from Pakistan, so as to generate mtDNA reference database for forensic casework in Pakistan and to analyze phylogenetic relationship of this particular ethnic group with geographically proximal populations. Complete mtDNA control region (nt 16024-576) sequences were generated through Sanger Sequencing for 319 Hazara individuals from Quetta, Baluchistan. The population sample set showed a total of 189 distinct haplotypes, belonging mainly to West Eurasian (51.72%), East & Southeast Asian (29.78%) and South Asian (18.50%) haplogroups. Compared with other populations from Pakistan, the Hazara population had a relatively high haplotype diversity (0.9945) and a lower random match probability (0.0085). The dataset has been incorporated into EMPOP database under accession number EMP00680. The data herein comprises the largest, and likely most thoroughly examined, control region mtDNA dataset from Hazaras of Pakistan. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 76 FR 19281 - Proposed Amendment of Class E Airspace; Bozeman, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-07

    ... Instrument Landing System (ILS) Localizer (LOC) standard instrument approach procedures at the airport. The... extending upward from 700 feet or more above the surface of the earth. * * * * * ANM MT E5 Bozeman, MT...

  4. African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

    PubMed Central

    Ely, Bert; Wilson, Jamie Lee; Jackson, Fatimah; Jackson, Bruce A

    2006-01-01

    Background Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. Results When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from

  5. 75 FR 41075 - Amendment of Class E Airspace; Bozeman, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ...-1220; Airspace Docket No. 09-ANM-30] Amendment of Class E Airspace; Bozeman, MT AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action will amend Class E airspace at... proposed rulemaking to amend Class E airspace at Bozeman, MT (75 FR 20321). Interested parties were invited...

  6. Mt. Kilimanjaro expedition in earth science education

    NASA Astrophysics Data System (ADS)

    Sparrow, Elena; Yoshikawa, Kenji; Narita, Kenji; Brettenny, Mark; Yule, Sheila; O'Toole, Michael; Brettenny, Rogeline

    2010-05-01

    Mt. Kilimanjaro, Africa's highest mountain is 5,895 meters above sea level and is located 330 km south of the equator in Tanzania. In 1976 glaciers covered most of Mt. Kilimanjaro's summit; however in 2000, an estimated eighty percent of the ice cap has disappeared since the last thorough survey done in 1912. There is increased scientific interest in Mt. Kilimanjaro with the increase in global and African average temperatures. A team of college and pre-college school students from Tanzania, South Africa and Kenya, teachers from South Africa and the United States, and scientists from the University of Alaska Fairbanks in the United States and Akita University in Japan, climbed to the summit of Mt Kilimanjaro in October 2009. They were accompanied by guides, porters, two expedition guests, and a videographer. This expedition was part of the GLOBE Seasons and Biomes Earth System Science Project and the GLOBE Africa science education initiative, exploring and contributing to climate change studies. Students learned about earth science experientially by observing their physical and biological surroundings, making soil and air temperature measurements, participating in discussions, journaling their experience, and posing research questions. The international trekkers noted the change in the biomes as the altitude, temperature and conditions changed, from cultivated lands, to rain forest, heath zone, moorland, alpine desert, and summit. They also discovered permafrost, but not at the summit as expected. Rather, it was where the mountain was not covered by a glacier and thus more exposed to low extreme temperatures. This was the first report of permafrost on Mt. Kilimanjaro. Classrooms from all over the world participated in the expedition virtually. They followed the trek through the expedition website (http://www.xpeditiononline.com/) where pictures and journals were posted, and posed their own questions which were answered by the expedition and base camp team members

  7. New geophysical views of Mt.Melbourne Volcano (East Antarctica)

    NASA Astrophysics Data System (ADS)

    Armadillo, E.; Gambetta, M.; Ferraccioli, F.; Corr, H.; Bozzo, E.

    2009-05-01

    Mt. Melbourne volcano is located along the transition between the Transantarctic Mountains and the West Antarctic Rift System. Recent volcanic activity is suggested by the occurrence of blankets of pyroclastic pumice and scoria fall around the eastern and southern flanks of Mt Melbourne and by pyroclastic layers interbedded with the summit snows. Geothermal activity in the crater area of Mount Melbourne may be linked to the intrusion of dykes within the last 200 years. Geophysical networks suggest that Mount Melbourne is a quiescent volcano, possibly characterised by slow internal dynamics. During the 2002-2003 Italian Antarctic campaign a high-resolution aeromagnetic survey was performed within the TIMM (Tectonics and Interior of Mt. Melbourne area) project. This helicopter-borne survey was flown at low-altitude and in drape-mode configuration (305 m above terrain) with a line separation less than 500 m. Our new high-resolution magnetic maps reveal the largely ice-covered magmatic and tectonic patters in the Mt. Melbourne volcano area. Additionally, in the frame of the UK-Italian ISODYN-WISE project (2005-06), an airborne ice-sounding radar survey was flown. We combine the sub-ice topography with images and models of the interior of Mt. Melbourne volcano, as derived from the high resolution aeromagnetic data and land gravity data. Our new geophysical maps and models also provide a new tool to study the regional setting of the volcano. In particular we re-assess whether there is geophysical evidence for coupling between strike-slip faulting, the Terror Rift, and Mount Melbourne volcano.

  8. MtMAPKK4 is an essential gene for growth and reproduction of Medicago truncatula.

    PubMed

    Chen, Tao; Zhou, Bo; Duan, Liujian; Zhu, Hui; Zhang, Zhongming

    2017-04-01

    Mitogen-activated protein kinase (MAPK) cascades are universal signaling modules in eukaryotes, including yeasts, animals and plants. They are involved in responses to various biotic and abiotic stresses, hormones, cell division and developmental processes. A MAPK cascade is composed of three functionally tiered protein kinases, namely MAPK, MAPK kinases (MAPKKs) and MAPK kinase kinases (MAPKKKs). These kinases have been intensively studied for their roles in developmental and physiological processes in various organisms. In this study, a Medicago truncatula MtMAPKK4 mutant with the tobacco retrotransposon Tnt1 insertion was identified using reverse genetics methods. No homozygous progeny could be produced by self-pollination of mapkk4/+ heterozygotes for 5 generations. Heterozygous mapkk4/+ mutant plants exhibited growth retardation, chlorosis symptoms and significantly reduced numbers of infection threads and nodules. The interaction between MtMAPKK4 and MtMAPK3/6 occurred both in yeast and in planta. Green fluorescent protein-tagged MtMAPKK4, MtMAPK3 and MtMAPK6 were all localized to membranes, cytoplasm and nuclei. Expression of MtMAPKK4, MtMAPK3 and MtMAPK6 was detected in various tissues of M. truncatula plants at the nodule maturation stage. Transcript levels of these genes were decreased in roots at the early symbiotic stage. © 2016 Scandinavian Plant Physiology Society.

  9. MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis

    PubMed Central

    Miller, Mary-Clare; Manning, Hugh B.; Jain, Abhilash; Troeberg, Linda; Dudhia, Jayesh; Essex, David; Sandison, Ann; Seiki, Motoharu; Nanchahal, Jagdeep; Nagase, Hideaki; Itoh, Yoshifumi

    2010-01-01

    Objective A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness. Methods Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined. Results MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. Conclusion MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA. PMID:19248098

  10. Construct Validity of the MMPI-2 College Maladjustment (Mt) Scale

    ERIC Educational Resources Information Center

    Barthlow, Deanna L.; Graham, John R.; Ben-Porath, Yossef S.; McNulty, John L

    2004-01-01

    The construct validity of the MMPI-2 (Minnesota Multiphasic Personality Inventory-2) College Maladjustment (Mt) Scale was examined using 376 student clients at a university psychological clinic. A principal components analysis and correlations of Mt scale scores with clients' and therapists' ratings of symptoms and functioning showed that the Mt…

  11. Critical Role of Transient Activity of MT1-MMP for ECM Degradation in Invadopodia

    PubMed Central

    Watanabe, Ayako; Hosino, Daisuke; Koshikawa, Naohiko; Seiki, Motoharu; Suzuki, Takashi; Ichikawa, Kazuhisa

    2013-01-01

    Focal degradation of extracellular matrix (ECM) is the first step in the invasion of cancer cells. MT1-MMP is a potent membrane proteinase employed by aggressive cancer cells. In our previous study, we reported that MT1-MMP was preferentially located at membrane protrusions called invadopodia, where MT1-MMP underwent quick turnover. Our computer simulation and experiments showed that this quick turnover was essential for the degradation of ECM at invadopodia (Hoshino, D., et al., (2012) PLoS Comp. Biol., 8: e1002479). Here we report on characterization and analysis of the ECM-degrading activity of MT1-MMP, aiming at elucidating a possible reason for its repetitive insertion in the ECM degradation. First, in our computational model, we found a very narrow transient peak in the activity of MT1-MMP followed by steady state activity. This transient activity was due to the inhibition by TIMP-2, and the steady state activity of MT1-MMP decreased dramatically at higher TIMP-2 concentrations. Second, we evaluated the role of the narrow transient activity in the ECM degradation. When the transient activity was forcibly suppressed in computer simulations, the ECM degradation was heavily suppressed, indicating the essential role of this transient peak in the ECM degradation. Third, we compared continuous and pulsatile turnover of MT1-MMP in the ECM degradation at invadopodia. The pulsatile insertion showed basically consistent results with the continuous insertion in the ECM degradation, and the ECM degrading efficacy depended heavily on the transient activity of MT1-MMP in both models. Unexpectedly, however, low-frequency/high-concentration insertion of MT1-MMP was more effective in ECM degradation than high-frequency/low-concentration pulsatile insertion even if the time-averaged amount of inserted MT1-MMP was the same. The present analysis and characterization of ECM degradation by MT1-MMP together with our previous report indicate a dynamic nature of MT1-MMP at

  12. Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

    PubMed Central

    Wimer, H.F.; Yamada, S.S.; Yang, T.; Holmbeck, K.; Foster, B.L.

    2016-01-01

    Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP−/−) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data

  13. [Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGM™ Platform].

    PubMed

    Cao, Y; Zou, K N; Huang, J P; Ma, K; Ping, Y

    2017-08-01

    To analyze and detect the whole genome sequence of human mitochondrial DNA (mtDNA) by Ion Torrent PGM™ platform and to study the differences of mtDNA sequence in different tissues. Samples were collected from 6 unrelated individuals by forensic postmortem examination, including chest blood, hair, costicartilage, nail, skeletal muscle and oral epithelium. Amplification of whole genome sequence of mtDNA was performed by 4 pairs of primer. Libraries were constructed with Ion Shear™ Plus Reagents kit and Ion Plus Fragment Library kit. Whole genome sequencing of mtDNA was performed using Ion Torrent PGM™ platform. Sanger sequencing was used to determine the heteroplasmy positions and the mutation positions on HVⅠ region. The whole genome sequence of mtDNA from all samples were amplified successfully. Six unrelated individuals belonged to 6 different haplotypes. Different tissues in one individual had heteroplasmy difference. The heteroplasmy positions and the mutation positions on HVⅠ region were verified by Sanger sequencing. After a consistency check by the Kappa method, it was found that the results of mtDNA sequence had a high consistency in different tissues. The testing method used in present study for sequencing the whole genome sequence of human mtDNA can detect the heteroplasmy difference in different tissues, which have good consistency. The results provide guidance for the further applications of mtDNA in forensic science. Copyright© by the Editorial Department of Journal of Forensic Medicine

  14. 76 FR 53049 - Amendment of Class E Airspace; Shelby, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-25

    ...-0536; Airspace Docket No. 11-ANM-13] Amendment of Class E Airspace; Shelby, MT AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action modifies Class E airspace at Shelby, MT, to... E airspace designations are published in paragraph 6005 of FAA Order 7400.9U dated August 18, 2010...

  15. How good are indirect tests at detecting recombination in human mtDNA?

    PubMed

    White, Daniel James; Bryant, David; Gemmell, Neil John

    2013-07-08

    Empirical proof of human mitochondrial DNA (mtDNA) recombination in somatic tissues was obtained in 2004; however, a lack of irrefutable evidence exists for recombination in human mtDNA at the population level. Our inability to demonstrate convincingly a signal of recombination in population data sets of human mtDNA sequence may be due, in part, to the ineffectiveness of current indirect tests. Previously, we tested some well-established indirect tests of recombination (linkage disequilibrium vs. distance using D' and r(2), Homoplasy Test, Pairwise Homoplasy Index, Neighborhood Similarity Score, and Max χ(2)) on sequence data derived from the only empirically confirmed case of human mtDNA recombination thus far and demonstrated that some methods were unable to detect recombination. Here, we assess the performance of these six well-established tests and explore what characteristics specific to human mtDNA sequence may affect their efficacy by simulating sequence under various parameters with levels of recombination (ρ) that vary around an empirically derived estimate for human mtDNA (population parameter ρ = 5.492). No test performed infallibly under any of our scenarios, and error rates varied across tests, whereas detection rates increased substantially with ρ values > 5.492. Under a model of evolution that incorporates parameters specific to human mtDNA, including rate heterogeneity, population expansion, and ρ = 5.492, successful detection rates are limited to a range of 7-70% across tests with an acceptable level of false-positive results: the neighborhood similarity score incompatibility test performed best overall under these parameters. Population growth seems to have the greatest impact on recombination detection probabilities across all models tested, likely due to its impact on sequence diversity. The implications of our findings on our current understanding of mtDNA recombination in humans are discussed.

  16. How Good Are Indirect Tests at Detecting Recombination in Human mtDNA?

    PubMed Central

    White, Daniel James; Bryant, David; Gemmell, Neil John

    2013-01-01

    Empirical proof of human mitochondrial DNA (mtDNA) recombination in somatic tissues was obtained in 2004; however, a lack of irrefutable evidence exists for recombination in human mtDNA at the population level. Our inability to demonstrate convincingly a signal of recombination in population data sets of human mtDNA sequence may be due, in part, to the ineffectiveness of current indirect tests. Previously, we tested some well-established indirect tests of recombination (linkage disequilibrium vs. distance using D′ and r2, Homoplasy Test, Pairwise Homoplasy Index, Neighborhood Similarity Score, and Max χ2) on sequence data derived from the only empirically confirmed case of human mtDNA recombination thus far and demonstrated that some methods were unable to detect recombination. Here, we assess the performance of these six well-established tests and explore what characteristics specific to human mtDNA sequence may affect their efficacy by simulating sequence under various parameters with levels of recombination (ρ) that vary around an empirically derived estimate for human mtDNA (population parameter ρ = 5.492). No test performed infallibly under any of our scenarios, and error rates varied across tests, whereas detection rates increased substantially with ρ values > 5.492. Under a model of evolution that incorporates parameters specific to human mtDNA, including rate heterogeneity, population expansion, and ρ = 5.492, successful detection rates are limited to a range of 7−70% across tests with an acceptable level of false-positive results: the neighborhood similarity score incompatibility test performed best overall under these parameters. Population growth seems to have the greatest impact on recombination detection probabilities across all models tested, likely due to its impact on sequence diversity. The implications of our findings on our current understanding of mtDNA recombination in humans are discussed. PMID:23665874

  17. Snow Depth Depicted on Mt. Lyell by NASA Airborne Snow Observatory

    NASA Image and Video Library

    2013-05-02

    A natural color image of Mt. Lyell, the highest point in the Tuolumne River Basin top image is compared with a three-dimensional color composite image of Mt. Lyell from NASA Airborne Snow Observatory depicting snow depth bottom image.

  18. MT3D-USGS version 1: A U.S. Geological Survey release of MT3DMS updated with new and expanded transport capabilities for use with MODFLOW

    USGS Publications Warehouse

    Bedekar, Vivek; Morway, Eric D.; Langevin, Christian D.; Tonkin, Matthew J.

    2016-09-30

    MT3D-USGS, a U.S. Geological Survey updated release of the groundwater solute transport code MT3DMS, includes new transport modeling capabilities to accommodate flow terms calculated by MODFLOW packages that were previously unsupported by MT3DMS and to provide greater flexibility in the simulation of solute transport and reactive solute transport. Unsaturated-zone transport and transport within streams and lakes, including solute exchange with connected groundwater, are among the new capabilities included in the MT3D-USGS code. MT3D-USGS also includes the capability to route a solute through dry cells that may occur in the Newton-Raphson formulation of MODFLOW (that is, MODFLOW-NWT). New chemical reaction Package options include the ability to simulate inter-species reactions and parent-daughter chain reactions. A new pump-and-treat recirculation package enables the simulation of dynamic recirculation with or without treatment for combinations of wells that are represented in the flow model, mimicking the above-ground treatment of extracted water. A reformulation of the treatment of transient mass storage improves conservation of mass and yields solutions for better agreement with analytical benchmarks. Several additional features of MT3D-USGS are (1) the separate specification of the partitioning coefficient (Kd) within mobile and immobile domains; (2) the capability to assign prescribed concentrations to the top-most active layer; (3) the change in mass storage owing to the change in water volume now appears as its own budget item in the global mass balance summary; (4) the ability to ignore cross-dispersion terms; (5) the definition of Hydrocarbon Spill-Source Package (HSS) mass loading zones using regular and irregular polygons, in addition to the currently supported circular zones; and (6) the ability to specify an absolute minimum thickness rather than the default percent minimum thickness in dry-cell circumstances.Benchmark problems that implement the new

  19. Viscosity controlled magma-carbonate interaction: a comparison of Mt. Vesuvius (Italy) and Mt. Merapi (Indonesia).

    NASA Astrophysics Data System (ADS)

    Blythe, L. S.; Misiti, V.; Masotta, M.; Taddeucci, J.; Freda, C.; Troll, V. R.; Deegan, F. M.; Jolis, E. M.

    2012-04-01

    Magma-carbonate interaction is increasingly seen as a viable and extremely important cause of magma contamination, and the generation of a crustally sourced CO2 phase (Goff et al., 2001; Freda et al., 2010). Even though the process is well recognized at certain volcanoes e.g. Popocatépetl, (Mexico); Merapi, (Indonesia); and Colli Albani, (Italy) (Goff et al., 2001; Deegan et al., 2010; Freda et al., 2010), neither the kinetics of carbonate assimilation nor its consequences for controlling the explosivity of eruptions have been constrained. Here we show the results of magma-carbonate interaction experiments conducted at 1200 °C and 0.5 GPa for varying durations (0 s, 60 s, 90 s and 300 s) for the Mt. Merapi (Indonesia) and Mt. Vesuvius (Italy) volcanic systems. We performed experiments using glassy starting materials specific to each volcano (shoshonite for Mt. Vesuvius, basaltic-andesite for Mt. Merapi) with different degrees of hydration (anhydrous vs hydration with ~ 2 wt % water) and using carbonate fragments of local origin; see Deegan et al., (2010) and Jolis et al., (2011). Experimental products include a gas phase (CO2-rich) and two melt phases, one pristine (Ca-normal) and one contaminated (Ca-rich) separated by a 'contamination front' which propagates outwards from the carbonate clast. Vesicles appear to nucleate in the contaminated glass and then migrate into the pristine one. Both contamination front propagation and bubble migration away from the carbonate are slower in anhydrous basaltic-andesite (Merapi anhydrous series) than in hydrated basaltic-andesite and shoshonite (Merapi and Vesuvius hydrated series), suggesting that assimilation speed is strongly controlled by the degree of hydration and the SiO2 content, both of which influence melt viscosity and hence diffusivity. As the carbonate dissolution proceeds in our experiments, initially dissolved and eventually exsolved CO2 builds up in the contaminated Ca-rich melt phase. Once melt volatile

  20. Thermodynamics of Pb(ii) and Zn(ii) binding to MT-3, a neurologically important metallothionein.

    PubMed

    Carpenter, M C; Shami Shah, A; DeSilva, S; Gleaton, A; Su, A; Goundie, B; Croteau, M L; Stevenson, M J; Wilcox, D E; Austin, R N

    2016-06-01

    Isothermal titration calorimetry (ITC) was used to quantify the thermodynamics of Pb(2+) and Zn(2+) binding to metallothionein-3 (MT-3). Pb(2+) binds to zinc-replete Zn7MT-3 displacing each zinc ion with a similar change in free energy (ΔG) and enthalpy (ΔH). EDTA chelation measurements of Zn7MT-3 and Pb7MT-3 reveal that both metal ions are extracted in a tri-phasic process, indicating that they bind to the protein in three populations with different binding thermodynamics. Metal binding is entropically favoured, with an enthalpic penalty that reflects the enthalpic cost of cysteine deprotonation accompanying thiolate ligation of the metal ions. These data indicate that Pb(2+) binding to both apo MT-3 and Zn7MT-3 is thermodynamically favourable, and implicate MT-3 in neuronal lead biochemistry.

  1. Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA.

    PubMed

    Karavaeva, Iuliia E; Golyshev, Sergey A; Smirnova, Ekaterina A; Sokolov, Svyatoslav S; Severin, Fedor F; Knorre, Dmitry A

    2017-04-01

    Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8 , ATG32 or ATG33 , implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes. © 2017. Published by The Company of Biologists Ltd.

  2. Transformation of MT Resistivity Sections into Geologically Meaningful Images

    NASA Astrophysics Data System (ADS)

    Park, S. K.

    2004-05-01

    Earthscope offers an unprecedented opportunity for interdisciplinary studies of North America. In addition to a continent-wide seismic study, it includes the acquisition of magnetotelluric (MT) data at many of the Bigfoot array sites. Earthscope will thus provide a uniform 3-D MT survey over regional scales when completed. MT interpreters will be able to include 3-D regional effects in their models for the first time whether they are interpreting local studies. However, the full value of the interdisciplinary nature of Earthscope will be realized only if MT sections and maps are useful to other earth scientists. The standard final product from any 2-D or 3-D MT interpretation is a spatial distribution of electrical resistivity. Inference of the physicochemical state from bulk resistivity is complicated because a variety of factors influence the property including temperature, intrinsic conduction of silicates, and small amounts of interconnected conducting materials (e.g., graphite, metallic minerals, partial melt, fluid). Here, I use petrophysical measurements and a petrological model to transform a resistivity section into cross sections of temperature and partial melt fraction in the mantle beneath the Sierra Nevada. In this manner, I am able to separate the contributions of increasing temperature and melt fraction to the bulk resistivity. Predicted melt fractions match observations from xenoliths relatively well but temperatures are systematically 200C higher than those observed. A small amount of dissolved hydrogen (~70 ppm H/Si) lowers the predicted temperatures to match those from the xenoliths, however. I conclude that while this transformation is a simple first step based on many assumptions, initial results are promising.

  3. TipMT: Identification of PCR-based taxon-specific markers.

    PubMed

    Rodrigues-Luiz, Gabriela F; Cardoso, Mariana S; Valdivia, Hugo O; Ayala, Edward V; Gontijo, Célia M F; Rodrigues, Thiago de S; Fujiwara, Ricardo T; Lopes, Robson S; Bartholomeu, Daniella C

    2017-02-11

    Molecular genetic markers are one of the most informative and widely used genome features in clinical and environmental diagnostic studies. A polymerase chain reaction (PCR)-based molecular marker is very attractive because it is suitable to high throughput automation and confers high specificity. However, the design of taxon-specific primers may be difficult and time consuming due to the need to identify appropriate genomic regions for annealing primers and to evaluate primer specificity. Here, we report the development of a Tool for Identification of Primers for Multiple Taxa (TipMT), which is a web application to search and design primers for genotyping based on genomic data. The tool identifies and targets single sequence repeats (SSR) or orthologous/taxa-specific genes for genotyping using Multiplex PCR. This pipeline was applied to the genomes of four species of Leishmania (L. amazonensis, L. braziliensis, L. infantum and L. major) and validated by PCR using artificial genomic DNA mixtures of the Leishmania species as templates. This experimental validation demonstrates the reliability of TipMT because amplification profiles showed discrimination of genomic DNA samples from Leishmania species. The TipMT web tool allows for large-scale identification and design of taxon-specific primers and is freely available to the scientific community at http://200.131.37.155/tipMT/ .

  4. Post Eruption Hazards at Mt. Pinatubo, Philippines

    NASA Technical Reports Server (NTRS)

    Mouginis-Mark, Peter J.

    2004-01-01

    Our project focused on the investigation of the post-eruption hazards at Mt. Pinatubo (Philippines) using remote sensing data, and field observations of the 1991 eruption deposits. Through the use of multiple satellite images, field work, and the 1996/2000 PacRim data sets, we conducted studies of the co- and post-eruption hazards of the volcano due to erosion and re-deposition of the extensive pyroclastic flow deposits. A major part of this project was the assembly and analysis of a database of over 50 high resolution (1 - 50 m/pixel) images that will facilitate this study. We collected Ikonos, SPOT, SIR-C/X-SAR, Landsat, ERS, RADARSAT, and ASTER images of the area around Mt. Pinatubo. An example of the changes that could be seen in these data is shown. Our investigation focused on a retrospective analysis of the erosion, redeposition, and re-vegetation of the 1991 pyroclastic flow deposits of Mt. Pinatubo. The primary geologic goal of our work was the analysis of the spatial distribution and volume change of the sources and sinks of materials associated with mudflow ('lahar') events. This included the measurement of river valley gradients and cross-sections using TOPSAR digital elevation data, as we are participating in the PacRim 2000 deployment to the Philippines specifically so that we can collect a second set of TOPSAR data that can then be used to create a topographic difference image of the volcano. The main results from this multi-sensor study have been published as Torres et al.. A discussion of the methodology that we used to assemble an appropriate database was included in Mouginis-Mark and Domergue-Schmidt. As part of an educational outreach effort, we also helped the Philippine Institute of Volcanology and Seismology (PHIVOLCS) in the Philippines to use NASA data to study Mt. Pinatubo and other Filipino volcanoes.

  5. Mitochondrial comparative genomics and phylogenetic signal assessment of mtDNA among arbuscular mycorrhizal fungi.

    PubMed

    Nadimi, Maryam; Daubois, Laurence; Hijri, Mohamed

    2016-05-01

    Mitochondrial (mt) genes, such as cytochrome C oxidase genes (cox), have been widely used for barcoding in many groups of organisms, although this approach has been less powerful in the fungal kingdom due to the rapid evolution of their mt genomes. The use of mt genes in phylogenetic studies of Dikarya has been met with success, while early diverging fungal lineages remain less studied, particularly the arbuscular mycorrhizal fungi (AMF). Advances in next-generation sequencing have substantially increased the number of publically available mtDNA sequences for the Glomeromycota. As a result, comparison of mtDNA across key AMF taxa can now be applied to assess the phylogenetic signal of individual mt coding genes, as well as concatenated subsets of coding genes. Here we show comparative analyses of publically available mt genomes of Glomeromycota, augmented with two mtDNA genomes that were newly sequenced for this study (Rhizophagus irregularis DAOM240159 and Glomus aggregatum DAOM240163), resulting in 16 complete mtDNA datasets. R. irregularis isolate DAOM240159 and G. aggregatum isolate DAOM240163 showed mt genomes measuring 72,293bp and 69,505bp with G+C contents of 37.1% and 37.3%, respectively. We assessed the phylogenies inferred from single mt genes and complete sets of coding genes, which are referred to as "supergenes" (16 concatenated coding genes), using Shimodaira-Hasegawa tests, in order to identify genes that best described AMF phylogeny. We found that rnl, nad5, cox1, and nad2 genes, as well as concatenated subset of these genes, provided phylogenies that were similar to the supergene set. This mitochondrial genomic analysis was also combined with principal coordinate and partitioning analyses, which helped to unravel certain evolutionary relationships in the Rhizophagus genus and for G. aggregatum within the Glomeromycota. We showed evidence to support the position of G. aggregatum within the R. irregularis 'species complex'. Copyright © 2016

  6. Single-cell analysis of intercellular heteroplasmy of mtDNA in Leber hereditary optic neuropathy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kobayashi, Y.; Sharpe, H.; Brown, N.

    1994-07-01

    The authors have investigated the distribution of mutant mtDNA molecules in single cells from a patient with Leber hereditary optic neuropathy (LHON). LHON is a maternally inherited disease that is characterized by a sudden-onset bilateral loss of central vision, which typically occurs in early adulthood. More than 50% of all LHON patients carry an mtDNA mutation at nucleotide position 11778. This nucleotide change converts a highly conserved arginine residue to histidine at codon 340 in the NADH-ubiquinone oxidoreductase subunit 4 (ND4) gene of mtDNA. In the present study, the authors used PCR amplification of mtDNA from lymphocytes to investigate mtDNAmore » heteroplasmy at the single-cell level in a LHON patient. They found that most cells were either homoplasmic normal or homoplasmic mutant at nucleotide position 11778. Some (16%) cells contained both mutant and normal mtDNA.« less

  7. The M-T Hook Structure Is Critical for Design of HIV-1 Fusion Inhibitors*

    PubMed Central

    Chong, Huihui; Yao, Xue; Sun, Jianping; Qiu, Zonglin; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Cui, Sheng; He, Yuxian

    2012-01-01

    CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal heptad repeat of gp41. We recently identified that its N-terminal residues Met-626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus stabilizing the interaction of the inhibitor with the deep pocket on the N-terminal heptad repeat. In this study, we further demonstrated that the M-T hook structure is a key determinant of CP621-652 in terms of its thermostability and anti-HIV activity. To directly define the structure and function of the M-T hook, we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution crystal structure (1.9 Å) of MT-C34 complexed by an N-terminal heptad repeat-derived peptide reveals that the M-T hook conformation is well preserved at the N-terminal extreme of the inhibitor. Strikingly, addition of two hook residues could dramatically enhance the binding affinity and thermostability of 6-helix bundle core. Compared with C34, MT-C34 exhibited significantly increased activity to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5-fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher increase than C34 in blocking 6-helix bundle formation. We further showed that MT-C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1 variants. Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors. PMID:22879603

  8. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kukat, Alexandra; Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases; Edgar, Daniel

    2011-06-10

    Highlights: {yields} Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. {yields} This process is independent of endogenous ROS production. {yields} Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of themore » molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O{sub 2}) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.« less

  9. MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis.

    PubMed

    Rebustini, Ivan T; Myers, Christopher; Lassiter, Keyonica S; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G; Hoffman, Matthew P

    2009-10-01

    Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis.

  10. Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism

    PubMed Central

    Johnston, Iain G; Burgstaller, Joerg P; Havlicek, Vitezslav; Kolbe, Thomas; Rülicke, Thomas; Brem, Gottfried; Poulton, Jo; Jones, Nick S

    2015-01-01

    Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck. DOI: http://dx.doi.org/10.7554/eLife.07464.001 PMID:26035426

  11. Reservoir uncertainty, Precambrian topography, and carbon sequestration in the Mt. Simon Sandstone, Illinois Basin

    USGS Publications Warehouse

    Leetaru, H.E.; McBride, J.H.

    2009-01-01

    Sequestration sites are evaluated by studying the local geological structure and confirming the presence of both a reservoir facies and an impermeable seal not breached by significant faulting. The Cambrian Mt. Simon Sandstone is a blanket sandstone that underlies large parts of Midwest United States and is this region's most significant carbon sequestration reservoir. An assessment of the geological structure of any Mt. Simon sequestration site must also include knowledge of the paleotopography prior to deposition. Understanding Precambrian paleotopography is critical in estimating reservoir thickness and quality. Regional outcrop and borehole mapping of the Mt. Simon in conjunction with mapping seismic reflection data can facilitate the prediction of basement highs. Any potential site must, at the minimum, have seismic reflection data, calibrated with drill-hole information, to evaluate the presence of Precambrian topography and alleviate some of the uncertainty surrounding the thickness or possible absence of the Mt. Simon at a particular sequestration site. The Mt. Simon is thought to commonly overlie Precambrian basement granitic or rhyolitic rocks. In places, at least about 549 m (1800 ft) of topographic relief on the top of the basement surface prior to Mt. Simon deposition was observed. The Mt. Simon reservoir sandstone is thin or not present where basement is topographically high, whereas the low areas can have thick Mt. Simon. The paleotopography on the basement and its correlation to Mt. Simon thickness have been observed at both outcrops and in the subsurface from the states of Illinois, Ohio, Wisconsin, and Missouri. ?? 2009. The American Association of Petroleum Geologists/Division of Environmental Geosciences. All rights reserved.

  12. Type of featural attention differentially modulates hMT+ responses to illusory motion aftereffects.

    PubMed

    Castelo-Branco, Miguel; Kozak, Lajos R; Formisano, Elia; Teixeira, João; Xavier, João; Goebel, Rainer

    2009-11-01

    Activity in the human motion complex (hMT(+)/V5) is related to the perception of motion, be it either real surface motion or an illusion of motion such as apparent motion (AM) or motion aftereffect (MAE). It is a long-lasting debate whether illusory motion-related activations in hMT(+) represent the motion itself or attention to it. We have asked whether hMT(+) responses to MAEs are present when shifts in arousal are suppressed and attention is focused on concurrent motion versus nonmotion features. Significant enhancement of hMT(+) activity was observed during MAEs when attention was focused either on concurrent spatial angle or color features. This observation was confirmed by direct comparison of adapting (MAE inducing) versus nonadapting conditions. In contrast, this effect was diminished when subjects had to report on concomitant speed changes of superimposed AM. The same finding was observed for concomitant orthogonal real motion (RM), suggesting that selective attention to concurrent illusory or real motion was interfering with the saliency of MAE signals in hMT(+). We conclude that MAE-related changes in the global activity of hMT(+) are present provided selective attention is not focused on an interfering feature such as concurrent motion. Accordingly, there is a genuine MAE-related motion signal in hMT(+) that is neither explained by shifts in arousal nor by selective attention.

  13. 77 FR 24159 - Proposed Modification of Class E Airspace; Plentywood, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-23

    ... action proposes to modify Class E airspace at Plentywood Sher-Wood Airport, Plentywood, MT. Controlled...) standard instrument approach procedures at Plentywood Sher-Wood Airport. The FAA is proposing this action... Sher-Wood Airport, Plentywood, MT. Controlled airspace is necessary to accommodate aircraft using RNAV...

  14. Insertion of a self-splicing intron into the mtDNA of atriploblastic animal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valles, Y.; Halanych, K.; Boore, J.L.

    2006-04-14

    Nephtys longosetosa is a carnivorous polychaete worm that lives in the intertidal and subtidal zones with worldwide distribution (pleijel&rouse2001). Its mitochondrial genome has the characteristics typical of most metazoans: 37 genes; circular molecule; almost no intergenic sequence; and no significant gene rearrangements when compared to other annelid mtDNAs (booremoritz19981995). Ubiquitous features as small intergenic regions and lack of introns suggested that metazoan mtDNAs are under strong selective pressures to reduce their genome size allowing for faster replication requirements (booremoritz19981995Lynch2005). Yet, in 1996 two type I introns were found in the mtDNA of the basal metazoan Metridium senile (FigureX). Breaking amore » long-standing rule (absence of introns in metazoan mtDNA), this finding was later supported by the further presence of group I introns in other cnidarians. Interestingly, only the class Anthozoa within cnidarians seems to harbor such introns. Although several hundreds of triploblastic metazoan mtDNAs have been sequenced, this study is the first evidence of mitochondrial introns in triploblastic metazoans. The cox1 gene of N. longosetosa has an intron of almost 2 kbs in length. This finding represents as well the first instance of a group II intron (anthozoans harbor group I introns) in all metazoan lineages. Opposite trends are observed within plants, fungi and protist mtDNAs, where introns (both group I and II) and other non-coding sequences are widespread. Plant, fungal and protist mtDNA structure and organization differ enormously from that of metazoan mtDNA. Both, plant and fungal mtDNA are dynamic molecules that undergo high rates of recombination, contain long intergenic spacer regions and harbor both group I and group II introns. However, as metazoans they have a conserved gene content. Protists, on the other hand have a striking variation of gene content and introns that account for the genome size variation. In

  15. Evidence of animal mtDNA recombination between divergent populations of the potato cyst nematode Globodera pallida.

    PubMed

    Hoolahan, Angelique H; Blok, Vivian C; Gibson, Tracey; Dowton, Mark

    2012-03-01

    Recombination is typically assumed to be absent in animal mitochondrial genomes (mtDNA). However, the maternal mode of inheritance means that recombinant products are indistinguishable from their progenitor molecules. The majority of studies of mtDNA recombination assess past recombination events, where patterns of recombination are inferred by comparing the mtDNA of different individuals. Few studies assess contemporary mtDNA recombination, where recombinant molecules are observed as direct mosaics of known progenitor molecules. Here we use the potato cyst nematode, Globodera pallida, to investigate past and contemporary recombination. Past recombination was assessed within and between populations of G. pallida, and contemporary recombination was assessed in the progeny of experimental crosses of these populations. Breeding of genetically divergent organisms may cause paternal mtDNA leakage, resulting in heteroplasmy and facilitating the detection of recombination. To assess contemporary recombination we looked for evidence of recombination between the mtDNA of the parental populations within the mtDNA of progeny. Past recombination was detected between a South American population and several UK populations of G. pallida, as well as between two South American populations. This suggests that these populations may have interbred, paternal mtDNA leakage occurred, and the mtDNA of these populations subsequently recombined. This evidence challenges two dogmas of animal mtDNA evolution; no recombination and maternal inheritance. No contemporary recombination between the parental populations was detected in the progeny of the experimental crosses. This supports current arguments that mtDNA recombination events are rare. More sensitive detection methods may be required to adequately assess contemporary mtDNA recombination in animals.

  16. mtDNA Mutagenesis Disrupts Pluripotent Stem Cell Function by Altering Redox Signaling

    PubMed Central

    Hämäläinen, Riikka H.; Ahlqvist, Kati J.; Ellonen, Pekka; Lepistö, Maija; Logan, Angela; Otonkoski, Timo; Murphy, Michael P.; Suomalainen, Anu

    2015-01-01

    Summary mtDNA mutagenesis in somatic stem cells leads to their dysfunction and to progeria in mouse. The mechanism was proposed to involve modification of reactive oxygen species (ROS)/redox signaling. We studied the effect of mtDNA mutagenesis on reprogramming and stemness of pluripotent stem cells (PSCs) and show that PSCs select against specific mtDNA mutations, mimicking germline and promoting mtDNA integrity despite their glycolytic metabolism. Furthermore, mtDNA mutagenesis is associated with an increase in mitochondrial H2O2, reduced PSC reprogramming efficiency, and self-renewal. Mitochondria-targeted ubiquinone, MitoQ, and N-acetyl-L-cysteine efficiently rescued these defects, indicating that both reprogramming efficiency and stemness are modified by mitochondrial ROS. The redox sensitivity, however, rendered PSCs and especially neural stem cells sensitive to MitoQ toxicity. Our results imply that stem cell compartment warrants special attention when the safety of new antioxidants is assessed and point to an essential role for mitochondrial redox signaling in maintaining normal stem cell function. PMID:26027936

  17. mtDNAmanager: a Web-based tool for the management and quality analysis of mitochondrial DNA control-region sequences

    PubMed Central

    Lee, Hwan Young; Song, Injee; Ha, Eunho; Cho, Sung-Bae; Yang, Woo Ick; Shin, Kyoung-Jin

    2008-01-01

    Background For the past few years, scientific controversy has surrounded the large number of errors in forensic and literature mitochondrial DNA (mtDNA) data. However, recent research has shown that using mtDNA phylogeny and referring to known mtDNA haplotypes can be useful for checking the quality of sequence data. Results We developed a Web-based bioinformatics resource "mtDNAmanager" that offers a convenient interface supporting the management and quality analysis of mtDNA sequence data. The mtDNAmanager performs computations on mtDNA control-region sequences to estimate the most-probable mtDNA haplogroups and retrieves similar sequences from a selected database. By the phased designation of the most-probable haplogroups (both expected and estimated haplogroups), mtDNAmanager enables users to systematically detect errors whilst allowing for confirmation of the presence of clear key diagnostic mutations and accompanying mutations. The query tools of mtDNAmanager also facilitate database screening with two options of "match" and "include the queried nucleotide polymorphism". In addition, mtDNAmanager provides Web interfaces for users to manage and analyse their own data in batch mode. Conclusion The mtDNAmanager will provide systematic routines for mtDNA sequence data management and analysis via easily accessible Web interfaces, and thus should be very useful for population, medical and forensic studies that employ mtDNA analysis. mtDNAmanager can be accessed at . PMID:19014619

  18. The fate of MtBE during Fenton-like treatments through laboratory scale column tests.

    PubMed

    Piscitelli, Daniela; Zingaretti, Daniela; Verginelli, Iason; Gavasci, Renato; Baciocchi, Renato

    2015-12-01

    In Situ Chemical Oxidation (ISCO) based on the Fenton's process is a proven technology for the treatment of groundwater contaminated by organic compounds. Nevertheless, the application of this treatment process to methyl tert-butyl ether (MtBE) is questioned, as there are concerns about its capacity to achieve complete mineralization. Many existing studies have focused on water contaminated by MtBE and are thus not representative of in situ treatments since they do not consider the presence of soil. In this work, the effectiveness of a Fenton-like process for MtBE treatment was proven in soil column tests performed at operating conditions (i.e., oxidant and contaminant concentration and flow rates) resembling those typically used for in situ applications. No MtBE by-products were detected in any of the tested conditions, thus suggesting that the tert-butyl group of MtBE was completely degraded. A mass balance based on the CO2 produced was used as evidence that most of the MtBE removed was actually mineralized. Finally, the obtained results show that preconditioning of soil with a chelating agent (EDTA) significantly enhanced MtBE oxidation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication.

    PubMed

    Zhang, Yi; Chen, Yong; Gucek, Marjan; Xu, Hong

    2016-05-17

    Early embryonic development features rapid nuclear DNA replication cycles, but lacks mtDNA replication. To meet the high-energy demands of embryogenesis, mature oocytes are furnished with vast amounts of mitochondria and mtDNA However, the cellular machinery driving massive mtDNA replication in ovaries remains unknown. Here, we describe a Drosophila AKAP protein, MDI that recruits a translation stimulator, La-related protein (Larp), to the mitochondrial outer membrane in ovaries. The MDI-Larp complex promotes the synthesis of a subset of nuclear-encoded mitochondrial proteins by cytosolic ribosomes on the mitochondrial surface. MDI-Larp's targets include mtDNA replication factors, mitochondrial ribosomal proteins, and electron-transport chain subunits. Lack of MDI abolishes mtDNA replication in ovaries, which leads to mtDNA deficiency in mature eggs. Targeting Larp to the mitochondrial outer membrane independently of MDI restores local protein synthesis and rescues the phenotypes of mdi mutant flies. Our work suggests that a selective translational boost by the MDI-Larp complex on the outer mitochondrial membrane might be essential for mtDNA replication and mitochondrial biogenesis during oogenesis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  20. The Mt. Mitchell scenery assessment

    Treesearch

    Robert F. Scheele; Gary W. Johnson

    1979-01-01

    The scenery assessment process for the Mt. Mitchell Suitability/Feasibility Study was conducted by National Park Service personnel and consultants in 1977-78. It combined approaches designed by Lewis (1962) and Jones (1976) in a comparative evaluation of the scenery of two large landscapes in the Appalachian physiographic province. The purpose of this study was to...

  1. Recreation conflicts on Mt. Evans

    Treesearch

    Jerry J. Vaske; Karin Wittmann; Susan Laidlaw; Maureen P. Donnelly

    1995-01-01

    This study examines recreation conflict at Mt. Evans, Colorado; a high visibility area that attracts both hunters and non-hunters. Two types of conflict were distinguished: goal interference and conflict of values. Data were obtained from a series of on-site and mailed surveys. For hunting related events (e.g. seeing an animal being shot, hearing...

  2. The amount and integrity of mtDNA in maize decline with development.

    PubMed

    Oldenburg, Delene J; Kumar, Rachana A; Bendich, Arnold J

    2013-02-01

    In maize and other grasses there is a developmental gradient from the meristematic cells at the base of the stalk to the differentiated cells at the leaf tip. This gradient presents an opportunity to investigate changes in mitochondrial DNA (mtDNA) that accompany growth under light and dark conditions, as done previously for plastid DNA. Maize mtDNA was analyzed by DAPI-DNA staining of individual mitochondria, gel electrophoresis/blot hybridization, and real-time qPCR. Both the amount and integrity of the mtDNA were found to decline with development. There was a 20-fold decline in mtDNA copy number per cell from the embryo to the light-grown leaf blade. The amount of DNA per mitochondrial particle was greater in dark-grown leaf blade (24 copies, on average) than in the light (2 copies), with some mitochondria lacking any detectable DNA. Three factors that influence the demise of mtDNA during development are considered: (1) the decision to either repair or degrade mtDNA molecules that are damaged by the reactive oxygen species produced as byproducts of respiration; (2) the generation of ATP by photophosphorylation in chloroplasts, reducing the need for respiratory-competent mitochondria; and (3) the shift in mitochondrial function from energy-generating respiration to photorespiration during the transition from non-green to green tissue.

  3. Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria.

    PubMed

    Haen, Karri M; Pett, Walker; Lavrov, Dennis V

    2010-10-01

    Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa.

  4. 78 FR 67299 - Modification of Class E Airspace; Cut Bank, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ...-0664; Airspace Docket No. 13-ANM-22] Modification of Class E Airspace; Cut Bank, MT AGENCY: Federal... Cut Bank, MT, to accommodate new Area Navigation (RNAV) Global Positioning System (GPS) standard instrument approach procedures at Cut Bank Municipal Airport. This improves the safety and management of...

  5. No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline

    PubMed Central

    Hagström, Erik; Freyer, Christoph; Battersby, Brendan J.; Stewart, James B.; Larsson, Nils-Göran

    2014-01-01

    Variants of mitochondrial DNA (mtDNA) are commonly used as markers to track human evolution because of the high sequence divergence and exclusive maternal inheritance. It is assumed that the inheritance is clonal, i.e. that mtDNA is transmitted between generations without germline recombination. In contrast to this assumption, a number of studies have reported the presence of recombinant mtDNA molecules in cell lines and animal tissues, including humans. If germline recombination of mtDNA is frequent, it would strongly impact phylogenetic and population studies by altering estimates of coalescent time and branch lengths in phylogenetic trees. Unfortunately, this whole area is controversial and the experimental approaches have been widely criticized as they often depend on polymerase chain reaction (PCR) amplification of mtDNA and/or involve studies of transformed cell lines. In this study, we used an in vivo mouse model that has had germline heteroplasmy for a defined set of mtDNA mutations for more than 50 generations. To assess recombination, we adapted and validated a method based on cloning of single mtDNA molecules in the λ phage, without prior PCR amplification, followed by subsequent mutation analysis. We screened 2922 mtDNA molecules and found no germline recombination after transmission of mtDNA under genetically and evolutionary relevant conditions in mammals. PMID:24163253

  6. Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion.

    PubMed

    Hakonen, Anna H; Isohanni, Pirjo; Paetau, Anders; Herva, Riitta; Suomalainen, Anu; Lönnqvist, Tuula

    2007-11-01

    Twinkle is a mitochondrial replicative helicase, the mutations of which have been associated with autosomal dominant progressive external ophthalmoplegia (adPEO), and recessively inherited infantile onset spinocerebellar ataxia (IOSCA). We report here a new phenotype in two siblings with compound heterozygous Twinkle mutations (A318T and Y508C), characterized by severe early onset encephalopathy and signs of liver involvement. The clinical manifestations included hypotonia, athetosis, sensory neuropathy, ataxia, hearing deficit, ophthalmoplegia, intractable epilepsy and elevation of serum transaminases. The liver showed mtDNA depletion, whereas the muscle mtDNA was only slightly affected. Alpers-Huttenlocher syndrome has previously been associated with mutations of polymerase gamma, a replicative polymerase of mtDNA. We show here that recessive mutations of the close functional partner of the polymerase, the Twinkle helicase, can also manifest as early encephalopathy with liver involvement, a phenotype reminiscent of Alpers syndrome, and are a new genetic cause underlying tissue-specific mtDNA depletion.

  7. Skewed segregation of the mtDNA nt 8993 (T-->G) mutation in human oocytes.

    PubMed Central

    Blok, R B; Gook, D A; Thorburn, D R; Dahl, H H

    1997-01-01

    Rapid changes in mtDNA variants between generations have led to the bottleneck theory, which proposes a dramatic reduction in mtDNA numbers during early oogenesis. We studied oocytes from a woman with heteroplasmic expression of the mtDNA nt 8993 (T-->G) mutation. Of seven oocytes analyzed, one showed no evidence of the mutation, and the remaining six had a mutant load > 95%. This skewed expression of the mutation in oocytes is not compatible with the conventional bottleneck theory. A possible explanation is that, during amplification of mtDNA in the developing oocyte, mtDNA from one mitochondrion is preferentially amplified. Thus, subsequent mature oocytes may contain predominantly wild-type or mutant mitochondrial genomes. Images Figure 2 Figure 3 PMID:9199572

  8. MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis

    PubMed Central

    Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G.; Hoffman, Matthew P.

    2009-01-01

    Summary Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Importantly, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA-treatment, increasing MT-MMP and pro-proliferative gene expression via β1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA-treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. PMID:19853562

  9. 78 FR 54415 - Proposed Establishment of Class E Airspace; Ennis, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-04

    ... action proposes to establish Class E airspace at Ennis- Big Sky Airport, Ennis, MT. Controlled airspace...) standard instrument approach procedures at Ennis-Big Sky Airport, Ennis, MT. The FAA is proposing this... parties are invited to participate in this proposed rulemaking by submitting such written data, views, or...

  10. 77 FR 61248 - Establishment of Class E Airspace; Deer Lodge, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-09

    ...-0379; Airspace Docket No. 12-ANM-7 Establishment of Class E Airspace; Deer Lodge, MT AGENCY: Federal... at Deer Lodge-City- County Airport, Deer Lodge, MT. Controlled airspace is necessary to accommodate... procedures at Deer Lodge-City-County Airport. This improves the safety and management of Instrument Flight...

  11. 78 FR 65556 - Establishment of Class E Airspace; Cut Bank, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ...-0532; Airspace Docket No. 13-ANM-21] Establishment of Class E Airspace; Cut Bank, MT AGENCY: Federal... at the Cut Bank VHF Omni-Directional Radio Range Tactical Air Navigational Aid (VORTAC) navigation aid, Cut Bank, MT, to facilitate vectoring of Instrument Flight Rules (IFR) aircraft under control of...

  12. A Signal, from Human mtDNA, of Postglacial Recolonization in Europe

    PubMed Central

    Torroni, Antonio; Bandelt, Hans-Jürgen; Macaulay, Vincent; Richards, Martin; Cruciani, Fulvio; Rengo, Chiara; Martinez-Cabrera, Vicente; Villems, Richard; Kivisild, Toomas; Metspalu, Ene; Parik, Jüri; Tolk, Helle-Viivi; Tambets, Kristiina; Forster, Peter; Karger, Bernd; Francalacci, Paolo; Rudan, Pavao; Janicijevic, Branka; Rickards, Olga; Savontaus, Marja-Liisa; Huoponen, Kirsi; Laitinen, Virpi; Koivumäki, Satu; Sykes, Bryan; Hickey, Eileen; Novelletto, Andrea; Moral, Pedro; Sellitto, Daniele; Coppa, Alfredo; Al-Zaheri, Nadia; Santachiara-Benerecetti, A. Silvana; Semino, Ornella; Scozzari, Rosaria

    2001-01-01

    Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T→C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed “pre*V,” since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory. PMID:11517423

  13. Ultrashort echo time magnetization transfer (UTE-MT) imaging of cortical bone.

    PubMed

    Chang, Eric Y; Bae, Won C; Shao, Hongda; Biswas, Reni; Li, Shihong; Chen, Jun; Patil, Shantanu; Healey, Robert; D'Lima, Darryl D; Chung, Christine B; Du, Jiang

    2015-07-01

    Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T2 tissues such as cortical bone. Ultrashort echo time (UTE) sequences with TE values as low as 8 µs can detect signals from different water components in cortical bone. In this study we aim to evaluate two-dimensional UTE-MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by micro-computed tomography (μCT) and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE-MT MR imaging, μCT, and biomechanical testing. Off-resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with μCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderately strong negative correlation was observed between OSR and μCT porosity (R(2)  = 0.46-0.51), while a moderate positive correlation was observed between OSR and yield stress (R(2)  = 0.25-0.30) and failure stress (R(2)  = 0.31-0.35), and a weak positive correlation (R(2)  = 0.09-0.12) between OSR and Young's modulus at all off-resonance saturation frequencies. OSR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Novel Scalable 3-D MT Inverse Solver

    NASA Astrophysics Data System (ADS)

    Kuvshinov, A. V.; Kruglyakov, M.; Geraskin, A.

    2016-12-01

    We present a new, robust and fast, three-dimensional (3-D) magnetotelluric (MT) inverse solver. As a forward modelling engine a highly-scalable solver extrEMe [1] is used. The (regularized) inversion is based on an iterative gradient-type optimization (quasi-Newton method) and exploits adjoint sources approach for fast calculation of the gradient of the misfit. The inverse solver is able to deal with highly detailed and contrasting models, allows for working (separately or jointly) with any type of MT (single-site and/or inter-site) responses, and supports massive parallelization. Different parallelization strategies implemented in the code allow for optimal usage of available computational resources for a given problem set up. To parameterize an inverse domain a mask approach is implemented, which means that one can merge any subset of forward modelling cells in order to account for (usually) irregular distribution of observation sites. We report results of 3-D numerical experiments aimed at analysing the robustness, performance and scalability of the code. In particular, our computational experiments carried out at different platforms ranging from modern laptops to high-performance clusters demonstrate practically linear scalability of the code up to thousands of nodes. 1. Kruglyakov, M., A. Geraskin, A. Kuvshinov, 2016. Novel accurate and scalable 3-D MT forward solver based on a contracting integral equation method, Computers and Geosciences, in press.

  15. Synthetic Modeling of A Geothermal System Using Audio-magnetotelluric (AMT) and Magnetotelluric (MT)

    NASA Astrophysics Data System (ADS)

    Mega Saputra, Rifki; Widodo

    2017-04-01

    Indonesia has 40% of the world’s potential geothermal resources with estimated capacity of 28,910 MW. Generally, the characteristic of the geothermal system in Indonesia is liquid-dominated systems, which driven by volcanic activities. In geothermal exploration, electromagnetic methods are used to map structures that could host potential reservoirs and source rocks. We want to know the responses of a geothermal system using synthetic data of Audio-magnetotelluric (AMT) and Magnetotelluric (MT). Due to frequency range, AMT and MT data can resolve the shallow and deeper structure, respectively. 1-D models have been performed using AMT and MT data. The results indicate that AMT and MT data give detailed conductivity distribution of geothermal structure.

  16. Mt. Spurr's 1992 eruptions

    USGS Publications Warehouse

    1993-01-01

    On 27 June, 1992, the Crater Peak vent on the south side of Mt. Spurr awoke from 39 years of dormancy and burst into sub-plinian eruption after 10 months of elevated seismicity. Two more eruptions followed in August and September. The volcano lies 125 km west of Anchorage, Alaska's largest city and an important international hub for air travel. The Alaska Volcano Observatory (AVO) was able to warn communities and the aviation industry well in advance of these eruptions.

  17. Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas

    PubMed Central

    Oteo, M.; Romero, E.; Cámara, J. A.; de Martino, A.; Arroyo, A. G.; Morcillo, M. Á.; Squatrito, M.; Martinez-Torrecuadrada, J. L.; Mulero, F.

    2016-01-01

    Background A critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models. Methods An anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments. Results 89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models. Conclusion A new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In

  18. Use of Modality and Negation in Semantically-Informed Syntactic MT

    DTIC Science & Technology

    2012-06-01

    Longman Dictionary of Contemporary English (LDOCE). 422 Baker et al. Modality and Negation in SIMT We produced the full English MN lexicon semi...English sentence pairs, and a bilingual dictionary with 113,911 entries. For our development and test sets, we split the NIST MT-08 test set into two...for combining MT and semantics (termed distillation) to answer the informa- tion needs of monolingual speakers using multilingual sources. Proper

  19. Asian affinities and continental radiation of the four founding Native American mtDNAs.

    PubMed Central

    Torroni, A; Schurr, T G; Cabell, M F; Brown, M D; Neel, J V; Larsen, M; Smith, D G; Vullo, C M; Wallace, D C

    1993-01-01

    The mtDNA variation of 321 individuals from 17 Native American populations was examined by high-resolution restriction endonuclease analysis. All mtDNAs were amplified from a variety of sources by using PCR. The mtDNA of a subset of 38 of these individuals was also analyzed by D-loop sequencing. The resulting data were combined with previous mtDNA data from five other Native American tribes, as well as with data from a variety of Asian populations, and were used to deduce the phylogenetic relationships between mtDNAs and to estimate sequence divergences. This analysis revealed the presence of four haplotype groups (haplogroups A, B, C, and D) in the Amerind, but only one haplogroup (A) in the Na-Dene, and confirmed the independent origins of the Amerinds and the Na-Dene. Further, each haplogroup appeared to have been founded by a single mtDNA haplotype, a result which is consistent with a hypothesized founder effect. Most of the variation within haplogroups was tribal specific, that is, it occurred as tribal private polymorphisms. These observations suggest that the process of tribalization began early in the history of the Amerinds, with relatively little intertribal genetic exchange occurring subsequently. The sequencing of 341 nucleotides in the mtDNA D-loop revealed that the D-loop sequence variation correlated strongly with the four haplogroups defined by restriction analysis, and it indicated that the D-loop variation, like the haplotype variation, arose predominantly after the migration of the ancestral Amerinds across the Bering land bridge. Images Figure 4 PMID:7688932

  20. Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations.

    PubMed

    Auré, Karine; Dubourg, Odile; Jardel, Claude; Clarysse, Lucie; Sternberg, Damien; Fournier, Emmanuel; Laforêt, Pascal; Streichenberger, Nathalie; Petiot, Philippe; Gervais-Bernard, Hélène; Vial, Christophe; Bedat-Millet, Anne-Laure; Drouin-Garraud, Valérie; Bouillaud, Frédéric; Vandier, Christophe; Fontaine, Bertrand; Lombès, Anne

    2013-11-19

    To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide. Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts. Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations. The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation. Significant defect of complexes V and I as well as oxidative stress were observed in both primary fibroblasts and cybrid cells with 100% m.9185T>C mutation. Permanent plasma membrane depolarization and altered permeability to K(+) in fibroblasts provided a link with the paralysis episodes. Screening of 9 patients, based on their clinical phenotype, identified 4 patients with similar deleterious MT-ATP6 mutations (twice m.9185T>C and once m.9176T>C or m.8893T>C). A fifth patient presented with an original potentially deleterious MT-ATP8 mutation (m.8403T>C). All mutations were associated with almost-normal complex V activity but significant oxidative stress and permanent plasma membrane depolarization. Homoplasmic mutations in the MT-ATP6/8 genes may cause episodic weakness responding to acetazolamide treatment.

  1. Recombinant expression of thermostable processive MtEG5 endoglucanase and its synergism with MtLPMO from Myceliophthora thermophila during the hydrolysis of lignocellulosic substrates.

    PubMed

    Karnaouri, Anthi; Muraleedharan, Madhu Nair; Dimarogona, Maria; Topakas, Evangelos; Rova, Ulrika; Sandgren, Mats; Christakopoulos, Paul

    2017-01-01

    Filamentous fungi are among the most powerful cellulolytic organisms in terrestrial ecosystems. To perform the degradation of lignocellulosic substrates, these microorganisms employ both hydrolytic and oxidative mechanisms that involve the secretion and synergism of a wide variety of enzymes. Interactions between these enzymes occur on the level of saccharification, i.e., the release of neutral and oxidized products, but sometimes also reflected in the substrate liquefaction. Although the synergism regarding the yield of neutral sugars has been extensively studied, further studies should focus on the oxidized sugars, as well as the effect of enzyme combinations on the viscosity properties of the substrates. In the present study, the heterologous expression of an endoglucanase (EG) and its combined activity together with a lytic polysaccharide monooxygenase (LPMO), both from the thermophilic fungus Myceliophthora thermophila , are described. The EG gene, belonging to the glycoside hydrolase family 5, was functionally expressed in the methylotrophic yeast Pichia pastoris . The produced Mt EG5A (75 kDa) featured remarkable thermal stability and showed high specific activity on microcrystalline cellulose compared to CMC, which is indicative of its processivity properties. The enzyme was capable of releasing high amounts of cellobiose from wheat straw, birch, and spruce biomass. Addition of Mt LPMO9 together with Mt EG5A showed enhanced enzymatic hydrolysis yields against regenerated amorphous cellulose (PASC) by improving the release not only of the neutral but also of the oxidized sugars. Assessment of activity of Mt EG5A on the reduction of viscosity of PASC and pretreated wheat straw using dynamic viscosity measurements revealed that the enzyme is able to perform liquefaction of the model substrate and the natural lignocellulosic material, while when added together with Mt LPMO9, no further synergistic effect was observed. The endoglucanase Mt EG5A from the

  2. No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation

    PubMed Central

    Hellberg, Michael E

    2006-01-01

    Background The mitochondrial DNA (mtDNA) of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin), by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans) known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea). Results The mtDNA surveyed (630 bp of cytochrome oxidase subunit I) was invariant among individuals sampled from 18 populations spanning 3000 km of the range of B. elegans, despite high levels of variation and population subdivision for allozymes over these same populations. The synonymous substitution rate between B. elegans and T. coccinea (0.05%/site/106 years) is similar to that in most plants, but 50–100 times lower than rates typical for most animals. In addition, while substitutions to mtDNA in most animals exhibit a strong bias toward transitions, mtDNA from these corals does not. Conclusion Slow rates of mitochondrial nucleotide substitution result in low levels of intraspecific mtDNA variation in corals, even when nuclear loci vary. Slow mtDNA evolution appears to be the basal condition among eukaryotes. mtDNA substitution rates switch from slow to fast abruptly and unidirectionally. This switch may stem from the loss of just one or a few mitochondrion-specific DNA repair or replication genes. PMID:16542456

  3. Background sequence characteristics influence the occurrence and severity of disease-causing mtDNA mutations

    PubMed Central

    Wei, Wei; Hudson, Gavin

    2017-01-01

    Inherited mitochondrial DNA (mtDNA) mutations have emerged as a common cause of human disease, with mutations occurring multiple times in the world population. The clinical presentation of three pathogenic mtDNA mutations is strongly associated with a background mtDNA haplogroup, but it is not clear whether this is limited to a handful of examples or is a more general phenomenon. To address this, we determined the characteristics of 30,506 mtDNA sequences sampled globally. After performing several quality control steps, we ascribed an established pathogenicity score to the major alleles for each sequence. The mean pathogenicity score for known disease-causing mutations was significantly different between mtDNA macro-haplogroups. Several mutations were observed across all haplogroup backgrounds, whereas others were only observed on specific clades. In some instances this reflected a founder effect, but in others, the mutation recurred but only within the same phylogenetic cluster. Sequence diversity estimates showed that disease-causing mutations were more frequent on young sequences, and genomes with two or more disease-causing mutations were more common than expected by chance. These findings implicate the mtDNA background more generally in recurrent mutation events that have been purified through natural selection in older populations. This provides an explanation for the low frequency of mtDNA disease reported in specific ethnic groups. PMID:29253894

  4. Phylogenetic analysis of mtDNA lineages in South American mummies.

    PubMed

    Monsalve, M V; Cardenas, F; Guhl, F; Delaney, A D; Devine, D V

    1996-07-01

    Some studies of mtDNA propose that contemporary Amerindians have descended from four haplotype groups, each defined by specific sets of polymorphisms. One recent study also found evidence of other potential founder haplotypes. We wanted to determine whether the four haplotypes in modern populations were also present in ancient South American aboriginals. We subjected mtDNA from Colombian mummies (470 to 1849 AD) to PCR amplification and restriction endonuclease analysis. The mtDNA D-loop region was surveyed for sequence variation by restriction analysis and a segment of this region was sequenced for each mummy to characterize the haplotypes. Our mummies exhibited three of the four major characteristic haplotypes of Amerindian populations defined by four markers. With sequence data obtained in the ancient samples and published data on contemporary Amerindians it was possible to infer the origin of these six mummies.

  5. Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions.

    PubMed

    Belmonte, Frances R; Martin, James L; Frescura, Kristin; Damas, Joana; Pereira, Filipe; Tarnopolsky, Mark A; Kaufman, Brett A

    2016-04-28

    Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error.

  6. Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

    PubMed Central

    Belmonte, Frances R.; Martin, James L.; Frescura, Kristin; Damas, Joana; Pereira, Filipe; Tarnopolsky, Mark A.; Kaufman, Brett A.

    2016-01-01

    Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error. PMID:27122135

  7. Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales.

    PubMed

    Palumbi, S R; Baker, C S

    1994-05-01

    Powerful analyses of population structure require information from multiple genetic loci. To help develop a molecular toolbox for obtaining this information, we have designed universal oligonucleotide primers that span conserved intron-exon junctions in a wide variety of animal phyla. We test the utility of exon-primed, intron-crossing amplifications by analyzing the variability of actin intron sequences from humpback, blue, and bowhead whales and comparing the results with mitochondrial DNA (mtDNA) haplotype data. Humpback actin introns fall into two major clades that exist in different frequencies in different oceanic populations. It is surprising that Hawaii and California populations, which are very distinct in mtDNAs, are similar in actin intron alleles. This discrepancy between mtDNA and nuclear DNA results may be due either to differences in genetic drift in mitochondrial and nuclear genes or to preferential movement of males, which do not transmit mtDNA to offspring, between separate breeding grounds. Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden patterns of structure in natural populations.

  8. A three-dimensional spatiotemporal receptive field model explains responses of area MT neurons to naturalistic movies

    PubMed Central

    Nishimoto, Shinji; Gallant, Jack L.

    2012-01-01

    Area MT has been an important target for studies of motion processing. However, previous neurophysiological studies of MT have used simple stimuli that do not contain many of the motion signals that occur during natural vision. In this study we sought to determine whether views of area MT neurons developed using simple stimuli can account for MT responses under more naturalistic conditions. We recorded responses from macaque area MT neurons during stimulation with naturalistic movies. We then used a quantitative modeling framework to discover which specific mechanisms best predict neuronal responses under these challenging conditions. We find that the simplest model that accurately predicts responses of MT neurons consists of a bank of V1-like filters, each followed by a compressive nonlinearity, a divisive nonlinearity and linear pooling. Inspection of the fit models shows that the excitatory receptive fields of MT neurons tend to lie on a single plane within the three-dimensional spatiotemporal frequency domain, and suppressive receptive fields lie off this plane. However, most excitatory receptive fields form a partial ring in the plane and avoid low temporal frequencies. This receptive field organization ensures that most MT neurons are tuned for velocity but do not tend to respond to ambiguous static textures that are aligned with the direction of motion. In sum, MT responses to naturalistic movies are largely consistent with predictions based on simple stimuli. However, models fit using naturalistic stimuli reveal several novel properties of MT receptive fields that had not been shown in prior experiments. PMID:21994372

  9. Evaluation of next generation mtGenome sequencing using the Ion Torrent Personal Genome Machine (PGM)☆

    PubMed Central

    Parson, Walther; Strobl, Christina; Huber, Gabriela; Zimmermann, Bettina; Gomes, Sibylle M.; Souto, Luis; Fendt, Liane; Delport, Rhena; Langit, Reina; Wootton, Sharon; Lagacé, Robert; Irwin, Jodi

    2013-01-01

    Insights into the human mitochondrial phylogeny have been primarily achieved by sequencing full mitochondrial genomes (mtGenomes). In forensic genetics (partial) mtGenome information can be used to assign haplotypes to their phylogenetic backgrounds, which may, in turn, have characteristic geographic distributions that would offer useful information in a forensic case. In addition and perhaps even more relevant in the forensic context, haplogroup-specific patterns of mutations form the basis for quality control of mtDNA sequences. The current method for establishing (partial) mtDNA haplotypes is Sanger-type sequencing (STS), which is laborious, time-consuming, and expensive. With the emergence of Next Generation Sequencing (NGS) technologies, the body of available mtDNA data can potentially be extended much more quickly and cost-efficiently. Customized chemistries, laboratory workflows and data analysis packages could support the community and increase the utility of mtDNA analysis in forensics. We have evaluated the performance of mtGenome sequencing using the Personal Genome Machine (PGM) and compared the resulting haplotypes directly with conventional Sanger-type sequencing. A total of 64 mtGenomes (>1 million bases) were established that yielded high concordance with the corresponding STS haplotypes (<0.02% differences). About two-thirds of the differences were observed in or around homopolymeric sequence stretches. In addition, the sequence alignment algorithm employed to align NGS reads played a significant role in the analysis of the data and the resulting mtDNA haplotypes. Further development of alignment software would be desirable to facilitate the application of NGS in mtDNA forensic genetics. PMID:23948325

  10. Joint Inversion of 3d Mt/gravity/magnetic at Pisagua Fault.

    NASA Astrophysics Data System (ADS)

    Bascur, J.; Saez, P.; Tapia, R.; Humpire, M.

    2017-12-01

    This work shows the results of a joint inversion at Pisagua Fault using 3D Magnetotellurics (MT), gravity and regional magnetic data. The MT survey has a poor coverage of study area with only 21 stations; however, it allows to detect a low resistivity zone aligned with the Pisagua Fault trace that it is interpreted as a damage zone. The integration of gravity and magnetic data, which have more dense sampling and coverage, adds more detail and resolution to the detected low resistivity structure and helps to improve the structure interpretation using the resulted models (density, magnetic-susceptibility and electrical resistivity). The joint inversion process minimizes a multiple target function which includes the data misfit, model roughness and coupling norms (crossgradient and direct relations) for all geophysical methods considered (MT, gravity and magnetic). This process is solved iteratively using the Gauss-Newton method which updates the model of each geophysical method improving its individual data misfit, model roughness and the coupling with the other geophysical models. For solving the model updates of magnetic and gravity methods were developed dedicated 3D inversion software codes which include the coupling norms with additionals geophysical parameters. The model update of the 3D MT is calculated using an iterative method which sequentially filters the priority model and the output model of a single 3D MT inversion process for obtaining the resistivity model coupled solution with the gravity and magnetic methods.

  11. RadNet Air Data From Kalispell, MT

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Kalispell, MT from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  12. RadNet Air Data From Billings, MT

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Billings, MT from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  13. Recombination or mutational hot spots in human mtDNA?

    PubMed

    Innan, Hideki; Nordborg, Magnus

    2002-07-01

    Awadalla, Eyre-Walker, and Maynard Smith (1999) recently argued that there might be recombination in human mitochondrial DNA (mtDNA). Their claim was based on their observation of decaying linkage disequilibrium (LD) as a function of physical distance. Their study was much criticized, and follow-up studies have failed to find any evidence for recombination. We argue that the criticisms levied, even if correct, could not possibly explain the findings of Awadalla, Eyre-Walker, and Maynard Smith (1999). Nonetheless, the test proposed by Awadalla, Eyre-Walker, and Maynard Smith (1999 ) is not robust because recombination is not the only explanation for decay of LD. We show that such a pattern can be caused by mutational hot spots as well. However, a closer look at the data suggests that the pattern observed was not caused by mutational hot spots but rather by chance. Thus, there appears to be no evidence for recombination in the mtDNA polymorphism data. In conclusion, we discuss the possibility of detecting recombination in mtDNA and the implications of its existence.

  14. OXPHOS Defects Due to mtDNA Mutations: Glutamine to the Rescue!

    PubMed

    Chinopoulos, Christos

    2018-06-05

    Mutations in mtDNA associated with OXPHOS defects preclude energy harnessing by OXPHOS. The work of Chen et al. (2018) is previewed, reporting flux pathways of glutamine catabolism in mtDNA mutant cells yielding high-energy phosphates through substrate-level phosphorylation and the influence exerted by the severity of OXPHOS impairment. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Myopathic mtDNA Depletion Syndrome Due to Mutation in TK2 Gene.

    PubMed

    Martín-Hernández, Elena; García-Silva, María Teresa; Quijada-Fraile, Pilar; Rodríguez-García, María Elena; Hernández-Laín, Aurelio; Coca-Robinot, David; Rivera, Henry; Fernández-Toral, Joaquín; Arenas, Joaquín; Martín, MiguelÁngel; Martínez-Azorín, Francisco

    2016-02-29

    Whole-exome sequencing (WES) was used to identify the disease gene(s) in a Spanish girl with failure to thrive, muscle weakness, mild facial weakness, elevated creatine kinase (CK), deficiency of mitochondrial complex III and depletion of mtDNA. With WES data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The analysis of whole exome uncovered a homozygous pathogenic mutation in Thymidine kinase 2 gene (TK2; NM_004614.4:c.323C>T, p.T108M). TK2 mutations have been identified mainly in patients with the myopathic form of mtDNA depletion syndromes (MDS). This patient presents an atypical TK2 related-myopathic form of MDS, because despite having a very low content of mtDNA (<20%), she presents a slower and less severe evolution of the disease. In conclusion, our data confirm the role of TK2 gene in MDS and expanded the phenotypic spectrum.

  16. Can indirect tests detect a known recombination event in human mtDNA?

    PubMed

    White, Daniel James; Gemmell, Neil John

    2009-07-01

    Whether human mitochondrial DNA (mtDNA) recombines sufficiently to influence its evolution, evolutionary analysis, and disease etiology, remains equivocal. Overall, evidence from indirect studies of population genetic data suggests that recombination is not occurring at detectable levels. This may be explained by no, or low, recombination or, alternatively, current indirect tests may be incapable of detecting recombination in human mtDNA. To investigate the latter, we have tested whether six well-established indirect tests of recombination could detect recombination in a human mtDNA data set, in which its occurrence had been empirically confirmed. Three showed statistical evidence for recombination (r(2) vs. distance, the Homoplasy test, Neighborhood Similarity Score), and three did not (D' vs. distance, Max Chi Squared, Pairwise Homoplasy Index). Possible reasons for detection failure are discussed. Further, evidence from earlier studies suggesting a lack of recombination in mtDNA in humans is reconsidered, taking into account the appropriateness of the tests used, based on our new findings.

  17. 76 FR 41725 - Proposed Amendment of Class E Airspace; Miles City, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ... Class E Airspace; Miles City, MT AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of..., Miles City, MT, to accommodate aircraft using new Area Navigation (RNAV) Global Positioning System (GPS... airspace and Class E airspace extending upward from 700 feet above the surface at Frank Wiley Field, Miles...

  18. 78 FR 45474 - Proposed Establishment of Class E Airspace; Cut Bank, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-29

    ...-0532; Airspace Docket No. 13-ANM-21] Proposed Establishment of Class E Airspace; Cut Bank, MT AGENCY... action proposes to establish Class E airspace at the Cut Bank VHF Omni-Directional Radio Range Tactical Air Navigational Aid (VORTAC) navigation aid, Cut Bank, MT, to facilitate vectoring of Instrument...

  19. Spectral Signatures of Feedforward and Recurrent Circuitry in Monkey Area MT.

    PubMed

    Solomon, Selina S; Morley, John W; Solomon, Samuel G

    2017-05-01

    Recordings of local field potential (LFP) in the visual cortex can show rhythmic activity at gamma frequencies (30-100 Hz). While the gamma rhythms in the primary visual cortex have been well studied, the structural and functional characteristics of gamma rhythms in extrastriate visual cortex are less clear. Here, we studied the spatial distribution and functional specificity of gamma rhythms in extrastriate middle temporal (MT) area of visual cortex in marmoset monkeys. We found that moving gratings induced narrowband gamma rhythms across cortical layers that were coherent across much of area MT. Moving dot fields instead induced a broadband increase in LFP in middle and upper layers, with weaker narrowband gamma rhythms in deeper layers. The stimulus dependence of LFP response in middle and upper layers of area MT appears to reflect the presence (gratings) or absence (dot fields and other textures) of strongly oriented contours. Our results suggest that gamma rhythms in these layers are propagated from earlier visual cortex, while those in the deeper layers may emerge in area MT. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. The CAFE Experiment: A Joint Seismic and MT Investigation of the Cascadia Subduction System

    DTIC Science & Technology

    2013-02-01

    In this thesis we present results from inversion of data using dense arrays of collocated seismic and magnetotelluric stations located in the Cascadia...implicit in the standard MT inversion provides tools that enable us to generate a more accurate MT model. This final MT model clearly demonstrates...references within, Hacker, 2008) have given us the tools to better interpret geophysical evidence. Improvements in the thermal modeling of subduction zones

  1. Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.

    PubMed

    Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

    2015-04-02

    Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.

  2. WSJointInv2D-MT-DCR: An efficient joint two-dimensional magnetotelluric and direct current resistivity inversion

    NASA Astrophysics Data System (ADS)

    Amatyakul, Puwis; Vachiratienchai, Chatchai; Siripunvaraporn, Weerachai

    2017-05-01

    An efficient joint two-dimensional direct current resistivity (DCR) and magnetotelluric (MT) inversion, referred to as WSJointInv2D-MT-DCR, was developed with FORTRAN 95 based on the data space Occam's inversion algorithm. Our joint inversion software can be used to invert just the MT data or the DCR data, or invert both data sets simultaneously to get the electrical resistivity structures. Since both MT and DCR surveys yield the same resistivity structures, the two data types enhance each other leading to a better interpretation. Two synthetic and a real field survey are used here to demonstrate that the joint DCR and MT surveys can help constrain each other to reduce the ambiguities occurring when inverting the DCR or MT alone. The DCR data increases the lateral resolution of the near surface structures while the MT data reveals the deeper structures. When the MT apparent resistivity suffers from the static shift, the DCR apparent resistivity can serve as a replacement for the estimation of the static shift factor using the joint inversion. In addition, we also used these examples to show the efficiency of our joint inversion code. With the availability of our new joint inversion software, we expect the number of joint DCR and MT surveys to increase in the future.

  3. Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

    PubMed

    Peñaloza-Espinosa, Rosenda I; Arenas-Aranda, Diego; Cerda-Flores, Ricardo M; Buentello-Malo, Leonor; González-Valencia, Gerardo; Torres, Javier; Alvarez, Berenice; Mendoza, Irma; Flores, Mario; Sandoval, Lucila; Loeza, Francisco; Ramos, Irma; Muñoz, Leopoldo; Salamanca, Fabio

    2007-06-01

    In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2, C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two principal components accounted for 95.9% of the total variation in the sample. The mtDNA haplogroup frequencies in the Purépecha and Zitlala were intermediate to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa). The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from the rest of the populations. According to these findings, the distribution of mtDNA haplogroups found in Mexican indigenous groups is similar to other Amerindian haplogroups, except for the African haplogroup found in one population.

  4. Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism.

    PubMed

    Fernández, Rosa; Esteva, Isabel; Gómez-Gil, Esther; Rumbo, Teresa; Almaraz, Mari Cruz; Roda, Ester; Haro-Mora, Juan-Jesús; Guillamón, Antonio; Pásaro, Eduardo

    2014-12-01

    The etiology of male-to-female (MtF) transsexualism is unknown. Both genetic and neurological factors may play an important role. To investigate the possible influence of the genetic factor on the etiology of MtF transsexualism. We carried out a cytogenetic and molecular analysis in 442 MtFs and 473 healthy, age- and geographical origin-matched XY control males. The karyotype was investigated by G-banding and by high-density array in the transsexual group. The molecular analysis involved three tandem variable regions of genes estrogen receptor β (ERβ) (CA tandem repeats in intron 5), androgen receptor (AR) (CAG tandem repeats in exon 1), and CYP19A1 (TTTA tandem repeats in intron 4). The allele and genotype frequencies, after division into short and long alleles, were obtained. We investigated the association between genotype and transsexualism by performing a molecular analysis of three variable regions of genes ERβ, AR, and CYP19A1 in 915 individuals (442 MtFs and 473 control males). Most MtFs showed an unremarkable 46,XY karyotype (97.96%). No specific chromosome aberration was associated with MtF transsexualism, and prevalence of aneuploidy (2.04%) was slightly higher than in the general population. Molecular analyses showed no significant difference in allelic or genotypic distribution of the genes examined between MtFs and controls. Moreover, molecular findings presented no evidence of an association between the sex hormone-related genes (ERβ, AR, and CYP19A1) and MtF transsexualism. The study suggests that the analysis of karyotype provides limited information in these subjects. Variable regions analyzed from ERβ, AR, and CYP19A1 are not associated with MtF transsexualism. Nevertheless, this does not exclude other polymorphic regions not analyzed. © 2014 International Society for Sexual Medicine.

  5. Transportation Observations, Considerations, and Recommendations for Mt. Baker-Snoqualmie National Forest and Mt. Rainier National Park Provided by the Interagency Transportation Assistance Group (TAG) / Alternative Transportation in Parks and Public Land

    DOT National Transportation Integrated Search

    2007-09-25

    A field investigation of the current transportation infrastructure and issues at Mt. Baker-Snoqualmie National Forest and Mt. Rainier National Park by the interagency Transportation Assistance Group (TAG) was conducted September 25-27, 2007, on behal...

  6. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) on prostate cancer cell lines.

    PubMed

    Nagakawa, O; Murakami, K; Yamaura, T; Fujiuchi, Y; Murata, J; Fuse, H; Saiki, I

    2000-07-31

    Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase, which activates proMMP-2 and expressed on the cell surface in many invasive cancer cells. We investigated the expression of MT1-MMP in prostate cancer cell lines. MT1-MMP protein and mRNA were expressed in PC-3, DU-145 and TSU-pr1 cells (androgen-independent prostate cancer cell lines), but in LNCaP cells (androgen-dependent prostate cancer cell line). MT1-MMP protein was negative and mRNA was low to detect by RT-PCR. Cell lysate of PC-3 cleaved proMMP-2 to the active form. In addition, both hepatocyte growth factor (HGF) and gastrin-releasing peptide (GRP) increased Matrigel invasion and induced the expression of MT1-MMP protein in DU-145 prostate cancer cells. These results suggest that MT1-MMP is indeed the tumor-specific activator of proMMP-2 in androgen-independent prostate cancer cells and plays an important role in the invasive properties of prostate cancer cells.

  7. 78 FR 33047 - Humboldt-Toiyabe National Forest, Carson Ranger District Mt. Rose Ski Tahoe-Atoma Area...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    ... the effects of a proposal from Mt. Rose Ski Tahoe (Mt. Rose) to expand its lift and terrain network... to create the Atoma lift and trail ``Pod'' to the north of the Mt. Rose Highway. The proposed Atoma... facilitate construction and [[Page 33048

  8. Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček

    Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators.more » We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent

  9. Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML.

    PubMed

    Liyanage, Sanduni U; Hurren, Rose; Voisin, Veronique; Bridon, Gaëlle; Wang, Xiaoming; Xu, ChangJiang; MacLean, Neil; Siriwardena, Thirushi P; Gronda, Marcela; Yehudai, Dana; Sriskanthadevan, Shrivani; Avizonis, Daina; Shamas-Din, Aisha; Minden, Mark D; Bader, Gary D; Laposa, Rebecca; Schimmer, Aaron D

    2017-05-11

    Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2'3'-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2'3'-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. © 2017 by The American Society of Hematology.

  10. Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML

    PubMed Central

    Liyanage, Sanduni U.; Hurren, Rose; Voisin, Veronique; Bridon, Gaëlle; Wang, Xiaoming; Xu, ChangJiang; MacLean, Neil; Siriwardena, Thirushi P.; Gronda, Marcela; Yehudai, Dana; Sriskanthadevan, Shrivani; Avizonis, Daina; Shamas-Din, Aisha; Minden, Mark D.; Bader, Gary D.; Laposa, Rebecca

    2017-01-01

    Mitochondrial DNA (mtDNA) biosynthesis requires replication factors and adequate nucleotide pools from the mitochondria and cytoplasm. We performed gene expression profiling analysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA biosynthesis pathway expression compared with normal hematopoietic cells. Genes that support mitochondrial nucleotide pools, including mitochondrial nucleotide transporters and a subset of cytoplasmic nucleoside kinases, were also increased in AML compared with normal hematopoietic samples. Knockdown of cytoplasmic nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaining mtDNA. To assess cytoplasmic nucleoside kinase pathway activity, we used a nucleoside analog 2′3′-dideoxycytidine (ddC), which is phosphorylated to the activated antimetabolite, 2′3′-dideoxycytidine triphosphate by cytoplasmic nucleoside kinases. ddC is a selective inhibitor of the mitochondrial DNA polymerase γ. ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor cells. ddC treatment inhibited mtDNA replication, oxidative phosphorylation, and induced cytotoxicity in a panel of AML cell lines. Furthermore, ddC preferentially inhibited mtDNA replication in a subset of primary human leukemia cells and selectively targeted leukemia cells while sparing normal progenitor cells. In animal models of human AML, treatment with ddC decreased mtDNA, electron transport chain proteins, and induced tumor regression without toxicity. ddC also targeted leukemic stem cells in secondary AML xenotransplantation assays. Thus, AML cells have increased cytidine nucleoside kinase activity that regulates mtDNA biogenesis and can be leveraged to selectively target oxidative phosphorylation in AML. PMID:28283480

  11. Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number

    PubMed Central

    Spadafora, Domenico; Kozhukhar, Natalia; Alexeyev, Mikhail F.

    2016-01-01

    Due to the essential role played by mitochondrial DNA (mtDNA) in cellular physiology and bioenergetics, methods for establishing cell lines with altered mtDNA content are of considerable interest. Here, we report evidence for the existence in mammalian cells of a novel, low- efficiency, presequence-independent pathway for mitochondrial protein import, which facilitates mitochondrial uptake of such proteins as Chlorella virus ligase (ChVlig) and Escherichia coli LigA. Mouse cells engineered to depend on this pathway for mitochondrial import of the LigA protein for mtDNA maintenance had severely (up to >90%) reduced mtDNA content. These observations were used to establish a method for the generation of mouse cell lines with reduced mtDNA copy number by, first, transducing them with a retrovirus encoding LigA, and then inactivating in these transductants endogenous Lig3 with CRISPR-Cas9. Interestingly, mtDNA depletion to an average level of one copy per cell proceeds faster in cells engineered to maintain mtDNA at low copy number. This makes a low-mtDNA copy number phenotype resulting from dependence on mitochondrial import of DNA ligase through presequence-independent pathway potentially useful for rapidly shifting mtDNA heteroplasmy through partial mtDNA depletion. PMID:27031233

  12. Eudialyte-group minerals in rocks of Lovozero layered complex at Mt. Karnasurt and Mt. Kedykvyrpakhk

    NASA Astrophysics Data System (ADS)

    Ivanyuk, G. Yu.; Pakhomovsky, Ya. A.; Yakovenchuk, V. N.

    2015-12-01

    Eudialyte-bearing interbeds within layers I-4 (Mt. Karnasurt) and II-4 (Mt. Kedykvyrpakhk) in the layered complex of the Lovozero Pluton are localized symmetrically relative to the loparite-bearing ijolite-malignite layer; the content of eudialyte decreases from underlying nepheline syenite to overlying foidolite. Eudialyte-group minerals fill the interstices between nepheline, sodalite, and microcline-perthite crystals in all rock types and are partially replaced with georgechaoite and minerals of the lovozerite group as a result of hydrothermal alteration. Variations in the chemical composition of the eudialyte-group minerals are mainly controlled by block substitution NaFeZrCl ↔ LnMn(Nb,Ti)S producing eudialyte proper, manganoeudialyte (sharply predominant), kentbrooksite, alluaivite, and a phase intermediate between manganoeudialyte and alluaivite. As the total Ln2O3 content increases, the relative amounts of Ce and La oxides increases linearly in the proportion Ce2O3: La2O3 = 2.5: 1. In the phases containing lower than 3 wt % La2O3, Nd becomes the next REE after Ce. It is very likely that (mangano)eudialyte was mostly formed after parakeldyshite and other anhydrous zirconium-silicate under effect of residual fluids enriched in Ca and Mn, which took part in fenitization of basalt, tuff, and tuffite of the Lovozero Formation.

  13. High-throughput investigation of endothelial-to-mesenchymal transformation (EndMT) with combinatorial cellular microarrays.

    PubMed

    Wang, Zongjie; Calpe, Blaise; Zerdani, Jalil; Lee, Youngsang; Oh, Jonghyun; Bae, Hojae; Khademhosseini, Ali; Kim, Keekyoung

    2016-07-01

    In the developing heart, a specific subset of endocardium undergoes an endothelial-to-mesenchymal transformation (EndMT) thus forming nascent valve leaflets. Extracellular matrix (ECM) proteins and growth factors (GFs) play important roles in regulating EndMT but the combinatorial effect of GFs with ECM proteins is less well understood. Here we use microscale engineering techniques to create single, binary, and tertiary component microenvironments to investigate the combinatorial effects of ECM proteins and GFs on the attachment and transformation of adult ovine mitral valve endothelial cells to a mesenchymal phenotype. With the combinatorial microenvironment microarrays, we utilized 60 different combinations of ECM proteins (Fibronectin, Collagen I, II, IV, Laminin) and GFs (TGF-β1, bFGF, VEGF) and were able to identify new microenvironmental conditions capable of modulating EndMT in MVECs. Experimental results indicated that TGF-β1 significantly upregulated the EndMT while either bFGF or VEGF downregulated EndMT process markedly. Also, ECM proteins could influence both the attachment of MVECs and the response of MVECs to GFs. In terms of attachment, fibronectin is significantly better for the adhesion of MVECs among the five tested proteins. Overall collagen IV and fibronectin appeared to play important roles in promoting EndMT process. Great consistency between macroscale and microarrayed experiments and present studies demonstrates that high-throughput cellular microarrays are a promising approach to study the regulation of EndMT in valvular endothelium. Biotechnol. Bioeng. 2016;113: 1403-1412. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  14. mtDNA-Server: next-generation sequencing data analysis of human mitochondrial DNA in the cloud.

    PubMed

    Weissensteiner, Hansi; Forer, Lukas; Fuchsberger, Christian; Schöpf, Bernd; Kloss-Brandstätter, Anita; Specht, Günther; Kronenberg, Florian; Schönherr, Sebastian

    2016-07-08

    Next generation sequencing (NGS) allows investigating mitochondrial DNA (mtDNA) characteristics such as heteroplasmy (i.e. intra-individual sequence variation) to a higher level of detail. While several pipelines for analyzing heteroplasmies exist, issues in usability, accuracy of results and interpreting final data limit their usage. Here we present mtDNA-Server, a scalable web server for the analysis of mtDNA studies of any size with a special focus on usability as well as reliable identification and quantification of heteroplasmic variants. The mtDNA-Server workflow includes parallel read alignment, heteroplasmy detection, artefact or contamination identification, variant annotation as well as several quality control metrics, often neglected in current mtDNA NGS studies. All computational steps are parallelized with Hadoop MapReduce and executed graphically with Cloudgene. We validated the underlying heteroplasmy and contamination detection model by generating four artificial sample mix-ups on two different NGS devices. Our evaluation data shows that mtDNA-Server detects heteroplasmies and artificial recombinations down to the 1% level with perfect specificity and outperforms existing approaches regarding sensitivity. mtDNA-Server is currently able to analyze the 1000G Phase 3 data (n = 2,504) in less than 5 h and is freely accessible at https://mtdna-server.uibk.ac.at. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. [Application of mtDNA polymorphism in species identification of sarcosaphagous insects].

    PubMed

    Li, Xiang; Cai, Ji-feng

    2011-04-01

    Species identification of sarcosaphagous insects is one of the important steps in forensic research based on the knowledge of entomology. Recent studies reveal that the application of molecular biology, especially the mtDNA sequences analysis, works well in the species identification of sarcosaphagous insects. The molecular biology characteristics, structures, polymorphism of mtDNA of sarcosaphagous insects, and the recent studies in species identification of sarcosaphagous insects are reviewed in this article.

  16. Recombination-dependent mtDNA partitioning: in vivo role of Mhr1p to promote pairing of homologous DNA.

    PubMed

    Ling, Feng; Shibata, Takehiko

    2002-09-02

    Yeast mhr1-1 was isolated as a defective mutation in mitochondrial DNA (mtDNA) recombination. About half of mhr1-1 cells lose mtDNA during growth at a higher temperature. Here, we show that mhr1-1 exhibits a defect in the partitioning of nascent mtDNA into buds and is a base-substitution mutation in MHR1 encoding a mitochondrial matrix protein. We found that the Mhr1 protein (Mhr1p) has activity to pair single-stranded DNA and homologous double-stranded DNA to form heteroduplex joints in vitro, and that mhr1-1 causes the loss of this activity, indicating its role in homologous mtDNA recombination. While the majority of the mtDNA in the mother cells consists of head-to-tail concatemers, more than half of the mtDNA in the buds exists as genome-sized monomers. The mhr1-1 deltacce1 double mutant cells do not maintain any mtDNA, indicating the strict dependence of mtDNA maintenance on recombination functions. These results suggest a mechanism for mtDNA inheritance similar to that operating in the replication and packaging of phage DNA.

  17. 77 FR 52217 - Amendment of Class D and Class E Airspace; Bozeman, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... Bozeman Yellowstone International Airport. This improves the safety and management of Instrument Flight... Class E airspace at Bozeman Yellowstone International Airport, Bozeman, MT. This action aligns two Class... airspace designated as an extension to Class D, at Bozeman Yellowstone International Airport, Bozeman, MT...

  18. ASTER Images Mt. Usu Volcano

    NASA Image and Video Library

    2000-04-26

    On April 3, the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra Satellite captured this image of the erupting Mt. Usu volcano in Hokkaido, Japan. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image the Earth for the next 6 years to map and monitor the changing surface of our planet. This false color infrared image of Mt Usu volcano is dominated by Lake Toya, an ancient volcanic caldera. On the south shore is the active Usu volcano. On Friday, March 31, more than 11,000 people were evacuated by helicopter, truck and boat from the foot of Usu, that began erupting from the northwest flank, shooting debris and plumes of smoke streaked with blue lightning thousands of feet in the air. Although no lava gushed from the mountain, rocks and ash continued to fall after the eruption. The region was shaken by thousands of tremors before the eruption. People said they could taste grit from the ash that was spewed as high as 2,700 meters (8,850 ft) into the sky and fell to coat surrounding towns with ash. "Mount Usu has had seven significant eruptions that we know of, and at no time has it ended quickly with only a small scale eruption," said Yoshio Katsui, a professor at Hokkaido University. This was the seventh major eruption of Mount Usu in the past 300 years. Fifty people died when the volcano erupted in 1822, its worst known eruption. In the image, most of the land is covered by snow. Vegetation, appearing red in the false color composite, can be seen in the agricultural fields, and forests in the mountains. Mt. Usu is crossed by three dark streaks. These are the paths of ash deposits that rained out from eruption plumes two days earlier. The prevailing wind was from the northwest, carrying the ash away from the main city of Date. Ash deposited can be traced on the image as far away as 10 kilometers (16 miles

  19. The Making of the African mtDNA Landscape

    PubMed Central

    Salas, Antonio; Richards, Martin; De la Fe, Tomás; Lareu, María-Victoria; Sobrino, Beatriz; Sánchez-Diz, Paula; Macaulay, Vincent; Carracedo, Ángel

    2002-01-01

    Africa presents the most complex genetic picture of any continent, with a time depth for mitochondrial DNA (mtDNA) lineages >100,000 years. The most recent widespread demographic shift within the continent was most probably the Bantu dispersals, which archaeological and linguistic evidence suggest originated in West Africa 3,000–4,000 years ago, spreading both east and south. Here, we have carried out a thorough phylogeographic analysis of mtDNA variation in a total of 2,847 samples from throughout the continent, including 307 new sequences from southeast African Bantu speakers. The results suggest that the southeast Bantu speakers have a composite origin on the maternal line of descent, with ∼44% of lineages deriving from West Africa, ∼21% from either West or Central Africa, ∼30% from East Africa, and ∼5% from southern African Khoisan-speaking groups. The ages of the major founder types of both West and East African origin are consistent with the likely timing of Bantu dispersals, with those from the west somewhat predating those from the east. Despite this composite picture, the southeastern African Bantu groups are indistinguishable from each other with respect to their mtDNA, suggesting that they either had a common origin at the point of entry into southeastern Africa or have undergone very extensive gene flow since. PMID:12395296

  20. Alterations in mtDNA, gastric carcinogenesis and early diagnosis.

    PubMed

    Rodrigues-Antunes, S; Borges, B N

    2018-05-26

    Gastric cancer remains one of the most prevalent cancers in the world. Due to this, efforts are being made to improve the diagnosis of this neoplasm and the search for molecular markers that may be involved in its genesis. Within this perspective, the mitochondrial DNA is considered as a potential candidate, since it has several well documented changes and is readily accessible. However, numerous alterations have been reported in mtDNA, not facilitating the visualization of which alterations and molecular markers are truly involved with gastric carcinogenesis. This review presents a compilation of the main known changes relating mtDNA to gastric cancer and their clinical significance.

  1. Body composition and hematological changes following ascents of Mt. Aconcagua and Mt. Everest.

    PubMed

    Wagner, Dale R

    2010-11-01

    Both Mt. Aconcagua (22,841.2 ft/6962 m) and Mt. Everest (29,035.4 ft/ 8850 m) are highly prized summits by mountaineers, yet there are no published studies comparing the physiological adaptations that occur from climbing both peaks. This case study compares the changes in body composition and hematology of a mountaineer who ascended both peaks. The male subject was 41 yr of age during the Aconcagua ascent and 43 yr of age during the Everest ascent, and had a history of ascents above 19,685 ft (6000 m). Baseline body composition measurements and blood draws were done within a few days of departure for both expeditions. Body composition was assessed by air displacement plethysmography and the blood draw consisted of a complete blood count (CBC). Post-expedition measurements were taken 10-14 d after reaching the summits. The ascent of Aconcagua resulted in a 2.0-kg drop in body mass and a reduction in body fat (15.5% to 12.1%), but blood chemistry remained within +/- 2% of baseline values. Body mass was reduced from 65.0 kg to 60.5 kg during the Everest expedition with a drop in body fat from 17.3% to 10.2%. Despite no change in RBCs there were increases in hemoglobin and mean corpuscular hemoglobin of 12.7% and 13.7%, respectively. It took the subject 12 d to reach the summit of Aconcagua, whereas it took 50 d to reach the summit of Everest. The longer duration at higher altitude for the Everest expedition resulted in more dramatic physiological changes.

  2. Assessing the damage at Mt. Coffee

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, J.C.; Macauley, L.D.

    1995-12-31

    The Mt. Coffee Hydroelectric Project was damaged during the Liberian civil unrest in early 1990`s. A team of engineers performed a damage assessment of the project with the hope that funding could be obtained to reconstruct the project. The damage done to the plant had far greater impacts to the country than merely the cost to rebuild the facility.

  3. Roles of MPBQ-MT in Promoting α/γ-Tocopherol Production and Photosynthesis under High Light in Lettuce

    PubMed Central

    Tang, Yueli; Fu, Xueqing; Shen, Qian; Tang, Kexuan

    2016-01-01

    2-methyl-6-phytyl-1, 4-benzoquinol methyltransferase (MPBQ-MT) is a vital enzyme catalyzing a key methylation step in both α/γ-tocopherol and plastoquinone biosynthetic pathway. In this study, the gene encoding MPBQ-MT was isolated from lettuce (Lactuca sativa) by rapid amplification of cDNA ends (RACE), named LsMT. Overexpression of LsMT in lettuce brought about a significant increase of α- and γ-tocopherol contents with a reduction of phylloquinone (vitamin K1) content, suggesting a competition for a common substrate phytyl diphosphate (PDP) between the two biosynthetic pathways. Besides, overexpression of LsMT significantly increased plastoquinone (PQ) level. The increase of tocopherol and plastoquinone levels by LsMT overexpression conduced to the improvement of plants’ tolerance and photosynthesis under high light stress, by directing excessive light energy toward photosynthetic production rather than toward generation of more photooxidative damage. These findings suggest that the role and function of MPBQ-MT can be further explored for enhancing vitamin E value, strengthening photosynthesis and phototolerance under high light in plants. PMID:26867015

  4. Nonsynonymous Polymorphisms in the Human AS3MT Arsenic Methylation Gene: Implications for Arsenic Toxicity

    PubMed Central

    2017-01-01

    Arsenic methylation, the primary biotransformation in the human body, is catalyzed by the enzyme As(III) S-adenosylmethionine (SAM) methyltransferases (hAS3MT). This process is thought to be protective from acute high-level arsenic exposure. However, with long-term low-level exposure, hAS3MT produces intracellular methylarsenite (MAs(III)) and dimethylarsenite (DMAs(III)), which are considerably more toxic than inorganic As(III) and may contribute to arsenic-related diseases. Several single nucleotide polymorphisms (SNPs) in putative regulatory elements of the hAS3MT gene have been shown to be protective. In contrast, three previously identified exonic SNPs (R173W, M287T, and T306I) may be deleterious. The goal of this study was to examine the effect of single amino acid substitutions in hAS3MT on the activity of the enzyme that might explain their contributions to adverse health effects of environmental arsenic. We identified five additional intragenic variants in hAS3MT (H51R, C61W, I136T, W203C, and R251H). We purified the eight polymorphic hAS3MT proteins and characterized their enzymatic properties. Each enzyme had low methylation activity through decreased affinity for substrate, lower overall rates of catalysis, or lower stability. We propose that amino acid substitutions in hAS3MT with decreased catalytic activity lead to detrimental responses to environmental arsenic and may increase the risk of arsenic-related diseases. PMID:28537708

  5. Evidence for recombination of mtDNA in the marine mussel Mytilus trossulus from the Baltic.

    PubMed

    Burzyński, Artur; Zbawicka, Małgorzata; Skibinski, David O F; Wenne, Roman

    2003-03-01

    A number of studies have claimed that recombination occurs in animal mtDNA, although this evidence is controversial. Ladoukakis and Zouros (2001) provided strong evidence for mtDNA recombination in the COIII gene in gonadal tissue in the marine mussel Mytilus galloprovincialis from the Black Sea. The recombinant molecules they reported had not however become established in the population from which experimental animals were sampled. In the present study, we provide further evidence of the generality of mtDNA recombination in Mytilus by reporting recombinant mtDNA molecules in a related mussel species, Mytilus trossulus, from the Baltic. The mtDNA region studied begins in the 16S rRNA gene and terminates in the cytochrome b gene and includes a major noncoding region that may be analogous to the D-loop region observed in other animals. Many bivalve species, including some Mytilus species, are unusual in that they have two mtDNA genomes, one of which is inherited maternally (F genome) the other inherited paternally (M genome). Two recombinant variants reported in the present study have population frequencies of 5% and 36% and appear to be mosaic for F-like and M-like sequences. However, both variants have the noncoding region from the M genome, and both are transmitted to sperm like the M genome. We speculate that acquisition of the noncoding region by the recombinant molecules has conferred a paternal role on mtDNA genomes that otherwise resemble the F genome in sequence.

  6. Different degree of paternal mtDNA leakage between male and female progeny in interspecific Drosophila crosses

    PubMed Central

    Dokianakis, Emmanouil; Ladoukakis, Emmanuel D

    2014-01-01

    Maternal transmission of mitochondrial DNA (mtDNA) in animals is thought to prevent the spread of selfish deleterious mtDNA mutations in the population. Various mechanisms have been evolved independently to prevent the entry of sperm mitochondria in the embryo. However, the increasing number of instances of paternal mtDNA leakage suggests that these mechanisms are not very effective. The destruction of sperm mitochondria in mammalian embryos is mediated by nuclear factors. Also, the destruction of paternal mitochondria in intraspecific crosses is more effective than in interspecific ones. These observations have led to the hypothesis that leakage of paternal mtDNA (and consequently mtDNA recombination owing to ensuing heteroplasmy) might be more common in inter- than in intraspecific crosses and that it should increase with phylogenetic distance of hybridizing species. We checked paternal leakage in inter- and intraspecific crosses in Drosophila and found little evidence for this hypothesis. In addition, we have observed a higher level of leakage among male than among female progeny from the same cross. This is the first report of sex-specific leakage of paternal mtDNA. It suggests that paternal mtDNA leakage might not be a stochastic result of an error-prone mechanism, but rather, it may be under complex genetic control. PMID:25077015

  7. Different degree of paternal mtDNA leakage between male and female progeny in interspecific Drosophila crosses.

    PubMed

    Dokianakis, Emmanouil; Ladoukakis, Emmanuel D

    2014-07-01

    Maternal transmission of mitochondrial DNA (mtDNA) in animals is thought to prevent the spread of selfish deleterious mtDNA mutations in the population. Various mechanisms have been evolved independently to prevent the entry of sperm mitochondria in the embryo. However, the increasing number of instances of paternal mtDNA leakage suggests that these mechanisms are not very effective. The destruction of sperm mitochondria in mammalian embryos is mediated by nuclear factors. Also, the destruction of paternal mitochondria in intraspecific crosses is more effective than in interspecific ones. These observations have led to the hypothesis that leakage of paternal mtDNA (and consequently mtDNA recombination owing to ensuing heteroplasmy) might be more common in inter- than in intraspecific crosses and that it should increase with phylogenetic distance of hybridizing species. We checked paternal leakage in inter- and intraspecific crosses in Drosophila and found little evidence for this hypothesis. In addition, we have observed a higher level of leakage among male than among female progeny from the same cross. This is the first report of sex-specific leakage of paternal mtDNA. It suggests that paternal mtDNA leakage might not be a stochastic result of an error-prone mechanism, but rather, it may be under complex genetic control.

  8. Geophysical model of Mt. Labo geothermal field, Southeastern Luzon, Philippines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Los Banos, C.F. Jr.; Layugan, D.B.; Maneja, F.C.

    1996-12-31

    The geophysical model of Mt. Labo geothermal field, based on the results of the regional gravity and magnetotelluric (MT) surveys, indicates a geothermal reservoir centered beneath the Mabahong Labo thermal ground. The heat source of the present hydrothermal system is provided by a cooling intrusive body, mapped as a gravity high, associated with the Mt. Labo volcanic activity. The geothermal fluids circulate along fractures within the low-density reservoir rocks of the Susung Dalaga Formation. This reservoir rock shows relatively high resistivity values of 30 to 40 ohm-m. Directly overlying the resistive reservoir, occurring between -1000 m to -1500 m, ismore » a thick alteration halo formed within the basal unit of the Labo Volcanics (Lbu). The predominantly hydrous, low-temperature clay minerals which compose the alteration halo give low resistivity values of 1 to 4 ohm-m. Outflow of hot fluids to the south-southwest, which possibly feeds the thermal springs at Kilbay and Alawihaw, may be channeled along the thinning low resistivity Lbu. The geophysical model also shows a possible separate hydrothermal system in the west associated with a relatively shallower intrusive body, also defined by positive gravity values. This intrusion, which could be related to the cluster of volcanic domes located south of Bakilid Fault, may provide the heat that drives the hot springs at Kilbay and Alawihaw. It could also be possible that the Kilbay and Alawihaw springs originate from both systems. Based on the interpretation of the gravity and MT data, wells LB-1D and LB-5D lie closest to the intrusive, LB-313 and LB-4D are located in the center of the resource, while LB-2D and LB-6D lie along the margin or outside of the resource. The size of this resource, as defined by the 5 ohm-m MT low resistivity anomaly, is about 10 sq. km.« less

  9. Contrast Responsivity in MT+ Correlates with Phonological Awareness and Reading Measures in Children

    PubMed Central

    Ben-Shachar, Michal; Dougherty, Robert F.; Deutsch, Gayle K.; Wandell, Brian A.

    2007-01-01

    There are several independent sets of findings concerning the neural basis of reading. One set demonstrates a powerful relationship between phonological processing and reading skills. Another set reveals a relationship between visual responses in the motion pathways and reading skills. It is widely assumed that these two findings are unrelated. We tested the hypothesis that phonological awareness is related to motion responsivity in children’s MT+. We measured BOLD signals to drifting gratings as a function of contrast. Subjects were 35 children ages 7–12y with a wide range of reading skills. Contrast responsivity in MT+, but not V1, was correlated with phonological awareness and to a lesser extent with two other measures of reading. No correlation was found between MT+ signals and rapid naming, age or general IQ measures. These results establish an important link between visual and phonological processing in children and suggest that MT+ responsivity is a marker for healthy reading development. PMID:17689981

  10. Mt. St. Helens

    NASA Technical Reports Server (NTRS)

    2001-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] Figure 1 Movie

    This 3-D anaglyph image of Mt. St. Helens volcano combines the nadir-looking and back-looking band 3 images of ASTER. To view the image in stereo, you will need blue-red glasses. Make sure to look through the red lens with your left eye. Figure 1: This ASTER image of Mt. St. Helens volcano in Washington was acquired on August 8, 2000 and covers an area of 37 by 51 km. Mount Saint Helens, a volcano in the Cascade Range of southwestern Washington that had been dormant since 1857, began to show signs of renewed activity in early 1980. On 18 May 1980, it erupted with such violence that the top of the mountain was blown off, spewing a cloud of ash and gases that rose to an altitude of 19 kilometers. The blast killed about 60 people and destroyed all life in an area of some 180 square kilometers (some 70 square miles), while a much larger area was covered with ash and debris. It continues to spit forth ash and steam intermittently. As a result of the eruption, the mountain's elevation decreased from 2,950 meters to 2,549 meters. The image is centered at 46.2 degrees north latitude, 122.2 degrees west longitude.

    Movie: The simulated fly-over was produced by draping ASTER visible and near infrared image data over a digital topography model, created from ASTER's 3-D stereo bands. The color was computer enhanced to create a natural color image, where the vegetation appears green. The topography has been exaggerated 2 times to enhance the appearance of the relief.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  11. MtPAR MYB transcription factor acts as an on switch for proanthocyanidin biosynthesis in Medicago truncatula

    PubMed Central

    Verdier, Jerome; Zhao, Jian; Torres-Jerez, Ivone; Ge, Shujun; Liu, Chenggang; He, Xianzhi; Mysore, Kirankumar S.; Dixon, Richard A.; Udvardi, Michael K.

    2012-01-01

    MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one-hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid–PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals. PMID:22307644

  12. DNA Barcoding the Medusozoa using mtCOI

    NASA Astrophysics Data System (ADS)

    Ortman, Brian D.; Bucklin, Ann; Pagès, Francesc; Youngbluth, Marsh

    2010-12-01

    The Medusozoa are a clade within the Cnidaria comprising the classes Hydrozoa, Scyphozoa, and Cubozoa. Identification of medusozoan species is challenging, even for taxonomic experts, due to their fragile forms and complex, morphologically-distinct life history stages. In this study 231 sequences for a portion of the mitochondrial Cytochrome Oxidase I (mtCOI) gene were obtained from 95 species of Medusozoans including; 84 hydrozoans (61 siphonophores, eight anthomedusae, four leptomedusae, seven trachymedusae, and four narcomedusae), 10 scyphozoans (three coronatae, four semaeostomae, two rhizostomae, and one stauromedusae), and one cubozoan. This region of mtCOI has been used as a DNA barcode (i.e., a molecular character for species recognition and discrimination) for a diverse array of taxa, including some Cnidaria. Kimura 2-parameter (K2P) genetic distances between sequence variants within species ranged from 0 to 0.057 (mean 0.013). Within the 13 genera for which multiple species were available, K2P distance between congeneric species ranged from 0.056 to 0.381. A cluster diagram generated by Neighbor Joining (NJ) using K2P distances reliably clustered all barcodes of the same species with ≥99% bootstrap support, ensuring accurate identification of species. Intra- and inter-specific variation of the mtCOI gene for the Medusozoa are appropriate for this gene to be used as a DNA barcode for species-level identification, but not for phylogenetic analysis or taxonomic classification of unknown sequences at higher taxonomic levels. This study provides a set of molecular tools that can be used to address questions of speciation, biodiversity, life-history, and population boundaries in the Medusozoa.

  13. Modeling variably saturated subsurface solute transport with MODFLOW-UZF and MT3DMS

    USGS Publications Warehouse

    Morway, Eric D.; Niswonger, Richard G.; Langevin, Christian D.; Bailey, Ryan T.; Healy, Richard W.

    2013-01-01

    The MT3DMS groundwater solute transport model was modified to simulate solute transport in the unsaturated zone by incorporating the unsaturated-zone flow (UZF1) package developed for MODFLOW. The modified MT3DMS code uses a volume-averaged approach in which Lagrangian-based UZF1 fluid fluxes and storage changes are mapped onto a fixed grid. Referred to as UZF-MT3DMS, the linked model was tested against published benchmarks solved analytically as well as against other published codes, most frequently the U.S. Geological Survey's Variably-Saturated Two-Dimensional Flow and Transport Model. Results from a suite of test cases demonstrate that the modified code accurately simulates solute advection, dispersion, and reaction in the unsaturated zone. Two- and three-dimensional simulations also were investigated to ensure unsaturated-saturated zone interaction was simulated correctly. Because the UZF1 solution is analytical, large-scale flow and transport investigations can be performed free from the computational and data burdens required by numerical solutions to Richards' equation. Results demonstrate that significant simulation runtime savings can be achieved with UZF-MT3DMS, an important development when hundreds or thousands of model runs are required during parameter estimation and uncertainty analysis. Three-dimensional variably saturated flow and transport simulations revealed UZF-MT3DMS to have runtimes that are less than one tenth of the time required by models that rely on Richards' equation. Given its accuracy and efficiency, and the wide-spread use of both MODFLOW and MT3DMS, the added capability of unsaturated-zone transport in this familiar modeling framework stands to benefit a broad user-ship.

  14. Whole brain inhomogeneous magnetization transfer (ihMT) imaging: Sensitivity enhancement within a steady-state gradient echo sequence.

    PubMed

    Mchinda, Samira; Varma, Gopal; Prevost, Valentin H; Le Troter, Arnaud; Rapacchi, Stanislas; Guye, Maxime; Pelletier, Jean; Ranjeva, Jean-Philippe; Alsop, David C; Duhamel, Guillaume; Girard, Olivier M

    2018-05-01

    To implement, characterize, and optimize an interleaved inhomogeneous magnetization transfer (ihMT) gradient echo sequence allowing for whole-brain imaging within a clinically compatible scan time. A general framework for ihMT modelling was developed based on the Provotorov theory of radiofrequency saturation, which accounts for the dipolar order underpinning the ihMT effect. Experimental studies and numerical simulations were performed to characterize and optimize the ihMT-gradient echo dependency with sequence timings, saturation power, and offset frequency. The protocol was optimized in terms of maximum signal intensity and the reproducibility assessed for a nominal resolution of 1.5 mm isotropic. All experiments were performed on healthy volunteers at 1.5T. An important mechanism driving signal optimization and leading to strong ihMT signal enhancement that relies on the dynamics of radiofrequency energy deposition has been identified. By taking advantage of the delay allowed for readout between ihMT pulse bursts, it was possible to boost the ihMT signal by almost 2-fold compared to previous implementation. Reproducibility of the optimal protocol was very good, with an intra-individual error < 2%. The proposed sensitivity-boosted and time-efficient steady-state ihMT-gradient echo sequence, implemented and optimized at 1.5T, allowed robust high-resolution 3D ihMT imaging of the whole brain within a clinically compatible scan time. Magn Reson Med 79:2607-2619, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  15. MT71x: Multi-Temperature Library Based on ENDF/B-VII.1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Conlin, Jeremy Lloyd; Parsons, Donald Kent; Gray, Mark Girard

    The Nuclear Data Team has released a multitemperature transport library, MT71x, based upon ENDF/B-VII.1 with a few modifications as well as additional evaluations for a total of 427 isotope tables. The library was processed using NJOY2012.39 into 23 temperatures. MT71x consists of two sub-libraries; MT71xMG for multigroup energy representation data and MT71xCE for continuous energy representation data. These sub-libraries are suitable for deterministic transport and Monte Carlo transport applications, respectively. The SZAs used are the same for the two sub-libraries; that is, the same SZA can be used for both libraries. This makes comparisons between the two libraries and betweenmore » deterministic and Monte Carlo codes straightforward. Both the multigroup energy and continuous energy libraries were verified and validated with our checking codes checkmg and checkace (multigroup and continuous energy, respectively) Then an expanded suite of tests was used for additional verification and, finally, verified using an extensive suite of critical benchmark models. We feel that this library is suitable for all calculations and is particularly useful for calculations sensitive to temperature effects.« less

  16. Biochemical signatures mimicking multiple carboxylase deficiency in children with mutations in MT-ATP6.

    PubMed

    Larson, Austin A; Balasubramaniam, Shanti; Christodoulou, John; Burrage, Lindsay C; Marom, Ronit; Graham, Brett H; Diaz, George A; Glamuzina, Emma; Hauser, Natalie; Heese, Bryce; Horvath, Gabriella; Mattman, Andre; van Karnebeek, Clara; Lane Rutledge, S; Williamson, Amy; Estrella, Lissette; Van Hove, Johan K L; Weisfeld-Adams, James D

    2018-01-04

    Elevations of specific acylcarnitines in blood reflect carboxylase deficiencies, and have utility in newborn screening for life-threatening organic acidemias and other inherited metabolic diseases. In this report, we describe a newly-identified association of biochemical features of multiple carboxylase deficiency in individuals harboring mitochondrial DNA (mtDNA) mutations in MT-ATP6 and in whom organic acidemias and multiple carboxylase deficiencies were excluded. Using retrospective chart review, we identified eleven individuals with abnormally elevated propionylcarnitine (C3) or hydroxyisovalerylcarnitine (C5OH) with mutations in MT-ATP6, most commonly m.8993T>G in high heteroplasmy or homoplasmy. Most patients were ascertained on newborn screening; most had normal enzymatic or molecular genetic testing to exclude biotinidase and holocarboxylase synthetase deficiencies. MT-ATP6 is associated with some cases of Leigh disease; clinical outcomes in our cohort ranged from death from neurodegenerative disease in early childhood to clinically and developmentally normal after several years of follow-up. These cases expand the biochemical phenotype associated with MT-ATP6 mutations, especially m.8993T>G, to include acylcarnitine abnormalities mimicking carboxylase deficiency states. Clinicians should be aware of this association and its implications for newborn screening, and consider mtDNA sequencing in patients exhibiting similar acylcarnitine abnormalities that are biotin-unresponsive and in whom other enzymatic deficiencies have been excluded. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  17. TOP1MT deficiency promotes GC invasion and migration via the enhancements of LDHA expression and aerobic glycolysis.

    PubMed

    Wang, Hongqiang; Zhou, Rui; Sun, Li; Xia, Jianling; Yang, Xuchun; Pan, Changqie; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

    2017-11-01

    Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I ( TOP1MT ) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues. TOP1MT knockdown significantly promoted GC migration and invasion in vitro and in vivo Importantly, TOP1MT silencing increased glucose consumption, lactate production, glucose transporter 1 expression and the epithelial-mesenchymal transition (EMT) in GC. Additionally, regulation of glucose metabolism induced by TOP1MT was significantly associated with lactate dehydrogenase A (LDHA) expression. A retrospective analysis of clinical data from 295 patients with GC demonstrated that low TOP1MT expression was associated with lymph node metastasis, recurrence and high mortality rates. TOP1MT deficiency enhanced glucose aerobic glycolysis by stimulating LDHA to promote GC progression. © 2017 The authors.

  18. In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment.

    PubMed

    Naundorf, Stefanie; Preithner, Susanne; Mayer, Petra; Lippold, Sandra; Wolf, Andreas; Hanakam, Frank; Fichtner, Iduna; Kufer, Peter; Raum, Tobias; Riethmüller, Gert; Baeuerle, Patrick A; Dreier, Torsten

    2002-07-01

    In our study, a novel, fully human, recombinant monoclonal antibody of the IgG1 isotype, called MT201, was characterized for its binding properties, complement-dependent (CDC) and antibody-dependent cellular cytotoxicity (ADCC), as well as for its in vivo antitumor activity in a nude mouse model. MT201 was found to bind its target, the epithelial cell adhesion molecule (Ep-CAM; also called 17-1A antigen, KSA, EGP-2, GA733-2), with low affinity in a range similar to that of the clinically validated, murine monoclonal IgG2a antibody edrecolomab (Panorex(R)). MT201 exhibited Ep-CAM-specific CDC with a potency similar to that of edrecolomab. However, the efficacy of ADCC of MT201, as mediated by human immune effector cells, was by 2 orders of magnitude higher than that of edrecolomab. Addition of human serum reduced the ADCC of MT201 while it essentially abolished ADCC of edrecolomab within the concentration range tested. In a nude mouse xenograft model, growth of tumors derived from the human colon carcinoma line HT-29 was significantly and comparably suppressed by MT201 and edrecolomab. The fully human nature and the improved ADCC of MT201 with human effector cells will make MT201 a promising candidate for the clinical development of a novel pan-carcinoma antibody that is superior to edrecolomab. Copyright 2002 Wiley-Liss, Inc.

  19. Comparison of minichromosome maintenance proteins (MCM-3, MCM-7) and metallothioneins (MT-I/II, MT-III) expression in relation to clinicopathological data in ovarian cancer.

    PubMed

    Kobierzycki, Christopher; Pula, Bartosz; Skiba, Mateusz; Jablonska, Karolina; Latkowski, Krzysztof; Zabel, Maciej; Nowak-Markwitz, Ewa; Spaczynski, Marek; Kedzia, Witold; Podhorska-Okolow, Marzena; Dziegiel, Piotr

    2013-12-01

    Despite great progress in the understanding of ovarian cancer biology, clinicopathological data (i.e. grade, stage, histological type and residual disease after surgery) seem to be the most important prognostic factors. The present study aimed to investigate the relationship between expression of minichromosome maintenance proteins (MCM-3, MCM-7), metallothioneins (MT-I/II, MT-III), and Ki-67 in 103 ovarian cancer cases, mostly of the serous histological type. Statistical analysis revealed strong positive correlations in the expression of MCM-3 vs. Ki-67 (r=0.492), MCM-7 vs. Ki-67 (r=0.651), and MCM-3 vs. MCM-7 (r=0.515) (all p<0.0001). The Kruskal-Wallis test showed an association of increased expression of MCM-3 and Ki-67 with increasing grade of histological malignancy (p=0.0011, p=0.029, respectively). Regarding clinical progression, cytoplasmic MT-I/II expression was significantly higher in more advanced disease stages (III+IV vs. I+II; p=0.0247). Due to the correlations shown here, the determination of MCM proteins as proliferation markers of ovarian cancer, should be strongly considered.

  20. Decrease of 3243 A→G mtDNA Mutation from Blood in MELAS Syndrome: A Longitudinal Study

    PubMed Central

    Rahman, S.; Poulton, J.; Marchington, D.; Suomalainen, A.

    2001-01-01

    It is widely held that changes in the distribution of mutant mtDNAs underlie the progressive nature of mtDNA diseases, but there are few data documenting such changes. We compared the levels of 3243 A→G mutant mtDNA in blood at birth from Guthrie cards and at the time of diagnosis in a blood DNA sample from patients with mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome. Paired blood DNA samples separated by 9–19 years were obtained from six patients with MELAS. Quantification of mutant load, by means of a solid-phase minisequencing technique, demonstrated a decline (range 12%–29%) in the proportion of mutant mtDNA in all cases (P=.0015, paired t-test). These results suggest that mutant mtDNA is slowly selected from rapidly dividing blood cells in MELAS. PMID:11085913

  1. MtDNA and Y-chromosome variation in Kurdish groups.

    PubMed

    Nasidze, Ivan; Quinque, Dominique; Ozturk, Murat; Bendukidze, Nina; Stoneking, Mark

    2005-07-01

    In order to investigate the origins and relationships of Kurdish-speaking groups, mtDNA HV1 sequences, eleven Y chromosome bi-allelic markers, and 9 Y-STR loci were analyzed among three Kurdish groups: Zazaki and Kurmanji speakers from Turkey, and Kurmanji speakers from Georgia. When compared with published data from other Kurdish groups and from European, Caucasian, and West and Central Asian groups, Kurdish groups are most similar genetically to other West Asian groups, and most distant from Central Asian groups, for both mtDNA and the Y-chromosome. However, Kurdish groups show a closer relationship with European groups than with Caucasian groups based on mtDNA, but the opposite based on the Y-chromosome, indicating some differences in their maternal and paternal histories. The genetic data indicate that the Georgian Kurdish group experienced a bottleneck effect during their migration to the Caucasus, and that they have not had detectable admixture with their geographic neighbours in Georgia. Our results also do not support the hypothesis of the origin of the Zazaki-speaking group being in northern Iran; genetically they are more similar to other Kurdish groups. Genetic analyses of recent events, such as the origins and migrations of Kurdish-speaking groups, can therefore lead to new insights into such migrations.

  2. Melatonin Suppresses Neuropathic Pain via MT2-Dependent and -Independent Pathways in Dorsal Root Ganglia Neurons of Mice

    PubMed Central

    Lin, Jia-Ji; Lin, Ye; Zhao, Tian-Zhi; Zhang, Chun-Kui; Zhang, Ting; Chen, Xiao-Li; Ding, Jia-Qi; Chang, Ting; Zhang, Zhuo; Sun, Chao; Zhao, Dai-Di; Zhu, Jun-Lin; Li, Zhu-Yi; Li, Jin-Lian

    2017-01-01

    Melatonin (Mel) and its receptors (MT1 and MT2) have a well-documented efficacy in treating different pain conditions. However, the anti-nociceptive effects of Mel and Mel receptors in neuropathic pain (NP) are poorly understood. To elucidate this process, pain behaviors were measured in a dorsal root ganglia (DRG)-friendly sciatic nerve cuffing model. We detected up-regulation of MT2 expression in the DRGs of cuff-implanted mice and its activation by the agonist 8-M-PDOT (8MP). Also, Mel attenuated the mechanical and thermal allodynia induced by cuff implantation. Immunohistochemical analysis demonstrated the expression of MT2 in the DRG neurons, while MT1 was expressed in the satellite cells. In cultured primary neurons, microarray analysis and gene knockdown experiments demonstrated that MT2 activation by 8MP or Mel suppressed calcium signaling pathways via MAPK1, which were blocked by RAR-related orphan receptor alpha (RORα) activation with a high dose of Mel. Furthermore, expression of nitric oxide synthase 1 (NOS1) was down-regulated upon Mel treatment regardless of MT2 or RORα. Application of Mel or 8MP in cuff-implanted models inhibited the activation of peptidergic neurons and neuro-inflammation in the DRGs by down-regulating c-fos, calcitonin gene-related peptide [CGRP], and tumor necrosis factor-1α [TNF-1α] and interleukin-1β [IL-1β]. Addition of the MT2 antagonist luzindole blocked the effects of 8MP but not those of Mel. In conclusion, only MT2 was expressed in the DRG neurons and up-regulated upon cuff implantation. The analgesic effects of Mel in cuff-implanted mice were closely associated with both MT2-dependent (MAPK-calcium channels) and MT2-independent (NOS1) pathways in the DRG. PMID:28656058

  3. FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line.

    PubMed

    Matsuzaki, Hidenori; Lee, Suni; Maeda, Megumi; Kumagai-Takei, Naoko; Nishimura, Yasumitsu; Otsuki, Takemi

    2016-09-01

    Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.

  4. Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

    PubMed

    Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

    2016-11-15

    The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Immobilization of metallothionein to carbon paste electrode surface via anti-MT antibodies and its use for biosensing of silver.

    PubMed

    Trnkova, Libuse; Krizkova, Sona; Adam, Vojtech; Hubalek, Jaromir; Kizek, Rene

    2011-01-15

    In this paper, heavy metal biosensor based on immobilization of metallothionein (MT) to the surface of carbon paste electrode (CPE) via anti-MT-antibodies is reported. First, the evaluation of MT electroactivity was done. The attention was focused on the capturing of MT to the CPE surface. Antibodies incorporated and mixed into carbon paste were stable; even after two weeks the observed changes in signal height were lower than 5%. Further, the interaction of MT with polyclonal chicken antibodies incorporated in carbon paste electrode was determined by square-wave voltammetry. In the voltammogram, two signals--labelled as cys(MT) and W(a)--were observed. The cys(MT) corresponded to -SH moieties of MT and W(a) corresponded to tryptophan residues of chicken antibodies. Time of interaction (300 s) and MT concentration (125 μg/ml) were optimized to suggest a silver(I) ions biosensor. Biosensor (CPE modified with anti-MT antibody) prepared under the optimized conditions was then used for silver(I) ions detection. The detection limit (3 S/N) for silver(I) ions was estimated as 0.5 nM. The proposed biosensor was tested by detection spiking of silver(I) ions in various water samples (from very pure distilled water to rainwater). Recoveries varied from 74 to 104%. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. The tephrostratigraphy of Mt. Berlin volcano, Antarctica: Integrating blue ice tephra and ice core tephra records

    NASA Astrophysics Data System (ADS)

    Iverson, N. A.; Dunbar, N. W.; McIntosh, W. C.; Kurbatov, A.

    2016-12-01

    Reconstructing volcanic activity in Antarctica is difficult because of the limited outcrop exposure. However, ice is an excellent medium for sampling tephra, allowing for a more complete eruptive record than can be found in other depositional environments. Furthermore, because of low ambient temperature, glass shards trapped in ice remain unaltered and unhydrated. Mt. Berlin is an ice covered volcano in Marie Byrd Land, Antarctica, and, because of heavy glaciation, eruptive records on the volcano itself are sparse. Here, we present the integration of two different records of Mt. Berlin volcanism: the blue ice record found at Mt. Moulton (Dunbar et al., 2008) and the ice core record from the WAIS Divide ice core. Tephra from Mt. Berlin are also found in other ice and marine core records, and these have been correlated and integrated into the combined volcanic record. The Mt. Moulton blue ice area is located 30 km from Mt. Berlin and hosts a fabulous tephra record spanning the last 500 ka. A total of 36 tephra from Mt. Berlin were sampled in stratigraphic order and nine were directly dated by 40Ar/39Ar dating method. Twenty five tephra from WAIS Divide have been analyzed and are geochemically similar to Mt. Berlin with ice core ages dating back to 70 ka. The two tephra records were integrated using their respective timescales. In locations where the Mt. Moulton record does not have precise chronology, the δ18O records from Mt. Moulton (Popp, 2008) and WAIS (WAIS, 2015) were used to integrate the stratigraphy. In total 61 tephra from both ice sections provide an excellent record of the magmatic evolution of Mt. Berlin over the past 500 ka. EMP analyses on glass shards show a gradual change in Fe and S over time. Most of the other major elements remain relatively unchanged. The trend in Fe and S could be produced by progressive tapping of a single, stratified magma chamber, but the long duration of volcanism makes this unlikely. We instead favor small batches of

  7. b-value distribution in and around Mt. Tarumae, Japan

    NASA Astrophysics Data System (ADS)

    Chiba, K.

    2017-12-01

    Mt. Tarumae is an active volcano located in southeastern Shikotsu caldera, Hokkaido, Japan. Recently, crustal expansion occurred in 1999-2000 and 2013 near the summit of Mt. Tarumae, with a M5.6 earthquake recorded west of the summit on 8 July 2014. In this study, I determined hypocenter distributions and then performed b-value analysis for the period between 1 August 2014 and 12 August 2016 to improve our understanding of the magma system geometry beneath the summit of Mt. Tarumae. Hypocenters are mainly distributed in two regions: 3 - 5 km west of Mt. Tarumae, and beneath the volcano. I then determined b-value distributions. Regions with relatively high b-values ( 1.3) are located at depths of -0.5 to 2.0 km beneath the summit and at depths greater than 6.0 km in the northwestern part at about 1.5 - 3.0 km from the summit, while a region with relatively low b-values ( 0.6) is located at depths of 2.0 - 6.0 km beneath the summit. Compared the b-value distributions with other geophysical observations, it was found that the high b-value region from -0.5 to 2.0 km depth corresponds to regions of lower resistivity, positive self-potential anomaly, and an inflation source observed in 1999-2000. It is thus inferred that this region is generated by crustal heterogeneity, a decrease in effective normal stress, and change of a frictional property due to the development of faults and fissures, and the circulation of hydrothermal fluids. On the other hand, the inflation source observed in 2013 was located near the boundary between the low b-value region beneath the summit and the deeper high b-value region in the northwestern part at about 1.5 - 3.0 km from the summit. Studies of other volcanoes suggest that such a high-b-value region likely corresponds to a magma chamber. From the deeper high b-value region estimated in this study, I am able to point out that the magma chamber is located to depths greater than 6.0 km in the northwestern part at about 1.5 - 3.0 km from the

  8. Speed skills: measuring the visual speed analyzing properties of primate MT neurons.

    PubMed

    Perrone, J A; Thiele, A

    2001-05-01

    Knowing the direction and speed of moving objects is often critical for survival. However, it is poorly understood how cortical neurons process the speed of image movement. Here we tested MT neurons using moving sine-wave gratings of different spatial and temporal frequencies, and mapped out the neurons' spatiotemporal frequency response profiles. The maps typically had oriented ridges of peak sensitivity as expected for speed-tuned neurons. The preferred speed estimate, derived from the orientation of the maps, corresponded well to the preferred speed when moving bars were presented. Thus, our data demonstrate that MT neurons are truly sensitive to the object speed. These findings indicate that MT is not only a key structure in the analysis of direction of motion and depth perception, but also in the analysis of object speed.

  9. Constitutional Rights: A View from Mt. Healthy.

    ERIC Educational Resources Information Center

    Gee, E. Gordon

    In their 1977 decision, "Mt. Healthy City School District Board of Education v. Doyle," the Supreme Court held that if a government employee who had a reasonable expectation of continued employment is dismissed and can show that his dismissal was motivated by his taking actions that are constitutionally protected, the employing agency…

  10. 76 FR 59479 - Montana Disaster Number MT-00062

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12714 and 12715] Montana Disaster Number MT-00062 AGENCY: U.S. Small Business Administration. ACTION: Amendment 2. SUMMARY: This is an amendment of... information in the original declaration remains unchanged. (Catalog of Federal Domestic Assistance Numbers...

  11. Mt. Elgon, Africa, Shaded Relief and Colored Height

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The striking contrast of geologic structures in Africa is shown in this shaded relief image of Mt. Elgon on the left and a section of the Great Rift Valley on the right.

    Mt. Elgon is a solitary extinct volcano straddling the border between Uganda and Kenya, and at 4,321 meters (14,178 feet) tall is the eighth highest mountain in Africa. It is positioned on the Pre-Cambriam bedrock of the Trans Nzoia Plateau, and is similar to other such volcanoes in East Africa in that it is associated with the formation of the Rift Valley. However one thing that sets Mt. Elgon apart is its age.

    Although there is no verifiable evidence of its earliest volcanic activity, Mt. Elgon is estimated to be at least 24 million years old, making it the oldest extinct volcano in East Africa. This presents a striking comparison to Mt. Kilimanjaro, the highest mountain in Africa at 5,895 meters (19,341 feet), which is just over one million years old. Judging by the diameter of its base, it is a common belief among geological experts that Mt. Elgon was once the highest mountains in Africa, however erosion has played a significant role in reducing the height to its present value.

    Juxtaposed with this impressive mountain is a section of the Great Rift Valley, a geological fault system that extends for about 4,830 kilometers (2,995 miles) from Syria to central Mozambique. Erosion has concealed some sections, but in some sections like that shown here, there are sheer cliffs several thousand feet high. The present configuration of the valley, which dates from the mid-Pleistocene epoch, results from a rifting process associated with thermal currents in the Earth's mantle.

    Two visualization methods were combined to produce the image: shading and color coding of topographic height. The shade image was derived by computing topographic slope in the northwest-southeast direction, so that northwest slopes appear bright and southeast slopes appear dark. Color coding is directly

  12. Modeling variably saturated subsurface solute transport with MODFLOW-UZF and MT3DMS.

    PubMed

    Morway, Eric D; Niswonger, Richard G; Langevin, Christian D; Bailey, Ryan T; Healy, Richard W

    2013-03-01

    The MT3DMS groundwater solute transport model was modified to simulate solute transport in the unsaturated zone by incorporating the unsaturated-zone flow (UZF1) package developed for MODFLOW. The modified MT3DMS code uses a volume-averaged approach in which Lagrangian-based UZF1 fluid fluxes and storage changes are mapped onto a fixed grid. Referred to as UZF-MT3DMS, the linked model was tested against published benchmarks solved analytically as well as against other published codes, most frequently the U.S. Geological Survey's Variably-Saturated Two-Dimensional Flow and Transport Model. Results from a suite of test cases demonstrate that the modified code accurately simulates solute advection, dispersion, and reaction in the unsaturated zone. Two- and three-dimensional simulations also were investigated to ensure unsaturated-saturated zone interaction was simulated correctly. Because the UZF1 solution is analytical, large-scale flow and transport investigations can be performed free from the computational and data burdens required by numerical solutions to Richards' equation. Results demonstrate that significant simulation runtime savings can be achieved with UZF-MT3DMS, an important development when hundreds or thousands of model runs are required during parameter estimation and uncertainty analysis. Three-dimensional variably saturated flow and transport simulations revealed UZF-MT3DMS to have runtimes that are less than one tenth of the time required by models that rely on Richards' equation. Given its accuracy and efficiency, and the wide-spread use of both MODFLOW and MT3DMS, the added capability of unsaturated-zone transport in this familiar modeling framework stands to benefit a broad user-ship. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  13. Preliminary Marine MT Results from the Anisotropy and Physics of the Pacific Lithosphere Experiment (APPLE)

    NASA Astrophysics Data System (ADS)

    Heinson, G.; Key, K.; Constable, S.; White, A.

    2002-12-01

    We present preliminary magnetotelluric (MT) and geomagnetic depth sounding (GDS) results from the Anisotropy and Physics of the Pacific Lithosphere Experiment (APPLE). APPLE included both controlled source EM and MT components in order to provide constraints on the depth and alignment of anisotropic conductivity structure in both the crust and upper mantle. A key goal of the MT component is to provide insights into electrical conduction mechanisms in the mantle, particularly the proposal that hydrogen dissolved in olivine enhances the conduction in the a axis direction. The main survey was located on 30 Ma old lithosphere, about 1000 km west of San Diego, USA. The core location consisted of two long period MT instruments (102 - 105 s), two broadband MT instruments (101-104 s) along with four long wire electric field receivers. Around the core eight additional instruments were positioned on a 30 km radius to provide constraints on lateral heterogeneities in conductivity structure that may masquerade as mantle anisotropy. Four long period instruments were also deployed along a transect from the core to the base of the continental slope to constrain the effect of the coast on the data. These were augmented with four broadband sites in 1500 m water on the continental shelf offshore San Diego and six broadband sites in 10-350 m water offshore Torrey Pines Beach, California. Processing the MT time series yielded impedance responses that are predominantly two dimensional (2D) with large splits between the two principal MT modes (up to a factor of 10 difference in apparent resistivity), with the greatest mode split and most significant GDS response occurring at sites nearest the continental margin. This suggests that much of this first order anisotropy in the MT response is due to the juxtaposition of the conductive ocean and the resistive continental crust, and indeed a 2D inversion that includes bathymetry of the coastline as fixed structure produces a model with

  14. Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

    PubMed Central

    Yunis, Juan J.; Yunis, Emilio J.

    2013-01-01

    The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest. PMID:24130438

  15. Biodegradation of 17alpha-methyltestosterone and isolation of MT-degrading bacterium from sediment of Nile tilapia masculinization pond.

    PubMed

    Homklin, Supreeda; Wattanodorn, Theerachit; Ong, Say Kee; Limpiyakorn, Tawan

    2009-01-01

    The fast growing and highly tolerant fish Nile tilapia is one of the most commonly raised fish in the aquaculture industry. To produce an all-male population, a common practice is to feed the Nile tilapia fry with 17alpha-methyltestosterone (MT)-impregnated food. Uneaten fish food with MT may accumulate in the masculinization ponds and be released into the receiving waters. Not much is known about the fate of MT in the fish farms and in the receiving streams. The objective of this study is to investigate the biodegradation of MT under aerobic condition and to isolate responsible microorganisms. Aerobic biodegradation tests were conducted with MT concentrations of 0.3, 1.0, 5.0, 7.0, and 10.0 mg/L using sediment from the masculinization pond as microbial seed. The results suggested that MT is biodegradable. Lag phase was not observed in all cases. With initial concentrations of 0.3, 1.0, 5.0, 7.0, and 10.0 mg/l, the first-order degradation rates were 0.52, 0.23, 0.17, 0.13 and 0.10 day(-1), respectively. Degradation rates were found to decrease with an increase in the initial MT concentration. Analysis of 16S rRNA gene sequences of a strain isolated from the sediment indicated that the strain was highly similar to Pimelobacter simplex strain S151 (100%) which is in the genus Nocardioidaceae. Using this strain, MT is degraded with a first-order degradation rate of 0.044 h(-1) excluding the lag phase. This is the first work reporting biodegradation of MT and isolation of MT-degrading bacterium from environment.

  16. Novel mitochondrial gene content and gene arrangement indicate illegitimate inter-mtDNA recombination in the chigger mite, Leptotrombidium pallidum.

    PubMed

    Shao, Renfu; Mitani, Harumi; Barker, Stephen C; Takahashi, Mamoru; Fukunaga, Masahito

    2005-06-01

    To better understand the evolution of mitochondrial (mt) genomes in the Acari (mites and ticks), we sequenced the mt genome of the chigger mite, Leptotrombidium pallidum (Arthropoda: Acari: Acariformes). This genome is highly rearranged relative to that of the hypothetical ancestor of the arthropods and the other species of Acari studied. The mt genome of L. pallidum has two genes for large subunit rRNA, a pseudogene for small subunit rRNA, and four nearly identical large noncoding regions. Nineteen of the 22 tRNAs encoded by this genome apparently lack either a T-arm or a D-arm. Further, the mt genome of L. pallidum has two distantly separated sections with identical sequences but opposite orientations of transcription. This arrangement cannot be accounted for by homologous recombination or by previously known mechanisms of mt gene rearrangement. The most plausible explanation for the origin of this arrangement is illegitimate inter-mtDNA recombination, which has not been reported previously in animals. In light of the evidence from previous experiments on recombination in nuclear and mt genomes of animals, we propose a model of illegitimate inter-mtDNA recombination to account for the novel gene content and gene arrangement in the mt genome of L. pallidum.

  17. Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

    PubMed Central

    Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

    2015-01-01

    Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

  18. Homopolymeric tract heteroplasmy in mtDNA from tissues and single oocytes: support for a genetic bottleneck.

    PubMed Central

    Marchington, D R; Hartshorne, G M; Barlow, D; Poulton, J

    1997-01-01

    While mtDNA polymorphisms at single base positions are common, the overwhelming majority of the mitochondrial genomes within a single individual are usually identical. When there is a point-mutation difference between a mother and her offspring, there may be a complete switching of mtDNA type within a single generation. It is generally assumed that there is a genetic bottleneck whereby a single or small number of founder mtDNA(s) populate the organism, but it is not known at which stages the restriction/amplification of mtDNA subtype(s) occur, and this uncertainty impedes antenatal diagnosis for mtDNA disorders. Length polymorphisms in homopolymeric tracts have been demonstrated in the large noncoding region of mtDNA. We have developed a new method, T-PCR (trimmed PCR), to quantitate heteroplasmy for two of these tracts (D310 and D16189). D310 variation is sufficient to indicate clonal origins of tissues and single oocytes. Tissues from normal individuals often possessed more than one length variant (heteroplasmy). However, there was no difference in the pattern of the length variants between somatic tissues in any control individual when bulk samples were taken. Oocytes from normal women undergoing in vitro fertilization were frequently heteroplasmic for length variants, and in two cases the modal length of the D310 tract differed in individual oocytes from the same woman. These data suggest that a restriction/amplification event, which we attribute to clonal expansion of founder mtDNA(s), has occurred by the time oocytes are mature, although further segregation may occur at a later stage. In contrast to controls, the length distribution of the D310 tract varied between tissues in a patient with heteroplasmic mtDNA rearrangements, suggesting that these mutants influence segregation. These findings have important implications for the genetic counselling of patients with pathogenic mtDNA mutations. Images Figure 2 Figure 1 Figure 3 Figure 4 Figure 5 PMID:9012414

  19. Mt. Vesuvius, Italy

    NASA Image and Video Library

    2001-10-22

    This ASTER image of Mt. Vesuvius Italy was acquired September 26, 2000, and covers an area of 36 by 45 km. Vesuvius overlooks the city of Naples and the Bay of Naples in central Italy. In 79 AD, Vesuvius erupted cataclysmically, burying all of the surrounding cites with up to 30 m of ash. The towns of Pompeii and Herculanaeum were rediscovered in the 18th century, and excavated in the 20th century. They provide a snapshot of Roman life from 2000 years ago: perfectly preserved are wooden objects, food items, and the casts of hundreds of victims. Vesuvius is intensively monitored for potential signs of unrest that could signal the beginning of another eruption. The image is centered at 40.8 degrees north latitude, 14.4 degrees east longitude. http://photojournal.jpl.nasa.gov/catalog/PIA11091

  20. Combining Feature Selection and Integration—A Neural Model for MT Motion Selectivity

    PubMed Central

    Beck, Cornelia; Neumann, Heiko

    2011-01-01

    Background The computation of pattern motion in visual area MT based on motion input from area V1 has been investigated in many experiments and models attempting to replicate the main mechanisms. Two different core conceptual approaches were developed to explain the findings. In integrationist models the key mechanism to achieve pattern selectivity is the nonlinear integration of V1 motion activity. In contrast, selectionist models focus on the motion computation at positions with 2D features. Methodology/Principal Findings Recent experiments revealed that neither of the two concepts alone is sufficient to explain all experimental data and that most of the existing models cannot account for the complex behaviour found. MT pattern selectivity changes over time for stimuli like type II plaids from vector average to the direction computed with an intersection of constraint rule or by feature tracking. Also, the spatial arrangement of the stimulus within the receptive field of a MT cell plays a crucial role. We propose a recurrent neural model showing how feature integration and selection can be combined into one common architecture to explain these findings. The key features of the model are the computation of 1D and 2D motion in model area V1 subpopulations that are integrated in model MT cells using feedforward and feedback processing. Our results are also in line with findings concerning the solution of the aperture problem. Conclusions/Significance We propose a new neural model for MT pattern computation and motion disambiguation that is based on a combination of feature selection and integration. The model can explain a range of recent neurophysiological findings including temporally dynamic behaviour. PMID:21814543

  1. mtDNA variation in caste populations of Andhra Pradesh, India.

    PubMed

    Bamshad, M; Fraley, A E; Crawford, M H; Cann, R L; Busi, B R; Naidu, J M; Jorde, L B

    1996-02-01

    Various anthropological analyses have documented extensive regional variation among populations on the subcontinent of India using morphological, protein, blood group, and nuclear DNA polymorphisms. These patterns are the product of complex population structure (genetic drift, gene flow) and a population history noted for numerous branching events. As a result, the interpretation of relationships among caste populations of South India and between Indians and continental populations remains controversial. The Hindu caste system is a general model of genetic differentiation among endogamous populations stratified by social forces (e.g., religion and occupation). The mitochondrial DNA (mtDNA) molecule has unique properties that facilitate the exploration of population structure. We analyzed 36 Hindu men born in Andhra Pradesh who were unrelated matrilineally through at least 3 generations and who represent 4 caste populations: Brahmin (9), Yadava (10), Kapu (7), and Relli (10). Individuals from Africa (36), Asia (36), and Europe (36) were sampled for comparison. A 200-base-pair segment of hypervariable segment 2 (HVS2) of the mtDNA control region was sequenced in all individuals. In the Indian castes 25 distinct haplotypes are identified. Aside from the Cambridge reference sequence, only two haplotypes are shared between caste populations. Middle castes form a highly supported cluster in a neighbor-joining network. Mean nucleotide diversity within each caste is 0.015, 0.012, 0.011, and 0.012 for the Brahmin, Yadava, Kapu, and Relli, respectively. mtDNA variation is highly structured between castes (GST = 0.17; p < 0.002). The effects of social structure on mtDNA variation are much greater than those on variation measured by traditional markers. Explanations for this discordance include (1) the higher resolving power of mtDNA, (2) sex-dependent gene flow, (3) differences in male and female effective population sizes, and (4) elements of the kinship structure. Thirty

  2. Propagation of dikes at Vesuvio (Italy) and the effect of Mt. Somma

    NASA Astrophysics Data System (ADS)

    Acocella, V.; Porreca, M.; Neri, M.; Massimi, E.; Mattei, M.

    2006-04-01

    Dikes provide crucial information on how magma propagates within volcanoes. Somma-Vesuvio (Italy) consists of the active Vesuvio cone, partly bordered by the older Mt. Somma edifice. Historical chronicles on the fissure eruptions in 1694-1944 are matched with an analytical solution to define the propagation path of the related dikes and to study any control of the Mt. Somma relief. The fissures always consisted of the downslope migration of vents from an open summit conduit, indicating lateral propagation as the predominant mechanism for shallow dike emplacement. No fissure emplaced beyond Mt. Somma, suggesting that its buttressing hinders the propagation of the radial dikes. An analytical solution is defined to describe the mechanism of formation of the laterally propagating dikes and to evaluate the effect of topography. The application to Somma-Vesuvio suggests that, under ordinary excess magmatic pressures, the dikes should not propagate laterally at depths >240-480 m below the surface, as the increased lithostatic pressure requires magmatic pressures higher than average. This implies that, when the conduit is open, the lateral emplacement of dikes is expectable on the S, W and E slopes. The lack of fissures N of Mt. Somma is explained by its buttressing, which hinders dike propagation.

  3. Stereo Image of Mt. Usu Volcano

    NASA Technical Reports Server (NTRS)

    2002-01-01

    On April 3, the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra Satellite captured this image of the erupting Mt. Usu volcano in Hokkaido, Japan. This anaglyph stereo image is of Mt Usu volcano. On Friday, March 31, more than 15,000 people were evacuated by helicopter, truck and boat from the foot of Usu, that began erupting from the northwest flank, shooting debris and plumes of smoke streaked with blue lightning thousands of feet in the air. Although no lava gushed from the mountain, rocks and ash continued to fall after the eruption. The region was shaken by thousands of tremors before the eruption. People said they could taste grit from the ash that was spewed as high as 2,700 meters (8,850 ft) into the sky and fell to coat surrounding towns with ash. A 3-D view can be obtained by looking through stereo glasses, with the blue film through your left eye and red film with your right eye at the same time. North is on your right hand side. For more information, see When Rivers of Rock Flow ASTER web page Image courtesy of MITI, ERSDAC, JAROS, and the U.S./Japan ASTER Science Team

  4. Microtron MT 25 as a source of neutrons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kralik, M.; Solc, J.; Chvatil, D.

    2012-08-15

    The objective was to describe Microtron MT25 as a source of neutrons generated by bremsstrahlung induced photonuclear reactions in U and Pb targets. Bremsstrahlung photons were produced by electrons accelerated at energy 21.6 MeV. Spectral fluence of the generated neutrons was calculated with MCNPX code and then experimentally determined at two positions by means of a Bonner spheres spectrometer in which the detector of thermal neutrons was replaced by activation Mn tablets or track detectors CR-39 with a {sup 10}B radiator. The measured neutron spectral fluence and the calculated anisotropy served for the estimation of neutron yield from the targetsmore » and for the determination of ambient dose equivalent rate at the place of measurement. Microtron MT25 is intended as one of the sources for testing neutron sensitive devices which will be sent into the space.« less

  5. Mt. Etna, Sicily as seen from STS-64

    NASA Image and Video Library

    1994-09-19

    STS064-71-037 (9-20 Sept. 1994) --- Mt. Etna on Sicily displays a steam plume from its summit. Geologists attribute the volcano's existence to the collision of tectonic plates. Unlike the sudden, explosive eruption at Rabaul, Mt. Etna's activity is ongoing and is generally not explosive - Etna's slopes have been settled with villages and cultivated land for centuries. Other Mediterranean volcanoes (like Santorini) have experienced large catastrophic eruptions. Etna recently finished a two-year eruption (ending in 1993), marked by relatively gentle lava flows down the eastern flank. It has been continually degassing since then, according to the geologists, producing an omnipresent steam plume, as seen here. The 1993 flow is difficult to identify in this image because it lies within shadows on the eastern flank, but small cinder cones on the western flank mark earlier episodes of volcanic activity. Photo credit: NASA or National Aeronautics and Space Administration

  6. Impact of Sleeping Altitude on Symptoms of Acute Mountain Sickness on Mt. Fuji.

    PubMed

    Horiuchi, Masahiro; Uno, Tadashi; Endo, Junko; Handa, Yoko; Hasegawa, Tatsuya

    2018-05-09

    Horiuchi, Masahiro, Tadashi Uno, Junko Endo, Yoko Handa, and Tatsuya Hasegawa. Impact of sleeping altitude on symptoms of acute mountain sickness on Mt. Fuji. High Alt Med Biol. 00:000-000, 2018. We sought to investigate the factors influencing acute mountain sickness (AMS) on Mt. Fuji in Japan, in particular, to assess the effects of sleeping altitude, by means of a questionnaire survey. This study involved 1932 participants who climbed Mt. Fuji, and obtained information regarding sex, age, and whether participants stayed at the mountain lodges. The AMS survey excluded the perceived sleep difficulties assessed with the Lake Louise Scoring (LLS) system for all climbers. The overall prevalence of AMS was 31.6% for all participants (LLS score ≥3 with headache, excluding sleep difficulties). A univariate analysis revealed that overnight stay at Mt. Fuji was associated with an increased prevalence of AMS, but that sex and age were not. For overnight lodgers, the mean sleeping altitude in participants with AMS was slightly higher than that in participants without AMS (p < 0.05). Moreover, participants who stayed above 2870 m were more likely to experience AMS than those who stayed below 2815 m (p < 0.001), but sex and age were not significantly associated with the probability of experiencing AMS. Staying overnight at a mountain lodge, especially one above 2870 m, may be associated with an increased prevalence of AMS on Mt. Fuji.

  7. A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with sever nephropathy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tabebi, Mouna, E-mail: mouna.biologiste@yahoo.com; Mkaouar-Rebai, Emna; Mnif, Mouna

    Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells. In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating thatmore » this mutation is maternally transmitted and suggest its implication in the observed phenotype. Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious » and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis. The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients. - Highlights: • MT-COX3 m.9267G>C (p.A21P), heteroplasmic substitution, is not reported in any database. • m.9267G>C can be responsible of the MIDD associated with nephropaty. • This substitution can modify the function and the stability of the MT-CO3 protein. • This substitution can modify MT-CO3 structure (2D and 3D). • MT-COX3 m.9267G>C is

  8. A defect in the thymidine kinase 2 gene causing isolated mitochondrial myopathy without mtDNA depletion.

    PubMed

    Leshinsky-Silver, E; Michelson, M; Cohen, S; Ginsberg, M; Sadeh, M; Barash, V; Lerman-Sagie, T; Lev, D

    2008-07-01

    Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.

  9. Mt. Kilimanjaro's Receding Glaciers

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Mt. Kilimanjaro (Tanzania), the highest point in all Africa, was photographed by the crew of Space Shuttle mission STS-97 on December 2, 2000 (STS097-701-17). Kilimanjaro (Kilima Njaro or 'shining mountain' in Swahili) is capped by glaciers on its southern and southwestern flanks. The glaciers and snow cap covered a far greater area ten years prior to the view above. Compare the photograph above with a photograph of Kilimanjaro taken in November 1990 by the Space Shuttle mission STS-38 crew. Shuttle photograph provided by the Earth Sciences and Image Analysis Laboratory, Johnson Space Center. Additional photographs taken by astronauts and cosmonauts can be viewed via the NASA - JSC Gateway to Astronaut Photography of Earth.

  10. Hybridization and massive mtDNA unidirectional introgression between the closely related Neotropical toads Rhinella marina and R. schneideri inferred from mtDNA and nuclear markers

    PubMed Central

    2011-01-01

    Background The classical perspective that interspecific hybridization in animals is rare has been changing due to a growing list of empirical examples showing the occurrence of gene flow between closely related species. Using sequence data from cyt b mitochondrial gene and three intron nuclear genes (RPL9, c-myc, and RPL3) we investigated patterns of nucleotide polymorphism and divergence between two closely related toad species R. marina and R. schneideri. By comparing levels of differentiation at nuclear and mtDNA levels we were able to describe patterns of introgression and infer the history of hybridization between these species. Results All nuclear loci are essentially concordant in revealing two well differentiated groups of haplotypes, corresponding to the morphologically-defined species R. marina and R. schneideri. Mitochondrial DNA analysis also revealed two well-differentiated groups of haplotypes but, in stark contrast with the nuclear genealogies, all R. schneideri sequences are clustered with sequences of R. marina from the right Amazon bank (RAB), while R. marina sequences from the left Amazon bank (LAB) are monophyletic. An Isolation-with-Migration (IM) analysis using nuclear data showed that R. marina and R. schneideri diverged at ≈ 1.69 Myr (early Pleistocene), while R. marina populations from LAB and RAB diverged at ≈ 0.33 Myr (middle Pleistocene). This time of divergence is not consistent with the split between LAB and RAB populations obtained with mtDNA data (≈ 1.59 Myr), which is notably similar to the estimate obtained with nuclear genes between R. marina and R. schneideri. Coalescent simulations of mtDNA phylogeny under the speciation history inferred from nuclear genes rejected the hypothesis of incomplete lineage sorting to explain the conflicting signal between mtDNA and nuclear-based phylogenies. Conclusions The cytonuclear discordance seems to reflect the occurrence of interspecific hybridization between these two closely related

  11. Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

    PubMed

    Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

    2015-02-01

    Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats.

    PubMed

    Faria, Juliana A; Kinote, Andrezza; Ignacio-Souza, Letícia M; de Araújo, Thiago M; Razolli, Daniela S; Doneda, Diego L; Paschoal, Lívia B; Lellis-Santos, Camilo; Bertolini, Gisele L; Velloso, Lício A; Bordin, Silvana; Anhê, Gabriel F

    2013-07-15

    Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients.

  13. 76 FR 9991 - Television Broadcasting Services; Kalispell, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-23

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 11-224; MB Docket No. 11-20; RM-11619] Television Broadcasting Services; Kalispell, MT AGENCY: Federal Communications Commission. ACTION: Proposed... before March 25, 2011, and reply comments on or before April 11, 2011. ADDRESSES: Federal Communications...

  14. 76 FR 27914 - Television Broadcasting Services; Kalispell, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-20; RM-11619, DA 11-750] Television Broadcasting Services; Kalispell, MT AGENCY: Federal Communications Commission. ACTION: Final rule... rulemaking filed by Montana State University (``MSU'') requesting that channel *46 be transferred from the...

  15. Special issue “The phreatic eruption of Mt. Ontake volcano in 2014”

    USGS Publications Warehouse

    Yamaoka, Koshun; Geshi, Nobuo; Hashimoto, Tasheki; Ingebritsen, Steven E.; Oikawa, Teruki

    2016-01-01

    Mt. Ontake volcano erupted at 11:52 on September 27, 2014, claiming the lives of at least 58 hikers. This eruption was the worst volcanic disaster in Japan since the 1926 phreatic eruption of Mt. Tokachidake claimed 144 lives (Table 1). The timing of the eruption contributed greatly to the heavy death toll: near midday, when many hikers were near the summit, and during a weekend of clear weather conditions following several rainy weekends. The importance of this timing is reflected by the fact that a somewhat larger eruption of Mt. Ontake in 1979 resulted in injuries but no deaths. In 2014, immediate precursors were detected with seismometers and tiltmeters about 10 min before the eruption, but the eruption started before a warning was issued.

  16. Joint inversion of marine MT and CSEM data over Gemini prospect, Gulf of Mexico

    NASA Astrophysics Data System (ADS)

    Constable, S.; Orange, A. S.; Key, K.

    2013-12-01

    In 2003 we tested a prototype marine controlled-source electromagnetic (CSEM) transmitter over the Gemini salt body in the Gulf of Mexico, collecting one line of data over 15 seafloor receiver instruments using the Cox waveform with a 0.25 Hz fundamental, yielding 3 usable frequencies. Transmission current was 95 amps on a 150 m antenna. We had previously collected 16 sites of marine magnetotelluric (MT) data along this line during the development of broadband marine MT as a tool for mapping salt geometry. Recently we commissioned a finite element code capable of joint CSEM and MT 2D inversion incorporating bathymetry and anisotropy, and this heritage data set provided an opportunity to explore such inversions with real data. We reprocessed the CSEM data to obtain objective error estimates and inverted single frequency CSEM, multi-frequency CSEM, MT, and joint MT and CSEM data sets for a variety of target misfits, using the Occam regularized inversion algorithm. As expected, MT-only inversions produce a smoothed image of the salt and a resistive basement at 9 km depth. The CSEM data image a conductive cap over the salt body and have little sensitivity to the salt or structure at depths beyond about 1500 m below seafloor. However, the joint inversion yields more than the sum of the parts - the outline of the salt body is much sharper and there is much more structural detail even at depths beyond the resolution of the CSEM data. As usual, model complexity greatly depends on target misfit, and even with well-estimated errors the choice of misfit becomes a somewhat subjective decision. Our conclusion is a familiar one; more data are always good.

  17. Thymidine kinase and mtDNA depletion in human cardiomyopathy: epigenetic and translational evidence for energy starvation

    PubMed Central

    Koczor, Christopher A.; Torres, Rebecca A.; Fields, Earl J.; Boyd, Amy; He, Stanley; Patel, Nilamkumar; Lee, Eva K.; Samarel, Allen M.

    2013-01-01

    This study addresses how depletion of human cardiac left ventricle (LV) mitochondrial DNA (mtDNA) and epigenetic nuclear DNA methylation promote cardiac dysfunction in human dilated cardiomyopathy (DCM) through regulation of pyrimidine nucleotide kinases. Samples of DCM LV and right ventricle (n = 18) were obtained fresh at heart transplant surgery. Parallel samples from nonfailing (NF) controls (n = 12) were from donor hearts found unsuitable for clinical use. We analyzed abundance of mtDNA and nuclear DNA (nDNA) using qPCR. LV mtDNA was depleted in DCM (50%, P < 0.05 each) compared with NF. No detectable change in RV mtDNA abundance occurred. DNA methylation and gene expression were determined using microarray analysis (GEO accession number: GSE43435). Fifty-seven gene promoters exhibited DNA hypermethylation or hypomethylation in DCM LVs. Among those, cytosolic thymidine kinase 1 (TK1) was hypermethylated. Expression arrays revealed decreased abundance of the TK1 mRNA transcript with no change in transcripts for other relevant thymidine metabolism enzymes. Quantitative immunoblots confirmed decreased TK1 polypeptide steady state abundance. TK1 activity remained unchanged in DCM samples while mitochondrial thymidine kinase (TK2) activity was significantly reduced. Compensatory TK activity was found in cardiac myocytes in the DCM LV. Diminished TK2 activity is mechanistically important to reduced mtDNA abundance and identified in DCM LV samples here. Epigenetic and genetic changes result in changes in mtDNA and in nucleotide substrates for mtDNA replication and underpin energy starvation in DCM. PMID:23695887

  18. Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.

    PubMed

    Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Döbeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

    2013-01-01

    Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2(-/-) mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2(-/-) mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2(-/-) mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies.

  19. Thymidine Kinase 2 Deficiency-Induced mtDNA Depletion in Mouse Liver Leads to Defect β-Oxidation

    PubMed Central

    von Döbeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

    2013-01-01

    Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2−/−) that progressively loses its mtDNA. The TK2−/− mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2−/− mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2−/− mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2−/− mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2−/− mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies. PMID:23505564

  20. Regulation of microtubule (MT)-based cytoskeleton in the seminiferous epithelium during spermatogenesis

    PubMed Central

    Tang, Elizabeth I.; Mruk, Dolores D.; Cheng, C. Yan

    2016-01-01

    In rodents and humans, testicular cells, similar to other mammalian cells, are supported by actin-, microtubule (MT)- and intermediate filament-based cytoskeletons to regulate spermatogenesis during the epithelial cycle. However, most of the published findings in the literature are limited to studies that visualize these cytoskeletons in the seminiferous epithelium during spermatogenesis. Few are focus on the underlying molecular mechanism that regulates their organization in the epithelium in response to changes in the stages of the epithelial cycle remains largely explored. Functional studies in the last decade have begun to focus on the role of binding proteins that regulate these cytoskeletons, and some interesting data have been rapidly emerging in the field. Since the actin- and intermediate-based cytoskeletons have been recently reviewed, herein we focus on the MT-based cytoskeleton for two reasons. First, besides serving as a structural support cytoskeleton, MT is known to serve as the track to support and facilitate the transport of germ cells, such as preleptotene spermatocytes connected in clones and elongating/elongated spermatids during spermiogenesis across the blood-testis barrier (BTB) and the adluminal compartment, respectively, during spermatogenesis. While these cellular events are crucial to the completion of spermatogenesis, they have been largely ignored in the past. Second, MT-based cytoskeleton is working in concert with the actin-based cytoskeleton to provide structural support to the transport of intracellular organelles across the cell cytosol, such as endosome-based vesicles, and residual bodies, phagosomes in Sertoli cells, to maintain the cellular homeostasis in the seminiferous epithelium. We critically evaluate some recent published findings herein to support a hypothesis regarding the role of MT in conferring germ cell transport in the seminiferous epithelium. PMID:26791048

  1. Effect of feature-selective attention on neuronal responses in macaque area MT

    PubMed Central

    Chen, X.; Hoffmann, K.-P.; Albright, T. D.

    2012-01-01

    Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961

  2. Effect of feature-selective attention on neuronal responses in macaque area MT.

    PubMed

    Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A

    2012-03-01

    Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

  3. Canis mtDNA HV1 database: a web-based tool for collecting and surveying Canis mtDNA HV1 haplotype in public database.

    PubMed

    Thai, Quan Ke; Chung, Dung Anh; Tran, Hoang-Dung

    2017-06-26

    Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database. This database collects data on the HV1 582 bp region in dog mitochondrial DNA from the GenBank to screen and correct the inconsistencies. It also supports users in detection of new novel mutation profiles and assignment of new haplotypes. The Canis mtDNA HV1 database (CHD) contains 5567 nucleotide entries originating from 15 subspecies in the species Canis lupus. Of these entries, 3646 were haplotypes and grouped into 804 distinct sequences. 319 sequences were recognized as previously assigned haplotypes, while the remaining 485 sequences had new mutation profiles and were marked as new haplotype candidates awaiting further analysis for haplotype assignment. Of the 3646 nucleotide entries, only 414 were annotated with correct haplotype information, while 3232 had insufficient or lacked haplotype information and were corrected or modified before storing in the CHD. The CHD can be accessed at http://chd.vnbiology.com . It provides sequences, haplotype information, and a web-based tool for mtDNA HV1 haplotyping. The CHD is updated monthly and supplies all data for download. The Canis mtDNA HV1 database contains information about canine mitochondrial DNA HV1 sequences with reconciled annotation. It serves as a tool for detection of inconsistencies in GenBank and helps identifying new HV1 haplotypes. Thus, it supports the scientific community in naming new HV1 haplotypes and to reconcile existing annotation of HV1 582 bp sequences.

  4. Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release.

    PubMed

    Farhadnejad, Hassan; Mortazavi, Seyed Alireza; Erfan, Mohammad; Darbasizadeh, Behzad; Motasadizadeh, Hamidreza; Fatahi, Yousef

    2018-05-01

    The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN-as a model drug-was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. HMEC-1 adopt the mixed amoeboid-mesenchymal migration type during EndMT.

    PubMed

    Kryczka, Jakub; Przygodzka, Patrycja; Bogusz, Helena; Boncela, Joanna

    2017-06-01

    The contribution of endothelial cells to scar and fibrotic tissue formation is undisputedly connected to their ability to undergo the endothelial-to-mesenchymal transition (EndMT) towards fibroblast phenotype-resembling cells. The migration model of fibroblasts and fibroblast-resembling cells is still not fully understood. It may be either a Rho/ROCK-independent, an integrin- and MMP-correlated ECM degradation-dependent, a mesenchymal model or Rho/ROCK-dependent, integrin adhesion- and MMP activity-independent, an amoeboid model. Here, we hypothesized that microvascular endothelial cells (HMEC-1) undergoing EndMT adopt an intermediate state of drifting migration model between the mesenchymal and amoeboid protrusive types in the early stages of fibrosis. We characterized the response of HMEC-1 to TGF-β2, a well-known mediator of EndMT within the microvasculature. We observed that TGF-β2 induces up to an intermediate mesenchymal phenotype in HMEC-1. In parallel, MMP-2 is upregulated and is responsible for most proteolytic activity. Interestingly, the migration of HMEC-1 undergoing EndMT is dependent on both ECM degradation and invadosome formation associated with MMP-2 proteolytic activity and Rho/ROCK cytoskeleton contraction. In conclusion, the transition from mesenchymal towards amoeboid movement highlights a molecular plasticity mechanism in endothelial cell migration in skin fibrosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Superpartner Mass Measurement Technique using 1D Orthogonal Decompositions of the Cambridge Transverse Mass Variable MT2

    NASA Astrophysics Data System (ADS)

    Konar, Partha; Kong, Kyoungchul; Matchev, Konstantin T.; Park, Myeonghun

    2010-07-01

    We propose a new model-independent technique for mass measurements in missing energy events at hadron colliders. We illustrate our method with the most challenging case of a single-step decay chain. We consider inclusive same-sign chargino pair production in supersymmetry, followed by leptonic decays to sneutrinos χ+χ+→ℓ+ℓ'+ν˜ℓν˜ℓ' and invisible decays ν˜ℓ→νℓχ˜10. We introduce two one-dimensional decompositions of the Cambridge MT2 variable: MT2∥ and MT2⊥, on the direction of the upstream transverse momentum P→T and the direction orthogonal to it, respectively. We show that the sneutrino mass Mc can be measured directly by minimizing the number of events N(M˜c) in which MT2 exceeds a certain threshold, conveniently measured from the end point MT2⊥max⁡(M˜c).

  7. Onboard Photo of Mt. Everest

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Astronaut Daniel W. Bursch, Expedition Four flight engineer, was delighted in capturing this image of Mt. Everest in the Himalayan Range from aboard the International Space Station (ISS). The mountain is near frame center. Because the photo was taken close to orbital sunrise, the low sun angle gave tremendous relief to the mountains. Named for Sir George Everest, the British surveyor-general of India, Mount Everest is the tallest point on earth. Standing 29,028 feet tall, it is 5 1/2 miles above sea level. Mount Everest is located half in Nepal and half in Tibet.

  8. Molecular characterization and expression profile of the melatonin receptor MT1 in the ovary of Tianzhu white yak (Bos grunniens).

    PubMed

    Hu, Jun Jie; Zhang, Xiao Yu; Zhang, Yong; Zhao, Xing Xu; Li, Fa Di; Tao, Jin Zhong

    2017-02-01

    Melatonin plays crucial roles in a wide range of ovarian physiological functions via the melatonin receptors (MRs). Structure and function of MRs have been well studied in sheep, cattle, and humans, but little information exists on the genetic characterization and function of these receptors in the ovary of the white yak. In the present study, the melatonin receptor MT1 was cloned by RT-PCR in the ovary of white yak; the MT1 cDNA fragment obtained (843bp) comprised an open reading frame (827bp) encoding a protein containing 275 residues, characterized by seven transmembrane regions and an NRY motif, two distinct amino acid replacements were found. The white yak MT1 had a 83.9-98.6% protein sequence identity with that of nine other mammals. Using RT-PCR, the expression levels of MT1, MT2, and LHR in the ovary of pregnant and non-pregnant white yaks were compared, revealing higher levels of all genes in pregnant yaks: 3.83-fold increase for MT1 (P<0.05), 1.39-fold increase for MT2, and 15.32-fold increase for LHR (P<0.05). The distribution of MT1 in yak ovaries was observed using immunohistochemistry on paraffin embedded ovarian sections: MT1 was mainly present on primordial follicles (PF), granulosa cells (GCs), oocytes, and corpus luteum (CL) cells; MT1 expression showed an increasing tendency from PF to GCs to oocytes and to large CL cells. It is suggested that melatonin and MT1 are associated with the corpus luteum function of pregnancy maintenance and follicular development during oocyte maturation in the white yak. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Segregation of mtDNA Throughout Human Embryofetal Development: m.3243A > G as a Model System

    PubMed Central

    Monnot, Sophie; Gigarel, Nadine; Samuels, David C; Burlet, Philippe; Hesters, Laetitia; Frydman, Nelly; Frydman, René; Kerbrat, Violaine; Funalot, Benoit; Martinovic, Jelena; Benachi, Alexandra; Feingold, Josué; Munnich, Arnold; Bonnefont, Jean-Paul; Steffann, Julie

    2011-01-01

    Mitochondrial DNA (mtDNA) mutations cause a wide range of serious diseases with high transmission risk and maternal inheritance. Tissue heterogeneity of the heteroplasmy rate (“mutant load”) accounts for the wide phenotypic spectrum observed in carriers. Owing to the absence of therapy, couples at risk to transmit such disorders commonly ask for prenatal (PND) or preimplantation diagnosis (PGD). The lack of data regarding heteroplasmy distribution throughout intrauterine development, however, hampers the implementation of such procedures. We tracked the segregation of the m.3243A > G mutation (MT-TL1 gene) responsible for the MELAS syndrome in the developing embryo/fetus, using tissues and cells from eight carrier females, their 38 embryos and 12 fetuses. Mutant mtDNA segregation was found to be governed by random genetic drift, during oogenesis and somatic tissue development. The size of the bottleneck operating for m.3243A > G during oogenesis was shown to be individual-dependent. Comparison with data we achieved for the m.8993T > G mutation (MT-ATP6 gene), responsible for the NARP/Leigh syndrome, indicates that these mutations differentially influence mtDNA segregation during oogenesis, while their impact is similar in developing somatic tissues. These data have major consequences for PND and PGD procedures in mtDNA inherited disorders. Hum Mutat 32:116–125, 2011. © 2010 Wiley-Liss, Inc. PMID:21120938

  10. Co-ordinated expression of MMP-2 and its putative activator, MT1-MMP, in human placentation.

    PubMed

    Bjørn, S F; Hastrup, N; Lund, L R; Danø, K; Larsen, J F; Pyke, C

    1997-08-01

    The spatial expression of mRNA for matrix metalloproteinase 2 (MMP-2), its putative activator, the membrane-type 1 matrix metalloproteinase (MT1-MMP), and the MMP-2 substrate type IV collagen was investigated in human placentas of both normal and tubal ectopic pregnancies and in cyclic endometrium using in-situ hybridization. Cytokeratin staining applied to adjacent sections was used to identify epithelial and trophoblast cells. In both normal and tubal pregnancies MT1-MMP, MMP-2 and type IV collagen mRNA were highly expressed and co-localized in the extravillous cytotrophoblasts of anchoring villi, in cytotrophoblasts that had penatrated into the placental bed and in cytotrophoblastic cell islands. In addition, the decidual cells of normal pregnancies in some areas co-expressed MT1-MMP and MMP-2 mRNA, with moderate signals for both components. Fibroblast-like stromal cells in tubal pregnancies were positive for MMP-2 mRNA but generally negative for MT1-MMP mRNA. The consistent co-localization of MT1-MMP with MMP-2 and type IV collagen in the same subset of cytotrophoblasts strongly suggests that all three components co-operate in the tightly regulated fetal invasion process. The co-expression of MT1-MMP and MMP-2 mRNA in some of the decidual cells indicates that these cells are also actively involved in the placentation process.

  11. Organization of area hV5/MT+ in subjects with homonymous visual field defects.

    PubMed

    Papanikolaou, Amalia; Keliris, Georgios A; Papageorgiou, T Dorina; Schiefer, Ulrich; Logothetis, Nikos K; Smirnakis, Stelios M

    2018-04-06

    Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following early visual cortical lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. mtDNA and the Origin of the Icelanders: Deciphering Signals of Recent Population History

    PubMed Central

    Helgason, Agnar; Sigurðardóttir, Sigrún; Gulcher, Jeffrey R.; Ward, Ryk; Stefánsson, Kári

    2000-01-01

    Previous attempts to investigate the origin of the Icelanders have provided estimates of ancestry ranging from a 98% British Isles contribution to an 86% Scandinavian contribution. We generated mitochondrial sequence data for 401 Icelandic individuals and compared these data with >2,500 other European sequences from published sources, to determine the probable origins of women who contributed to Iceland’s settlement. Although the mean number of base-pair differences is high in the Icelandic sequences and they are widely distributed in the overall European mtDNA phylogeny, we find a smaller number of distinct mitochondrial lineages, compared with most other European populations. The frequencies of a number of mtDNA lineages in the Icelanders deviate noticeably from those in neighboring populations, suggesting that founder effects and genetic drift may have had a considerable influence on the Icelandic gene pool. This is in accordance with available demographic evidence about Icelandic population history. A comparison with published mtDNA lineages from European populations indicates that, whereas most founding females probably originated from Scandinavia and the British Isles, lesser contributions from other populations may also have taken place. We present a highly resolved phylogenetic network for the Icelandic data, identifying a number of previously unreported mtDNA lineage clusters and providing a detailed depiction of the evolutionary relationships between European mtDNA clusters. Our findings indicate that European populations contain a large number of closely related mitochondrial lineages, many of which have not yet been sampled in the current comparative data set. Consequently, substantial increases in sample sizes that use mtDNA data will be needed to obtain valid estimates of the diverse ancestral mixtures that ultimately gave rise to contemporary populations. PMID:10712214

  13. Molecular and pharmacological evidence for MT1 melatonin receptor subtype in the tail artery of juvenile Wistar rats

    PubMed Central

    Ting, K N; Blaylock, N A; Sugden, D; Delagrange, P; Scalbert, E; Wilson, V G

    1999-01-01

    In this study reverse transcriptase-polymerase chain reaction (RT–PCR) has been used to identify mt1 and MT2 receptor mRNA expression in the rat tail artery. The contributions of both receptors to the functional response to melatonin were examined with the putative selective MT2 receptor antagonists, 4-phenyl-2-propionamidotetraline (4-P-PDOT) and 2-benzyl-N-pentanoyltryptamine. In addition, the action of melatonin on the second messenger cyclic AMP was investigated.Using RT–PCR, mt1 receptor mRNA was detected in the tail artery from seven rats. In contrast MT2 receptor mRNA was not detected even after nested PCR.At low concentrations of the MT2 selective ligands, neither 10 nM 4-P-PDOT (pEC50=8.70±0.31 (control) vs 8.73±0.16, n=6) nor 60 nM 2-benzyl-N-pentanoyltryptamine (pEC50=8.53±0.20 (control) vs 8.83±0.38, n=6) significantly altered the potency of melatonin in the rat tail artery.At concentrations non-selective for mt1 and MT2 receptors, 4-P-PDOT (3 μM) and 2-benzyl-N-pentanoyltryptamine (5 μM) caused a significant rightward displacement of the vasoconstrictor effect of melatonin. In the case of 4-P-PDOT, the estimated pKB (6.17±0.16, n=8) is similar to the binding affinity for mt1 receptor.Pre-incubation with 1 μM melatonin did not affect the conversion of [3H]-adenine to [3H]-cyclic AMP under basal condition (0.95±0.19% conversion (control) vs 0.92±0.19%, n=4) or following exposure to 30 μM forskolin (5.20±1.30% conversion (control) vs 5.35±0.90%, n=4).Based on the above findings, we conclude that melatonin receptor on the tail artery belongs to the MT1 receptor subtype, and that this receptor is probably independent of the adenylyl cyclase pathway. PMID:10433507

  14. Winter water relations at the upper elevational limits of hemlock on Mt. Ascutney, Vermont

    Treesearch

    Chandra B. Vostral; Richard L. Boyce

    2000-01-01

    Winter water relations have been monitored in hemlock (Tsuga canadensis (L.) Carr.) at their upper elevational limits for three winters, 1997, 1998, and 1999, on Mt. Ascutney, Vermont. Hemlock and white pine trees (Pinus strobus L.) reach their elevational limit on Mt. Ascutney at 640 m (2100?), while the summit has an elevation of...

  15. [Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

    PubMed

    Balanovskiĭ, O P; Koshel', S M; Zaporozhchenko, V V; Pshenichnov, A S; Frolova, S A; Kuznetsova, M A; Baranova, E E; Teuchezh, I E; Kuznetsova, A A; Romashkina, M V; Utevskaia, O M; Churnosov, M I; Villems, R; Balanovskaia, E V

    2011-11-01

    Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

  16. The origin of Chinese domestic horses revealed with novel mtDNA variants.

    PubMed

    Yang, Yunzhou; Zhu, Qiyun; Liu, Shuqin; Zhao, Chunjiang; Wu, Changxin

    2017-01-01

    The origin of domestic horses in China was a controversial issue and several hypotheses including autochthonous domestication, introduction from other areas, and multiple-origins from both introduction and local wild horse introgression have been proposed, but none of them have been fully supported by DNA data. In the present study, mitochondrial DNA (mtDNA) sequences of 714 Chinese indigenous horses were analyzed. The results showed that Chinese domestic horses harbor some novel mtDNA haplogroups and suggested that local domestication events may have occurred, but they are not the dominant haplogroups and the geographical distributions of the novel mtDNA haplogroups were rather restricted. Conclusively, our results support the hypothesis that the domestic horses in China originated from both the introduced horses from outside of China and the local wild horses' introgression into the domestic populations. Results of genetic diversity analysis suggested a possibility that the introduced horses entered China through northern regions from the Eurasian steppe. © 2016 Japanese Society of Animal Science.

  17. The iron chelator Dp44mT suppresses osteosarcoma’s proliferation, invasion and migration: in vitro and in vivo

    PubMed Central

    Li, Pengcheng; Zheng, Xun; Shou, Kangquan; Niu, Yahui; Jian, Chao; Zhao, Yong; Yi, Wanrong; Hu, Xiang; Yu, Aixi

    2016-01-01

    Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), the novel iron chelator, has been reported to inhibit the tumorigenesis and progression of various cancer cells, including neuroblastoma, neuroepithelioma and prostate cancer. However, whether Dp44mT has anticancer effects in osteosarcoma is still unknown. Here, we investigated the antitumor action of Dp44mT in osteosarcoma and its underlying mechanisms. A human osteosarcoma 143B cell line in vitro and 143B xenograft in nude mice in vivo were utilized, the anticancer effects of Dp44mT were examined through methods of MTT assay, transwell, wound healing assay, flow cytometry, western blot, immunohistochemistry and H&E staining. We showed that Dp44mT inhibits cell proliferation, invasion and migration in vitro. In addition, flow cytometry further illustrated that Dp44mT suppression of 143B cell proliferation, invasion and migration were partially due to induction of cell apoptosis, cell cycle arrest in S phase and ROS production. Also in vitro and in vivo, the expression levels of Bcl2, Bax, Caspase3, Caspase9, LC3-II, β-catenin and its downstream targets such as C-myc and Cyclin D1 demonstrated that cell apoptosis and autophagy, as well as Wnt/β-catenin pathway were involved in Dp44mT induced osteosarcoma suppression. The Dp44mT inhibition of osteosarcoma was further verified via animal models. The findings indicated that in vivo Dp44mT showed a significant reduction in the 143B xenograft tumor growth and metastasis. In conclusion, our data demonstrated that Dp44mT has effective anticancer capability in osteosarcoma and that may represent a promising treatment strategy for osteosarcoma. PMID:28078009

  18. Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion.

    PubMed

    Dong, Zhaogang; Xu, Xiaofei; Du, Lutao; Yang, Yongmei; Cheng, Huanhuan; Zhang, Xin; Li, Zewu; Wang, Lili; Li, Juan; Liu, Hui; Qu, Xun; Wang, Chuanxin

    2013-05-01

    Leptin overexpression is closely correlated with gastric cancer (GC) invasion, but its exact effect and the underlying mechanism in tumorigenesis remain poorly understood. Membrane type 1-matrix metalloproteinase (MT1-MMP), a surface-anchored 'master switch' proteinase, is overexpressed and plays crucial roles in tumor invasion. Here, we characterized the influence of leptin on the generation and surface localization of MT1-MMP in GC and elucidated its molecular mechanisms. Our results revealed that leptin promoted GC cell invasion in vitro by upregulating MT1-MMP expression. Furthermore, cell surface biotinylation assay and flow cytometry demonstrated that the surface expression of MT1-MMP was also enhanced by leptin, and knockdown of kinesin family member 1B (KIF1B, a microtubule plus end-directed monomeric motor protein) by small interference RNA inhibited this process. Notably, coimmunoprecipitation analysis indicated that leptin enhanced the interaction of MT1-MMP with KIF1B in a time-dependent manner, which consequently contributed to GC cell invasion. Moreover, leptin increased MT1-MMP or KIF1B expression by the protein kinase B (AKT) pathway and extracellular signal-regulated kinase 1/2 partially participated in this process. However, only AKT was implicated in the leptin-mediated membrane localization of MT1-MMP. Immunohistochemistry analysis revealed that leptin, MT1-MMP and KIF1B are overexpressed in GC tissues, and they positively correlated with clinical stage and lymph node metastasis. These observations indicate that this regulatory network exists in vivo. Taken together, our findings suggest that leptin is an effective intracellular stimulator of MT1-MMP and that leptin-enhanced cell surface localization of MT1-MMP is dependent on KIF1B, which consequently plays a critical role in GC invasion.

  19. Conflicting Values: Spirituality and Wilderness at Mt. Shasta

    Treesearch

    Maria Fernandez-Gimenez; Lynn Huntsinger; Catherine Phillips; Barbara Allen-Diaz

    1992-01-01

    Many people from a variety of backgrounds believe that Mt. Shasta is a major spiritual center. Although these "spiritual users" value the area's natural features, their spiritual and social activities, including construction of sweat lodges, medicine wheels, altars, meditation pads, trails, and campsites, are leading to rapid ecological degradation. This...

  20. Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.

    PubMed

    Lorenz, Carmen; Lesimple, Pierre; Bukowiecki, Raul; Zink, Annika; Inak, Gizem; Mlody, Barbara; Singh, Manvendra; Semtner, Marcus; Mah, Nancy; Auré, Karine; Leong, Megan; Zabiegalov, Oleksandr; Lyras, Ekaterini-Maria; Pfiffer, Vanessa; Fauler, Beatrix; Eichhorst, Jenny; Wiesner, Burkhard; Huebner, Norbert; Priller, Josef; Mielke, Thorsten; Meierhofer, David; Izsvák, Zsuzsanna; Meier, Jochen C; Bouillaud, Frédéric; Adjaye, James; Schuelke, Markus; Wanker, Erich E; Lombès, Anne; Prigione, Alessandro

    2017-05-04

    Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment. High-content screening of FDA-approved drugs using the MMP phenotype highlighted avanafil, which we found was able to partially rescue the calcium defect in patient NPCs and differentiated neurons. Overall, our results show that iPSC-derived NPCs provide an effective model for drug screening to target mtDNA disorders that affect the nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Melatonin Synergizes the Chemotherapeutic Effect of Cisplatin in Ovarian Cancer Cells Independently of MT1 Melatonin Receptors.

    PubMed

    Zemła, Agata; Grzegorek, Irmina; Dzięgiel, Piotr; Jabłońska, Karolina

    2017-01-01

    Melatonin (MLT), through the interaction with membrane melatonin receptors MT1, can improve the effectiveness of cytostatic agents, including cisplatin (CP). The aim of this study was to examine the synergistic effect of MLT and CP in three cell lines: IOSE 364, SK-OV-3 and OVCAR-3, as well as to assess the role of MT1 receptors in this mechanism. Using the SRB assay we investigated the effect of different concentrations of CP and MLT on cell viability. Tests, using luzindole - MT1 inhibitor, allowed us to assess the potential involvement of MT1 in the mechanism of MLT action. MLT at certain concentrations demonstrated a synergistic effect in combination with CP. The addition of luzindole did not affect the action of MLT in combination with CP. In summary, the synergistic effect of MLT with CP seems to be independent of membrane MT1 receptors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Mt. Vesuvius, Italy

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This ASTER image of Mt. Vesuvius Italy was acquired September 26, 2000, and covers an area of 36 by 45 km. Vesuvius overlooks the city of Naples and the Bay of Naples in central Italy. In 79 AD, Vesuvius erupted cataclysmically, burying all of the surrounding cites with up to 30 m of ash. The towns of Pompeii and Herculanaeum were rediscovered in the 18th century, and excavated in the 20th century. They provide a snapshot of Roman life from 2000 years ago: perfectly preserved are wooden objects, food items, and the casts of hundreds of victims. Vesuvius is intensively monitored for potential signs of unrest that could signal the beginning of another eruption. The image is centered at 40.8 degrees north latitude, 14.4 degrees east longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  3. MitoTALEN: A General Approach to Reduce Mutant mtDNA Loads and Restore Oxidative Phosphorylation Function in Mitochondrial Diseases

    PubMed Central

    Hashimoto, Masami; Bacman, Sandra R; Peralta, Susana; Falk, Marni J; Chomyn, Anne; Chan, David C; Williams, Sion L; Moraes, Carlos T

    2015-01-01

    We have designed mitochondrially targeted transcription activator-like effector nucleases or mitoTALENs to cleave specific sequences in the mitochondrial DNA (mtDNA) with the goal of eliminating mtDNA carrying pathogenic point mutations. To test the generality of the approach, we designed mitoTALENs to target two relatively common pathogenic mtDNA point mutations associated with mitochondrial diseases: the m.8344A>G tRNALys gene mutation associated with myoclonic epilepsy with ragged red fibers (MERRF) and the m.13513G>A ND5 mutation associated with MELAS/Leigh syndrome. Transmitochondrial cybrid cells harbouring the respective heteroplasmic mtDNA mutations were transfected with the respective mitoTALEN and analyzed after different time periods. MitoTALENs efficiently reduced the levels of the targeted pathogenic mtDNAs in the respective cell lines. Functional assays showed that cells with heteroplasmic mutant mtDNA were able to recover respiratory capacity and oxidative phosphorylation enzymes activity after transfection with the mitoTALEN. To improve the design in the context of the low complexity of mtDNA, we designed shorter versions of the mitoTALEN specific for the MERRF m.8344A>G mutation. These shorter mitoTALENs also eliminated the mutant mtDNA. These reductions in size will improve our ability to package these large sequences into viral vectors, bringing the use of these genetic tools closer to clinical trials. PMID:26159306

  4. Messenger RNA for membrane-type 2 matrix metalloproteinase, MT2-MMP, is expressed in human placenta of first trimester.

    PubMed

    Bjørn, S F; Hastrup, N; Larsen, J F; Lund, L R; Pyke, C

    2000-01-01

    An intimately regulated cell surface activation of matrix metalloproteinases (MMPs) is believed to be of critical importance for the control of trophoblast invasion. A histological investigation of the expression and localization of three different MMPs, the membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP, MT2-MMP) and matrix metalloproteinase 2 (MMP-2/gelatinase A) was performed by in situ hybridization on consecutive sections from human placentae of first trimester pregnancies. Cytokeratin immunostaining identified trophoblast cells. Both normal and tubal implantation sites were studied. We observed a high degree of coexpression of MT2-MMP, MT1-MMP and MMP-2 mRNAs in single extravillous cytotrophoblasts that had invaded the endometrium and tubal wall. Furthermore, mRNAs for all three genes were also seen in cytotrophoblasts of cell islands. In contrast to this coexpression pattern, MT2-MMP expression was absent from cell columns and decidual cells, in which signals for MT1-MMP and MMP-2 mRNAs were seen. The present data on the cellular expression of MT2-MMP mRNA in placenta extend our knowledge of the proteolytic events that take place during early pregnancy. The data suggest that MT2-MMP, capable of activating MMP-2 in vitro, is involved in the invasion of extravillous cytotrophoblast, possibly related to the physiological activation of MMP-2. Copyright 2000 Harcourt Publishers Ltd.

  5. The past, present and future of mitochondrial genomics: have we sequenced enough mtDNAs?

    PubMed

    Smith, David Roy

    2016-01-01

    The year 2014 saw more than a thousand new mitochondrial genome sequences deposited in GenBank-an almost 15% increase from the previous year. Hundreds of peer-reviewed articles accompanied these genomes, making mitochondrial DNAs (mtDNAs) the most sequenced and reported type of eukaryotic chromosome. These mtDNA data have advanced a wide range of scientific fields, from forensics to anthropology to medicine to molecular evolution. But for many biological lineages, mtDNAs are so well sampled that newly published genomes are arguably no longer contributing significantly to the progression of science, and in some cases they are tying up valuable resources, particularly journal editors and referees. Is it time to acknowledge that as a research community we have published enough mitochondrial genome papers? Here, I address this question, exploring the history, milestones and impacts of mitochondrial genomics, the benefits and drawbacks of continuing to publish mtDNAs at a high rate and what the future may hold for such an important and popular genetic marker. I highlight groups for which mtDNAs are still poorly sampled, thus meriting further investigation, and recommend that more energy be spent characterizing aspects of mitochondrial genomes apart from the DNA sequence, such as their chromosomal and transcriptional architectures. Ultimately, one should be mindful before writing a mitochondrial genome paper. Consider perhaps sending the sequence directly to GenBank instead, and be sure to annotate it correctly before submission. © The Author 2015. Published by Oxford University Press.

  6. Polynesian genetic affinities with Southeast Asian populations as identified by mtDNA analysis.

    PubMed Central

    Melton, T; Peterson, R; Redd, A J; Saha, N; Sofro, A S; Martinson, J; Stoneking, M

    1995-01-01

    Polynesian genetic affinities to populations of Asia were studied using mtDNA markers. A total of 1,037 individuals from 12 populations were screened for a 9-bp deletion in the intergenic region between the COII and tRNA(Lys) genes that approaches fixation in Polynesians. Sequence-specific oligonucleotide probes that identify specific mtDNA control region nucleotide substitutions were used to describe variation in individuals with the 9-bp deletion. The 9-bp deletion was not observed in northern Indians, Bangladeshis, or Pakistanis but was seen at low to moderate frequencies in the nine other Southeast Asian populations. Three substitutions in the control region at positions 16217, 16247, and 16261 have previously been observed at high frequency in Polynesian mtDNAs; this "Polynesian motif" was observed in 20% of east Indonesians with the 9-bp deletion but was observed in only one additional individual. mtDNA types related to the Polynesian motif are highest in frequency in the corridor from Taiwan south through the Philippines and east Indonesia, and the highest diversity for these types is in Taiwan. These results are consistent with linguistic evidence of a Taiwanese origin for the proto-Polynesian expansion, which spread throughout Oceania by way of Indonesia. PMID:7668267

  7. Coexistence of minicircular and a highly rearranged mtDNA molecule suggests that recombination shapes mitochondrial genome organization.

    PubMed

    Mao, Meng; Austin, Andrew D; Johnson, Norman F; Dowton, Mark

    2014-03-01

    Recombination has been proposed as a possible mechanism to explain mitochondrial (mt) gene rearrangements, although the issue of whether mtDNA recombination occurs in animals has been controversial. In this study, we sequenced the entire mt genome of the megaspilid wasp Conostigmus sp., which possessed a highly rearranged mt genome. The sequence of the A+T-rich region contained a number of different types of repeats, similar to those reported previously in the nematode Meloidogyne javanica, in which recombination was discovered. In Conostigmus, we detected the end products of recombination: a range of minicircles. However, using isolated (cloned) fragments of the A+T-rich region, we established that some of these minicircles were found to be polymerase chain reaction (PCR) artifacts. It appears that regions with repeats are prone to PCR template switching or PCR jumping. Nevertheless, there is strong evidence that one minicircle is real, as amplification primers that straddle the putative breakpoint junction produce a single strong amplicon from genomic DNA but not from the cloned A+T-rich region. The results provide support for the direct link between recombination and mt gene rearrangement. Furthermore, we developed a model of recombination which is important for our understanding of mtDNA evolution.

  8. The 2001 Mt. Etna eruption: new constraints on the intrusive mechanism from ground deformation data

    NASA Astrophysics Data System (ADS)

    Palano, Mimmo; González, Pablo J.

    2013-04-01

    The occurrence of seismic swarms beneath the SW flank of Mt. Etna, often observed just a few months before an eruption, has been considered as the fragile response to a magma intrusion (Bonanno et al., 2011 and reference therein). These intrusions and/or pressurization of deep magmatic bodies, have been able to significantly affect the seismic pattern within the volcano edifice, leading to a changes in the local stress field. For example, during the months preceding the 1991-1993 Mt. Etna eruption, shallow intense seismic swarms (4-6 km deep) occurring in the SW flank (e.g. Cocina et al., 1998), related to the magma intrusion before the eruption onset, were observed contemporaneously with a rotation of stress field of about 90°. A similar scenario was observed during January 1998, when a magma recharging phases induced a local rotation of stress tensor, forcing a buried fault zone located beneath the SW flank of Mt. Etna to slip as a right-lateral strike-slip fault (Bonanno et al., 2011). This fault system was forced to slip again, during late April 2001 (more than 200 events in less than 5 days; maximum Magnitude = 3.6) by the pressurization of the magmatic bodies feeding the July-August 2001 Mt. Etna eruption. Here we analyzed in detail the July-August 2001 Mt. Etna eruption as well as the dynamics preceding this event, by using a large dataset of geodetic data (GPS and synthetic aperture radar interferometry) collected between July 2000 and August 2001. References Cocina, O., Neri, G., Privitera, E. and Spampinato S., 1998. Seismogenic stress field beneath Mt. Etna South Italy and possible relationships with volcano-tectonic features. J. Volcanol. Geotherm. Res., 83, 335-348. Bonanno A., Palano M., Privitera E., Gresta S., Puglisi G., 2011. Magma intrusion mechanisms and redistribution of seismogenic stress at Mt. Etna volcano (1997-1998). Terra Nova, 23, 339-348, doi: 10.1111/j.1365-3121.2011.01019.x, 2011.

  9. Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates

    PubMed Central

    Large, I.; Bridge, H.; Ahmed, B.; Clare, S.; Kolasinski, J.; Lam, W. W.; Miller, K. L.; Dyrby, T. B.; Parker, A. J.; Smith, J. E. T.; Daubney, G.; Sallet, J.; Bell, A. H.; Krug, K.

    2016-01-01

    Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture. PMID:27371764

  10. 3-D Inversion of the MT EarthScope Data, Collected Over the East Central United States

    NASA Astrophysics Data System (ADS)

    Gribenko, A. V.; Zhdanov, M. S.

    2017-12-01

    The magnetotelluric (MT) data collected as a part of the EarthScope project provided a unique opportunity to study the conductivity structure of the deep interior of the North American continent. Besides the scientific value of the recovered subsurface models, the data also allowed inversion practitioners to test the robustness of their algorithms applied to regional long-period data. In this paper, we present the results of MT inversion of a subset of the second footprint of the MT data collection covering the East Central United States. Our inversion algorithm implements simultaneous inversion of the full MT impedance data both for the 3-D conductivity distribution and for the distortion matrix. The distortion matrix provides the means to account for the effect of the near-surface geoelectrical inhomogeneities on the MT data. The long-period data do not have the resolution for the small near-surface conductivity anomalies, which makes an application of the distortion matrix especially appropriate. The determined conductivity model of the region agrees well with the known geologic and tectonic features of the East Central United States. The conductivity anomalies recovered by our inversion indicate a possible presence of the hot spot track in the area.

  11. 76 FR 35967 - Amendment of Class E Airspace; Bozeman, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ..., Gallatin Field Airport, Bozeman, MT, to accommodate aircraft using Instrument Landing System (ILS... 6005 Class E airspace areas extending upward from 700 feet or more above the surface of the earth...

  12. MT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib

    PubMed Central

    Yip, Cassandre; Foidart, Pierre; Somja, Joan; Truong, Alice; Lienard, Mehdi; Feyereisen, Emilie; Schroeder, Hélène; Gofflot, Stéphanie; Donneau, Anne-Françoise; Collignon, Joëlle; Delvenne, Philippe; Sounni, Nor Eddine; Jerusalem, Guy; Noël, Agnès

    2017-01-01

    Background: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. Methods: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays. Results: Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours. Conclusions: We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs. PMID:28196064

  13. Superpartner mass measurement technique using 1D orthogonal decompositions of the Cambridge transverse mass variable M(T2).

    PubMed

    Konar, Partha; Kong, Kyoungchul; Matchev, Konstantin T; Park, Myeonghun

    2010-07-30

    We propose a new model-independent technique for mass measurements in missing energy events at hadron colliders. We illustrate our method with the most challenging case of a single-step decay chain. We consider inclusive same-sign chargino pair production in supersymmetry, followed by leptonic decays to sneutrinos χ+ χ+ → ℓ+ ℓ'+ ν(ℓ)ν(ℓ') and invisible decays ν(ℓ) → ν(ℓ) χ(1)(0). We introduce two one-dimensional decompositions of the Cambridge MT2 variable: M(T2∥) and M(T2⊥), on the direction of the upstream transverse momentum P→T and the direction orthogonal to it, respectively. We show that the sneutrino mass Mc can be measured directly by minimizing the number of events N(Mc) in which MT2 exceeds a certain threshold, conveniently measured from the end point M(T2⊥)(max) (Mc).

  14. The rapid detection of methyl tert-butyl ether (MtBE) in water using a prototype gas sensor system.

    PubMed

    de Lacy Costello, B P J; Sivanand, P S; Ratcliffe, N M; Reynolds, D M

    2005-01-01

    The gasoline additive Methyl-tertiary-Butyl Ether (MtBE) is the second most common contaminant of groundwater in the USA and represents an important soil contaminant. This compound has been detected in the groundwater in at least 27 states as a result of leaking underground storage facilities (gasoline storage tanks and pipelines). Since the health effects of MtBE are unclear the potential threat to drinking water supplies is serious. Therefore, the ability to detect MtBE at low levels (ppb) and on-line at high-risk groundwater sites would be highly desirable. This paper reports the use of 'commercial' and metal oxide sensor arrays for the detection of MtBE in drinking and surface waters at low ppb level (microg.L(-1) range). The output responses from some of the sensors were found to correlate well with MtBE concentrations under laboratory conditions.

  15. Global microphysical simulation of stratospheric sulfate aerosol after the Mt. Pinatubo eruption

    NASA Astrophysics Data System (ADS)

    Sekiya, T.; Sudo, K.

    2014-12-01

    An explosive volcanic eruption can inject a large amount of SO2 into the stratosphere, which is oxidized to form sulfate aerosol. Such aerosol has an impact on the Earth's radiative budget by enhancing back-scattering of the solar radiation. Changes in the size distribution of the aerosol were observed after large volcanic eruptions. Representing the changes in size distribution is important for climate simulation, because the changes affect climate responses to large volcanic eruptions. This study newly developed an aerosol microphysics module and investigated changes in stratospheric sulfate aerosol after the Mt. Pinatubo eruption in the framework of a chemistry-aerosol coupled climate model MIROC-CHASER/SPRINTARS. The module represents aerosol size distribution with three lognormal modes (nucleation, Aitken, and accumulation modes) and includes nucleation, condensation growth/evaporation, and coagulation processes. As a model evaluation, we tested reproducibility of the impacts of the Mt. Pinatubo eruption. We carried out a simulation, in which 20 Mt of SO2 and 100 Mt of volcanic ash were injected respectively into 25 km and 16—22 km altitudes over Mt. Pinatubo (120.4°E, 15.1°N) on June 15th 1991. We compared the model results with space-borne and balloon-borne observations. Although our model overestimated a near-global mean (60°N—60°S) of stratospheric aerosol optical depth (SAOD) observed by SAGE II instrument until one year after the eruption, it reproduced the observed SAOD in the subsequent period. The model well captured the observed increase of effective radius at 20 km altitude in the northern midlatitudes. In addition, we analyzed the pathway of volcanic sulfur from SO2 to sulfate aerosol. The most amount of the volcanic sulfur was converted from SO2 to accumulation mode aerosol by 100 days after the eruption. The conversion into the accumulation mode aerosol is attributable to coagulation until the first 14 days and to condensation growth

  16. Preliminary interpretation of high resolution 3D seismic data from offshore Mt. Etna, Italy

    NASA Astrophysics Data System (ADS)

    Gross, F.; Krastel, S.; Chiocci, F. L.; Ridente, D.; Cukur, D.; Bialas, J.; Papenberg, C. A.; Crutchley, G.; Koch, S.

    2013-12-01

    In order to gain knowledge about subsurface structures and its correlation to seafloor expressions, a hydro-acoustic dataset was collected during RV Meteor Cruise M86/2 (December 2011/January 2012) in Messina Straits and offshore Mt. Etna. Especially offshore Mt. Etna, the data reveals an obvious connection between subsurface structures and previously known morphological features at the sea floor. Therefore a high resolution 3D seismic dataset was acquired between Riposto Ridge and Catania Canyon close to the shore of eastern Sicily. The study area is characterized by a major structural high, which hosts several ridge-like features at the seafloor. These features are connected to a SW-NE trending fault system. The ridges are bended in their NE-SW direction and host major escarpments at the seafloor. Furthermore they are located directly next to a massive amphitheater structure offshore Mt. Etna with slope gradients of up to 35°, which is interpreted as remnants of a massive submarine mass wasting event off Sicily. The new 3D seismic dataset allows an in depth analysis of the ongoing deformation of the east flank of Mt. Etna.

  17. The GHEP–EMPOP collaboration on mtDNA population data—A new resource for forensic casework

    PubMed Central

    Prieto, L.; Zimmermann, B.; Goios, A.; Rodriguez-Monge, A.; Paneto, G.G.; Alves, C.; Alonso, A.; Fridman, C.; Cardoso, S.; Lima, G.; Anjos, M.J.; Whittle, M.R.; Montesino, M.; Cicarelli, R.M.B.; Rocha, A.M.; Albarrán, C.; de Pancorbo, M.M.; Pinheiro, M.F.; Carvalho, M.; Sumita, D.R.; Parson, W.

    2011-01-01

    Mitochondrial DNA (mtDNA) population data for forensic purposes are still scarce for some populations, which may limit the evaluation of forensic evidence especially when the rarity of a haplotype needs to be determined in a database search. In order to improve the collection of mtDNA lineages from the Iberian and South American subcontinents, we here report the results of a collaborative study involving nine laboratories from the Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) and EMPOP. The individual laboratories contributed population data that were generated throughout the past 10 years, but in the majority of cases have not been made available to the scientific community. A total of 1019 haplotypes from Iberia (Basque Country, 2 general Spanish populations, 2 North and 1 Central Portugal populations), and Latin America (3 populations from São Paulo) were collected, reviewed and harmonized according to defined EMPOP criteria. The majority of data ambiguities that were found during the reviewing process (41 in total) were transcription errors confirming that the documentation process is still the most error-prone stage in reporting mtDNA population data, especially when performed manually. This GHEP–EMPOP collaboration has significantly improved the quality of the individual mtDNA datasets and adds mtDNA population data as valuable resource to the EMPOP database (www.empop.org). PMID:21075696

  18. A goodness-of-fit test for capture-recapture model M(t) under closure

    USGS Publications Warehouse

    Stanley, T.R.; Burnham, K.P.

    1999-01-01

    A new, fully efficient goodness-of-fit test for the time-specific closed-population capture-recapture model M(t) is presented. This test is based on the residual distribution of the capture history data given the maximum likelihood parameter estimates under model M(t), is partitioned into informative components, and is based on chi-square statistics. Comparison of this test with Leslie's test (Leslie, 1958, Journal of Animal Ecology 27, 84- 86) for model M(t), using Monte Carlo simulations, shows the new test generally outperforms Leslie's test. The new test is frequently computable when Leslie's test is not, has Type I error rates that are closer to nominal error rates than Leslie's test, and is sensitive to behavioral variation and heterogeneity in capture probabilities. Leslie's test is not sensitive to behavioral variation in capture probabilities but, when computable, has greater power to detect heterogeneity than the new test.

  19. Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling

    PubMed Central

    Clay, Hayley B.; Parl, Angelika K.; Mitchell, Sabrina L.; Singh, Larry; Bell, Lauren N.; Murdock, Deborah G.

    2016-01-01

    Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means of creating fatty acids via the mitochondrial fatty acid synthesis (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand the role of mtFASII in the cell, we used thin layer chromatography to characterize the contribution of the mtFASII pathway to the fatty acid composition of selected mitochondrial lipids. Next, we performed metabolomic analysis on HeLa cells in which the mtFASII pathway was either hypofunctional (through knockdown of mitochondrial acyl carrier protein, ACP) or hyperfunctional (through overexpression of mitochondrial enoyl-CoA reductase, MECR). Our results indicate that the mtFASII pathway contributes little to the fatty acid composition of mitochondrial lipid species examined. Additionally, loss of mtFASII function results in changes in biochemical pathways suggesting alterations in glucose utilization and redox state. Interestingly, levels of bioactive lipids, including lysophospholipids and sphingolipids, directly correlate with mtFASII function, indicating that mtFASII may be involved in the regulation of bioactive lipid levels. Regulation of bioactive lipid levels by mtFASII implicates the pathway as a mediator of intracellular signaling. PMID:26963735

  20. High-altitude adaptation of Tibetan chicken from MT-COI and ATP-6 perspective.

    PubMed

    Zhao, Xiaoling; Wu, Nan; Zhu, Qing; Gaur, Uma; Gu, Ting; Li, Diyan

    2016-09-01

    The problem of hypoxia adaptation in high altitudes is an unsolved brainteaser in the field of life sciences. As one of the best chicken breeds with adaptability to highland environment, the Tibetan chicken, is genetically different from lowland chicken breeds. In order to gain a better understanding of the mechanism of hypoxic adaptability in high altitude, in the present study, we focused on the MT-COI together with ATP-6 gene to explore the regulatory mechanisms for hypoxia adaptability in Tibet chicken. Here, we sequenced MT-COI of 29 Tibetan chickens and 30 Chinese domestic chickens and ATP-6 gene of 28 Tibetan chickens and 29 Chinese domestic chickens. In MT-COI gene, 9 single nucleotide polymorphisms (SNPs) were detected though none of these was a missense mutation, confirming the fact that MT-COI gene is a largely conservative sequence. In ATP-6 gene, 6 single nucleotide polymorphisms (SNPs) were detected and we found a missense mutation (m.9441G > A) in the ATP-6 gene of Tibetan chicken resulting in an amino acid substitution. Due to the critical role of ATP-6 gene in the proton translocation and energy metabolism, we speculated the possibility of this mutation playing an important role in easier energy conversion and metabolism in Tibetan chickens than Chinese domestic chickens so as to better adapt to the harsh environment of the high-altitude areas. The Median-joining profile also suggested that haplotype Ha2 has the ancestral position to the other haplotypes and has significant relationship with high-altitude adaptation in ATP-6 gene. Therefore, we considered that the polymorphism (m.9441G > A) in the ATP-6 gene may affect the specific functions of ATP-6 enzyme relating to high-altitude adaptation of Tibetan chicken and MT-COI gene is a largely conservative sequence.

  1. Mt. Etna, Sicily as seen from STS-62

    NASA Image and Video Library

    1994-03-05

    STS062-85-195 (4-18 March 1994) --- A thin plume of steam blows southward from the summit of Mt. Etna, the active volcano on the island of Sicily. The summit is capped with snow but the dark lava flow along the eastern flank (the 1991-93 flow) is clearly visible. The coastal city south of Etna is Catania.

  2. Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) alters mitochondrial DNA (mtDNA) and mitochondrial polypeptide abundance: transgenic TK2, mtDNA, and antiretrovirals.

    PubMed

    Hosseini, Seyed H; Kohler, James J; Haase, Chad P; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

    2007-03-01

    Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-gamma. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity.

  3. Precise hypocenter locations of midcrustal low-frequency earthquakes beneath Mt. Fuji, Japan

    USGS Publications Warehouse

    Nakamichi, H.; Ukawa, M.; Sakai, S.

    2004-01-01

    Midcrustal low-frequency earthquakes (MLFs) have been observed at seismic stations around Mt. Fuji, Japan. In September - December 2000 and April - May 2001, abnormally high numbers of MLFs occurred. We located hypocenters for the 80 MLFs during 1998-2003 by using the hypoDD earthquake location program (Waldhauser and Ellsworth, 2000). The MLF hypocenters define an ellipsoidal volume some 5 km in diameter ranging from 11 to 16 km in focal depth. This volume is centered 3 km northeast of the summit and its long axis is directed NW-SE. The direction of the axis coincides with the major axis of tectonic compression around Mt. Fuji. The center of the MLF epicenters gradually migrated upward and 2-3 km from southeast to northwest during 1998-2001. We interpret that the hypocentral migration of MLFs reflects magma movement associated with a NW-SE oriented dike beneath Mt. Fuji. Copyright ?? The Society of Geomagnetism and Earth, Planetary and Space Sciences (SGEPSS); The Seismological Society of Japan; The Volcanological Society of Japan; The Geodetic Society of Japan; The Japanese Society for Planetary Sciences.

  4. Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity

    PubMed Central

    Pokrzywinski, Kaytee L.; Biel, Thomas G.; Kryndushkin, Dmitry; Rao, V. Ashutosh

    2016-01-01

    Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis. PMID:28030582

  5. Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity.

    PubMed

    Pokrzywinski, Kaytee L; Biel, Thomas G; Kryndushkin, Dmitry; Rao, V Ashutosh

    2016-01-01

    Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis.

  6. MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation.

    PubMed

    Zhang, Zhixiang; Meng, Tao; Yang, Na; Wang, Wei; Xiong, Bing; Chen, Yi; Ma, Lanping; Shen, Jingkang; Miao, Ze-Hong; Ding, Jian

    2011-07-01

    Microtubule-targeted drugs are now indispensable for the therapy of various cancer types worldwide. In this article, we report MT119 [6-[2-(4-methoxyphenyl) -ethyl]-9-[(pyridine-3-ylmethyl)amino]pyrido[2',1':2,3]imida-zo[4,5-c]isoquinolin-5(6H)-one] as a new microtubule-targeted agent. MT119 inhibited tubulin polymerization significantly both in tumor cells and in cell-free systems, which was followed by the disruption of mitotic spindle assembly. Surface plasmon resonance-based analyses showed that MT119 bound to purified tubulin directly, with the K(D) value of 10.6 μM. The binding of MT119 in turn caused tubulin conformational changes as evidenced by the quenched tryptophan fluorescence, the reduction of the bis-ANS reactivity and the decreased DTNB-sulfhydryl reaction rate. Competitive binding assays further revealed that MT119 bound to tubulin at its colchicine site. Consequently, by inhibiting tubulin polymerization, MT119 arrested different tumor cells at mitotic phase, which contributed to its potent antitumor activity in vitro. MT119 was also similarly cytotoxic to vincristine-, adriamycin- or mitoxantrone-resistant cancer cells and to their corresponding parental cells. Together, these data indicate that MT119 represents a new class of colchicine-site-targeted inhibitors against tubulin polymerization, which might be a promising starting point for future cancer therapeutics. Copyright © 2010 UICC.

  7. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

    PubMed Central

    Safdar, Adeel; Bourgeois, Jacqueline M.; Ogborn, Daniel I.; Little, Jonathan P.; Hettinga, Bart P.; Akhtar, Mahmood; Thompson, James E.; Melov, Simon; Mocellin, Nicholas J.; Kujoth, Gregory C.; Prolla, Tomas A.; Tarnopolsky, Mark A.

    2011-01-01

    A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. PMID:21368114

  8. Dynamics of the functional link between area MT LFPs and motion detection

    PubMed Central

    Smith, Jackson E. T.; Beliveau, Vincent; Schoen, Alan; Remz, Jordana; Zhan, Chang'an A.

    2015-01-01

    The evolution of a visually guided perceptual decision results from multiple neural processes, and recent work suggests that signals with different neural origins are reflected in separate frequency bands of the cortical local field potential (LFP). Spike activity and LFPs in the middle temporal area (MT) have a functional link with the perception of motion stimuli (referred to as neural-behavioral correlation). To cast light on the different neural origins that underlie this functional link, we compared the temporal dynamics of the neural-behavioral correlations of MT spikes and LFPs. Wide-band activity was simultaneously recorded from two locations of MT from monkeys performing a threshold, two-stimuli, motion pulse detection task. Shortly after the motion pulse occurred, we found that high-gamma (100–200 Hz) LFPs had a fast, positive correlation with detection performance that was similar to that of the spike response. Beta (10–30 Hz) LFPs were negatively correlated with detection performance, but their dynamics were much slower, peaked late, and did not depend on stimulus configuration or reaction time. A late change in the correlation of all LFPs across the two recording electrodes suggests that a common input arrived at both MT locations prior to the behavioral response. Our results support a framework in which early high-gamma LFPs likely reflected fast, bottom-up, sensory processing that was causally linked to perception of the motion pulse. In comparison, late-arriving beta and high-gamma LFPs likely reflected slower, top-down, sources of neural-behavioral correlation that originated after the perception of the motion pulse. PMID:25948867

  9. Neural Representation of Motion-In-Depth in Area MT

    PubMed Central

    Sanada, Takahisa M.

    2014-01-01

    Neural processing of 2D visual motion has been studied extensively, but relatively little is known about how visual cortical neurons represent visual motion trajectories that include a component toward or away from the observer (motion in depth). Psychophysical studies have demonstrated that humans perceive motion in depth based on both changes in binocular disparity over time (CD cue) and interocular velocity differences (IOVD cue). However, evidence for neurons that represent motion in depth has been limited, especially in primates, and it is unknown whether such neurons make use of CD or IOVD cues. We show that approximately one-half of neurons in macaque area MT are selective for the direction of motion in depth, and that this selectivity is driven primarily by IOVD cues, with a small contribution from the CD cue. Our results establish that area MT, a central hub of the primate visual motion processing system, contains a 3D representation of visual motion. PMID:25411481

  10. Locating the depth of magma supply for volcanic eruptions, insights from Mt. Cameroon

    PubMed Central

    Geiger, Harri; Barker, Abigail K.; Troll, Valentin R.

    2016-01-01

    Mt. Cameroon is one of the most active volcanoes in Africa and poses a possible threat to about half a million people in the area, yet knowledge of the volcano’s underlying magma supply system is sparse. To characterize Mt. Cameroon’s magma plumbing system, we employed mineral-melt equilibrium thermobarometry on the products of the volcano’s two most recent eruptions of 1999 and 2000. Our results suggest pre-eruptive magma storage between 20 and 39 km beneath Mt. Cameroon, which corresponds to the Moho level and below. Additionally, the 1999 eruption products reveal several shallow magma pockets between 3 and 12 km depth, which are not detected in the 2000 lavas. This implies that small-volume magma batches actively migrate through the plumbing system during repose intervals. Evolving and migrating magma parcels potentially cause temporary unrest and short-lived explosive outbursts, and may be remobilized during major eruptions that are fed from sub-Moho magma reservoirs. PMID:27713494

  11. Locating the depth of magma supply for volcanic eruptions, insights from Mt. Cameroon.

    PubMed

    Geiger, Harri; Barker, Abigail K; Troll, Valentin R

    2016-10-07

    Mt. Cameroon is one of the most active volcanoes in Africa and poses a possible threat to about half a million people in the area, yet knowledge of the volcano's underlying magma supply system is sparse. To characterize Mt. Cameroon's magma plumbing system, we employed mineral-melt equilibrium thermobarometry on the products of the volcano's two most recent eruptions of 1999 and 2000. Our results suggest pre-eruptive magma storage between 20 and 39 km beneath Mt. Cameroon, which corresponds to the Moho level and below. Additionally, the 1999 eruption products reveal several shallow magma pockets between 3 and 12 km depth, which are not detected in the 2000 lavas. This implies that small-volume magma batches actively migrate through the plumbing system during repose intervals. Evolving and migrating magma parcels potentially cause temporary unrest and short-lived explosive outbursts, and may be remobilized during major eruptions that are fed from sub-Moho magma reservoirs.

  12. Recombinant Human Melatonin Receptor MT1 Isolated in Mixed Detergents Shows Pharmacology Similar to That in Mammalian Cell Membranes

    PubMed Central

    Logez, Christel; Berger, Sylvie; Legros, Céline; Banères, Jean-Louis; Cohen, William; Delagrange, Philippe; Nosjean, Olivier; Boutin, Jean A.; Ferry, Gilles

    2014-01-01

    The human melatonin MT1 receptor—belonging to the large family of G protein-coupled receptors (GPCRs)—plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches. PMID:24959712

  13. Recombinant human melatonin receptor MT1 isolated in mixed detergents shows pharmacology similar to that in mammalian cell membranes.

    PubMed

    Logez, Christel; Berger, Sylvie; Legros, Céline; Banères, Jean-Louis; Cohen, William; Delagrange, Philippe; Nosjean, Olivier; Boutin, Jean A; Ferry, Gilles; Simonin, Frédéric; Wagner, Renaud

    2014-01-01

    The human melatonin MT1 receptor-belonging to the large family of G protein-coupled receptors (GPCRs)-plays a key role in circadian rhythm regulation and is notably involved in sleep disorders and depression. Structural and functional information at the molecular level are highly desired for fine characterization of this receptor; however, adequate techniques for isolating soluble MT1 material suitable for biochemical and biophysical studies remain lacking. Here we describe the evaluation of a panel of constructs and host systems for the production of recombinant human MT1 receptors, and the screening of different conditions for their solubilization and purification. Our findings resulted in the establishment of an original strategy using a mixture of Fos14 and CHAPS detergents to extract and purify a recombinant human MT1 from Pichia pastoris membranes. This procedure enabled the recovery of relatively pure, monomeric and ligand-binding active MT1 receptor in the near-milligram range. A comparative study based on extensive ligand-binding characterization highlighted a very close correlation between the pharmacological profiles of MT1 purified from yeast and the same receptor present in mammalian cell membranes. The high quality of the purified MT1 was further confirmed by its ability to activate its cognate Gαi protein partner when reconstituted in lipid discs, thus opening novel paths to investigate this receptor by biochemical and biophysical approaches.

  14. Activation of the Human MT Complex by Motion in Depth Induced by a Moving Cast Shadow

    PubMed Central

    Katsuyama, Narumi; Usui, Nobuo; Taira, Masato

    2016-01-01

    A moving cast shadow is a powerful monocular depth cue for motion perception in depth. For example, when a cast shadow moves away from or toward an object in a two-dimensional plane, the object appears to move toward or away from the observer in depth, respectively, whereas the size and position of the object are constant. Although the cortical mechanisms underlying motion perception in depth by cast shadow are unknown, the human MT complex (hMT+) is likely involved in the process, as it is sensitive to motion in depth represented by binocular depth cues. In the present study, we examined this possibility by using a functional magnetic resonance imaging (fMRI) technique. First, we identified the cortical regions sensitive to the motion of a square in depth represented via binocular disparity. Consistent with previous studies, we observed significant activation in the bilateral hMT+, and defined functional regions of interest (ROIs) there. We then investigated the activity of the ROIs during observation of the following stimuli: 1) a central square that appeared to move back and forth via a moving cast shadow (mCS); 2) a segmented and scrambled cast shadow presented beside the square (sCS); and 3) no cast shadow (nCS). Participants perceived motion of the square in depth in the mCS condition only. The activity of the hMT+ was significantly higher in the mCS compared with the sCS and nCS conditions. Moreover, the hMT+ was activated equally in both hemispheres in the mCS condition, despite presentation of the cast shadow in the bottom-right quadrant of the stimulus. Perception of the square moving in depth across visual hemifields may be reflected in the bilateral activation of the hMT+. We concluded that the hMT+ is involved in motion perception in depth induced by moving cast shadow and by binocular disparity. PMID:27597999

  15. Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP.

    PubMed

    Waheed, Sana; Dorjbal, Batsukh; Hamilton, Chad A; Maxwell, G Larry; Rodriguez, Gustavo C; Syed, Viqar

    2017-12-26

    Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients.

  16. Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP

    PubMed Central

    Waheed, Sana; Dorjbal, Batsukh; Hamilton, Chad A.; Maxwell, G. Larry; Rodriguez, Gustavo C.; Syed, Viqar

    2017-01-01

    Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients. PMID:29371931

  17. The Music Therapy Session Assessment Scale (MT-SAS): Validation of a new tool for music therapy process evaluation.

    PubMed

    Raglio, Alfredo; Gnesi, Marco; Monti, Maria Cristina; Oasi, Osmano; Gianotti, Marta; Attardo, Lapo; Gontero, Giulia; Morotti, Lara; Boffelli, Sara; Imbriani, Chiara; Montomoli, Cristina; Imbriani, Marcello

    2017-11-01

    Music therapy (MT) interventions are aimed at creating and developing a relationship between patient and therapist. However, there is a lack of validated observational instruments to consistently evaluate the MT process. The purpose of this study was the validation of Music Therapy Session Assessment Scale (MT-SAS), designed to assess the relationship between therapist and patient during active MT sessions. Videotapes of a single 30-min session per patient were considered. A pilot study on the videotapes of 10 patients was carried out to help refine the items, define the scoring system and improve inter-rater reliability among the five raters. Then, a validation study on 100 patients with different clinical conditions was carried out. The Italian MT-SAS was used throughout the process, although we also provide an English translation. The final scale consisted of 7 binary items accounting for eye contact, countenance, and nonverbal and sound-music communication. In the pilot study, raters were found to share an acceptable level of agreement in their assessments. Explorative factorial analysis disclosed a single homogeneous factor including 6 items (thus supporting an ordinal total score), with only the item about eye contact being unrelated to the others. Moreover, the existence of 2 different archetypal profiles of attuned and disattuned behaviours was highlighted through multiple correspondence analysis. As suggested by the consistent results of 2 different analyses, MT-SAS is a reliable tool that globally evaluates sonorous-musical and nonverbal behaviours related to emotional attunement and empathetic relationship between patient and therapist during active MT sessions. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma.

    PubMed

    Tatsukawa, Ryoko; Koga, Kaori; Aoki, Mikiko; Koshikawa, Naohiko; Imafuku, Shinichi; Nakayama, Juichiro; Nabeshima, Kazuki

    2016-07-01

    Erythropoietin-producing hepatocellular receptor-2 (EphA2) overexpression is prevalent in many types of human cancers, and it has been reported that high EphA2 expression is correlated with malignancy. Recent studies revealed that processing of EphA2 by cleaving off the N-terminal portion by membrane-type 1 matrix metalloproteinase (MT1-MMP) promotes invasion via stimulation of Ras in cancer cells in vitro. The objectives of this study were to investigate the presence and role of EphA2 processing in cutaneous squamous cell carcinoma (SCC) tissues. EphA2 (C-terminal and N-terminal) and MT1-MMP expression patterns and levels were analyzed immunohistochemically in SCC (n = 70) and Bowen disease (BD; n = 20). Levels of MT1-MMP and EphA2 expression were evaluated using digital image analysis. Proximity between MT1-MMP and EphA2 in cancer cells and its effect on EphA2 processing were investigated using a combination of in situ proximity ligation assay (PLA) and Western blotting. Immunohistochemical analyses showed that levels of EphA2 N-terminal expression were significantly lower than those of EphA2 C-terminal expression in SCC, whereas levels of EphA2 C- and N-terminal expression were similar in BD. Western blotting showed processed EphA2 fragments in human SCC tissues. Expression levels of MT1-MMP, EphA2, and processed EphA2 fragments were higher in SCC than BD. Proximity between MT1-MMP and EphA2 in SCC was demonstrated by in situ PLA. Our results suggest possible involvement of MT1-MMP processing of EphA2 in invasiveness of cutaneous SCC.

  19. Anaerobic degradation of a mixture of MtBE, EtBE, TBA, and benzene under different redox conditions.

    PubMed

    van der Waals, Marcelle J; Pijls, Charles; Sinke, Anja J C; Langenhoff, Alette A M; Smidt, Hauke; Gerritse, Jan

    2018-04-01

    The increasing use of biobased fuels and fuel additives can potentially change the typical fuel-related contamination in soil and groundwater. Anaerobic biotransformation of the biofuel additive ethyl tert-butyl ether (EtBE), as well as of methyl tert-butyl ether (MtBE), benzene, and tert-butyl alcohol (TBA, a possible oxygenate metabolite), was studied at an industrially contaminated site and in the laboratory. Analysis of groundwater samples indicated that in the field MtBE was degraded, yielding TBA as major product. In batch microcosms, MtBE was degraded under different conditions: unamended control, with medium without added electron acceptors, or with ferrihydrite or sulfate (with or without medium) as electron acceptor, respectively. Degradation of EtBE was not observed under any of these conditions tested. TBA was partially depleted in parallel with MtBE. Results of microcosm experiments with MtBE substrate analogues, i.e., syringate, vanillate, or ferulate, were in line with the hypothesis that the observed TBA degradation is a cometabolic process. Microcosms with ferulate, syringate, isopropanol, or diethyl ether showed EtBE depletion up to 86.5% of the initial concentration after 83 days. Benzene was degraded in the unamended controls, with medium without added electron acceptors and with ferrihydrite, sulfate, or chlorate as electron acceptor, respectively. In the presence of nitrate, benzene was only degraded after addition of an anaerobic benzene-degrading community. Nitrate and chlorate hindered MtBE, EtBE, and TBA degradation.

  20. MODFLOW/MT3DMS-based simulation of variable-density ground water flow and transport

    USGS Publications Warehouse

    Langevin, C.D.; Guo, W.

    2006-01-01

    This paper presents an approach for coupling MODFLOW and MT3DMS for the simulation of variable-density ground water flow. MODFLOW routines were modified to solve a variable-density form of the ground water flow equation in which the density terms are calculated using an equation of state and the simulated MT3DMS solute concentrations. Changes to the MODFLOW and MT3DMS input files were kept to a minimum, and thus existing data files and data files created with most pre- and postprocessors can be used directly with the SEAWAT code. The approach was tested by simulating the Henry problem and two of the saltpool laboratory experiments (low- and high-density cases). For the Henry problem, the simulated results compared well with the steady-state semianalytic solution and also the transient isochlor movement as simulated by a finite-element model. For the saltpool problem, the simulated breakthrough curves compared better with the laboratory measurements for the low-density case than for the high-density case but showed good agreement with the measured salinity isosurfaces for both cases. Results from the test cases presented here indicate that the MODFLOW/MT3DMS approach provides accurate solutions for problems involving variable-density ground water flow and solute transport. ?? 2006 National Ground Water Association.

  1. Species mtDNA genetic diversity explained by infrapopulation size in a host-symbiont system.

    PubMed

    Doña, Jorge; Moreno-García, Marina; Criscione, Charles D; Serrano, David; Jovani, Roger

    2015-12-01

    Understanding what shapes variation in genetic diversity among species remains a major challenge in evolutionary ecology, and it has been seldom studied in parasites and other host-symbiont systems. Here, we studied mtDNA variation in a host-symbiont non-model system: 418 individual feather mites from 17 feather mite species living on 17 different passerine bird species. We explored how a surrogate of census size, the median infrapopulation size (i.e., the median number of individual parasites per infected host individual), explains mtDNA genetic diversity. Feather mite species genetic diversity was positively correlated with mean infrapopulation size, explaining 34% of the variation. As expected from the biology of feather mites, we found bottleneck signatures for most of the species studied but, in particular, three species presented extremely low mtDNA diversity values given their infrapopulation size. Their star-like haplotype networks (in contrast with more reticulated networks for the other species) suggested that their low genetic diversity was the consequence of severe bottlenecks or selective sweeps. Our study shows for the first time that mtDNA diversity can be explained by infrapopulation sizes, and suggests that departures from this relationship could be informative of underlying ecological and evolutionary processes.

  2. Electrochemical detection of the MT-ND6 gene and its enzymatic digestion: application in human genomic sample.

    PubMed

    Mazloum-Ardakani, Mohammad; Ahmadi, Roya; Heidari, Mohammad Mehdi; Sheikh-Mohseni, Mohammad Ali

    2014-06-15

    A simple electrochemical biosensor was developed for the detection of the mitochondrial NADH dehydrogenase 6 gene (MT-ND6) and its enzymatic digestion by BamHI enzyme. This biosensor was fabricated by modification of a glassy carbon electrode with gold nanoparticles (AuNPs/GCE) and a probe oligonucleotide (ssDNA/AuNPs/GCE). The probe, which is a thiolated segment of the MT-ND6 gene, was deposited by self-assembling immobilization on AuNPs/GCE. Two indicators including methylene blue (MB) and neutral red (NR) were used as the electroactive indicators and the electrochemical response of the modified electrode was measured by differential pulse voltammetry. The proposed biosensor can detect the complementary sequences of the MT-ND6 gene. Also the modified electrode was used for the detection of an enzymatic digestion process by BamHI enzyme. The electrochemical biosensor can detect the MT-ND6 gene and its enzymatic digestion in polymerase chain reaction (PCR)-amplified DNA extracted from human blood. Also the biosensor was used directly for detection of the MT-ND6 gene in all of the human genome. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Transportation observations, considerations and recommendations for Mt. Hood National Forest

    DOT National Transportation Integrated Search

    2009-06-24

    A field investigation of the current transportation infrastructure and operations at Mt. Hood : National Forest (MHNF) by the interagency Transportation Assistance Group (TAG) was conducted June : 24-26, 2009, on behalf of the U.S. Forest Service (US...

  4. Mt. Pinatubo Volcano - Post Eruption, Luzon, Philippines

    NASA Image and Video Library

    1992-08-08

    Mt. Pinatubo on the island of Luzon (15.0N, 120.0E) erupted catastrophically in June 1991 after over 600 years of inactivity. In this vertical view, the full extent of the eruption is obvious. Thick layers of ash completely surrounds the crater and the effect of mudflows in this previously heavily forested and agricultural region can be traced as ribbons flowing downhill. Clark AFB, once the crossroads of the SW Pacific can only partially be seen.

  5. Associations between the Transsexual Voice Questionnaire (TVQ[superscript MtF) and Self-Report of Voice Femininity and Acoustic Voice Measures

    ERIC Educational Resources Information Center

    Dacakis, Georgia; Oates, Jennifer; Douglas, Jacinta

    2017-01-01

    Background: The Transsexual Voice Questionnaire (TVQ[Superscript MtF]) was designed to capture the voice-related perceptions of individuals whose gender identity as female is the opposite of their birth-assigned gender (MtF women). Evaluation of the psychometric properties of the TVQ[Superscript MtF]is ongoing. Aims: To investigate associations…

  6. Mod3DMT and EMTF: Free Software for MT Data Processing and Inversion

    NASA Astrophysics Data System (ADS)

    Egbert, G. D.; Kelbert, A.; Meqbel, N. M.

    2017-12-01

    "ModEM" was developed at Oregon State University as a modular system for inversion of electromagnetic (EM) geophysical data (Egbert and Kelbert, 2012; Kelbert et al., 2014). Although designed for more general (frequency domain) EM applications, and originally intended as a testbed for exploring inversion search and regularization strategies, our own initial uses of ModEM were for 3-D imaging of the deep crust and upper mantle at large scales. Since 2013 we have offered a version of the source code suitable for 3D magnetotelluric (MT) inversion on an "as is, user beware" basis for free for non-commercial applications. This version, which we refer to as Mod3DMT, has since been widely used by the international MT community. Over 250 users have registered to download the source code, and at least 50 MT studies in the refereed literature, covering locations around the globe at a range of spatial scales, cite use of ModEM for 3D inversion. For over 30 years I have also made MT processing software available for free use. In this presentation, I will discuss my experience with these freely available (but perhaps not truly open-source) computer codes. Although users are allowed to make modifications to the codes (on conditions that they provide a copy of the modified version) only a handful of users have tried to make any modification, and only rarely are modifications even reported, much less provided back to the developers.

  7. MtMOT1.2 is responsible for molybdate supply to Medicago truncatula nodules.

    PubMed

    Gil-Díez, Patricia; Tejada-Jiménez, Manuel; León-Mediavilla, Javier; Wen, Jiangqi; Mysore, Kirankumar S; Imperial, Juan; González-Guerrero, Manuel

    2018-06-25

    Symbiotic nitrogen fixation in legume root nodules requires a steady supply of molybdenum for synthesis of the iron-molybdenum cofactor of nitrogenase. This nutrient has to be provided by the host plant from the soil, crossing several symplastically disconnected compartments through molybdate transporters, including members of the MOT1 family. MtMOT1.2 is a Medicago truncatula MOT1 family member located in the endodermal cells in roots and nodules. Immunolocalization of a tagged MtMOT1.2 indicates that it is associated to the plasma membrane and to intracellular membrane systems, where it would be transporting molybdate towards the cytosol, as indicated in yeast transport assays. Loss-of-function mot1.2-1 mutant showed reduced growth compared to wild-type plants when nitrogen fixation was required, but not when nitrogen was provided as nitrate. While no effect on molybdenum-dependent nitrate reductase activity was observed, nitrogenase activity was severely affected, explaining the observed difference of growth depending on nitrogen source. This phenotype was the result of molybdate not reaching the nitrogen-fixing nodules, since genetic complementation with a wild-type MtMOT1.2 gene or molybdate-fortification of the nutrient solution, both restored wild-type levels of growth and nitrogenase activity. These results support a model in which MtMOT1.2 would mediate molybdate delivery by the vasculature into the nodules. This article is protected by copyright. All rights reserved.

  8. The Mt. Currie Indian Community School: Innovation and Endurance.

    ERIC Educational Resources Information Center

    Wyatt, June D.

    1985-01-01

    In the 1970s, the Mt. Currie school in British Columbia was transformed into a locally controlled Native Canadian Indian institution. Using interview data, this articles reviews changing role relationships of the school board and staff. Recommendations applicable to other community education ventures across North America are made. (Author/BS)

  9. The Stoichiometric Transition from Zn6Cu1-Metallothionein to Zn7-Metallothionein Underlies the Up-regulation of Metallothionein (MT) Expression

    PubMed Central

    Alvarez, Lydia; Gonzalez-Iglesias, Hector; Garcia, Montserrat; Ghosh, Sikha; Sanz-Medel, Alfredo; Coca-Prados, Miguel

    2012-01-01

    We examined the profiling of gene expression of metallothioneins (MTs) in human tissues from cadaver eyes with microarray-based analysis. All MT1 isoforms, with the exception of MT1B, were abundantly expressed in lens and corneal tissue. Along with MT1B, MT4 was not detected in any tissues. Antibodies to MT1/2 labeled the corneal epithelial and endothelial cells, whereas MT3 label the retinal ganglion cells. We studied the effects of zinc and cytokines on the gene expression of MT isoforms in a corneal epithelial cell line (HCEsv). Zinc exerted an up-regulation of the expression of MT isoforms, and this effect was further potentiated in the presence of IL1α or TNFα. Zinc also elicited a strong down-regulation of the expression of inflammatory cytokines, and this effect was blocked in the presence of TNFα or IL1α. The concentration of MTs, bound zinc, and the metal stoichiometry of MTs in cultured HCEsv were determined by mass spectrometry. The total concentration of MTs was 0.24 ± 0.03 μm and, after 24 h of zinc exposure, increased to 0.96 ± 0.01 μm. The combination of zinc and IL1α further enhanced the level of MTs to 1.13 ± 0.03 μm. The average metal stoichiometry of MTs was Zn6Cu1-MT, and after exposure to the different treatments, it changed to Zn7-MT. Actinomycin D blocked transcription, and cycloheximide attenuated synthesis of MTs in the presence or absence of zinc, suggesting transcriptional regulation. Overall the data provide molecular and analytical evidence on the interplay between zinc, MTs, and proinflammatory cytokines in HCEsv cells, with potential implications on cell-based inflammatory eye diseases. PMID:22722935

  10. Controls on Magmatic and Hydrothermal Processes at Yellowstone Supervolcano: The Wideband Magnetotelluric Component of an Integrated MT/Seismic Investigation

    NASA Astrophysics Data System (ADS)

    Schultz, A.; Bennington, N. L.; Bowles-martinez, E.; Imamura, N.; Cronin, R. A.; Miller, D. J.; Hart, L.; Gurrola, R. M.; Neal, B. A.; Scholz, K.; Fry, B.; Carbonari, R.

    2017-12-01

    Previous seismic and magnetotelluric (MT) studies beneath Yellowstone (YS) have provided insight into the origin and migration of magmatic fluids within the volcanic system. However, important questions remain concerning the generation of magmatism at YS, the migration and storage of these magmatic fluids, as well as their relationships to hydrothermal expressions. Analysis of regional-scale EarthScope MT data collected previously suggests a relative absence of continuity in crustal partial melt accumulations directly beneath YS. This is in contrast to some seismic interpretations, although such long-period MT data have limited resolving power in the upper-to-mid crustal section. A wideband MT experiment was designed as a component of an integrated MT/seismic project to examine: the origin and location of magmatic fluids at upper mantle/lower crustal depths, the preferred path of migration for these magmatic fluids into the mid- to upper-crust, the resulting distribution of the magma reservoir, the composition of the magma reservoir, and implications for future volcanism at YS. A high-resolution wideband MT survey was carried out in the YS region in the summer of 2017, with more than forty-five wideband stations installed within and immediately surrounding the YS National Park boundary. These data provided nearly six decades of bandwidth ( 10-3 Hz -to- 103 Hz). Extraordinary permitting restrictions prevented us from using conventional installation methods at many of our sites, and an innovative "no-dig" subaerial method of wideband MT was developed and used successfully. Using these new data along with existing MT datasets, we are inverting for the 3D resistivity structure at upper crustal through upper mantle scales at YS. Complementary to this MT work, a joint inversion for the 3D crustal velocity structure is being carried out using both ambient noise and earthquake travel time data. Taken together, these data should better constrain the crustal velocity

  11. Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

    PubMed Central

    Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

    2011-01-01

    Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

  12. MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants

    PubMed Central

    Stumpf, Jeffrey D.; Copeland, William C.

    2014-01-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  13. MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

    PubMed

    Stumpf, Jeffrey D; Copeland, William C

    2014-10-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  14. MtGimC, a novel archaeal chaperone related to the eukaryotic chaperonin cofactor GimC/prefoldin.

    PubMed

    Leroux, M R; Fändrich, M; Klunker, D; Siegers, K; Lupas, A N; Brown, J R; Schiebel, E; Dobson, C M; Hartl, F U

    1999-12-01

    Group II chaperonins in the eukaryotic and archaeal cytosol assist in protein folding independently of the GroES-like cofactors of eubacterial group I chaperonins. Recently, the eukaryotic chaperonin was shown to cooperate with the hetero-oligomeric protein complex GimC (prefoldin) in folding actin and tubulins. Here we report the characterization of the first archaeal homologue of GimC, from Methanobacterium thermoautotrophicum. MtGimC is a hexamer of 87 kDa, consisting of two alpha and four beta subunits of high alpha-helical content that are predicted to contain extended coiled coils and represent two evolutionarily conserved classes of Gim subunits. Reconstitution experiments with MtGimC suggest that two subunits of the alpha class (archaeal Gimalpha and eukaryotic Gim2 and 5) form a dimer onto which four subunits of the beta class (archaeal Gimbeta and eukaryotic Gim1, 3, 4 and 6) assemble. MtGimalpha and beta can form hetero-complexes with yeast Gim subunits and MtGimbeta partially complements yeast strains lacking Gim1 and 4. MtGimC is a molecular chaperone capable of stabilizing a range of non-native proteins and releasing them for subsequent chaperonin-assisted folding. In light of the absence of Hsp70 chaperones in many archaea, GimC may fulfil an ATP-independent, Hsp70-like function in archaeal de novo protein folding.

  15. MtGimC, a novel archaeal chaperone related to the eukaryotic chaperonin cofactor GimC/prefoldin.

    PubMed Central

    Leroux, M R; Fändrich, M; Klunker, D; Siegers, K; Lupas, A N; Brown, J R; Schiebel, E; Dobson, C M; Hartl, F U

    1999-01-01

    Group II chaperonins in the eukaryotic and archaeal cytosol assist in protein folding independently of the GroES-like cofactors of eubacterial group I chaperonins. Recently, the eukaryotic chaperonin was shown to cooperate with the hetero-oligomeric protein complex GimC (prefoldin) in folding actin and tubulins. Here we report the characterization of the first archaeal homologue of GimC, from Methanobacterium thermoautotrophicum. MtGimC is a hexamer of 87 kDa, consisting of two alpha and four beta subunits of high alpha-helical content that are predicted to contain extended coiled coils and represent two evolutionarily conserved classes of Gim subunits. Reconstitution experiments with MtGimC suggest that two subunits of the alpha class (archaeal Gimalpha and eukaryotic Gim2 and 5) form a dimer onto which four subunits of the beta class (archaeal Gimbeta and eukaryotic Gim1, 3, 4 and 6) assemble. MtGimalpha and beta can form hetero-complexes with yeast Gim subunits and MtGimbeta partially complements yeast strains lacking Gim1 and 4. MtGimC is a molecular chaperone capable of stabilizing a range of non-native proteins and releasing them for subsequent chaperonin-assisted folding. In light of the absence of Hsp70 chaperones in many archaea, GimC may fulfil an ATP-independent, Hsp70-like function in archaeal de novo protein folding. PMID:10581246

  16. MtDNA mutations are a common cause of severe disease phenotypes in children with Leigh syndrome.

    PubMed

    Naess, Karin; Freyer, Christoph; Bruhn, Helene; Wibom, Rolf; Malm, Gunilla; Nennesmo, Inger; von Döbeln, Ulrika; Larsson, Nils-Göran

    2009-05-01

    Leigh syndrome is a common clinical manifestation in children with mitochondrial disease and other types of inborn errors of metabolism. We characterised clinical symptoms, prognosis, respiratory chain function and performed extensive genetic analysis of 25 Swedish children suffering from Leigh syndrome with the aim to obtain insights into the molecular pathophysiology and to provide a rationale for genetic counselling. We reviewed the clinical history of all patients and used muscle biopsies in order to perform molecular, biochemical and genetic investigations, including sequencing the entire mitochondrial DNA (mtDNA), the mitochondrial DNA polymerase (POLGA) gene and the surfeit locus protein 1 (SURF1) gene. Respiratory chain enzyme activity measurements identified five patients with isolated complex I deficiency and five with combined enzyme deficiencies. No patient presented with isolated complex IV deficiency. Seven patients had a decreased ATP production rate. Extensive sequence analysis identified eight patients with pathogenic mtDNA mutations and one patient with mutations in POLGA. Mutations of mtDNA are a common cause of LS and mtDNA analysis should always be included in the diagnosis of LS patients, whereas SURF1 mutations are not a common cause of LS in Sweden. Unexpectedly, age of onset, clinical symptoms and prognosis did not reveal any clear differences in LS patients with mtDNA or nuclear DNA mutations.

  17. Six years of atmospheric CO2 observations at Mt. Fuji recorded with a battery-powered measurement system

    NASA Astrophysics Data System (ADS)

    Nomura, Shohei; Mukai, Hitoshi; Terao, Yukio; Machida, Toshinobu; Nojiri, Yukihiro

    2017-03-01

    We developed a battery-powered carbon dioxide (CO2) measurement system for monitoring at the summit of Mt. Fuji (3776 m a.s.l.), which experiences very low temperatures (below -20 °C) and severe environmental conditions without access to gridded electricity for 10 months (from September to June). Our measurement system used 100 batteries to run the measurement unit during these months. These batteries were charged during the 2-month summer season when gridded electricity was available, using a specially designed automatic battery-charging system. We installed this system in summer 2009 at the Mt. Fuji weather station; observations of atmospheric CO2 concentration were taken through December 2015. Measurements were never interrupted by a lack of battery power except for two cases in which lightning damaged a control board. Thus we obtained CO2 data during about 94 % of the 6-year period. Analytical performances (stability and accuracy) were better than 0.1 ppm, as tested by checking working standards and comparisons with flask sampling.Observational results showed that CO2 mole fractions at Mt. Fuji demonstrated clear seasonal variation. The trend and the variability of the CO2 growth rate observed at Mt. Fuji were very similar to those of the Mauna Loa Observatory (MLO). Seasonally, the concentration at Mt. Fuji was 2-10 ppm lower in summer and 2-12 ppm higher in winter than those at MLO. The lower concentrations at Mt. Fuji in summer are mainly attributed to episodes of air mass transport from Siberia or China, where CO2 is taken up by the terrestrial biosphere. On the other hand, the relatively higher concentrations in winter seem to reflect the high percentage of air masses originating from China or Southeast Asia during this period, which carry increased anthropogenic carbon dioxide. These results show that Mt. Fuji is not very influenced by local sources but rather by the sources and sinks over a very large region.Thus we conclude that, as this system could

  18. Hydraulic properties of Mt. Simon aquifer, Prairie Island Indian community, southeastern Minnesota, 2001

    USGS Publications Warehouse

    Winterstein, Thomas A.

    2002-01-01

    Hantush and Theis methods type curves were fitted to the measured drawdown and recovery curves in the observation well. The results of matching the type curves to the measured data indicate that leakage is negligible from the overlying Eau Claire confining unit into the Mt. Simon aquifer. The transmissivity and storage coeffi-cients for the Mt. Simon aquifer, determined by both methods, are 3, 000 ft2/d and 3 x 10-4, respectively. The average hydraulic conductivity, assuming an aquifer thickness of 233 ft, is 10 ft/d.

  19. Toward the definition of stereochemical requirements for MT2-selective antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin derivatives.

    PubMed

    Bedini, Annalida; Lucarini, Simone; Spadoni, Gilberto; Tarzia, Giorgio; Scaglione, Francesco; Dugnani, Silvana; Pannacci, Marilou; Lucini, Valeria; Carmi, Caterina; Pala, Daniele; Rivara, Silvia; Mor, Marco

    2011-12-22

    New derivatives of 4-phenyl-2-propionamidotetralin (4-P-PDOT) were prepared and tested on cloned MT1 and MT2 receptors, with the purpose of merging previously reported pharmacophores for nonselective agonists and for MT2-selective antagonists. A 8-methoxy group increases binding affinity of both (±)-cis- and (±)-trans-4-P-PDOT, and it can be bioisosterically replaced by a bromine. Conformational analysis of 8-methoxy-4-P-PDOT by molecular dynamics, supported by NMR data, revealed an energetically favored conformation for the (2S,4S)-cis isomer and a less favorable conformation for the (2R,4S)-trans one, fulfilling the requirements of a pharmacophore model for nonselective melatonin receptor agonists. A new superposition model, including features characteristic of MT2-selective antagonists, suggests that MT1/MT2 agonists and MT2 antagonists can share the same arrangement for their pharmacophoric elements. The model correctly predicted the eutomers of (±)-cis- and (±)-trans-4-P-PDOT. The model was validated by preparing three dihydronaphthalene derivatives, either able or not able to reproduce the putative active conformation of 4-P-PDOT.

  20. Reservoir characterization of the Mt. Simon Sandstone, Illinois Basin, USA

    USGS Publications Warehouse

    Frailey, S.M.; Damico, J.; Leetaru, H.E.

    2011-01-01

    The integration of open hole well log analyses, core analyses and pressure transient analyses was used for reservoir characterization of the Mt. Simon sandstone. Characterization of the injection interval provides the basis for a geologic model to support the baseline MVA model, specify pressure design requirements of surface equipment, develop completion strategies, estimate injection rates, and project the CO2 plume distribution.The Cambrian-age Mt. Simon Sandstone overlies the Precambrian granite basement of the Illinois Basin. The Mt. Simon is relatively thick formation exceeding 800 meters in some areas of the Illinois Basin. In the deeper part of the basin where sequestration is likely to occur at depths exceeding 1000 m, horizontal core permeability ranges from less than 1 ?? 10-12 cm 2 to greater than 1 ?? 10-8 cm2. Well log and core porosity can be up to 30% in the basal Mt. Simon reservoir. For modeling purposes, reservoir characterization includes absolute horizontal and vertical permeability, effective porosity, net and gross thickness, and depth. For horizontal permeability, log porosity was correlated with core. The core porosity-permeability correlation was improved by using grain size as an indication of pore throat size. After numerous attempts to identify an appropriate log signature, the calculated cementation exponent from Archie's porosity and resistivity relationships was used to identify which porosity-permeability correlation to apply and a permeability log was made. Due to the relatively large thickness of the Mt. Simon, vertical permeability is an important attribute to understand the distribution of CO2 when the injection interval is in the lower part of the unit. Only core analyses and specifically designed pressure transient tests can yield vertical permeability. Many reservoir flow models show that 500-800 m from the injection well most of the CO2 migrates upward depending on the magnitude of the vertical permeability and CO2 injection

  1. Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life.

    PubMed

    Yu, Hsin-Hao; Chaplin, Tristan A; Egan, Gregory W; Reser, David H; Worthy, Katrina H; Rosa, Marcello G P

    2013-07-24

    Lesions of striate cortex [primary visual cortex (V1)] in adult primates result in blindness. In contrast, V1 lesions in neonates typically allow much greater preservation of vision, including, in many human patients, conscious perception. It is presently unknown how this marked functional difference is related to physiological changes in cortical areas that are spared by the lesions. Here we report a study of the middle temporal area (MT) of adult marmoset monkeys that received unilateral V1 lesions within 6 weeks of birth. In contrast with observations after similar lesions in adult monkeys, we found that virtually all neurons in the region of MT that was deprived of V1 inputs showed robust responses to visual stimulation. These responses were very similar to those recorded in neurons with receptive fields outside the lesion projection zones in terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal retinotopic organization of MT was maintained. Nonetheless, we found evidence of a very specific functional deficit: direction selectivity, a key physiological characteristic of MT that is known to be preserved in many cells after adult V1 lesions, was absent. These results demonstrate that lesion-induced reorganization of afferent pathways is sufficient to develop robust visual function in primate extrastriate cortex, highlighting a likely mechanism for the sparing of vision after neonatal V1 lesions. However, they also suggest that interactions with V1 in early postnatal life are critical for establishing stimulus selectivity in MT.

  2. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, M.D.; Sun, F.; Wallace, D.C.

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended tomore » be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.« less

  3. Himalayan Mtns. and Mt. Everest Earth observation taken by Dan Bursch during EXP. Four

    NASA Image and Video Library

    2002-03-20

    ISS004-E-8852 (20 March 2002) --- Astronaut Daniel W. Bursch, flight engineer for Expedition Four aboard the International Space Station, used a digital still camera to capture this image of Mt. Everest in the Himalayan Range. The mountain is near frame center. Here are the notes Bursch added in one of his reports to ground controllers: "One morning I happened to be up early. I glanced at our world map and saw that we’d be passing near Mt Everest soon. I checked the computer, realized that we were in an attitude that would allow me to open the window shutter and there was Mt Everest! It almost seemed to jump out at me. The low sun angle (it was close to orbital sunrise) gave tremendous relief to the mountains. It was just one of those sights that will be forever burned into my brain!"

  4. Swimming, swarming, twitching, and chemotactic responses of Cupriavidus metallidurans CH34 and Pseudomonas putida mt2 in the presence of cadmium.

    PubMed

    Shamim, Saba; Rehman, Abdul; Qazi, Mahmood Hussain

    2014-04-01

    To use of microorganisms for bioremediation purposes, the study of their motility behavior toward metals is essential. In the present study, Cupriavidus metallidurans CH34 and Pseudomonas putida mt2 were used as cadmium (Cd)-resistant and -sensitive bacteria, respectively, to evaluate the effects of Cd on their motility behaviors. Potassium morpholinopropane sulfonate (MOPS) buffer was used to observe the motility behavior of both isolates. Movement of mt2 was less in MOPS buffer compared with CH34, likely reflecting the mono-flagellated nature of mt2 and the peritrichous nature of CH34. The swimming, swarming, twitching, and chemotaxis behaviors of mt2 were greater in the presence of glucose than that of Cd. mt2 exhibited negative motility behaviors when exposed to Cd, but the opposite effect was seen in CH34. Cd was found to be a chemorepellent for mt2 but a chemoattractant for CH34, suggesting that CH34 is a potential candidate for metal (Cd) bioremediation.

  5. Gain Modulation as a Mechanism for Coding Depth from Motion Parallax in Macaque Area MT

    PubMed Central

    Kim, HyungGoo R.; Angelaki, Dora E.

    2017-01-01

    Observer translation produces differential image motion between objects that are located at different distances from the observer's point of fixation [motion parallax (MP)]. However, MP can be ambiguous with respect to depth sign (near vs far), and this ambiguity can be resolved by combining retinal image motion with signals regarding eye movement relative to the scene. We have previously demonstrated that both extra-retinal and visual signals related to smooth eye movements can modulate the responses of neurons in area MT of macaque monkeys, and that these modulations generate neural selectivity for depth sign. However, the neural mechanisms that govern this selectivity have remained unclear. In this study, we analyze responses of MT neurons as a function of both retinal velocity and direction of eye movement, and we show that smooth eye movements modulate MT responses in a systematic, temporally precise, and directionally specific manner to generate depth-sign selectivity. We demonstrate that depth-sign selectivity is primarily generated by multiplicative modulations of the response gain of MT neurons. Through simulations, we further demonstrate that depth can be estimated reasonably well by a linear decoding of a population of MT neurons with response gains that depend on eye velocity. Together, our findings provide the first mechanistic description of how visual cortical neurons signal depth from MP. SIGNIFICANCE STATEMENT Motion parallax is a monocular cue to depth that commonly arises during observer translation. To compute from motion parallax whether an object appears nearer or farther than the point of fixation requires combining retinal image motion with signals related to eye rotation, but the neurobiological mechanisms have remained unclear. This study provides the first mechanistic account of how this interaction takes place in the responses of cortical neurons. Specifically, we show that smooth eye movements modulate the gain of responses of neurons

  6. 77 FR 55690 - Amendment of Class E Airspace; Dillon, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-11

    ... aircraft using new Area Navigation (RNAV) Global positioning System (GPS) standard instrument approach... Airport, Dillon, MT, to accommodate IFR aircraft executing new RNAV (GPS) standard instrument approach.... Steven L. Vale, Acting Manager, Operations Support Group, Western Service Center. [FR Doc. 2012-22269...

  7. 77 FR 44120 - Establishment of Class E Airspace; Roundup, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ... at Roundup Airport, Roundup, MT, to accommodate aircraft using new Area Navigation (RNAV) Global Positioning System (GPS) standard instrument approach procedures at Roundup Airport. This improves the safety and management of Instrument Flight Rules (IFR) operations at the airport. DATES: Effective date, 0901...

  8. Design and synthesis of N-(3,3-diphenylpropenyl)alkanamides as a novel class of high-affinity MT2-selective melatonin receptor ligands.

    PubMed

    Bedini, Annalida; Spadoni, Gilberto; Gatti, Giuseppe; Lucarini, Simone; Tarzia, Giorgio; Rivara, Silvia; Lorenzi, Simone; Lodola, Alessio; Mor, Marco; Lucini, Valeria; Pannacci, Marilou; Scaglione, Francesco

    2006-12-14

    A novel series of melatonin receptor ligands was discovered by opening the cyclic scaffolds of known classes of high affinity melatonin receptor antagonists, while retaining the pharmacophore elements postulated by previously described 3D-QSAR and receptor models. Compounds belonging to the classes of 2,3- and [3,3-diphenylprop(en)yl]alkanamides and of o- or [(m-benzyl)phenyl]ethyl-alkanamides were synthesized and tested on MT(1) and MT(2) receptors. The class of 3,3-diphenyl-propenyl-alkanamides was the most interesting one, with compounds having MT(2) receptor affinity similar to that of MLT, remarkable MT(2) selectivity, and partial agonist or antagonist behavior. In particular, the (E)-m-methoxy cyclobutanecarboxamido derivative 18f and the di-(m-methoxy) acetamido one, 18g, have sub-nM affinity for the MT(2) subtype, with more than 100-fold selectivity over MT(1), 18f being an antagonist and 18g a partial agonist on GTPgammaS test. Docking of 18g into a previously developed MT(2) receptor model showed a binding scheme consistent with that of other antagonists. The MT(2) expected binding affinities of the new compounds were calculated by a previously developed 3D-QSAR CoMFA model, giving satisfactory predictions.

  9. Anticipating and addressing workplace static magnetic field effects at levels <0.5 mT.

    PubMed

    Emery, R J; Hopkins, J R; Charlton, M A

    2000-11-01

    Magnetic resonance, once a research tool limited to the basic sciences, has experienced an increase in popularity due to its unique ability to analyze certain living systems in vivo. Expanding applications in the biomedical sciences have resulted in magnetic sources being located in research institutions nationally. Space and resource limitations sometimes necessitate siting magnetic resonance units in proximity to other institutional operations. For magnetic field shielding and personnel protection considerations, the generally accepted 0.5 mT (milliTesla) limit for implanted cardiac devices is commonly used as the conservative basis for decisions. But the effects of magnetic fields on equipment can be easily observed at levels far below 0.5 mT, often resulting in concern and apprehension on the part of personnel in the surrounding areas. Responding to recurrent worker concerns spawned by noticeable effects on equipment at exposure levels <0.5 mT can strain finite radiation safety program resources. To enhance the ability to anticipate possible facility incompatibility issues associated with the installation of magnetic sources, a literature review was conducted to summarize documented equipment effects. Various types of equipment were found to be impacted at levels ranging down to perhaps 0.001 mT. Armed with this information, practicing radiation safety professionals can better anticipate facility incompatibility issues and improve their responses to worker concerns initiated by observed effects on equipment.

  10. Central Atlantic Lithosphere-Asthenosphere Boundary Study (CAL-LAB): Massive Coast effects in MT data

    NASA Astrophysics Data System (ADS)

    Reyes Ortega, V.; Constable, S.; Bassett, D.

    2017-12-01

    The Lithosphere-Asthenosphere Boundary (LAB) is the largest plate boundary on Earth yet is still poorly understood, with temperature, hydration, composition, melting, strain rate, and anisotropy all candidates to explain the location and behavior of this transition from convecting asthenosphere to rigid lithosphere. Electrical conductivity, estimated from magnetotelluric (MT) data and combined with seismic measurements, is increasingly being seen as a way to improve our understanding of the LAB. The Integrated LAB (iLAB) experiment brings together three institutions from three countries to collect MT data along with passive and active seismic data in the central equatorial Atlantic, over lithosphere from 0 to 80 My old. Thirty-nine seafloor MT instruments were deployed alongside ocean-bottom seismometers for over one year, and recorded data for 70 to 100 days before the batteries expired. Good quality MT responses were obtained from 10 to nearly 100,000 seconds period, but many sites exhibited up to -180 degree phase shifts at the highest frequencies. Forward modeling shows that this behavior is consistent with a coast effect from the African coastline 500-1500 kilometers away. The conductive mid-ocean ridge system modifies the coast effect for sites west of the ridge. Inverting these data for LAB geology in the presence of such a strong coast effect presents a considerable challenge.

  11. Medicago truncatula copper transporter 1 (MtCOPT1) delivers copper for symbiotic nitrogen fixation.

    PubMed

    Senovilla, Marta; Castro-Rodríguez, Rosario; Abreu, Isidro; Escudero, Viviana; Kryvoruchko, Igor; Udvardi, Michael K; Imperial, Juan; González-Guerrero, Manuel

    2018-04-01

    Copper is an essential nutrient for symbiotic nitrogen fixation. This element is delivered by the host plant to the nodule, where membrane copper (Cu) transporter would introduce it into the cell to synthesize cupro-proteins. COPT family members in the model legume Medicago truncatula were identified and their expression determined. Yeast complementation assays, confocal microscopy and phenotypical characterization of a Tnt1 insertional mutant line were carried out in the nodule-specific M. truncatula COPT family member. Medicago truncatula genome encodes eight COPT transporters. MtCOPT1 (Medtr4g019870) is the only nodule-specific COPT gene. It is located in the plasma membrane of the differentiation, interzone and early fixation zones. Loss of MtCOPT1 function results in a Cu-mitigated reduction of biomass production when the plant obtains its nitrogen exclusively from symbiotic nitrogen fixation. Mutation of MtCOPT1 results in diminished nitrogenase activity in nodules, likely an indirect effect from the loss of a Cu-dependent function, such as cytochrome oxidase activity in copt1-1 bacteroids. These data are consistent with a model in which MtCOPT1 transports Cu from the apoplast into nodule cells to provide Cu for essential metabolic processes associated with symbiotic nitrogen fixation. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

  12. Papua New Guinea MT: Looking where seismic is blind

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoversten, G.M.

    1996-11-01

    Hydrocarbon exploration in the Papuan fold belt is made extremely difficult by mountainous terrain, equatorial jungle and thick karstified Miocene limestones at the surface. The high-velocity karstified limestones at or near the surface often render the seismic technique useless for imaging the subsurface. In such areas magnetotellurics (MT) provides a valuable capability for mapping subsurface structure. Numerical and field data examples are presented which demonstrate the severity of the 1D errors and the improvements in accuracy which can be achieved using a 2D inverse solution. Two MT lines over adjacent anticlines, both with well control and seismic data, are usedmore » to demonstrate the application of 1D and 2D inversions for structural models. The example over the Hides anticline illustrates a situation where 1D inversion of either TE or TM mode provides essentially the same depth to base of Darai as 2D inversion of both TE and TM. The example over the Angore anticline illustrates the inadequacy of 1D inversion in structurally complex geology complicated by electrical statics. Four MT lines along the Angore anticline have been interpreted using 2D inversion. Three-dimensional modelling has been used to simulate 3D statics in an otherwise 2D earth. These data were used to test the Groom-Bailey (GB) decomposition for possible benefits in reducing static effects and estimating geoelectric strike in the Papua New Guinea (PNG) field data. It has been found that the GB decomposition can provide improved regional 2D strike estimates in 3D contaminated data. However, in situations such as PNG, where the regional 2D strike is well established and hence can be fixed, the GB decomposition provides apparent resistivities identical to those simply rotated to strike.« less

  13. 2. View from the roof of the M.T. Marcello Company ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. View from the roof of the M.T. Marcello Company building, facing northwest, with a detail of the refrigeration compressors. - M. T. Marcello Company Building, 105 Harris Avenue, Providence, Providence County, RI

  14. Fungi of Mt. Babia Gora. 2: Indicative value of macromycetes in forest associations. A: Initial considerations

    NASA Technical Reports Server (NTRS)

    Bujakiewicz, A.

    1984-01-01

    The role and value of fungi in forest associations of Mt. Babia Gora massif were determined. The general physiographic characteristics of the research terrain, the distribution of the fungi sites, a list of the 618 taxons noted in the subalpine forests of Mt. Babia Gora, and the initial characteristics of the forest mycoflora of this massif are presented.

  15. Quantitative two-dimensional ultrashort echo time magnetization transfer (2D UTE-MT) imaging of cortical bone.

    PubMed

    Ma, Ya-Jun; Tadros, Anthony; Du, Jiang; Chang, Eric Y

    2018-04-01

    To investigate quantitative 2D ultrashort echo time magnetization transfer (UTE-MT) imaging in ex vivo bovine cortical bone and in vivo human tibial cortical bone. Data were acquired from five fresh bovine cortical bone samples and five healthy volunteer tibial cortical bones using a 2D UTE-MT sequence on a clinical 3T scanner. The 2D UTE-MT sequence used four or five MT powers with five frequency offsets. Results were analyzed with a two-pool quantitative MT model, providing measurements of macromolecular fraction (f), macromolecular proton transverse relaxation times (T 2m ), proton exchange rates from water/macromolecular to the macromolecular/water pool (RM 0m /RM 0w ), and spin-lattice relaxation rate of water pool (R 1w ). A sequential air-drying study for a small bovine cortical bone chip was used to investigate whether above MT modeling parameters were sensitive to the water loss. Mean fresh bovine cortical bone values for f, T 2m , R 1w , RM 0m , and RM 0w were 59.9 ± 7.3%, 14.6 ± 0.3 μs, 9.9 ± 2.4 s -1 , 17.9 ± 3.6 s -1 , and 11.8 ± 2.0 s -1 , respectively. Mean in vivo human cortical bone values for f, T 2m , R 1w , RM 0m and RM 0w were 54.5 ± 4.9%, 15.4 ± 0.6 μs, 8.9 ± 1.1 s -1 , 11.5 ± 3.5 s -1 , and 9.5 ± 1.9 s -1 , respectively. The sequential air-drying study shows that f, RM 0m , and R 1w were increased with longer drying time. UTE-MT two-pool modeling provides novel and useful quantitative information for cortical bone. Magn Reson Med 79:1941-1949, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  16. Bayesian resolution of TEM, CSEM and MT soundings: a comparative study

    NASA Astrophysics Data System (ADS)

    Blatter, D. B.; Ray, A.; Key, K.

    2017-12-01

    We examine the resolution of three electromagnetic exploration methods commonly used to map the electrical conductivity of the shallow crust - the magnetotelluric (MT) method, the controlled-source electromagnetic (CSEM) method and the transient electromagnetic (TEM) method. TEM and CSEM utilize an artificial source of EM energy, while MT makes use of natural variations in the Earth's electromagnetic field. For a given geological setting and acquisition parameters, each of these methods will have a different resolution due to differences in the source field polarization and the frequency range of the measurements. For example, the MT and TEM methods primarily rely on induced horizontal currents and are most sensitive to conductive layers while the CSEM method generates vertical loops of current and is more sensitive to resistive features. Our study seeks to provide a robust resolution comparison that can help inform exploration geophysicists about which technique is best suited for a particular target. While it is possible to understand and describe a difference in resolution qualitatively, it remains challenging to fully describe it quantitatively using optimization based approaches. Part of the difficulty here stems from the standard electromagnetic inversion toolkit, which makes heavy use of regularization (often in the form of smoothing) to constrain the non-uniqueness inherent in the inverse problem. This regularization makes it difficult to accurately estimate the uncertainty in estimated model parameters - and therefore obscures their true resolution. To overcome this difficulty, we compare the resolution of CSEM, airborne TEM, and MT data quantitatively using a Bayesian trans-dimensional Markov chain Monte Carlo (McMC) inversion scheme. Noisy synthetic data for this study are computed from various representative 1D test models: a conductive anomaly under a conductive/resistive overburden; and a resistive anomaly under a conductive/resistive overburden. In

  17. Study on shearing force and impact force of a volcanic mud flow on Mt. Sakurajima

    Treesearch

    Yoshinobu Taniguchi

    1991-01-01

    Two kinds of shearing stress meters (type A and type B) were set on the channel bottom in the Arimura River and the Mochiki River on Mt. Sakurajima. Volcanic mud flows take place there about 100 times a year. The results of the surveys demonstrated that the actual shearing force of a volcanic mud flow on Mt. Sakurajima was from 0.46 to 2.50 kgf/cm2...

  18. MT6415CA: a 640×512-15µm CTIA ROIC for SWIR InGaAs detector arrays

    NASA Astrophysics Data System (ADS)

    Eminoglu, Selim; Isikhan, Murat; Bayhan, Nusret; Gulden, M. Ali; Incedere, O. Samet; Soyer, S. Tuncer; Kocak, Serhat; Yilmaz, Gokhan S.; Akin, Tayfun

    2013-06-01

    This paper reports the development of a new low-noise CTIA ROIC (MT6415CA) suitable for SWIR InGaAs detector arrays for low-light imaging applications. MT6415CA is the second product in the MT6400 series ROICs from Mikro-Tasarim Ltd., which is a fabless IC design house specialized in the development of monolithic imaging sensors and ROICs for hybrid imaging sensors. MT6415CA is a low-noise snapshot CTIA ROIC, has a format of 640 × 512 and pixel pitch of 15 µm, and has been developed with the system-on-chip architecture in mind, where all the timing and biasing for this ROIC are generated on-chip without requiring any external inputs. MT6415CA is a highly configurable ROIC, where many of its features can be programmed through a 3-wire serial interface allowing on-the-fly configuration of many ROIC features. It performs snapshot operation both using Integrate-Then-Read (ITR) and Integrate-While-Read (IWR) modes. The CTIA type pixel input circuitry has three gain modes with programmable full-well-capacity (FWC) values of 10.000 e-, 20.000 e-, and 350.000 e- in the very high gain (VHG), high-gain (HG), and low-gain (LG) modes, respectively. MT6415CA has an input referred noise level of less than 5 e- in the very high gain (VHG) mode, suitable for very low-noise SWIR imaging applications. MT6415CA has 8 analog video outputs that can be programmed in 8, 4, or 2-output modes with a selectable analog reference for pseudo-differential operation. The ROIC runs at 10 MHz and supports frame rate values up to 200 fps in the 8-output mode. The integration time can be programmed up to 1s in steps of 0.1 µs. The ROIC uses 3.3 V and 1.8V supply voltages and dissipates less than 150 mW in the 4-output mode. MT6415CA is fabricated using a modern mixed-signal CMOS process on 200 mm CMOS wafers, and tested parts are available at wafer or die levels with test reports and wafer maps. A compact USB 3.0 camera and imaging software have been developed to demonstrate the imaging

  19. Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model.

    PubMed

    Yao, Xiao; Carlson, Deborah; Sun, Yuxiao; Ma, Lisha; Wolf, Steven E; Minei, Joseph P; Zang, Qun S

    2015-01-01

    We have previously shown that mitochondria-targeted vitamin E (Mito-Vit-E), a mtROS specific antioxidant, improves cardiac performance and attenuates inflammation in a pneumonia-related sepsis model. In this study, we applied the same approaches to decipher the signaling pathway(s) of mtROS-dependent cardiac inflammation after sepsis. Sepsis was induced in Sprague Dawley rats by intratracheal injection of S. pneumoniae. Mito-Vit-E, vitamin E or vehicle was administered 30 minutes later. In myocardium 24 hours post-inoculation, Mito-Vit-E, but not vitamin E, significantly protected mtDNA integrity and decreased mtDNA damage. Mito-Vit-E alleviated sepsis-induced reduction in mitochondria-localized DNA repair enzymes including DNA polymerase γ, AP endonuclease, 8-oxoguanine glycosylase, and uracil-DNA glycosylase. Mito-Vit-E dramatically improved metabolism and membrane integrity in mitochondria, suppressed leakage of mtDNA into the cytoplasm, inhibited up-regulation of Toll-like receptor 9 (TLR9) pathway factors MYD88 and RAGE, and limited RAGE interaction with its ligand TFAM in septic hearts. Mito-Vit-E also deactivated NF-κB and caspase 1, reduced expression of the essential inflammasome component ASC, and decreased inflammatory cytokine IL-1β. In vitro, both Mito-Vit-E and TLR9 inhibitor OND-I suppressed LPS-induced up-regulation in MYD88, RAGE, ASC, active caspase 1, and IL-1β in cardiomyocytes. Since free mtDNA escaped from damaged mitochondria function as a type of DAMPs to stimulate inflammation through TLR9, these data together suggest that sepsis-induced cardiac inflammation is mediated, at least partially, through mtDNA-TLR9-RAGE. At last, Mito-Vit-E reduced the circulation of myocardial injury marker troponin-I, diminished apoptosis and amended morphology in septic hearts, suggesting that mitochondria-targeted antioxidants are a potential cardioprotective approach for sepsis.

  20. Differences in the epigenetic regulation of MT-3 gene expression between parental and Cd+2 or As+3 transformed human urothelial cells

    PubMed Central

    2011-01-01

    Background Studies have shown that metallothionein 3 (MT-3) is not expressed in normal urothelium or in the UROtsa cell line, but is expressed in urothelial cancer and in tumors generated from the UROtsa cells that have been transformed by cadmium (Cd+2) or arsenite (As+3).The present study had two major goals. One, to determine if epigenetic modifications control urothelial MT-3 gene expression and if regulation is altered by malignant transformation by Cd+2 or As+3. Two, to determine if MT-3 expression might translate clinically as a biomarker for malignant urothelial cells released into the urine. Results The histone deacetylase inhibitor MS-275 induced MT-3 mRNA expression in both parental UROtsa cells and their transformed counterparts. The demethylating agent, 5-Aza-2'-deoxycytidine (5-AZC) had no effect on MT-3 mRNA expression. ChIP analysis showed that metal-responsive transformation factor-1 (MTF-1) binding to metal response elements (MRE) elements of the MT-3 promoter was restricted in parental UROtsa cells, but MTF-1 binding to the MREs was unrestricted in the transformed cell lines. Histone modifications at acetyl H4, trimethyl H3K4, trimethyl H3K27, and trimethyl H3K9 were compared between the parental and transformed cell lines in the presence and absence of MS-275. The pattern of histone modifications suggested that the MT-3 promoter in the Cd+2 and As+3 transformed cells has gained bivalent chromatin structure, having elements of being "transcriptionally repressed" and "transcription ready", when compared to parental cells. An analysis of MT-3 staining in urinary cytologies showed that a subset of both active and non-active patients with urothelial cancer shed positive cells in their urine, but that control patients only rarely shed MT-3 positive cells. Conclusion The MT-3 gene is silenced in non-transformed urothelial cells by a mechanism involving histone modification of the MT-3 promoter. In contrast, transformation of the urothelial cells with

  1. Challenging the Metallothionein (MT) Gene of Biomphalaria glabrata: Unexpected Response Patterns Due to Cadmium Exposure and Temperature Stress.

    PubMed

    Niederwanger, Michael; Dvorak, Martin; Schnegg, Raimund; Pedrini-Martha, Veronika; Bacher, Katharina; Bidoli, Massimo; Dallinger, Reinhard

    2017-08-11

    Metallothioneins (MTs) are low-molecular-mass, cysteine-rich, metal binding proteins. In most animal species, they are involved in metal homeostasis and detoxification, and provide protection from oxidative stress. Gastropod MTs are highly diversified, exhibiting unique features and adaptations like metal specificity and multiplications of their metal binding domains. Here, we show that the MT gene of Biomphalaria glabrata , one of the largest MT genes identified so far, is composed in a unique way. The encoding for an MT protein has a three-domain structure and a C-terminal, Cys-rich extension. Using a bioinformatic approach involving structural and in silico analysis of putative transcription factor binding sites (TFBs), we found that this MT gene consists of five exons and four introns. It exhibits a regulatory promoter region containing three metal-responsive elements (MREs) and several TFBs with putative involvement in environmental stress response, and regulation of gene expression. Quantitative real-time polymerase chain reaction (qRT-PCR) data indicate that the MT gene is not inducible by cadmium (Cd) nor by temperature challenges (heat and cold), despite significant Cd uptake within the midgut gland and the high Cd tolerance of metal-exposed snails.

  2. Challenging the Metallothionein (MT) Gene of Biomphalaria glabrata: Unexpected Response Patterns Due to Cadmium Exposure and Temperature Stress

    PubMed Central

    Dvorak, Martin; Schnegg, Raimund; Pedrini-Martha, Veronika; Bacher, Katharina; Bidoli, Massimo; Dallinger, Reinhard

    2017-01-01

    Metallothioneins (MTs) are low-molecular-mass, cysteine-rich, metal binding proteins. In most animal species, they are involved in metal homeostasis and detoxification, and provide protection from oxidative stress. Gastropod MTs are highly diversified, exhibiting unique features and adaptations like metal specificity and multiplications of their metal binding domains. Here, we show that the MT gene of Biomphalaria glabrata, one of the largest MT genes identified so far, is composed in a unique way. The encoding for an MT protein has a three-domain structure and a C-terminal, Cys-rich extension. Using a bioinformatic approach involving structural and in silico analysis of putative transcription factor binding sites (TFBs), we found that this MT gene consists of five exons and four introns. It exhibits a regulatory promoter region containing three metal-responsive elements (MREs) and several TFBs with putative involvement in environmental stress response, and regulation of gene expression. Quantitative real-time polymerase chain reaction (qRT-PCR) data indicate that the MT gene is not inducible by cadmium (Cd) nor by temperature challenges (heat and cold), despite significant Cd uptake within the midgut gland and the high Cd tolerance of metal-exposed snails. PMID:28800079

  3. New stratigraphic constraints on Holocene glacier advances at Mt. Baker, Washington

    NASA Astrophysics Data System (ADS)

    Clark, D.; Ryane, C.; Tucker, D.; Davis, T.; Bowerman, N.; Osborn, G.; Clague, J.; Menounos, B.; Scott, K.; Guilderson, T.; Riedel, J.; Steig, E.

    2007-12-01

    New data from a lake sediment core and moraine exposures at Mt. Baker, WA, indicate that a purported early Holocene glacier advance occurred earlier, likely at the end of the Pleistocene. Previous workers used 14C ages associated with small cirque moraines on the SW flank of Mt. Baker, along with the apparent absence of a distinctive scoria (set SC; 8850 14C yr BP, ~9900 cal yr BP) from other moraines on Mt. Baker, as evidence for an advance at ~8400 14C yr BP (~9450 cal yr BP). Such an advance is important to test because it would contrast with glacial records throughout most of the rest of western North America. A 1.2-m sediment core collected from Pocket Lake, which is dammed by one of the previously dated cirque moraines, contains three tephras: Baker set BA (~5800 14C yr BP; 6600 cal yr BP), Mazama ash (6800 14C yr BP; 7600 cal yr BP), and a basal set of ash beds that are tentatively identified as Baker set SC. The lowest macrofossil in the core, ~2 cm above the top of the basal ash beds, yielded an age of 7640 ± 50 14C yr BP (~8400 cal yr BP), consistent with the tephra being SC. Initial geochemical analyses of the tephra also support this identification. These findings indicate that the previous age on the cirque moraine, from organics near the surface of the till, provides a minimum rather than a direct age for the advance that formed the moraine. A 14C age of 11,400 ± 110 14C yr BP (~13,300 cal yr BP) on bulk sediments below the basal ash is likely contaminated and therefore too old. Tephra overlying other ridges at Mt. Baker that were previously identified as post-SC, early-Holocene moraines has been identified as set SC. The ridges thus are actually pre-SC rather than post-SC in age; they may not be moraines in any event. Meanwhile, abundant 14C ages on tills below Deming Glacier indicate both Younger Dryas and Neoglacial advances, but no early Holocene advances. Together, these observations indicate that glaciers in the Mt. Baker area advanced during

  4. Joint TEM and MT aquifer study in the Atacama Desert, North Chile

    NASA Astrophysics Data System (ADS)

    Ruthsatz, Alexander D.; Sarmiento Flores, Alvaro; Diaz, Daniel; Reinoso, Pablo Salazar; Herrera, Cristian; Brasse, Heinrich

    2018-06-01

    The Atacama Desert represents one of the driest regions on earth, and despite the absence of sustainable clean water reserves the demand has increased drastically since 1970 as a result of growing population and expanding mining activities. Magnetotelluric (MT) and Transient Electromagnetic (TEM) measurements were carried out for groundwater exploration in late 2015 in the area of the Profeta Basin at the western margin of the Chilean Precordillera. Both methods complement each other: While MT in general attains larger penetration depths, TEM allows better resolution of near surface layers; furthermore TEM is free from galvanic distortion. Data were collected along three profiles, enabling a continuous resistivity image from the surface to at least several hundred meters depth. TEM data were inverted in a 1-D manner, consistently yielding a poorly conductive near-surface layer with a thickness of approximately 30 m and below a well-conducting layer which we interpret as the aquifer with resistivities around 10 Ωm. At marginal sites of the main SW-NE-profile the resistive basement was found in 150 m. These depths are confirmed by interpretation of the MT soundings. Those were firstly inverted with a 2-D approach and then by 3-D inversion as clear indications of three-dimensionality exist. Several modeling runs were performed with different combinations of transfer functions and smoothing parameters. Generally, MT and TEM results agree reasonably well and an overall image of the resistivity structures in the Profeta Basin could be achieved. The aquifer reaches depths of more than 500 m in parts and, by applying Archie's law, resistivities of 1 Ωm can be assumed, indicating highly saline fluids from the source region of the surrounding high Andes under persisting arid conditions.

  5. mtDNA and Y-chromosome polymorphisms in four Native American populations from southern Mexico.

    PubMed Central

    Torroni, A.; Chen, Y. S.; Semino, O.; Santachiara-Beneceretti, A. S.; Scott, C. R.; Lott, M. T.; Winter, M.; Wallace, D. C.

    1994-01-01

    mtDNA sequence variation was examined in 60 Native Americans (Mixtecs from the Alta, Mixtecs from the Baja, Valley Zapotecs, and Highland Mixe) from southern Mexico by PCR amplification and high-resolution restriction endonuclease analysis. Four groups of mtDNA haplotypes (haplogroups A, B, C, and D) characterize Amerind populations, but only three (haplogroups A, B, and C) were observed in these Mexican populations. The comparison of their mtDNA variation with that observed in other populations from Mexico and Central America permits a clear distinction among the different Middle American tribes and raises questions about some of their linguistic affiliations. The males of these population samples were also analyzed for Y-chromosome RFLPs with the probes 49a, 49f, and 12f2. This analysis suggests that certain Y-chromosome haplotypes were brought from Asia during the colonization of the Americas, and a differential gene flow was introduced into Native American populations from European males and females. Images Figure 4 PMID:8304347

  6. Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: new evidence for panselective evolution.

    PubMed

    Valenzuela, Carlos Y

    2010-01-01

    Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA), the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9) was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.

  7. Human area MT+ shows load-dependent activation during working memory maintenance with continuously morphing stimulation.

    PubMed

    Galashan, Daniela; Fehr, Thorsten; Kreiter, Andreas K; Herrmann, Manfred

    2014-07-11

    Initially, human area MT+ was considered a visual area solely processing motion information but further research has shown that it is also involved in various different cognitive operations, such as working memory tasks requiring motion-related information to be maintained or cognitive tasks with implied or expected motion.In the present fMRI study in humans, we focused on MT+ modulation during working memory maintenance using a dynamic shape-tracking working memory task with no motion-related working memory content. Working memory load was systematically varied using complex and simple stimulus material and parametrically increasing retention periods. Activation patterns for the difference between retention of complex and simple memorized stimuli were examined in order to preclude that the reported effects are caused by differences in retrieval. Conjunction analysis over all delay durations for the maintenance of complex versus simple stimuli demonstrated a wide-spread activation pattern. Percent signal change (PSC) in area MT+ revealed a pattern with higher values for the maintenance of complex shapes compared to the retention of a simple circle and with higher values for increasing delay durations. The present data extend previous knowledge by demonstrating that visual area MT+ presents a brain activity pattern usually found in brain regions that are actively involved in working memory maintenance.

  8. Design, synthesis and evaluation of photoactivatable derivatives of microtubule (MT)-active [1,2,4]triazolo[1,5-a]pyrimidines.

    PubMed

    Oukoloff, Killian; Kovalevich, Jane; Cornec, Anne-Sophie; Yao, Yuemang; Owyang, Zachary A; James, Michael; Trojanowski, John Q; Lee, Virginia M-Y; Smith, Amos B; Brunden, Kurt R; Ballatore, Carlo

    2018-05-05

    The [1,2,4]triazolo[1,5-a]pyrimidines comprise a promising class of non-naturally occurring microtubule (MT)-active compounds. Prior studies revealed that different triazolopyrimidine substitutions can yield molecules that either promote MT stabilization or disrupt MT integrity. These differences can have important ramifications in the therapeutic applications of triazolopyrimidines and suggest that different analogues may exhibit different binding modes within the same site or possibly interact with tubulin/MTs at alternative binding sites. To help discern these possibilities, a series of photoactivatable triazolopyrimidine congeners was designed, synthesized and evaluated in cellular assays with the goal of identifying candidate probes for photoaffinity labeling experiments. These studies led to the identification of different derivatives that incorporate a diazirine ring in the amine substituent at position 7 of the triazolopyrimidine heterocycle, resulting in molecules that either promote stabilization of MTs or disrupt MT integrity. These photoactivatable candidate probes hold promise to investigate the mode of action of MT-active triazolopyrimidines. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh.

    PubMed

    Rodrigues, Ema G; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C

    2012-05-01

    We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

  10. Surveyor nuclease detection of mutations and polymorphisms of mtDNA in children.

    PubMed

    Pilch, Jacek; Asman, Marek; Jamroz, Ewa; Kajor, Maciej; Kotrys-Puchalska, Elżbieta; Goss, Małgorzata; Krzak, Maria; Witecka, Joanna; Gmiński, Jan; Sieroń, Aleksander L

    2010-11-01

    Mitochondrial encephalomyopathies are complex disorders with wide range of clinical manifestations. Particularly time-consuming is the identification of mutations in mitochondrial DNA. A group of 20 children with clinical manifestations of mitochondrial encephalomyopathies was selected for molecular studies. The aims were (a) to identify mutations in mtDNA isolated from muscle and (b) to verify detected mutations in DNA isolated from blood, in order to assess the utility of a Surveyor nuclease assay kit for patient screening. The most common changes found were polymorphisms, including a few missense mutations altering the amino acid sequence of mitochondrial proteins. In two boys with MELAS (i.e., mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), a mutation A→G3243 was detected in the tRNALeu gene of mtDNA isolated from muscle and blood. In one boy, the carrier status of his mother was confirmed, based on molecular analysis of DNA isolated from blood. A method using Surveyor nuclease allows systematic screening for small mutations in mtDNA, using as its source blood of the patients and asymptomatic carriers. The method still requires confirmation studying a larger group. In some patients, the use of this method should precede and might limit indications for traumatic muscle and skin biopsy. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Toward a mtDNA locus-specific mutation database using the LOVD platform.

    PubMed

    Elson, Joanna L; Sweeney, Mary G; Procaccio, Vincent; Yarham, John W; Salas, Antonio; Kong, Qing-Peng; van der Westhuizen, Francois H; Pitceathly, Robert D S; Thorburn, David R; Lott, Marie T; Wallace, Douglas C; Taylor, Robert W; McFarland, Robert

    2012-09-01

    The Human Variome Project (HVP) is a global effort to collect and curate all human genetic variation affecting health. Mutations of mitochondrial DNA (mtDNA) are an important cause of neurogenetic disease in humans; however, identification of the pathogenic mutations responsible can be problematic. In this article, we provide explanations as to why and suggest how such difficulties might be overcome. We put forward a case in support of a new Locus Specific Mutation Database (LSDB) implemented using the Leiden Open-source Variation Database (LOVD) system that will not only list primary mutations, but also present the evidence supporting their role in disease. Critically, we feel that this new database should have the capacity to store information on the observed phenotypes alongside the genetic variation, thereby facilitating our understanding of the complex and variable presentation of mtDNA disease. LOVD supports fast queries of both seen and hidden data and allows storage of sequence variants from high-throughput sequence analysis. The LOVD platform will allow construction of a secure mtDNA database; one that can fully utilize currently available data, as well as that being generated by high-throughput sequencing, to link genotype with phenotype enhancing our understanding of mitochondrial disease, with a view to providing better prognostic information. © 2012 Wiley Periodicals, Inc.

  12. Toward a mtDNA Locus-Specific Mutation Database Using the LOVD Platform

    PubMed Central

    Elson, Joanna L.; Sweeney, Mary G.; Procaccio, Vincent; Yarham, John W.; Salas, Antonio; Kong, Qing-Peng; van der Westhuizen, Francois H.; Pitceathly, Robert D.S.; Thorburn, David R.; Lott, Marie T.; Wallace, Douglas C.; Taylor, Robert W.; McFarland, Robert

    2015-01-01

    The Human Variome Project (HVP) is a global effort to collect and curate all human genetic variation affecting health. Mutations of mitochondrial DNA (mtDNA) are an important cause of neurogenetic disease in humans; however, identification of the pathogenic mutations responsible can be problematic. In this article, we provide explanations as to why and suggest how such difficulties might be overcome. We put forward a case in support of a new Locus Specific Mutation Database (LSDB) implemented using the Leiden Open-source Variation Database (LOVD) system that will not only list primary mutations, but also present the evidence supporting their role in disease. Critically, we feel that this new database should have the capacity to store information on the observed phenotypes alongside the genetic variation, thereby facilitating our understanding of the complex and variable presentation of mtDNA disease. LOVD supports fast queries of both seen and hidden data and allows storage of sequence variants from high-throughput sequence analysis. The LOVD platform will allow construction of a secure mtDNA database; one that can fully utilize currently available data, as well as that being generated by high-throughput sequencing, to link genotype with phenotype enhancing our understanding of mitochondrial disease, with a view to providing better prognostic information. PMID:22581690

  13. 78 FR 67024 - Establishment of Class E Airspace; Glasgow, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... aid, Glasgow, MT. A favorable comment from the National Business Aviation Association (NBAA) was.... SUPPLEMENTARY INFORMATION: History The FAA published a final rule in the Federal Register establishing Class E..., pursuant to the authority delegated to me, the description under the History heading, as published in the...

  14. 77 FR 41259 - Modification of Class E Airspace; Plentywood, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... Plentywood Sher-Wood Airport, Plentywood, MT. Controlled airspace is necessary to accommodate aircraft using... Plentywood Sher-Wood Airport. This improves the safety and management of Instrument Flight Rules (IFR... modifying Class E airspace extending upward from 700 feet above the surface at Plentywood Sher-Wood Airport...

  15. Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice.

    PubMed

    Shimizu, Akinori; Tani, Haruna; Takibuchi, Gaku; Ishikawa, Kaori; Sakurazawa, Ryota; Inoue, Takafumi; Hashimoto, Tetsuo; Nakada, Kazuto; Takenaga, Keizo; Hayashi, Jun-Ichi

    2017-11-04

    In a previous study, we generated transmitochondrial P29mtSAMP1 cybrids, which had nuclear DNA from the C57BL6 (referred to as B6) mouse strain-derived P29 tumor cells and mitochondrial DNA (mtDNA) exogenously-transferred from the allogeneic strain SAMP1. Because P29mtSAMP1 cybrids did not form tumors in syngeneic B6 mice, we proposed that allogeneic SAMP1 mtDNA suppressed tumor formation of P29mtSAMP1 cybrids. To test this hypothesis, current study generated P29mt(sp)B6 cybrids carrying all genomes (nuclear DNA and mtDNA) from syngeneic B6 mice by eliminating SAMP1 mtDNA from P29mtSAMP1 cybrids and reintroducing B6 mtDNA. However, the P29mt(sp)B6 cybrids did not form tumors in B6 mice, even though they had no SAMP1 mtDNA, suggesting that SAMP1 mtDNA is not involved in tumor suppression. Then, we examined another possibility of whether SAMP1 mtDNA fragments potentially integrated into the nuclear DNA of P29mtSAMP1 cybrids are responsible for tumor suppression. We generated P29 H (sp)B6 cybrids by eliminating nuclear DNA from P29mt(sp)B6 cybrids and reintroducing nuclear DNA with no integrated SAMP1 mtDNA fragment from mtDNA-less P29 cells resistant to hygromycin in selection medium containing hygromycin. However, the P29 H (sp)B6 cybrids did not form tumors in B6 mice, even though they carried neither SAMP1 mtDNA nor nuclear DNA with integrated SAMP1 mtDNA fragments. Moreover, overproduction of reactive oxygen species (ROS) and bacterial infection were not involved in tumor suppression. These observations suggest that tumor suppression was caused not by mtDNA with polymorphic mutations or infection of cytozoic bacteria but by hypothetical heritable cytoplasmic elements other than mtDNA from SAMP1 mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Mt. Etna Eruption

    NASA Technical Reports Server (NTRS)

    2002-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] Figure 1: Vis/NIR Image CloseupFigure 2: Difference Image

    October 2002 Mt. Etna, a volcano on the island of Sicily, erupted on October 26, 2002. Preliminary analysis of data taken by the Atmospheric Infrared Sounder (AIRS) on NASA's Aqua satellite on October 28 shows the instrument can provide an excellent means to study the evolution and structure of the sulfur dioxide (SO2) plume emitted from volcanoes. These data also demonstrate that AIRS can be used to obtain the total mass of SO2 injected into the atmosphere during a volcanic event, information that may help us to better understand these dangerous natural occurrences in the future.

    This image was made from a sensor on the AIRS instrument that is sensitive to the visible and near-infrared portions of the spectrum. The visible/near infrared data show the smoke plume from Mt. Etna. The view is of Europe and the central Mediterranean with Italy in the center. Since the visible/near infrared sensor on AIRS is sensitive to wavelengths that are different than the human eye, vegetated regions appear red (compare the red color of Europe with the tan desert of North Africa in the lower left). Figure 1 is a closer view of Sicily and shows a long, brownish smoke plume extending across the Mediterranean to Africa. This is consistent with the enhanced feature in the difference image in Figure 2 and helps validate the information inferred from that image.

    Figure 2 clearly shows the SO2 plume. This image was created by comparing data taken at two different frequencies, or channels, and creating one image that highlights the differences between these two channels. Both channels are sensitive to water vapor, but one of the channels is also sensitive to SO2. By subtracting out the common water vapor signal in both channels, the SO2 feature remains and shows up as an enhancement in the difference image.

    The

  17. Using geochemistry as a tool for correlating proximal andesitic tephra: Case studies from Mt Rainier (USA) and Mt Ruapehu (New Zealand)

    USGS Publications Warehouse

    Donoghue, S.L.; Vallance, J.; Smith, I.E.M.; Stewart, R.B.

    2007-01-01

    Volcanic hazards assessments at andesite stratovolcanoes rely on the assessment of frequency and magnitude of past events. The identification and correlation of proximal and distal andesitic tephra, which record the explosive eruptive history, are integral to such assessments. These tephra are potentially valuable stratigraphic marker beds useful to the temporal correlation and age dating of Quaternary volcanic, volcaniclastic and epiclastic sedimentary deposits with which they are interbedded. At Mt Ruapehu (New Zealand) and Mt Rainier (USA), much of the detail of the recent volcanic record remains unresolved because of the difficulty in identifying proximal tephra. This study investigates the value of geochemical methods in discriminating andesitic tephra. Our dataset comprises petrological and geochemical analyses of tephra that span the late Quaternary eruptive record of each volcano. Our data illustrate that andesitic tephra are remarkably heterogeneous in composition. Tephra compositions fluctuate widely over short time intervals, and there are no simple or systematic temporal trends in geochemistry within either eruptive record. This complexity in tephra geochemistry limits the application of geochemical approaches to tephrostratigraphic studies, beyond a general characterisation useful to provenance assignation. Petrological and geochemical data suggest that the products of andesite systems are inherently variable and therefore intractable to discrimination by simple geochemical methods alone. Copyright ?? 2006 John Wiley & Sons, Ltd.

  18. Comparison of Human Immunodeficiency Virus Type 1 Tropism Profiles in Clinical Samples by the Trofile and MT-2 Assays▿

    PubMed Central

    Coakley, Eoin; Reeves, Jacqueline D.; Huang, Wei; Mangas-Ruiz, Marga; Maurer, Irma; Harskamp, Agnes M.; Gupta, Soumi; Lie, Yolanda; Petropoulos, Christos J.; Schuitemaker, Hanneke; van 't Wout, Angélique B.

    2009-01-01

    The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most widely used to define tropism in the clinic prior to the use of a CCR5 antagonist. By comparison, the MT-2 assay has been used since early in the HIV epidemic to define tropism in clinical specimens. Given that there are few data from direct comparisons of these two assays, we evaluated the performance of the plasma-based Trofile assay and the peripheral blood mononuclear cell (PBMC)-based MT-2 assay for the detection of CXCR4 use in defining the tropism of HIV isolates derived from clinical samples. The various samples used for this comparison were derived from participants of the Amsterdam Cohort Studies on HIV infection and AIDS who underwent consecutive MT-2 assay testing of their PBMCs at approximately 3-month intervals. This unique sample set was specifically selected because consecutive MT-2 assays had demonstrated a shift from negative to positive in PBMCs, reflecting the first emergence of CXCR4-using virus in PBMCs above the level of detection of the assay in these individuals. Trofile testing was performed with clonal HIV type 1 (HIV-1) variants (n = 21), MT-2 cell culture-derived cells (n = 20) and supernatants (n = 42), and plasma samples (n = 76). Among the clonal HIV-1 variants and MT-2 cell culture-derived samples, the results of the Trofile and MT-2 assays demonstrated a high degree of concordance (95% to 98%). Among consecutive plasma samples, detection of CXCR4-using virus was at or before the time of first detection by the MT-2 assay in 5/10 patients by the original Trofile assay and in 9/10 patients by the enhanced-sensitivity Trofile assay. Differences in the time to the first detection of CXCR4 use between the MT-2 assay (PBMCs

  19. Comparison of human immunodeficiency virus type 1 tropism profiles in clinical samples by the Trofile and MT-2 assays.

    PubMed

    Coakley, Eoin; Reeves, Jacqueline D; Huang, Wei; Mangas-Ruiz, Marga; Maurer, Irma; Harskamp, Agnes M; Gupta, Soumi; Lie, Yolanda; Petropoulos, Christos J; Schuitemaker, Hanneke; van 't Wout, Angélique B

    2009-11-01

    The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most widely used to define tropism in the clinic prior to the use of a CCR5 antagonist. By comparison, the MT-2 assay has been used since early in the HIV epidemic to define tropism in clinical specimens. Given that there are few data from direct comparisons of these two assays, we evaluated the performance of the plasma-based Trofile assay and the peripheral blood mononuclear cell (PBMC)-based MT-2 assay for the detection of CXCR4 use in defining the tropism of HIV isolates derived from clinical samples. The various samples used for this comparison were derived from participants of the Amsterdam Cohort Studies on HIV infection and AIDS who underwent consecutive MT-2 assay testing of their PBMCs at approximately 3-month intervals. This unique sample set was specifically selected because consecutive MT-2 assays had demonstrated a shift from negative to positive in PBMCs, reflecting the first emergence of CXCR4-using virus in PBMCs above the level of detection of the assay in these individuals. Trofile testing was performed with clonal HIV type 1 (HIV-1) variants (n = 21), MT-2 cell culture-derived cells (n = 20) and supernatants (n = 42), and plasma samples (n = 76). Among the clonal HIV-1 variants and MT-2 cell culture-derived samples, the results of the Trofile and MT-2 assays demonstrated a high degree of concordance (95% to 98%). Among consecutive plasma samples, detection of CXCR4-using virus was at or before the time of first detection by the MT-2 assay in 5/10 patients by the original Trofile assay and in 9/10 patients by the enhanced-sensitivity Trofile assay. Differences in the time to the first detection of CXCR4 use between the MT-2 assay (PBMCs

  20. The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

    PubMed Central

    Schneider, H C; Westermann, B; Neupert, W; Brunner, M

    1996-01-01

    Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

  1. Paleographic and sedimentologic significance of Mississippian sequence at Mt. Darby, Wyoming

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dejarnett, J.

    1985-05-01

    Mississippian strata at Mt. Darby comprise the Madison Group and the overlying Humbug Formation. This sequence, although initially transgressive, exhibits an overall regressive character produced by progradation of platform carbonates in response to sea level fluctuations related to Antler orogenic events. The Paine Member of the Lodgepole Limestone, the basal formation of the Madison Group, consists of relatively deep-water carbonates including a possible Waulsortian-type carbonate bank that accumulated on a Kinderhookian foreslope. At least five shoaling-upward grainstone cycles are recognizable in the Woodhurst Member of the Lodgepole Limestone. These cycles record Osagean deposition in shallow agitated environments that developed highmore » on a clinoform ramp. Shelf-margin and platform carbonates dominate the Mission Canyon Limestone, the upper formation of the Madison Group. this unit consists of two asymmetric deposition cycles, each with a thick regressive phase, capped by an evaporite solution breccia and an overlying thin transgressive phase. The Humbug Formation, a sequence of fine-grained carbonates and sandstones, represents part of a deltaic complex that developed offshore from the Meramecian karst plain. Humbug sediments were transported northward to the Mt. Darby area from the area of the present Uinta Mountains, or another deltaic system formed there. Deposition in the study area was apparently continuous upward from the Madison carbonates into the Humbug. The middle Meramecian shoreline trended northwest between the present locations of Mt. Darby and Haystack Peak.« less

  2. 77 FR 32896 - Modification of Class E Airspace; Billings, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-04

    ...-0316; Airspace Docket No. 12-ANM-1] Modification of Class E Airspace; Billings, MT AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action modifies Class E airspace at... were received. Class E airspace designations are published in paragraph 6005, of FAA Order 7400.9V...

  3. Insights into the Functions of M-T Hook Structure in HIV Fusion Inhibitor Using Molecular Modeling.

    PubMed

    Tan, Jianjun; Yuan, Hongling; Li, Chunhua; Zhang, Xiaoyi; Wang, Cunxin

    2016-04-01

    HIV-1 membrane fusion plays an important role in the process that HIV-1 entries host cells. As a treatment strategy targeting HIV-1 entry process, fusion inhibitors have been proposed. Nevertheless, development of a short peptide possessing high anti-HIV potency is considered a daunting challenge. He et al. found that two residues, Met626 and Thr627, located the upstream of the C-terminal heptad repeat of the gp41, formed a unique hook-like structure (M-T hook) that can dramatically improve the binding stability and anti-HIV activity of the inhibitors. In this work, we explored the molecular mechanism why M-T hook structure could improve the anti-HIV activity of inhibitors. Firstly, molecular dynamic simulation was used to obtain information on the time evolution between gp41 and ligands. Secondly, based on the simulations, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics Generalized Born surface area (MM-GBSA) methods were used to calculate the binding free energies. The binding free energy of the ligand with M-T hook was considerably higher than the other without M-T. Further studies showed that the hydrophobic interactions made the dominant contribution to the binding free energy. The numbers of Hydrogen bonds between gp41 and the ligand with M-T hook structure were more than the other. These findings should provide insights into the inhibition mechanism of the short peptide fusion inhibitors and be useful for the rational design of novel fusion inhibitors in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The mitochondrial DNA makeup of Romanians: A forensic mtDNA control region database and phylogenetic characterization.

    PubMed

    Turchi, Chiara; Stanciu, Florin; Paselli, Giorgia; Buscemi, Loredana; Parson, Walther; Tagliabracci, Adriano

    2016-09-01

    To evaluate the pattern of Romanian population from a mitochondrial perspective and to establish an appropriate mtDNA forensic database, we generated a high-quality mtDNA control region dataset from 407 Romanian subjects belonging to four major historical regions: Moldavia, Transylvania, Wallachia and Dobruja. The entire control region (CR) was analyzed by Sanger-type sequencing assays and the resulting 306 different haplotypes were classified into haplogroups according to the most updated mtDNA phylogeny. The Romanian gene pool is mainly composed of West Eurasian lineages H (31.7%), U (12.8%), J (10.8%), R (10.1%), T (9.1%), N (8.1%), HV (5.4%),K (3.7%), HV0 (4.2%), with exceptions of East Asian haplogroup M (3.4%) and African haplogroup L (0.7%). The pattern of mtDNA variation observed in this study indicates that the mitochondrial DNA pool is geographically homogeneous across Romania and that the haplogroup composition reveals signals of admixture of populations of different origin. The PCA scatterplot supported this scenario, with Romania located in southeastern Europe area, close to Bulgaria and Hungary, and as a borderland with respect to east Mediterranean and other eastern European countries. High haplotype diversity (0.993) and nucleotide diversity indices (0.00838±0.00426), together with low random match probability (0.0087) suggest the usefulness of this control region dataset as a forensic database in routine forensic mtDNA analysis and in the investigation of maternal genetic lineages in the Romanian population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Fast and Accurate Microplate Method (Biolog MT2) for Detection of Fusarium Fungicides Resistance/Sensitivity.

    PubMed

    Frąc, Magdalena; Gryta, Agata; Oszust, Karolina; Kotowicz, Natalia

    2016-01-01

    The need for finding fungicides against Fusarium is a key step in the chemical plant protection and using appropriate chemical agents. Existing, conventional methods of evaluation of Fusarium isolates resistance to fungicides are costly, time-consuming and potentially environmentally harmful due to usage of high amounts of potentially toxic chemicals. Therefore, the development of fast, accurate and effective detection methods for Fusarium resistance to fungicides is urgently required. MT2 microplates (Biolog(TM)) method is traditionally used for bacteria identification and the evaluation of their ability to utilize different carbon substrates. However, to the best of our knowledge, there is no reports concerning the use of this technical tool to determine fungicides resistance of the Fusarium isolates. For this reason, the objectives of this study are to develop a fast method for Fusarium resistance to fungicides detection and to validate the effectiveness approach between both traditional hole-plate and MT2 microplates assays. In presented study MT2 microplate-based assay was evaluated for potential use as an alternative resistance detection method. This was carried out using three commercially available fungicides, containing following active substances: triazoles (tebuconazole), benzimidazoles (carbendazim) and strobilurins (azoxystrobin), in six concentrations (0, 0.0005, 0.005, 0.05, 0.1, 0.2%), for nine selected Fusarium isolates. In this study, the particular concentrations of each fungicides was loaded into MT2 microplate wells. The wells were inoculated with the Fusarium mycelium suspended in PM4-IF inoculating fluid. Before inoculation the suspension was standardized for each isolates into 75% of transmittance. Traditional hole-plate method was used as a control assay. The fungicides concentrations in control method were the following: 0, 0.0005, 0.005, 0.05, 0.5, 1, 2, 5, 10, 25, and 50%. Strong relationships between MT2 microplate and traditional hole

  6. Fast and Accurate Microplate Method (Biolog MT2) for Detection of Fusarium Fungicides Resistance/Sensitivity

    PubMed Central

    Frąc, Magdalena; Gryta, Agata; Oszust, Karolina; Kotowicz, Natalia

    2016-01-01

    The need for finding fungicides against Fusarium is a key step in the chemical plant protection and using appropriate chemical agents. Existing, conventional methods of evaluation of Fusarium isolates resistance to fungicides are costly, time-consuming and potentially environmentally harmful due to usage of high amounts of potentially toxic chemicals. Therefore, the development of fast, accurate and effective detection methods for Fusarium resistance to fungicides is urgently required. MT2 microplates (BiologTM) method is traditionally used for bacteria identification and the evaluation of their ability to utilize different carbon substrates. However, to the best of our knowledge, there is no reports concerning the use of this technical tool to determine fungicides resistance of the Fusarium isolates. For this reason, the objectives of this study are to develop a fast method for Fusarium resistance to fungicides detection and to validate the effectiveness approach between both traditional hole-plate and MT2 microplates assays. In presented study MT2 microplate-based assay was evaluated for potential use as an alternative resistance detection method. This was carried out using three commercially available fungicides, containing following active substances: triazoles (tebuconazole), benzimidazoles (carbendazim) and strobilurins (azoxystrobin), in six concentrations (0, 0.0005, 0.005, 0.05, 0.1, 0.2%), for nine selected Fusarium isolates. In this study, the particular concentrations of each fungicides was loaded into MT2 microplate wells. The wells were inoculated with the Fusarium mycelium suspended in PM4-IF inoculating fluid. Before inoculation the suspension was standardized for each isolates into 75% of transmittance. Traditional hole-plate method was used as a control assay. The fungicides concentrations in control method were the following: 0, 0.0005, 0.005, 0.05, 0.5, 1, 2, 5, 10, 25, and 50%. Strong relationships between MT2 microplate and traditional hole

  7. Practical Examples of an Integrated Field Study Program at Mt. Fuji: Geosciences and the Arts

    NASA Astrophysics Data System (ADS)

    Ito, T.; Kamikuri, S. I.; Otsuji, H.; Kataguchi, N.; Maruyama, H.; Hashiura, H.

    2017-12-01

    Mt. Fuji is a symbol of existence for the Japanese and it also has been a religiously revered subject. In addition, as represented by the ukiyo-e of Hokusai and Hiroshige, it is a subject of paintings, as well as of various types of literary expression such as waka, haiku and novels. Historically, there was a time when Mt. Fuji was used as a symbol of the integration of the country; and it has long reflected the culture, life and thoughts of the Japanese. On another level, from the Earth scientific point of view, Mt. Fuji is one of the most active volcanoes in Japan. Teacher training colleges in Japan have created educational programs for all subjects taught at school. However, as there is no effective linkage among these subjects, students may have different opinions on them according to their curriculum. In this study, we adopted a multifaceted learning approach toward that most symbolic icon of our country. In FY2014 and FY2016, a course created by the College of Education at Ibaraki University, called "Fieldwork on Geology," was conducted at and around Mt. Fuji. In addition to conducting fieldwork from the viewpoint of earth science, it also had abundant artistic content. Academics in the fields of earth science, art and pedagogy worked closely together from the planning stage and participated in a field study with 25 university students. Specifically, we focused on how the experience of sketching a landscape affects field observations by broadening the viewpoint and deepening the understanding of students. To ascertain the bidirectional educational effects between earth sciences and art, students were asked: 1) to express an image of Mt. Fuji, and 2) to appreciate paintings of Mt. Fuji and express the information they garnered from the paintings, before and after the fieldwork. These two exercises are considered as providing insights into how the students' understanding had changed. In addition, reports and impressions submitted by the students were used as

  8. DAMAGE AND CORRESPOBDENCE OF LOCAL GOVERNMENTS AND BUSINESS ESTABLISHMENTS FOR Mt. SHINMOE 2011 ERUPTIONS

    NASA Astrophysics Data System (ADS)

    Uno, Kohji; Nakano, Susumu; Kasubuchi, Yoshio

    On Jan. 27, 2011, Mt. Shinmoe in the Kirishima mountain range on the border between Kagoshima and Miyazaki Prefectures began erupting for the first time in 52 years. In this study, to clarify the damage and correspondence of local governments and business establishments for a series of volcanic hazards of Mt. Shinmoe in 2011, we conducted interview research and document investigation. For endless volcanic hazard, not only the serious and sustained effots of disaster-affected area, but also the broad-based supoorts from neighboring local governments and business establishments are required.

  9. The Magmatic Structure of Mt. Vesuvius: Isotopic and Thermal Constraints

    NASA Astrophysics Data System (ADS)

    Civetta, L.; D'Antonio, M.; de Lorenzo, S.; Gasparini, P.

    2002-12-01

    Mt. Vesuvius is an active volcano famous for the AD 79 eruption that destroyed Pompeii, Herculaneum and Stabiae. Because of the intense urbanization around and on the volcano, the risk today is very high. Therefore, the knowledge of the structure and behavior of the magmatic system is fundamental both for the interpretation of any change in the dynamics of the volcano and for prediction of eruptions. A review of available and new isotopic data on rocks from Mt. Vesuvius, together with mineralogical and geochemical data and recent geophysical results, allow us to constrain a thermal modeling that describes history and present state of Mt. Vesuvius magmatic system. This system is formed by a "deep", complex magmatic reservoir where mantle-derived magmas arrive, stagnate and differentiate. The reservoir extends discontinuously between 10 and 20 km of depth, is hosted in densely fractured crustal rocks, where magmas and crust can interact, and has been fed more than once since 400 ka. The hypothesis of crustal contamination is favored by the high temperatures reached by crustal rocks as a consequence of repetitive intrusions of magma. From the "deep" reservoir magmas of K-basaltic to K-tephritic to K-phonotephritic composition rise to shallow depths where they stagnate at 3-5 km of depth before plinian eruptions, and through crystallization and mixing processes with the residual portion of the feeding systems, generate isotopically and geochemically layered reservoirs. Alternatively, during "open conduit" conditions deep, volatile-rich magma batches rise from the "deep" reservoir to less than 1 km of depth and mix with the crystal-rich, volatile-poor resident magma, triggering eruptions.

  10. The Multi-Stage History of Mt. Sharp

    NASA Technical Reports Server (NTRS)

    Allen, C.; Dapremont, A.

    2013-01-01

    The Curiosity rover is exploring Gale crater and Mt. Sharp, Gale's 5-km high central mound. We are investigating the history of alteration and erosion of Mt. Sharp using orbital imagery, spectroscopy and rover observations. Our results suggest a significant time gap between emplacement of the upper and lower sections of the mound. Crater counts show that the lower mound was formed soon after Gale itself, and that it contains distinct units ranging in altitude from approximately -4,500 to -1,800 m. Spectral data suggest that many units contain phyllosilicates. We found that these clay-bearing rocks occur in distinct layers concentrated below -2,900 m. Parts of the lower mound exhibit a transition from clays to sulfates with increasing altitude. The lower mound shows evidence of flowing water, including canyons and inverted channels. Wind erosion produced km-scale yardangs and scalloped cliffs. Our mapping shows that many yardangs in the lower mound are clay-bearing, with a predominant orientation of around N-S. Curiosity's ground-level images show myriad fine-scale, mainly horizontal layers in the lower mound. The rover has found stream beds and conglomerates, indicating that water once flowed on the crater floor. Drilling near the deepest point in Gale produced abundant clay, providing additional evidence of aqueous alteration. Upper mound units range in altitude from -2,100 m to +500 m, and mantle the lower mound above an angular unconformity. Most upper mound units are composed of layers. The formation age of the upper mound is unknown, since few craters are preserved. Clay-bearing layers are detectable in several locations, mainly at altitudes near -2,000 m. There is no evidence of water flow, but wind erosion has scalloped the surfaces and edges of layers, and fine-scale yardangs are common. Correlations between yardangs and clay spectra are apparent only in the lowermost units of the upper mound. Yardang orientations vary, and include N-S, NW-SE, and NE

  11. Developmental expression of membrane type 4-matrix metalloproteinase (Mt4-mmp/Mmp17) in the mouse embryo

    PubMed Central

    Clemente, Cristina; Montalvo, María Gregoria; Seiki, Motoharu; Arroyo, Alicia G.

    2017-01-01

    Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) moiety and with the catalytic site exposed to the extracellular space. Information about its function and substrates is very limited to date, and little has been reported on its role in the developing embryo. Here, we report a detailed expression analysis of Mt4-mmp during mouse embryonic development by using a LacZ reporter transgenic mouse line. We showed that Mt4-mmp is detected from early stages of development to postnatal stages following a dynamic and restricted pattern of expression. Mt4-mmp was first detected at E8.5 limited to the intersomitic vascularization, the endocardial endothelium and the dorsal aorta. Mt4-mmpLacZ/+ cells were also observed in the neural crest cells, somites, floor plate and notochord at early stages. From E10.5, expression localized in the limb buds and persists during limb development. A strong expression in the brain begins at E12.5 and continues to postnatal stages. Specifically, staining was observed in the olfactory bulb, cerebral cortex, hippocampus, striatum, septum, dorsal thalamus and the spinal cord. In addition, LacZ-positive cells were also detected during eye development, initially at the hyaloid artery and later on located in the lens and the neural retina. Mt4-mmp expression was confirmed by quantitative RT-PCR and western blot analysis in some embryonic tissues. Our data point to distinct functions for this metalloproteinase during embryonic development, particularly during brain formation, angiogenesis and limb development. PMID:28926609

  12. Joint 3D Inversion of ZTEM Airborne and Ground MT Data with Application to Geothermal Exploration

    NASA Astrophysics Data System (ADS)

    Wannamaker, P. E.; Maris, V.; Kordy, M. A.

    2017-12-01

    ZTEM is an airborne electromagnetic (EM) geophysical technique developed by Geotech Inc® where naturally propagated EM fields originating with regional and global lightning discharges (sferics) are measured as a means of inferring subsurface electrical resistivity structure. A helicopter-borne coil platform (bird) measuring the vertical component of magnetic (H) field variations along a flown profile is referenced to a pair of horizontal coils at a fixed location on the ground in order to estimate a tensor H-field transfer function. The ZTEM method is distinct from the traditional magnetotelluric (MT) method in that the electric (E) fields are not considered because of the technological challenge of measuring E-fields in the dielectric air medium. This can lend some non-uniqueness to ZTEM interpretation because a range of conductivity structures in the earth depending upon an assumed background earth resistivity model can fit ZTEM data to within tolerance. MT data do not suffer this particular problem, but they are cumbersome to acquire in their common need for land-based transport often in near-roadless areas and for laying out and digging the electrodes and H coils. The complementary nature of ZTEM and MT logistics and resolution has motivated development of schemes to acquire appropriate amounts of each data type in a single survey and to produce an earth image through joint inversion. In particular, consideration is given to surveys where only sparse MT soundings are needed to drastically reduce the non-uniqueness associated with background uncertainty while straining logistics minimally. Synthetic and field data are analysed using 2D and 3D finite element platforms developed for this purpose. Results to date suggest that indeed dense ZTEM surveys can provide detailed heterogeneous model images with large-scale averages constrained by a modest number of MT soundings. Further research is needed in determining the allowable degree of MT sparseness and the

  13. The melatonin-MT1 receptor axis modulates tumor growth in PTEN-mutated gliomas.

    PubMed

    Ma, Huihui; Wang, Zhen; Hu, Lei; Zhang, Shangrong; Zhao, Chenggang; Yang, Haoran; Wang, Hongzhi; Fang, Zhiyou; Wu, Lijun; Chen, Xueran

    2018-02-19

    More than 40% of glioma patients have tumors that harbor PTEN (phosphatase and tensin homologue deleted on chromosome ten) mutations; this disease is associated with poor therapeutic resistance and outcome. Such mutations are linked to increased cell survival and growth, decreased apoptosis, and drug resistance; thus, new therapeutic strategies focusing on inhibiting glioma tumorigenesis and progression are urgently needed. Melatonin, an indolamine produced and secreted predominantly by the pineal gland, mediates a variety of physiological functions and possesses antioxidant and antitumor properties. Here, we analyzed the relationship between PTEN and the inhibitory effect of melatonin in primary human glioma cells and cultured glioma cell lines. The results showed that melatonin can inhibit glioma cell growth both in culture and in vivo. This inhibition was associated with PTEN levels, which significantly correlated with the expression level of MT1 in patients. In fact, c-fos-mediated MT1 was shown to be a key modulator of the effect of melatonin on gliomas that harbor wild type PTEN. Taken together, these data suggest that melatonin-MT1 receptor complexes represent a potential target for the treatment of glioma. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. No evidence of persisting unrepaired nuclear DNA single strand breaks in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT.

    PubMed

    Korr, Hubert; Angstman, Nicholas B; Born, Tatjana B; Bosse, Kerstin; Brauns, Birka; Demmler, Martin; Fueller, Katja; Kántor, Orsolya; Kever, Barbara M; Rahimyar, Navida; Salimi, Sepideh; Silny, Jiri; Schmitz, Christoph

    2014-01-01

    It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT. In the present study we tested the hypothesis that MF exposure with lower flux densities (0.1 mT, i.e., the actual exposure limit for the population in most European countries, and 1.0 mT) shows similar results to those in the previous study. Experiments and data analysis were carried out in a similar way as in our previous study. Continuous eight-week 50 Hz MF exposure with 0.1 mT or 1.0 mT did not result in increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice. MF exposure with 1.0 mT led to reduced unscheduled DNA synthesis (UDS) in epithelial cells in the choroid plexus of the fourth ventricle in the brain (EC-CP) and epithelial cells of the cortical collecting duct in the kidney, as well as to reduced mtDNA synthesis in neurons of the caudate nucleus in the brain and in EC-CP. No evidence was found for increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT.

  15. Land, language, and loci: mtDNA in Native Americans and the genetic history of Peru.

    PubMed

    Lewis, Cecil M; Tito, Raúl Y; Lizárraga, Beatriz; Stone, Anne C

    2005-07-01

    Despite a long history of complex societies and despite extensive present-day linguistic and ethnic diversity, relatively few populations in Peru have been sampled for population genetic investigations. In order to address questions about the relationships between South American populations and about the extent of correlation between genetic distance, language, and geography in the region, mitochondrial DNA (mtDNA) hypervariable region I sequences and mtDNA haplogroup markers were examined in 33 individuals from the state of Ancash, Peru. These sequences were compared to those from 19 American Indian populations using diversity estimates, AMOVA tests, mismatch distributions, a multidimensional scaling plot, and regressions. The results show correlations between genetics, linguistics, and geographical affinities, with stronger correlations between genetics and language. Additionally, the results suggest a pattern of differential gene flow and drift in western vs. eastern South America, supporting previous mtDNA and Y chromosome investigations. (c) 2004 Wiley-Liss, Inc

  16. Pilot-scale ISCO treatment of a MtBE contaminated site using a Fenton-like process.

    PubMed

    Innocenti, Ivan; Verginelli, Iason; Massetti, Felicia; Piscitelli, Daniela; Gavasci, Renato; Baciocchi, Renato

    2014-07-01

    This paper reports about a pilot-scale feasibility study of In-Situ Chemical Oxidation (ISCO) application based on the use of stabilized hydrogen peroxide catalyzed by naturally occurring iron minerals (Fenton-like process) to a site formerly used for fuel storage and contaminated by MtBE. The stratigraphy of the site consists of a 2-3 meter backfill layer followed by a 3-4 meter low permeability layer, that confines the main aquifer, affected by a widespread MtBE groundwater contamination with concentrations up to 4000 μg/L, also with the presence of petroleum hydrocarbons. The design of the pilot-scale treatment was based on the integration of the results obtained from experimental and numerical modeling accounting for the technological and regulatory constraints existing in the site to be remediated. In particular, lab-scale batch tests allowed the selection of the most suitable operating conditions. Then, this information was implemented in a numerical software that allowed to define the injection and monitoring layout and to predict the propagation of hydrogen peroxide in groundwater. The pilot-scale field results confirmed the effective propagation of hydrogen peroxide in nearly all the target area (around 75 m(2) using 3 injection wells). As far as the MtBE removal is concerned, the ISCO application allowed us to meet the clean-up goals in an area of 60 m(2). Besides, the concentration of TBA, i.e. a potential by-product of MtBE oxidation, was actually reduced after the ISCO treatment. The results of the pilot-scale test suggest that ISCO may be a suitable option for the remediation of the groundwater plume contaminated by MtBE, providing the background data for the design and cost-estimate of the full-scale treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions.

    PubMed

    Taivassalo, Tanja; Gardner, Julie L; Taylor, Robert W; Schaefer, Andrew M; Newman, Jane; Barron, Martin J; Haller, Ronald G; Turnbull, Douglass M

    2006-12-01

    At present there are limited therapeutic interventions for patients with mitochondrial myopathies. Exercise training has been suggested as an approach to improve physical capacity and quality of life but it is uncertain whether it offers a safe and effective treatment for patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. The objectives of this study were to assess the effects of exercise training and detraining in eight patients with single, large-scale mtDNA deletions to determine: (i) the efficacy and safety of endurance training (14 weeks) in this patient population; (ii) to determine the effect of more prolonged (total of 28 weeks) exercise training upon muscle and cardiovascular function and (iii) to evaluate the effect of discontinued training (14 weeks) upon muscle and cardiovascular function. Our results show that: (i) 14 weeks of exercise training significantly improved tolerance of submaximal exercise and peak capacity for work, oxygen utilization and skeletal muscle oxygen extraction with no change in the level of deleted mtDNA; (ii) continued training for an additional 14 weeks maintained these beneficial adaptations; (iii) the cessation of training (detraining) resulted in loss of physiological adaptation to baseline capacity with no overall change in mutation load. Patients' self assessment of quality of life as measured by the SF-36 questionnaire improved with training and declined with detraining. Whilst our findings of beneficial effects of training on physiological outcome and quality of life without increases in the percentage of deleted mtDNA are encouraging, we did not observe changes in mtDNA copy number. Therefore there remains a need for longer term studies to confirm that endurance exercise is a safe and effective treatment for patients with mitochondrial myopathies. The effects of detraining clearly implicate physical inactivity as an important mechanism in reducing exercise capacity and quality of life in patients with

  18. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: Identification of an RGFRRR motif governing fungal cell entry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sagaram, Uma S.; El-Mounadi, Kaoutar; Buchko, Garry W.

    A highly conserved plant defensin MtDef4 potently inhibits the growth of a filamentous fungus Fusarium graminearum. MtDef4 is internalized by cells of F. graminearum. To determine its mechanism of fungal cell entry and antifungal action, NMR solution structure of MtDef4 has been determined. The analysis of its structure has revealed a positively charged patch on the surface of the protein consisting of arginine residues in its γ-core signature, a major determinant of the antifungal activity of MtDef4. Here, we report functional analysis of the RGFRRR motif of the γ-core signature of MtDef4. The replacement of RGFRRR to AAAARR or tomore » RGFRAA not only abolishes fungal cell entry but also results in loss of the antifungal activity of MtDef4. MtDef4 binds strongly to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Mutations of RGFRRR which abolish fungal cell entry of MtDef4 also impair its binding to PA. Our results suggest that RGFRRR motif is a translocation signal for entry of MtDef4 into fungal cells and that this positively charged motif likely mediates interaction of this defensin with PA as part of its antifungal action.« less

  19. Development of PEGylated peptide probes conjugated with (18)F-labeled BODIPY for PET/optical imaging of MT1-MMP activity.

    PubMed

    Kondo, Naoya; Temma, Takashi; Deguchi, Jun; Sano, Kohei; Ono, Masahiro; Saji, Hideo

    2015-12-28

    Since the processing activity of the matrix metalloproteinase MT1-MMP regulates various cellular functions such as motility, invasion, growth, differentiation and apoptosis, precise in vivo evaluation of MT1-MMP activity in cancers can provide beneficial information for both basic and clinical studies. For this purpose, we designed a cleavable Positron Emission Tomography (PET)/optical imaging probe consisting of BODIPY650/665 and polyethylene glycol (PEG) conjugated to opposite ends of MT1-MMP substrate peptides. We used in vitro and in vivo fluorescence experiments to select suitable substrate peptide sequences and PEG sizes for the MT1-MMP probes and obtained an optimized structure referred to here as MBP-2k. Radiofluorinated MBP-2k ([(18)F]MBP-2k) was then successfully synthesized via an (18)F-(19)F isotopic exchange reaction in BODIPY650/665. After intravenous injection into mice with xenografted tumors, [(18)F]MBP-2k showed significantly higher accumulation in HT1080 tumors with high MT1-MMP activity than in A549 tumors that have low MT1-MMP activity. Moreover, PET images showed better contrast in HT1080 tumors. These results show that [(18)F]MBP-2k can be used as a hybrid PET/optical imaging agent and is a promising probe for non-invasive monitoring of MT1-MMP activity in cancers. This probe may also efficiently combine targeted tumor imaging with image-guided surgery that could be beneficial for patients in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. [Characteristics of precipitation pH and conductivity at Mt. Huang].

    PubMed

    Shi, Chun-e; Deng, Xue-liang; Wu, Bi-wen; Hong, Jie; Zhang, Su; Yang, Yuan-jian

    2013-05-01

    To understand the general characteristics of pH distribution and pollution in precipitation at Mt. Huang, statistical analyses were conducted for the routine measurements of pH and conductivity (K) at Mt. Huang during 2006-2011. The results showed that: (1) Over the period of study, the annual volume weighted mean (VWM) precipitation pH varied from 4.81 to 5.57, with precipitation acidity strengthening before 2009 and weakening thereafter. The precipitation acidity showed evident seasonal variations, with the VWM pH lowest in winter (4.78), and highest in summer (5.33). The occurrence frequency of acid rain was 46% , accounting for 45% of total rainfalls and with the most frequent pH falling into weak acid to neutral rain. (2) The annual VWM K varied from 16.91 to 27.84 microS x cm(-1), with no evident trend. As for ions pollution, the precipitation was relatively clean at Mt. Huang, with the most frequent K range being below 15 microS x cm(-1), followed by 15-25 microS x cm(-1). From February 2010 to December 2011, precipitation samples were collected on daily basis for ions analysis, as well as pH and K measurement in lab. Detailed comparisons were conducted between the two sets of pH and K, one set from field measurement and the other from lab measurement. The results indicated: (1) The lab measured pH (K) was highly correlated with the field pH (K); however, the lab pH tended to move towards neutral comparing with the corresponding field pH, and the shift range was closely correlated with the field pH and rainfall. The shift range of K from field to lab was highly correlated with the total ion concentration of precipitation. The field K showed evident negative correlation with the field pH with a correlation coefficient of -0.51. (2) When sampling with nylon-polyethylene bags, the statistics showed smaller bias between two sets of pH, with higher correlation coefficient between two sets of K. Furthermore, the lab K also showed evident negative correlation with

  1. Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia.

    PubMed

    Torrell, Helena; Salas, Antonio; Abasolo, Nerea; Morén, Constanza; Garrabou, Glòria; Valero, Joaquín; Alonso, Yolanda; Vilella, Elisabet; Costas, Javier; Martorell, Lourdes

    2014-10-01

    It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia. © 2014 Wiley Periodicals, Inc.

  2. African human mtDNA phylogeography at-a-glance.

    PubMed

    Rosa, Alexandra; Brehem, António

    2011-01-01

    The mitochondrial DNA (mtDNA) genetic system has long proven to be useful for studying the demographic history of our species, since their proposed Southeast/East African origin 200 kya. Despite the weak archaeological and anthropologic records, which render a difficult understanding of early intra- continental migrations, the phylogenetic L0-L1'6 split at about 140-160 kya is thought to represent also an early sub-structuring of small and isolated communities in South and East Africa. Regional variation accumulated over the following millennia, with L2 and L3 lineages arising in Central and East Africa 100-75 kya. Their sub-Saharan dispersal not later than 60 kya, largely overwhelmed the L0'1 distribution, nowadays limited to South African Khoisan and Central African Pygmies. Cyclic expansions and retractions of the equatorial forest between 40 kya and the "Last Glacial Aridity Maximum" were able to reduce the genetic diversity of modern humans. Surviving regional-specific lineages have emerged from the Sahelian refuge areas, repopulating the region and contributing to the overall West African genetic similarity. Particular L1- L3 lineages mirror the substantial population growth made possible by moister and warmer conditions of the Sahara's Wet Phase and the adoption of agriculture and iron smelting techniques. The diffusion of the farming expertise from a Central African source towards South Africa was mediated by the Bantu people 3 kya. The strong impact of their gene flow almost erased the pre-existent maternal pool. Non-L mtDNAs testify for Eurasian lineages that have enriched the African maternal pool at different timeframes: i) Near and Middle Eastern influences in Upper Palaeolithic, probably link to the spread of Afro-Asiatic languages; ii) particular lineages from West Eurasia around or after the glacial period; iii) post-glacial mtDNA signatures from the Franco-Cantabrian refugia, that have crossed the Strait of Gibraltar and iv) Eurasian lineages

  3. Two M-T hook residues greatly improve the antiviral activity and resistance profile of the HIV-1 fusion inhibitor SC29EK

    PubMed Central

    2014-01-01

    Background Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 such as T20 (Enfuvirtide) and C34 are potent viral fusion inhibitors. We have recently found that two N-terminal residues (Met115 and Thr116) of CHR peptides form a unique M-T hook structure that can greatly enhance the binding and anti-HIV activity of inhibitors. Here, we applied two M-T hook residues to optimize SC29EK, an electrostatically constrained peptide inhibitor with a potent anti-HIV activity. Results The resulting peptide MT-SC29EK showed a dramatically increased binding affinity and could block the six-helical bundle (6-HB) formation more efficiently. As expected, MT-SC29EK potently inhibited HIV-1 entry and infection, especially against those T20- and SC29EK-resistant HIV-1 variants. More importantly, MT-SC29EK and its short form (MT-SC22EK) suffered from the difficulty to induce HIV-1 resistance during the in vitro selection, suggesting their high genetic barriers to the development of resistance. Conclusions Our studies have verified the M-T hook structure as a vital strategy to design novel HIV-1 fusion inhibitors and offered an ideal candidate for clinical development. PMID:24884671

  4. 76 FR 28418 - Voluntary Termination of Foreign-Trade Subzone 33C; Sony Corporation of America, Mt. Pleasant, PA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ...-Trade Subzone 33C; Sony Corporation of America, Mt. Pleasant, PA Pursuant to the authority granted in... Industrial Development Corporation of Southwestern Pennsylvania, (grantee of FTZ 33) authorizing the establishment of Foreign-Trade Subzone 33C at the Sony Corporation of America plant in Mt. Pleasant...

  5. A meteorological report for the Mt. Hopkins Observatory: 1968-1971. [Arizona

    NASA Technical Reports Server (NTRS)

    Pearlman, M. R.; Hogan, D.; Goodwin, K.; Kurtenbach, D.

    1972-01-01

    This document is a compilation of the weather data collected at the Mt. Hopkins Observatory in southern Arizona from 1968 to 1971. It is the second meteorological report aimed at assisting scientists in the scheduling of experiments at the Observatory site.

  6. Trek2a regulates gnrh3 expression under control of melatonin receptor Mt1 and α2-adrenoceptor.

    PubMed

    Loganathan, Kavinash; Moriya, Shogo; Parhar, Ishwar S

    2018-02-12

    Gonadotrophin-releasing hormone (GnRH) expression is associated with the two-pore domain potassium ion (K + ) channel-related K + (TREK) channel trek2a expression and melatonin levels. We aimed to investigate correlation of trek2a expression with gnrh3 expression, and regulatory mechanisms of trek2a expression by the melatonin receptor Mt1 and α 2 -adrenoceptor which are regulated by melatonin. trek2a specific siRNA, Mt1 antagonist luzindole and α 2 -adrenoceptor antagonist prazosin were administered into the adult zebrafish brain and gene expressions were examined by real-time PCR. trek2a specific siRNA administration significantly reduced expression levels of trek2a, gnrh3 and mt1. Luzindole administration suppressed trek2a and gnrh3 expressions. Prazosin administration reduced trek2a and gnrh3 expressions. It is suggested that Trek2a regulates gnrh3 expression under the control of Mt1 and α 2 -adrenoceptor. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. A role for MHR1, a gene required for mitochondrial genetic recombination, in the repair of damage spontaneously introduced in yeast mtDNA.

    PubMed

    Ling, F; Morioka, H; Ohtsuka, E; Shibata, T

    2000-12-15

    A nuclear recessive mutant in Saccharomyces cerevisiae, mhr1-1, is defective in mitochondrial genetic recombination at 30 degrees C and shows extensive vegetative petite induction by UV irradiation at 30 degrees C or when cultivated at a higher temperature (37 degrees C). It has been postulated that mitochondrial DNA (mtDNA) is oxidatively damaged by by-products of oxidative respiration. Since genetic recombination plays a critical role in DNA repair in various organisms, we tested the possibility that MHR1 plays a role in the repair of oxidatively damaged mtDNA using an enzyme assay. mtDNA isolated from cells grown under standard (aerobic) conditions contained a much higher level of DNA lesions compared with mtDNA isolated from anaerobically grown cells. Soon after a temperature shift from 30 to 37 degrees C the number of mtDNA lesions increased 2-fold in mhr1-1 mutant cells but not in MHR1 cells. Malonic acid, which decreased the oxidative stress in mitochondria, partially suppressed both petite induction and the temperature-induced increase in the amount of mtDNA damage in mhr1-1 cells at 37 degrees C. Thus, functional mitochondria require active MHR1, which keeps the extent of spontaneous oxidative damage in mtDNA within a tolerable level. These observations are consistent with MHR1 having a possible role in mtDNA repair.

  8. Conversion of Stationary to Invasive Tumor Initiating Cells (TICs): Role of Hypoxia in Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) Trafficking

    PubMed Central

    Li, Jian; Zucker, Stanley; Pulkoski-Gross, Ashleigh; Kuscu, Cem; Karaayvaz, Mihriban; Ju, Jingfang; Yao, Herui; Song, Erwei; Cao, Jian

    2012-01-01

    Emerging evidence has implicated the role of tumor initiating cells (TICs) in the process of cancer metastasis. The mechanism underlying the conversion of TICs from stationary to invasive remains to be characterized. In this report, we employed less invasive breast cancer TICs, SK-3rd, that displays CD44high/CD24low with high mammosphere-forming and tumorigenic capacities, to investigate the mechanism by which stationary TICs are converted to invasive TICs. Invasive ability of SK-3rd TICs was markedly enhanced when the cells were cultured under hypoxic conditions. Given the role of membrane type 1-matrix metalloproteinase (MT1-MMP) in cancer invasion/metastasis, we explored a possible involvement of MT1-MMP in hypoxia-induced TIC invasion. Silencing of MT1-MMP by a shRNA approach resulted in diminution of hypoxia-induced cell invasion in vitro and metastasis in vivo. Under hypoxic conditions, MT1-MMP redistributed from cytoplasmic storage pools to the cell surface of TICs, which coincides with the increased cell invasion. In addition, CD44, a cancer stem-like cell marker, inversely correlated with increased cell surface MT1-MMP. Interestingly, cell surface MT1-MMP gradually disappeared when the hypoxia-treated cells were switched to normoxia, suggesting the plasticity of TICs in response to oxygen content. Furthermore, we dissected the pathways leading to upregulated MT1-MMP in cytoplasmic storage pools under normoxic conditions, by demonstrating a cascade involving Twist1-miR10b-HoxD10 leading to enhanced MT1-MMP expression in SK-3rd TICs. These observations suggest that MT1-MMP is a key molecule capable of executing conversion of stationary TICs to invasive TICs under hypoxic conditions and thereby controlling metastasis. PMID:22679501

  9. Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women

    PubMed Central

    Money, Deborah M.; Wagner, Emily C.; Maan, Evelyn J.; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E.; Forbes, John C.; Burdge, David R.; Albert, Arianne Y. K.; Lohn, Zoe; Côté, Hélène C. F.

    2015-01-01

    Introduction Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. Methods This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30–40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Results Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). Conclusions In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is

  10. Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women.

    PubMed

    Money, Deborah M; Wagner, Emily C; Maan, Evelyn J; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E; Forbes, John C; Burdge, David R; Albert, Arianne Y K; Lohn, Zoe; Côté, Hélène C F

    2015-01-01

    Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30-40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety

  11. SG-ADVISER mtDNA: a web server for mitochondrial DNA annotation with data from 200 samples of a healthy aging cohort.

    PubMed

    Rueda, Manuel; Torkamani, Ali

    2017-08-18

    Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians. We have developed SG-ADVISER mtDNA, a web server to facilitate the analysis and interpretation of mtDNA genomic data coming from next generation sequencing (NGS) experiments. The server was built in the context of our SG-ADVISER framework and on top of the MtoolBox platform (Calabrese et al., Bioinformatics 30(21):3115-3117, 2014), and includes most of its functionalities (i.e., assembly of mitochondrial genomes, heteroplasmic fractions, haplogroup assignment, functional and prioritization analysis of mitochondrial variants) as well as a back-end and a front-end interface. The server has been tested with unpublished data from 200 individuals of a healthy aging cohort (Erikson et al., Cell 165(4):1002-1011, 2016) and their data is made publicly available here along with a preliminary analysis of the variants. We observed that individuals over ~90 years old carried low levels of heteroplasmic variants in their genomes. SG-ADVISER mtDNA is a fast and functional tool that allows for variant calling and annotation of human mtDNA data coming from NGS experiments. The server was built with simplicity in mind, and builds on our own experience in interpreting mtDNA variants in the context of sudden death and rare diseases. Our objective is to provide an interface for non-bioinformaticians aiming to acquire (or contrast) mtDNA annotations via MToolBox. SG-ADVISER web server is freely available to all users at https://genomics.scripps.edu/mtdna .

  12. 76 FR 3569 - Proposed Amendment of Class E Airspace; West Yellowstone, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ... accommodate aircraft using the Instrument Landing System (ILS) Localizer (LOC) standard instrument approach... airspace areas extending upward from 700 feet or more above the surface of the earth. * * * * * ANM MT E5...

  13. Volcanic eruptions and seismicity of Mt. Baekdu (Changbai) occurred in the historical time

    NASA Astrophysics Data System (ADS)

    Kang, T.; Baag, C.; Chu, K.

    2011-12-01

    Recently, it was reported that the Mt. Baekdu had large volcanic eruptions at least two times in the geological and historical times and the lake Cheonji (Tianchi in Chinese) had formed by collapse of the summit part of the mountain. The last one of the four eruptions occurred in the historical time. Geologists tried to measure the date of eruptions using carbon isotope, but the results show diversity ranging approximately form AD 8 to 14 centuries corresponding to the dates of two dynasties of Balhae (Bohai in Chinese) and Goryeo. Unfortunately, there is no distinct record of the eruptions in this period in historical literatures. In the current study, we could infer that the last great volcanic eruption occurred in the winter time with strong northwestern seasonal wind, considering the distribution of pumice on the satellite images and the thickness of the pumice layers measured at sites in relationship with the climatic environment. On the other hand, some researchers interpreted five events appearing in historical documents written in the Joseon dynasty to be related to volcanic eruptions of Mt. Baekdu. These events occurred in the years 1413, 1597, 1668, 1702, and 1903. Their interpretations have been widely cited in journals and books, However based on critical reviews of historical literature including Joseon Wangjo Sillok (Annals of the Joseon Dynasty), we find that three events of the five were not related to volcanic eruptions of the Mt. Baekdu. Events in the years 1413 and 1668 were phenomena of Asian dust. The event in 1903 recorded in a Chinese literature is found to be a shower type of rain drop with hail accompanied by thunder and lightning. Only the two events in 1597 and 1702 are confirmed to be related to volcanic activities of Mt. Baekdu. According to Joseon Wangjo Sillok, a large earthquake of maximum intensity 9 (Modified Mercalli Intensity, MMI) and its aftershocks occurred at the border region of Samsu county in Hamgyeongdo Province in the

  14. Tree-ring stable carbon isotope-based April-June relative humidity reconstruction since ad 1648 in Mt. Tianmu, China

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Ta, Weiyuan; Li, Qiang; Song, Huiming; Sun, Changfeng; Cai, Qiufang; Liu, Han; Wang, Lu; Hu, Sile; Sun, Junyan; Zhang, Wenbiao; Li, Wenzhu

    2018-03-01

    Based on accurate dating, we have determined the stable carbon isotope ratios (δ13C) of five Cryptomeria fortunei specimens from Mt. Tianmu, a subtropical area in southern China. The five δ13C time series records are combined into a single representative δ13C time series using a "numerical mix method." These are normalized to remove temporal variations of δ13 C in atmospheric CO2 to obtain a carbon isotopic discrimination (Δ13C) time series, in which we observe a distinct correlation between Δ13C and local April to June mean relative humidity ( RH AMJ ) (n = 64, r = 0.858, p < 0.0001). We use this relationship to reconstruct RH AMJ variations from ad 1648 to 2014 at Mt. Tianmu. The reconstructed sequence show that over the past 367 years, Mt. Tianmu area was relatively wet, but in the latter part of the twentieth century, under the influence of increasing global warming, it has experienced a sharp reduction in relative humidity. Spatial correlation analysis reveals a significant negative correlation between RH AMJ at Mt. Tianmu and Sea Surface Temperature (SSTs) in the western equatorial Pacific and Indian Ocean. In other words, there is a positive correlation between tree-ring δ13C in Mt. Tianmu and SSTs. Both observed and reconstructed RH AMJ show significant positive correlations with East Asian and South Asian monsoons from 1951 to 2014, which indicate that RH AMJ from Mt. Tianmu reflects the variability of the Asian summer monsoon intensity to a great extent. The summer monsoon has weakened since 1960. However, an increase in relative humidity since 2003 implies a recent enhancement in the summer monsoon.

  15. The impact of the eruptions of Mt. Pinatubo and Cerro Hudson on Antarctic aerosol levels during the 1991 Austral spring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pitts, M.C.; Thomason, L.W.

    1993-11-19

    At the beginning of 1991 Austral spring, volcanic aerosols from Mt. Pinatubo and Cerro Hudson were present in the polar stratosphere of the Southern Hemisphere. Satellite observations of aerosol extinction were used to identify and track the movement of these aerosols in the vicinity of the Antarctic vortex during August through November 1991. A layer of mature Mt. Pinatubo aerosols was identified near 21 km and a layer of fresh Cerro Hudson aerosols was identified near 12 km. This altitude separation of the Mt. Pinatubo and Cerro Hudson aerosols was observed throughout the period. Below 15 km, the polar stratospheremore » was subject to episodes of strong wave activity which transported the Cerro Hudson aerosols poleward and, after the middle of September, they became a persistent feature beneath the vortex. Above 15 km, signatures of Mt. Pinatubo aerosols were observed near the vortex boundary, but significant portions of the vortex interior remained free of any detectable intrusions of Mt. Pinatubo aerosols until the final warming in mid-November. 13 refs., 4 figs.« less

  16. Mt. San Antonio Community College Information Notebook; Volume Two, 1985.

    ERIC Educational Resources Information Center

    Mount San Antonio Community Coll. District, Walnut, CA.

    This databook contains some of the basic information to be used in decision making and planning in the Mt. San Antonio College (MSAC) District. Part I focuses on the demographic characteristics of the district population, feeder school districts, and data from other educational providers. Part II presents statewide data on potential enrollment by…

  17. Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing.

    PubMed

    Boucret, L; Bris, C; Seegers, V; Goudenège, D; Desquiret-Dumas, V; Domin-Bernhard, M; Ferré-L'Hotellier, V; Bouet, P E; Descamps, P; Reynier, P; Procaccio, V; May-Panloup, P

    2017-10-01

    Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing. This was an observational study of 53 immature oocyte-cumulus complexes retrieved from 35 women undergoing IVF at the University Hospital of Angers, France, from March 2013 to March 2014. The women were classified in two groups, one including 19 women showing signs of ovarian ageing objectified by a diminished ovarian reserve (DOR), and the other, including 16 women with a normal ovarian reserve (NOR), which served as a control group. mtDNA was extracted from isolated oocytes, and from their corresponding cumulus cells (CCs) considered as a somatic cell compartment. The average mtDNA content of each sample was assessed by using a quantitative real-time PCR technique. Deep sequencing was performed using the Ion Torrent Proton for Next-Generation Sequencing. Signal processing and base calling were done by the embedded pre-processing pipeline and the variants were analyzed using an in-house workflow. The distribution of the different variants between DOR and NOR patients, on one hand, and oocyte and CCs, on the other, was analyzed with the generalized mixed linear model to take into account the cluster of cells belonging to a given mother. There were no significant differences between the numbers of mtDNA variants between the DOR and the NOR patients, either in the oocytes (P = 0.867) or in the surrounding CCs (P = 0.154). There were also no differences in terms of variants with potential functional consequences. De-novo mtDNA variants were found in 28% of the oocytes and in 66% of the CCs with the mean number of variants being

  18. Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome

    PubMed Central

    Siegmund, Stephanie E; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A

    2017-01-01

    Abstract Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential ‘rapamycin metabolic signature.’ These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. PMID:28973153

  19. Neoglacial fluctuations of Deming Glacier, Mt. Baker, Washington USA.

    NASA Astrophysics Data System (ADS)

    Osborn, G.; Menounos, B.; Scott, K.; Clague, J. J.; Tucker, D.; Riedel, J.; Davis, P.

    2007-12-01

    Deming Glacier flows from the upper west slopes of Mt. Baker, a stratovolcano in the Cascade Range of Washington, USA. The north and south lateral moraines of Deming Glacier are composed of at least four tills separated by layers of detrital wood and sheared stumps in growth position. The stratigraphy records fluctuations of the glacier during the Holocene. The outer ten rings of an in situ stump from the middle wood layer, which is about 40 m below the north lateral moraine crest and 1.2 km downvalley from the present glacier terminus, yielded an age of 1750 ± 50~~ 14C yr BP [1810-1550 cal yr BP]. The stump revealed at least 300 rings and thus records a period of landscape stability and relatively restricted glaciation for several hundred years prior to ca. 1750 14C yr BP . Samples from the lowest wood layer also have been submitted for radiocarbon dating. Outer rings of detrital wood samples collected from two wood mats exposed in the south lateral moraine, 2.3 km downvalley of the glacier terminus, returned radiocarbon ages of 1600 ± 30~~ 14C yr BP [1550- 1410 cal yr BP] and 430 ± 30~~ 14C yr BP [AD 1420-1620]. These data indicate that Deming Glacier advanced over a vegetated moraine sometime after 1810 cal yr BP to a position less extensive that it achieved at the peak of the Little Ice Age. The glacier then receded before it began its final and most extensive Holocene advance after AD 1420. The older advance is correlative with the 'First Millennium AD' advance, recently recognized throughout western North America. The younger advance coincides with an advance of Mt. Baker's Easton Glacier [AD 1430-1630], and advances of many alpine glaciers elsewhere in western North America. Our data suggest that glaciers on Mt. Baker fluctuated in a similar manner to alpine glaciers in the Coast Mountains of British Columbia and in other mountain ranges of northwest North America during Neoglaciation.

  20. Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease.

    PubMed

    van der Walt, Elizna M; Smuts, Izelle; Taylor, Robert W; Elson, Joanna L; Turnbull, Douglass M; Louw, Roan; van der Westhuizen, Francois H

    2012-06-01

    Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by the diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in the muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81±26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup-defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full-length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.

  1. Acid-sensing ion channels in mouse olfactory bulb M/T neurons

    PubMed Central

    Li, Ming-Hua; Liu, Selina Qiuying; Inoue, Koichi; Lan, Jinquan; Simon, Roger P.

    2014-01-01

    The olfactory bulb contains the first synaptic relay in the olfactory pathway, the sensory system in which odorants are detected enabling these chemical stimuli to be transformed into electrical signals and, ultimately, the perception of odor. Acid-sensing ion channels (ASICs), a family of proton-gated cation channels, are widely expressed in neurons of the central nervous system. However, no direct electrophysiological and pharmacological characterizations of ASICs in olfactory bulb neurons have been described. Using a combination of whole-cell patch-clamp recordings and biochemical and molecular biological analyses, we demonstrated that functional ASICs exist in mouse olfactory bulb mitral/tufted (M/T) neurons and mainly consist of homomeric ASIC1a and heteromeric ASIC1a/2a channels. ASIC activation depolarized cultured M/T neurons and increased their intracellular calcium concentration. Thus, ASIC activation may play an important role in normal olfactory function. PMID:24821964

  2. nrDNA:mtDNA copy number ratios as a comparative metric for evolutionary and conservation genetics.

    PubMed

    Goodall-Copestake, William Paul

    2018-05-12

    Identifying genetic cues of functional relevance is key to understanding the drivers of evolution and increasingly important for the conservation of biodiversity. This study introduces nuclear ribosomal DNA (nrDNA) to mitochondrial DNA (mtDNA) copy number ratios as a metric with which to screen for this functional genetic variation prior to more extensive omics analyses. To illustrate the metric, quantitative PCR was used to estimate nrDNA (18S) to mtDNA (16S) copy number ratios in muscle tissue from samples of two zooplankton species: Salpa thompsoni caught near Elephant Island (Southern Ocean) and S. fusiformis sampled off Gough Island (South Atlantic). Average 18S:16S ratios in these samples were 9:1 and 3:1, respectively. nrDNA 45S arrays and mitochondrial genomes were then deep sequenced to uncover the sources of intra-individual genetic variation underlying these 18S:16S copy number differences. The deep sequencing profiles obtained were consistent with genetic changes resulting from adaptive processes, including an expansion of nrDNA and damage to mtDNA in S. thompsoni, potentially in response to the polar environment. Beyond this example from zooplankton, nrDNA:mtDNA copy number ratios offer a promising metric to help identify genetic variation of functional relevance in animals more broadly.

  3. Using groundwater age distributions to understand changes in methyl tert-butyl ether (MtBE) concentrations in ambient groundwater, northeastern United States

    USGS Publications Warehouse

    Lindsey, Bruce; Ayotte, Joseph; Jurgens, Bryant; DeSimone, Leslie A.

    2017-01-01

    Temporal changes in methyl tert-butyl ether (MtBE) concentrations in groundwater were evaluated in the northeastern United States, an area of the nation with widespread low-level detections of MtBE based on a national survey of wells selected to represent ambient conditions. MtBE use in the U.S. peaked in 1999 and was largely discontinued by 2007. Six well networks, each representing specific areas and well types (monitoring or supply wells), were each sampled at 10 year intervals between 1996 and 2012. Concentrations were decreasing or unchanged in most wells as of 2012, with the exception of a small number of wells where concentrations continue to increase. Statistically significant increasing concentrations were found in one network sampled for the second time shortly after the peak of MtBE use, and decreasing concentrations were found in two networks sampled for the second time about 10 years after the peak of MtBE use. Simulated concentrations from convolutions of estimates for concentrations of MtBE in recharge water with age distributions from environmental tracer data correctly predicted the direction of MtBE concentration changes in about 65 percent of individual wells. The best matches between simulated and observed concentrations were found when simulating recharge concentrations that followed the pattern of national MtBE use. Some observations were matched better when recharge was modeled as a plume moving past the well from a spill at one point in time. Modeling and sample results showed that wells with young median ages and narrow age distributions responded more quickly to changes in the contaminant source than wells with older median ages and broad age distributions. Well depth and aquifer type affect these responses. Regardless of the timing of decontamination, all of these aquifers show high susceptibility for contamination by a highly soluble, persistent constituent.

  4. Mental Rotation Meets the Motion Aftereffect: The Role of hV5/MT+ in Visual Mental Imagery

    ERIC Educational Resources Information Center

    Seurinck, Ruth; de Lange, Floris P.; Achten, Erik; Vingerhoets, Guy

    2011-01-01

    A growing number of studies show that visual mental imagery recruits the same brain areas as visual perception. Although the necessity of hV5/MT+ for motion perception has been revealed by means of TMS, its relevance for motion imagery remains unclear. We induced a direction-selective adaptation in hV5/MT+ by means of an MAE while subjects…

  5. PyMT: A Python package for model-coupling in the Earth sciences

    NASA Astrophysics Data System (ADS)

    Hutton, E.

    2016-12-01

    The current landscape of Earth-system models is not only broad in scientific scope, but also broad in type. On the one hand, the large variety of models is exciting, as it provides fertile ground for extending or linking models together in novel ways to answer new scientific questions. However, the heterogeneity in model type acts to inhibit model coupling, model development, or even model use. Existing models are written in a variety of programming languages, operate on different grids, use their own file formats (both for input and output), have different user interfaces, have their own time steps, etc. Each of these factors become obstructions to scientists wanting to couple, extend - or simply run - existing models. For scientists whose main focus may not be computer science these barriers become even larger and become significant logistical hurdles. And this is all before the scientific difficulties of coupling or running models are addressed. The CSDMS Python Modeling Toolkit (PyMT) was developed to help non-computer scientists deal with these sorts of modeling logistics. PyMT is the fundamental package the Community Surface Dynamics Modeling System uses for the coupling of models that expose the Basic Modeling Interface (BMI). It contains: Tools necessary for coupling models of disparate time and space scales (including grid mappers) Time-steppers that coordinate the sequencing of coupled models Exchange of data between BMI-enabled models Wrappers that automatically load BMI-enabled models into the PyMT framework Utilities that support open-source interfaces (UGRID, SGRID,CSDMS Standard Names, etc.) A collection of community-submitted models, written in a variety of programminglanguages, from a variety of process domains - but all usable from within the Python programming language A plug-in framework for adding additional BMI-enabled models to the framework In this presentation we intoduce the basics of the PyMT as well as provide an example of coupling

  6. Volcanic records of the Laschamp geomagnetic excursion from Mt Ruapehu, New Zealand

    NASA Astrophysics Data System (ADS)

    Ingham, E.; Turner, G. M.; Conway, C. E.; Heslop, D.; Roberts, A. P.; Leonard, G.; Townsend, D.; Calvert, A.

    2017-08-01

    We present palaeodirectional records of the Laschamp geomagnetic excursion from lavas on Mt Ruapehu, New Zealand. Fourteen lava flows on the northwestern and southern flanks of Mt Ruapehu, with 40Ar/39Ar weighted mean plateau ages that range from 46.3 ± 2.0 to 39.9 ± 1.4 ka, were studied. The youngest and older flows carry a normal polarity magnetization; however, six flows, dated between 46.3 ± 2.0 and 42.7 ± 1.8 ka, record excursional directions. Three of these flows record southerly palaeomagnetic declinations and negative inclinations that agree well with a published Laschamp record from the Auckland Volcanic Field (AVF). Together, the AVF and Mt Ruapehu lavas currently represent the only volcanic records of the Laschamp excursion outside the Chaîne des Puys region, France. Thus, they make an important contribution to the global set of Laschamp excursion records. Virtual geomagnetic pole (VGP) groups for the New Zealand and French records early in the excursion are compatible with a dipole-dominated field that rotated to an equatorial orientation while simultaneously decaying in strength. In contrast, younger excursional flows from France and New Zealand yield separate VGP groups, which suggest either that the field had a nondipolar morphology in this later phase, or that the VGP groups were not synchronous. 40Ar/39Ar ages for the Mt Ruapehu record are on average slightly older than published northern hemisphere ages and from the relative palaeointensity minimum in the GLOPIS sedimentary stack. Although few individual ages differ significantly at the 2σ level, the spread suggests an overall excursion duration that is longer than the currently accepted 1500 years. This age spread may result from excess Ar in magmas at the time of the eruption biasing the results to slightly older ages, or from non-synchronous excursional field behaviour at near-antipodal locations, or, possibly, a precursory phase prior to the main excursion.

  7. Spatial and seasonal variations of elemental composition in Mt. Everest (Qomolangma) snow/firn

    NASA Astrophysics Data System (ADS)

    Kang, Shichang; Zhang, Qianggong; Kaspari, Susan; Qin, Dahe; Cong, Zhiyuan; Ren, Jiawen; Mayewski, Paul A.

    In May 2005, a total of 14 surface snow (0-10 cm) samples were collected along the climbing route from the advanced base camp to the summit (6500-8844 m a.s.l.) on the northern slope of Mt. Everest (Qomolangma). A 108 m firn/ice core was retrieved from the col of the East Rongbuk Glacier (28.03°N, 86.96°E, 6518 m a.s.l.) on the north eastern saddle of Mt. Everest in September 2002. Surface snow and the upper 3.5 m firn samples from the core were analyzed for major and trace elements by inductively coupled plasma mass spectroscopy (ICP-MS). Measurements show that crustal elements dominated both surface snow and the firn core, suggesting that Everest snow chemistry is mainly influenced by crustal aerosols from local rock or prevalent spring dust storms over southern/central Asia. There are no clear trends for element variations with elevation due to local crustal aerosol inputs or redistribution of surface snow by strong winds during the spring. Seasonal variability in snow/firn elements show that high elemental concentrations occur during the non-monsoon season and low values during the monsoon season. Ca, Cr, Cs, and Sr display the most distinct seasonal variations. Elemental concentrations (especially for heavy metals) at Mt. Everest are comparable with polar sites, generally lower than in suburban areas, and far lower than in large cities. This indicates that anthropogenic activities and heavy metal pollution have little effect on the Mt. Everest atmospheric environment. Everest firn core REE concentrations are the first reported in the region and seem to be comparable with those measured in modern and Last Glacial Maximum snow/ice samples from Greenland and Antarctica, and with precipitation samples from Japan and the East China Sea. This suggests that REE concentrations measured at Everest are representative of the background atmospheric environment.

  8. Influence of Aerosol Heating on the Stratospheric Transport of the Mt. Pinatubo Eruption

    NASA Technical Reports Server (NTRS)

    Aquila, Valentina; Oman, Luke D.; Stolarski, Richard S.

    2011-01-01

    On June 15th, 1991 the eruption of Mt. Pinatubo (15.1 deg. N, 120.3 Deg. E) in the Philippines injected about 20 Tg of sulfur dioxide in the stratosphere, which was transformed into sulfuric acid aerosol. The large perturbation of the background aerosol caused an increase in temperature in the lower stratosphere of 2-3 K. Even though stratospheric winds climatological]y tend to hinder the air mixing between the two hemispheres, observations have shown that a large part of the SO2 emitted by Mt. Pinatubo have been transported from the Northern to the Southern Hemisphere. We simulate the eruption of Mt. Pinatubo with the Goddard Earth Observing System (GEOS) version 5 global climate model, coupled to the aerosol module GOCART and the stratospheric chemistry module StratChem, to investigate the influence of the eruption of Mt. Pinatubo on the stratospheric transport pattern. We perform two ensembles of simulations: the first ensemble consists of runs without coupling between aerosol and radiation. In these simulations the plume of aerosols is treated as a passive tracer and the atmosphere is unperturbed. In the second ensemble of simulations aerosols and radiation are coupled. We show that the set of runs with interactive aerosol produces a larger cross-equatorial transport of the Pinatubo cloud. In our simulations the local heating perturbation caused by the sudden injection of volcanic aerosol changes the pattern of the stratospheric winds causing more intrusion of air from the Northern into the Southern Hemisphere. Furthermore, we perform simulations changing the injection height of the cloud, and study the transport of the plume resulting from the different scenarios. Comparisons of model results with SAGE II and AVHRR satellite observations will be shown.

  9. ASTER Images Mt. Usu Volcano

    NASA Technical Reports Server (NTRS)

    2000-01-01

    On April 3, the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra Satellite captured this image of the erupting Mt. Usu volcano in Hokkaido, Japan. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image the Earth for the next 6 years to map and monitor the changing surface of our planet.

    This false color infrared image of Mt Usu volcano is dominated by Lake Toya, an ancient volcanic caldera. On the south shore is the active Usu volcano. On Friday, March 31, more than 11,000 people were evacuated by helicopter, truck and boat from the foot of Usu, that began erupting from the northwest flank, shooting debris and plumes of smoke streaked with blue lightning thousands of feet in the air. Although no lava gushed from the mountain, rocks and ash continued to fall after the eruption. The region was shaken by thousands of tremors before the eruption. People said they could taste grit from the ash that was spewed as high as 2,700 meters (8,850 ft) into the sky and fell to coat surrounding towns with ash. 'Mount Usu has had seven significant eruptions that we know of, and at no time has it ended quickly with only a small scale eruption,' said Yoshio Katsui, a professor at Hokkaido University. This was the seventh major eruption of Mount Usu in the past 300 years. Fifty people died when the volcano erupted in 1822, its worst known eruption.

    In the image, most of the land is covered by snow. Vegetation, appearing red in the false color composite, can be seen in the agricultural fields, and forests in the mountains. Mt. Usu is crossed by three dark streaks. These are the paths of ash deposits that rained out from eruption plumes two days earlier. The prevailing wind was from the northwest, carrying the ash away from the main city of Date. Ash deposited can be traced on the image as far away as 10 kilometers (16

  10. Modeling sulfur dioxide concentrations in Mt. Rainier area during prevent

    NASA Astrophysics Data System (ADS)

    Givati, Reuven; Flocchini, Robert G.; Cahill, Thomas A.

    The MATHEW/ADPIC models (a diagnostic wind model and a particle model) which were developed at Lawrence Livermore National Laboratory, were used to compute SO 2 concentrations in the Mt Rainier area during PREVENT (Pacific Northwest Regional Visibility Experiment Using Natural Tracers, June to September 1990). The modeled concentrations were compared to measured concentrations at two sampling locations (Tahoma Woods and Paradise near Mt Rainier) which are located in a valley. The SO 2 sources considered are located along the Puget Sound (Everett, Seattle and Tacoma area) and south of it. New formulations were included in the models for the oxidation of SO 2 and the interpolation of the wind field. Because of the paucity of the meteorological data near the sampling points, an estimation was made of the wind values in the valley, based on the phenomena of wind channeling, mountain and valley winds, and historical wind observations near Mt Rainier. The models were run for several non-rainy days during the PREVENT period when large SO 2 concentrations were observed, and for other special cases. Out of 14 days for which the emissions of the previous night were taken into account, for 12 days the ratio of the modeled to the measured SO 2 concentrations at Tahoma Woods during the daytime, was in the interval 0.45-2.00, considered a good agreement. However, the agreement at Tahoma Woods during the night, and at Paradise during the day and the night, were not as good. It seems that the wind flow near Tahoma Woods under the stable conditions at night, and near the steep terrain of Paradise, were not modeled correctly, with the limited input of available meteorological observations.

  11. Transmission of human mtDNA heteroplasmy in the Genome of the Netherlands families: support for a variable-size bottleneck

    PubMed Central

    Li, Mingkun; Rothwell, Rebecca; Vermaat, Martijn; Wachsmuth, Manja; Schröder, Roland; Laros, Jeroen F.J.; van Oven, Mannis; de Bakker, Paul I.W.; Bovenberg, Jasper A.; van Duijn, Cornelia M.; van Ommen, Gert-Jan B.; Slagboom, P. Eline; Swertz, Morris A.; Wijmenga, Cisca; Kayser, Manfred; Boomsma, Dorret I.; Zöllner, Sebastian; de Knijff, Peter; Stoneking, Mark

    2016-01-01

    Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies. PMID:26916109

  12. An mtDNA mutation accelerates liver aging by interfering with the ROS response and mitochondrial life cycle.

    PubMed

    Niemann, Jan; Johne, Cindy; Schröder, Susanne; Koch, Franziska; Ibrahim, Saleh M; Schultz, Julia; Tiedge, Markus; Baltrusch, Simone

    2017-01-01

    Mitochondrial dysfunction affects liver metabolism, but it remains unclear whether this interferes with normal liver aging. We investigated several mitochondrial pathways in hepatocytes and liver tissue from a conplastic mouse strain compared with the control C57BL/6NTac strain over 18 months of life. The C57BL/6NTac-mtNODLtJ mice differed from C57BL/6NTac mice by a point mutation in mitochondrial-encoded subunit 3 of cytochrome c oxidase. Young C57BL/6NTac-mtNODLtJ mice showed reduced mitochondrial metabolism but similar reactive oxygen species (ROS) production to C57BL/6NTac mice. Whereas ROS increased almost equally up to 9 months in both strains, different mitochondrial adaptation strategies resulted in decreasing ROS in advanced age in C57BL/6NTac mice, but persistent ROS production in C57BL/6NTac-mtNODLtJ mice. Only the conplastic strain developed elongated mitochondrial networks with artificial loop structures, depressed autophagy, high mitochondrial respiration and up-regulated antioxidative response. Our results indicate that mtDNA mutations accelerate liver ballooning degeneration and carry a serious risk of premature organ aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. High folic acid diet enhances tumour growth in PyMT-induced breast cancer

    PubMed Central

    Hansen, Mariann Fagernæs; Jensen, Sarah Østrup; Füchtbauer, Ernst-Martin; Martensen, Pia M

    2017-01-01

    Background: The B-vitamin folate is among the most studied bioactive food compound, and a dietary intake meeting the daily requirements has been found to reduce the risk of cancer and cardiovascular diseases as well as preventing neural tube defects during fetal development. Several countries have therefore introduced dietary fortification with folic acid. However, clinical and animal studies suggest that folic acid has a dual role in cancer development. Methods: During the period of initial tumour progression, MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice were fed with normal diet and high folic acid diet. Results: We found that PyMT-induced breast tumours highly express the cancer-specific folate receptor (FR), a feature they share with several human epithelial cancers in which expression of FRα correlates with tumour grade. Mice receiving a high folic acid diet displayed a significantly increased tumour volume compared with mice receiving normal diet. In the largest tumours, only found in mice on high folic acid diet, STAT3 was activated. In primary cells from PyMT tumours, STAT3 was activated upon treatment with folic acid in culture. Conclusions: Our results offer a novel molecular explanation for folic acid-induced growth of existing tumours. PMID:28152548

  14. mtDNA variation in the Yanomami: evidence for additional New World founding lineages.

    PubMed

    Easton, R D; Merriwether, D A; Crews, D E; Ferrell, R E

    1996-07-01

    Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types.

  15. mtDNA variation in the Yanomami: evidence for additional New World founding lineages.

    PubMed Central

    Easton, R. D.; Merriwether, D. A.; Crews, D. E.; Ferrell, R. E.

    1996-01-01

    Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types. PMID:8659527

  16. Atmospheric Carbon Dioxide Record from In Situ Measurements at Mt. Cimone (1979-1997)

    DOE Data Explorer

    Colombo, Tiziano [Italian Meteorological Service, Sestola (MO), Italy; Santaguida, Riccardo

    1998-01-01

    Continuous atmospheric CO2 measurements have been carried out at Mt. Cimone since 1979. Since December 1988, air samples have also been collected approximately once per week in a pair of 2-L, electropolished, stainless steel cylindrical flasks. From 1979 until December 1988, a Hartmann and Braun URAS-2T NDIR gas analyzer was used for CO2 determinations. Currently, CO2 determinations are made through the use of a Siemens Ultramat-5E NDIR gas analyzer. Water vapor is eliminated by passing the air through a U-tube placed in an alcohol bath at -600°C. Calibration of the Ultramat-5E is accomplished by using two CO2-in-air working standard gases. These working standard gas concentrations are checked 10 days apart against three CO2-in-air mixtures that serve as secondary standards. The secondary standards are checked every 6 months against five other CO2-in-air primary standards. Hourly CO2 values are routinely plotted together with wind data. Anomalous concentrations and those affected by instrument failures or local sources are rejected. Atmospheric CO2 concentrations from Mt. Cimone are reported in the 1993 WMO/Scripps mole fraction scale. For further details on the measurement apparatus and sampling techniques used at Mt. Cimone, see Cundari et al. (1990).

  17. mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory.

    PubMed

    Atkinson, Quentin D; Gray, Russell D; Drummond, Alexei J

    2008-02-01

    The relative timing and size of regional human population growth following our expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity carries a legacy of our population history. Given a set of sequences, we can use coalescent theory to estimate past population size through time and draw inferences about human population history. However, recent work has challenged the validity of using mtDNA diversity to infer species population sizes. Here we use Bayesian coalescent inference methods, together with a global data set of 357 human mtDNA coding-region sequences, to infer human population sizes through time across 8 major geographic regions. Our estimates of relative population sizes show remarkable concordance with the contemporary regional distribution of humans across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a good predictor of population size in humans. Plots of population size through time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a rapid expansion into Eurasia after the emergence of the first non-African mtDNA lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred in Southern Asia approximately 52 kya, followed by a succession of growth phases in Northern and Central Asia (approximately 49 kya), Australia (approximately 48 kya), Europe (approximately 42 kya), the Middle East and North Africa (approximately 40 kya), New Guinea (approximately 39 kya), the Americas (approximately 18 kya), and a second expansion in Europe (approximately 10-15 kya). Comparisons of relative regional population sizes through time suggest that between approximately 45 and 20 kya most of humanity lived in Southern Asia. These findings not only support the use of mtDNA data for estimating human population size but also provide a unique picture of human prehistory and demonstrate the importance of Southern Asia to our recent evolutionary past.

  18. MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

    PubMed Central

    van Asch, Barbara; Pereira, Luísa; Pereira, Filipe; Santa-Rita, Pedro; Lima, Manuela; Amorim, António

    2005-01-01

    Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143) of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a) breeds tend to display haplotypes belonging to different haplogroups; (b) haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c) haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d) genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal) and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog) and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the Azores Cattle Dog

  19. Native Teacher Education in a Community Setting: The Mt. Currie Program

    ERIC Educational Resources Information Center

    Wyatt, June

    1977-01-01

    Describes the Mt. Currie Native Teacher Education Program, based in a small reserve community 100 miles from Vancouver, Canada. Five basic issues involved in the development of the program are community involvement at the local level, incorporation of native language and culture, decentralization, entrance requirements and paraprofessional…

  20. 76 FR 12667 - Endangered and Threatened Wildlife and Plants; 12-Month Finding on a Petition To List the Mt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ...We, the Fish and Wildlife Service (Service), announce a 12- month finding on a petition to list the Mt. Charleston blue butterfly (Plebejus shasta charlestonensis) (formerly in genus Icaricia) as endangered or threatened under the Endangered Species Act of 1973, as amended. After review of all available scientific and commercial information, we find that listing the Mt. Charleston blue butterfly is warranted. Currently, however, listing of the Mt. Charleston blue is precluded by higher priority actions to amend the Lists of Endangered and Threatened Wildlife and Plants. Upon publication of this 12-month petition finding, we will add the Mt. Charleston blue butterfly to our candidate species list. If an emergency situation develops with this subspecies that warrants an emergency listing, we will act immediately to provide additional protection. We will develop a proposed rule to list this subspecies as our priorities allow. We will make any determination on critical habitat during development of the proposed listing rule.

  1. MT3825BA: a 384×288-25µm ROIC for uncooled microbolometer FPAs

    NASA Astrophysics Data System (ADS)

    Eminoglu, Selim; Gulden, M. Ali; Bayhan, Nusret; Incedere, O. Samet; Soyer, S. Tuncer; Ustundag, Cem M. B.; Isikhan, Murat; Kocak, Serhat; Turan, Ozge; Yalcin, Cem; Akin, Tayfun

    2014-06-01

    This paper reports the development of a new microbolometer Readout Integrated Circuit (ROIC) called MT3825BA. It has a format of 384 × 288 and a pixel pitch of 25μm. MT3825BA is Mikro-Tasarim's second microbolometer ROIC product, which is developed specifically for resistive surface micro-machined microbolometer detector arrays using high-TCR pixel materials, such as VOx and a-Si. MT3825BA has a system-on-chip architecture, where all the timing, biasing, and pixel non-uniformity correction (NUC) operations in the ROIC are applied using on-chip circuitry simplifying the use and system integration of this ROIC. The ROIC is designed to support pixel resistance values ranging from 30 KΩ to 100 KΩ. MT3825BA is operated using conventional row based readout method, where pixels in the array are read out in a row-by-row basis, where the applied bias for each pixel in a given row is updated at the beginning of each line period according to the applied line based NUC data. The NUC data is applied continuously in a row-by-row basis using the serial programming interface, which is also used to program user configurable features of the ROIC, such as readout gain, integration time, and number of analog video outputs. MT3825BA has a total of 4 analog video outputs and 2 analog reference outputs, placed at the top and bottom of the ROIC, which can be programmed to operate in the 1, 2, and 4-output modes, supporting frames rates well above 60 fps at a 3 MHz pixel output rate. The pixels in the array are read out with respect to reference pixels implemented above and below actual array pixels. The bias voltage of the pixels can be programmed over a 1.0 V range to compensate for the changes in the detector resistance values due to the variations coming from the manufacturing process or changes in the operating temperature. The ROIC has an on-chip integrated temperature sensor with a sensitivity of better than 5 mV / K, and the output of the temperature sensor can be read out the

  2. Protective effect of KI in mtDNA in porcine thyroid: comparison with KIO₃ and nDNA.

    PubMed

    Karbownik-Lewinska, Malgorzata; Stepniak, Jan; Milczarek, Magdalena; Lewinski, Andrzej

    2015-03-01

    Iodine, bivalent iron (Fe²⁺), and hydrogen peroxide (H₂O₂), all significantly affecting the red-ox balance, are required for thyroid hormone synthesis. Intracellular iodine excess (≥10⁻³ M) transiently blocks thyroid hormonogenesis (an adaptive mechanism called Wolff-Chaikoff effect). The aim of the study was to evaluate the effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO₃), in concentrations corresponding to those typical for Wolff-Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions and in the presence of Fenton reaction (Fe²⁺+H₂O₂ → Fe³⁺+(·)OH + OH⁻) substrates. Thyroid nDNA and mtDNA were incubated in the presence of either KI or KIO₃ (2.5-50 mM), without/with FeSO₄ (30 µM) + H₂O₂ (0.5 mM). Index of DNA damage, i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine, was measured by HPLC. Neither KI nor KIO₃ increased the basal level of 8-oxodG in both nDNA and mtDNA. KI-in all used concentrations-completely prevented the damaging effect of Fenton reaction substrates in mtDNA, and it partially prevented this damage in nDNA. KIO₃ partially prevented Fe²⁺+H₂O₂-induced oxidative damage in both DNA only in its highest used concentrations (≥25 mM). Without additional prooxidative abuse, both iodine compounds, i.e., KI and KIO₃, seem to be safe in terms of their potential oxidative damage to DNA in the thyroid. The superiority of KI over KIO₃ relies on its stronger protective effects against oxidative damage to mtDNA, which constitutes an argument for its preferential utility in iodine prophylaxis.

  3. Population genetic structure of Santa Ynez rainbow trout – 2001 based on microsatellite and mtDNA analyses

    USGS Publications Warehouse

    Nielsen, Jennifer L.; Zimmerman, Christian E.; Olsen, Jeffrey B.; Wiacek, Talia; Kretschmer, E.J.; Greenwald, Glenn M.; Wenburg, John K.

    2003-01-01

    Microsatellite allelic and mitochondrial DNA (mtDNA) haplotype diversity are analyzed in eight rainbow trout (Oncorhynchus mykiss) collections: two from tributaries flowing into the upper Santa Ynez River watershed at Gibraltar Reservoir (Camuesa and Gidney creeks); three from tributaries between Gibraltar and Jameson reservoirs (Fox, Blue Canyon, and Alder creeks); one from a tributary above Jameson Reservoir (Juncal Creek); Jameson Reservoir; and one from the mainstem Santa Ynez River above the Jameson Reservoir. Both analyses reveal a high degree of population structure. Thirteen microsatellite loci are amplified from 376 fish. Population pairwise comparisons show significant differences in allelic frequency among all populations with the exception of Juncal Creek and Jameson Reservoir (p = 0.4). Pairwise Fst values range from 0.001 (Juncal Creek and Jameson Reservoir) to 0.17 (Camuesa and Juncal creeks) with an overall value of 0.021. Regression analyses (Slatkin 1993) supports an isolation-bydistance model in the five populations below Jameson Reservoir (intercept = 1.187, slope = -0.41, r2 = 0.67). A neighbor-joining bootstrap value of 100% (based on 2000 replicate trees) separates the populations sampled above and below Juncal Dam. Composite haplotypes from 321 fish generated using mtDNA sequence data (Dloop) reveal four previously described haplotypes (MYS1, MYS3, MYS5 and MYS8; Nielsen et al. 1994a), and one (MYS5) was found in all populations. Mean haplotype diversity is 0.48. Pairwise Fst values from mtDNA range from -0.019 to 0.530 (0.177 over all populations) and are larger than those for microsatellites in 26 of 28 pairwise comparisons. In addition, the mtDNA and microsatellites provide contrasting evidence of the relationship of Fox and Alder creeks to the other six populations. Discrepancies between the two markers are likely due to the unique properties of the two marker types and their value in revealing historic (mtDNA) versus contemporary

  4. Spine growth mechanisms: friction and seismicity at Mt. Unzen, Japan

    NASA Astrophysics Data System (ADS)

    Hornby, Adrian; Kendrick, Jackie; Hirose, Takehiro; Henton De Angelis, Sarah; De Angelis, Silvio; Umakoshi, Kodo; Miwa, Takahiro; Wadsworth, Fabian; Dingwell, Don; Lavallee, Yan

    2014-05-01

    The final episode of dome growth during the 1991-1995 eruption of Mt. Unzen was characterised by spine extrusion accompanied by repetitive seismicity. This type of cyclic activity has been observed at several dome-building volcanoes and recent work suggests a source mechanism of brittle failure of magma in the conduit. Spine growth may proceed by densification and closure of permeable pathways within the uppermost conduit magma, leading to sealing of the dome and inflation of the edifice. Amplified stresses on the wall rock and plug cause brittle failure near the conduit wall once static friction forces are overcome, and during spine growth these fractures may propagate to the dome surface. The preservation of these features is rare, and the conduit is typically inaccessible; therefore spines, the extruded manifestation of upper conduit material, provide the opportunity to study direct evidence of brittle processes in the conduit. At Mt. Unzen the spine retains evidence for brittle deformation and slip, however mechanical constraints on the formation of these features and their potential impact on eruption dynamics have not been well constrained. Here, we conduct an investigation into the process of episodic spine growth using high velocity friction apparatus at variable shear slip rate (0.4-1.5 m.s-1) and normal stress (0.4-3.5 MPa) on dome rock from Mt. Unzen, generating frictional melt at velocity >0.4 m.s-1 and normal stress >0.7 MPa. Our results show that the presence of frictional melt causes a deviation from Byerlee's frictional rule for rock friction. Melt generation is a disequilibrium process: initial amphibole breakdown leads to melt formation, followed by chemical homogenization of the melt layer. Ultimately, the experimentally generated frictional melts have a similar final chemistry, thickness and comminuted clast size distribution, thereby facilitating the extrapolation of a single viscoelastic model to describe melt-lubricated slip events at Mt

  5. Geothermal observation wells, Mt. Hood, Oregon. Final report, October 4, 1977-July 9, 1979

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Covert, W.F.; Meyer, H.J.

    1979-11-01

    Exploration drilling operations were conducted which included the deepening of an existing hole, designated as Old Maid Flat No. 1, from 1850 ft (564 m) to 4002 (1220 m) on the western approaches to Mt. Hood and the drilling of three new holes ranging from 940 ft (287 m) to 1340 ft (409 m). The Clear Fork hole, located in Old Maid Flat, was drilled to 1320 ft (402 m). The Zigzag hole was drilled to 940 ft (287 m) at the southwestern base of Mt. Hood in the Zigzag River valley. The remaining hole was drilled on the Timberlinemore » Lodge grounds which is on the south flank of Mt. Hood at an elevation of about 6000 ft (1829 m) above sea level. The deepening project designated as Old Maid Flat No. 1 encountered a maximum bottom hole temperature of about 180/sup 0/F (82/sup 0/C) and is to this date the deepest exploratory hole in the Mt. Hood vicinity. No significant drilling problems were encountered. The Clear Fork and Zigzag River holes were completed without significant problems. The Timberline Lodge hole encountered severe drilling conditions, including unconsolidated formations. Two strings of tools were left in the hole from structural collapse of the hole. The hole was scheduled as a 2000 ft (610 m) test. Drilling did not proceed beyond 1350 ft (412 m) and due to junk it was unobstructed to a depth of 838 ft (255 m). Observation pipe was installed to 735 ft (224 m) due to further disintegration of the hole. The work was prematurely terminated due to weather conditions.« less

  6. Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.

    PubMed

    Siegmund, Stephanie E; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A

    2017-12-01

    Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential 'rapamycin metabolic signature.' These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. © The Author 2017. Published by Oxford University Press.

  7. Structural control on the CO2 release west of Mt. Epomeo resurgent block (Ischia, Italy)

    NASA Astrophysics Data System (ADS)

    de Vita, S.; Marotta, E.; Ventura, G.; Chiodini, G.

    2003-04-01

    Volcanism at Ischia started more than 150 ka B.P. and continued until the last eruption occurred in 1302 A.D. Ischia is dominated by the caldera forming eruption of Mt. Epomeo Green Tuff (55 ka), which was followed by block resurgence inside the caldera from 33 ka B.P. Resurgence influenced the volcanic activity determining the conditions for magma ascent mainly along the eastern edge of the resurgent block. The resurgent area has a poligonal shape resulting from reactivation of regional faults and by activation of faults related to volcanotectonism. The western sector is bordered by inward dipping, high angle strike-slip/reverse faults testifying a compressional stress regime in this area. These features are cut by late outward dipping normal faults due to gravitational stress. The activity of the volcanic system is testified by seismicity and thermal manifestations. Fumarolic activity concentrates along the faults that borders westward the Mt. Epomeo resurgent block, where the Green Tuff overlies fractured lavas. The structural data show that, outside the most active degassing zone, fractures show a NNW-SSE strike and dip toward Mt. Epomeo. These fractures delimit the northern sector of Mt. Epomeo and show strike and dip consistent with the inward dipping reverse faults. Inside the degassing area fractures show a NW-SE strike and dip outward Mt. Epomeo. These gravity-related faults cut the lavas where the hydrothermal circulation is active. The dip direction of the NW-SE striking fractures within the degassing zone is not consistent with that of the strike-slip/reverse faults (i.e. towards NE) but agrees well with that of the gravity-induced faults (dip direction towards SW). Inside the degassing zone, NW-SE striking faults with lengths not exceeding the hydrothermalized extension occur. This arrangement indicate that the syn-resurgence faults act as permeability barriers, whereas the youngest faults act as the main fluid pathway.

  8. Environmental exposure to arsenic, AS3MT polymorphism and prevalence of diabetes in Mexico

    PubMed Central

    Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Sánchez-Peña, Luz C.; Barrera-Hernández, Angel; Stýblo, Miroslav; Loomis, Dana

    2014-01-01

    Exposure to arsenic in drinking water is associated with increased prevalence of diabetes. We previously reported an association of diabetes and urinary concentration of dimethylarsinite (DMAsIII), a toxic product of arsenic methylation by arsenic ( +3 oxidation state) methyltransferase (AS3MT). Here we examine associations between AS3MT polymorphism, arsenic metabolism and diabetes. Fasting blood glucose, oral glucose tolerance and self-reported diagnoses were used to identify diabetic individuals. Inorganic arsenic and its metabolites were measured in urine. Genotyping analysis focused on six polymorphic sites of AS3MT. Individuals with M287T and G4965C polymorphisms had higher levels of urinary DMAsIII and were more frequently diabetic than the respective wild-type carriers, although the excess was not statistically significant. Odds ratios were 11.4 (95% confidence interval (CI) 2.2–58.8) and 8.8 (95% CI 1.6–47.3) for the combined effects of arsenic exposure >75th percentile and 287T and 4965C genotypes, respectively. Carriers of 287T and 4965C may produce more DMAsIII and be more likely to develop diabetes when exposed to arsenic. PMID:23093101

  9. The Mitochondrial DNA-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination.

    PubMed

    Blomme, Jonas; Van Aken, Olivier; Van Leene, Jelle; Jégu, Teddy; De Rycke, Riet; De Bruyne, Michiel; Vercruysse, Jasmien; Nolf, Jonah; Van Daele, Twiggy; De Milde, Liesbeth; Vermeersch, Mattias; des Francs-Small, Catherine Colas; De Jaeger, Geert; Benhamed, Moussa; Millar, A Harvey; Inzé, Dirk; Gonzalez, Nathalie

    2017-05-01

    In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana Gain- and loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development. © 2017 American Society of Plant Biologists. All rights reserved.

  10. Structural and heat-flow implications of infrared anomalies at Mt. Hood, Oregon

    USGS Publications Warehouse

    Friedman, Jules D.; Frank, David

    1977-01-01

    Surface thermal features occur in an area of 9700 m2 at Mt. Hood, on the basis of an aerial line-scan survey made April 26, 1973. The distribution of the thermal areas below the summit of Mt. Hood, shown on planimetrically corrected maps at 1:12,000, suggests structural control by a fracture system and brecciated zone peripheral to a hornblende-dacite plug dome (Crater Rock), and by a concentric fracture system that may have been associated with development of the present crater. The extent and inferred temperature of the thermal areas permits a preliminary estimate of a heat discharge of 10 megawatts, by analogy with similar fumarole and thermal fields of Mt. Baker, Washington. This figure includes a heat loss of 4 megawatts (MW) via conduction, diffusion, evaporation, and radiation to the atmosphere, and a somewhat less certain loss of 6MW via fumarolic mass transfer of vapor and advective heat loss from runoff and ice melt. The first part of the estimate is based on two-point models for differential radiant exitance and differential flux via conduction, diffusion, evaporation, and radiation from heat balance of the ground surface. Alternate methods for estimating volcanogenic geothermal flux that assume a quasi-steady state heat flow also yield estimates in the 5-11 MW range. Heat loss equivalent to cooling of the dacite plug dome is judged to be insufficient to account for the heat flux at the fumarole fields.

  11. Magnetotelluric Investigations of Convergent Margins and of Incipient Rifting: Preliminary Results from the EarthScope MT Transportable Array and MT FlexArray Deployments in Cascadia and in the North American Mid-Continent Region

    NASA Astrophysics Data System (ADS)

    Schultz, A.; Bedrosian, P.; Key, K.; Livelybrooks, D.; Egbert, G. D.; Bowles-martinez, E.; Wannamaker, P. E.

    2014-12-01

    We report on preliminary analyses of data from the EarthScope MT Transportable Array, and from two high-resolution EarthScope MT studies in Cascadia. The first of these, iMUSH, is acquiring wideband MT data at 150 sites, as well as active and passive seismic data in SW Washington (including Mounts Saint Helens, Adams and Rainier). iMUSH seeks to determine details of crustal magma transport and storage, and to resolve major tectonic controls on volcanism along the arc. iMUSH may help to settle a debate over the origin of the SW Washington Crustal Conductor (SWCC), which covers ~5000 km2and that has alternately been attributed to accreted Eocene metasediments or to an extensive region of partial melt in the lower crust beneath the three volcanoes. The iMUSH array is continguous with an amphibious ~150 station MT experiment (MOCHA) onshore and offshore of the Washington and Oregon forearc. MOCHA iwill image the crust and upper mantle of the subduction system in 3D, constraining the fluid input to the system from offshore and the distribution of fluids released from the down-going slab, including along the transitional zone where Episodic Tremor and Slip occurs. Our goal is to refine our understanding of the segmentation, structure and fluid distribution along the convergent margin segments, and their relationship to the spatial pattern of ETS. In contrast to the active Cascadia margin, the Mid-Continent Rift (MCR) is the trace of a massive igneous event that nearly split North America 1.1 billion years ago. Initial results from 3D inversion of MT Transportable Array data show less fine-scale heterogeneity in the upper mantle (250 km depth) than is evident in western, tectonic North America, but a division at the base of thick lithosphere, with higher conductivities beneath and immediately south of the Great Lakes, than to the south. From the base of the lithosphere to the Moho, this high conductivity feature narrows, ultimately disappearing in the mid-crust. In the

  12. Trading genes along the silk road: mtDNA sequences and the origin of central Asian populations.

    PubMed Central

    Comas, D; Calafell, F; Mateu, E; Pérez-Lezaun, A; Bosch, E; Martínez-Arias, R; Clarimon, J; Facchini, F; Fiori, G; Luiselli, D; Pettener, D; Bertranpetit, J

    1998-01-01

    Central Asia is a vast region at the crossroads of different habitats, cultures, and trade routes. Little is known about the genetics and the history of the population of this region. We present the analysis of mtDNA control-region sequences in samples of the Kazakh, the Uighurs, the lowland Kirghiz, and the highland Kirghiz, which we have used to address both the population history of the region and the possible selective pressures that high altitude has on mtDNA genes. Central Asian mtDNA sequences present features intermediate between European and eastern Asian sequences, in several parameters-such as the frequencies of certain nucleotides, the levels of nucleotide diversity, mean pairwise differences, and genetic distances. Several hypotheses could explain the intermediate position of central Asia between Europe and eastern Asia, but the most plausible would involve extensive levels of admixture between Europeans and eastern Asians in central Asia, possibly enhanced during the Silk Road trade and clearly after the eastern and western Eurasian human groups had diverged. Lowland and highland Kirghiz mtDNA sequences are very similar, and the analysis of molecular variance has revealed that the fraction of mitochondrial genetic variance due to altitude is not significantly different from zero. Thus, it seems unlikely that altitude has exerted a major selective pressure on mitochondrial genes in central Asian populations. PMID:9837835

  13. Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

    PubMed Central

    Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

  14. Elastostatic effects around a magma reservoir and pathway due to historic earthquakes: a case study of Mt. Fuji, Japan

    NASA Astrophysics Data System (ADS)

    Hosono, Masaki; Mitsui, Yuta; Ishibashi, Hidemi; Kataoka, Jun

    2016-12-01

    We discuss elastostatic effects on Mt. Fuji, the tallest volcano in Japan, due to historic earthquakes in Japan. The 1707 Hoei eruption, which was the most explosive historic eruption of Mt. Fuji, occurred 49 days after the Hoei earthquake (Mw 8.7) along the Nankai Trough. It was previously suggested that the Hoei earthquake induced compression of a basaltic magma reservoir and unclamping of a dike-intruded region at depth, possibly triggering magma mixing and the subsequent Plinian eruption. Here, we show that the 1707 Hoei earthquake was a special case of induced volumetric strain and normal stress changes around the magma reservoir and pathway of Mt. Fuji. The 2011 Tohoku earthquake (Mw 9), along the Japan Trench, dilated the magma reservoir. It has been proposed that dilation of a magma reservoir drives the ascent of gas bubbles with magma and further depressurization, leading to a volcanic eruption. In fact, seismicity notably increased around Mt. Fuji during the first month after the 2011 Tohoku earthquake, even when we statistically exclude aftershocks, but the small amount of strain change (< 1 μ strain) may have limited the ascent of magma. For many historic earthquakes, the magma reservoir was compressed and the magma pathway was wholly clamped. This type of interaction has little potential to mechanically trigger the deformation of a volcano. Thus, Mt. Fuji may be less susceptible to elastostatic effects because of its location relative to the sources of large tectonic earthquakes. As an exception, a possible local earthquake in the Fujikawa-kako fault zone could induce a large amount of magma reservoir dilation beneath the southern flank of Mt. Fuji.

  15. MT-7716, a novel selective nonpeptidergic NOP receptor agonist, effectively blocks ethanol-induced increase in GABAergic transmission in the rat central amygdala

    PubMed Central

    Kallupi, Marsida; Oleata, Christopher S.; Luu, George; Teshima, Koji; Ciccocioppo, Roberto; Roberto, Marisa

    2014-01-01

    The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. A large body of evidence shows that Nociceptin/Orphanin FQ (N/OFQ) regulates ethanol intake and anxiety-like behavior. In the rat, ethanol significantly augments CeA GABA release, whereas N/OFQ diminishes it. Using electrophysiological techniques in an in vitro slice preparation, in this study we investigated the effects of a nonpeptidergic NOP receptor agonist, MT-7716 [(R)-2-3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl-N-methylacetamide hydrochloride hydrate], and its interaction with ethanol on GABAergic transmission in CeA slices of naïve rats. We found that MT-7716 dose-dependently (100–1000 nM) diminished evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) and increased paired-pulse facilitation (PPF) ratio of these evoked IPSPs, suggesting a presynaptic site of action of the MT-7716 by decreasing GABA release at CeA synapses. The presynaptic action of MT-7716 was also supported by the significant decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) induced by the nociceptin receptor (NOP) agonist. Interestingly, MT-7716 prevented the ethanol-induced augmentation of evoked IPSPs. A putative selective NOP antagonist, [Nphe1]Nociceptin(1–13)NH2, totally prevented the MT-7716-induced inhibition of IPSP amplitudes indicating that MT-7716 exerts its effect through NOPs. These data provide support for an interaction between the nociceptin and GABAergic systems in the CeA and for the anti-alcohol properties of the NOP activation. The development of a synthetic nonpeptidergic NOP receptor agonist such as MT-7716 may represent a useful therapeutic target for alcoholism. PMID:24600360

  16. The Mitochondrial DNA-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination[OPEN

    PubMed Central

    Vercruysse, Jasmien; Van Daele, Twiggy; De Milde, Liesbeth; Benhamed, Moussa; Inzé, Dirk

    2017-01-01

    In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gain- and loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development. PMID:28420746

  17. Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability.

    PubMed

    O'Rourke, Thomas W; Doudican, Nicole A; Zhang, Hong; Eaton, Jana S; Doetsch, Paul W; Shadel, Gerald S

    2005-07-18

    With the exception of base excision repair, conserved pathways and mechanisms that maintain mitochondrial genome stability have remained largely undelineated. In the budding yeast, Saccharomyces cerevisiae, Pif1p is a unique DNA helicase that is localized both to the nucleus and mitochondria, where it is involved in maintaining DNA integrity. We previously elucidated a role for Pif1p in oxidative mtDNA damage resistance that appears to be distinct from its postulated function in mtDNA recombination. Strains lacking Pif1p (pif1Delta) exhibit an increased rate of formation of petite mutants (an indicator of mtDNA instability) and elevated mtDNA point mutagenesis. Here we show that deletion of the RRM3 gene, which encodes a DNA helicase closely related to Pif1p, significantly rescues the petite-induction phenotype of a pif1Delta strain. However, suppression of this phenotype was not accompanied by a corresponding decrease in mtDNA point mutagenesis. Instead, deletion of RRM3 alone resulted in an increase in mtDNA point mutagenesis that was synergistic with that caused by a pif1Delta mutation. In addition, we found that over-expression of RNR1, encoding a large subunit of ribonucleotide reductase (RNR), rescued the petite-induction phenotype of a pif1Delta mutation to a similar extent as deletion of RRM3. This, coupled to our finding that the Rad53p protein kinase is phosphorylated in the rrm3Delta pif1Delta double-mutant strain, leads us to conclude that one mechanism whereby deletion of RRM3 influences mtDNA stability is by modulating mitochondrial deoxynucleoside triphosphate pools. We propose that this is accomplished by signaling through the conserved Mec1/Rad53, S-phase checkpoint pathway to induce the expression and activity of RNR. Altogether, our results define a novel role for Rrm3p in mitochondrial function and indicate that Pif1p and Rrm3p influence a common process (or processes) involved in mtDNA replication, repair, or stability.

  18. LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer.

    PubMed

    Zhang, Gang; Li, Shuwei; Lu, Jiafei; Ge, Yuqiu; Wang, Qiaoyan; Ma, Gaoxiang; Zhao, Qinghong; Wu, Dongdong; Gong, Weida; Du, Mulong; Chu, Haiyan; Wang, Meilin; Zhang, Aihua; Zhang, Zhengdong

    2018-05-02

    Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.

  19. Effects of Inorganic Arsenic, Methylated Arsenicals, and Arsenobetaine on Atherosclerosis in the apoE−/− Mouse Model and the Role of As3mt-Mediated Methylation

    PubMed Central

    Negro Silva, Luis Fernando; Lemaire, Maryse; Lemarié, Catherine A.; Plourde, Dany; Bolt, Alicia M.; Chiavatti, Christopher; Bohle, D. Scott; Slavkovich, Vesna; Graziano, Joseph H.; Lehoux, Stéphanie

    2017-01-01

    Background: Arsenic is metabolized through a series of oxidative methylation reactions by arsenic (3) methyltransferase (As3MT) to yield methylated intermediates. Although arsenic exposure is known to increase the risk of atherosclerosis, the contribution of arsenic methylation and As3MT remains undefined. Objectives: Our objective was to define whether methylated arsenic intermediates were proatherogenic and whether arsenic biotransformation by As3MT was required for arsenic-enhanced atherosclerosis. Methods: We utilized the apoE−/− mouse model to compare atherosclerotic plaque size and composition after inorganic arsenic, methylated arsenical, or arsenobetaine exposure in drinking water. We also generated apoE−/−/As3mt−/− double knockout mice to test whether As3MT-mediated biotransformation was required for the proatherogenic effects of inorganic arsenite. Furthermore, As3MT expression and function were assessed in in vitro cultures of plaque-resident cells. Finally, bone marrow transplantation studies were performed to define the contribution of As3MT-mediated methylation in different cell types to the development of atherosclerosis after inorganic arsenic exposure. Results: We found that methylated arsenicals, but not arsenobetaine, are proatherogenic and that As3MT is required for arsenic to induce reactive oxygen species and promote atherosclerosis. Importantly, As3MT was expressed and functional in multiple plaque-resident cell types, and transplant studies indicated that As3MT is required in extrahepatic tissues to promote atherosclerosis. Conclusion: Taken together, our findings indicate that As3MT acts to promote cardiovascular toxicity of arsenic and suggest that human AS3MT SNPs that correlate with enzyme function could predict those most at risk to develop atherosclerosis among the millions that are exposed to arsenic. https://doi.org/10.1289/EHP806 PMID:28728140

  20. Segregation and manifestations of the mtDNA tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Larsson, N.G.; Tulinius, M.H.; Holme, E.

    1992-12-01

    The authors have studied the segregation and manifestations of the tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA[sup Lys] mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, andmore » mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrone had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that >92% of mtDNA with the tRNA[sup Lys] mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA[sup Lys] mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. 30 refs., 3 figs., 5 tabs.« less

  1. Two applications of the Recently Developed UZF-MT3DMS Model for Evaluating Nonpoint-Source Fluxes (Invited)

    NASA Astrophysics Data System (ADS)

    Morway, E. D.; Niswonger, R. G.; Nishikawa, T.

    2013-12-01

    The solute-transport model MT3DMS was modified to simulate transport in the unsaturated-zone by incorporating the additional flow terms calculated by the Unsaturated-Zone Flow (UZF) package developed for MODFLOW. Referred to as UZF-MT3DMS, the model simulates advection and dispersion of conservative and reactive solutes in unsaturated and saturated porous media. Significant time savings are realized owing to the efficiency of the kinematic -wave approximation used by the UZF1 package relative to Richards' equation-based approaches, facilitating the use of automated parameter-estimation routines wherein thousands of model runs may be required. Currently, UZF-MT3DMS is applied to two real-world applications of existing MODFLOW and MT3DMS models retro-fitted to use the UZF1 package for simulating the unsaturated component of the sub-surface system. In the first application, two regional-scale investigations located in Colorado's Lower Arkansas River Valley (LARV) are developed to evaluate the extent and severity of unsaturated-zone salinization contributing to crop yield loss. Preliminary results indicate root zone concentrations over both regions are at or above salinity-thresholds of most crop types grown in the LARV. Regional-scale modeling investigations of salinization found in the literature commonly use lumped-parameter models rather than physically-based distributed-parameter models. In the second application, located near Joshua Tree, CA, nitrate loading to the underlying unconfined aquifer from domestic septic systems is evaluated. Due to the region's thick unsaturated-zone and correspondingly long unsaturated-zone residence times (multi-decade), UZF-MT3DMS enabled direct simulation of spatially-varying concentration break-through curves at the water table.

  2. Kleptoparasitic behavior and species richness at Mt. Graham red squirrel middens

    Treesearch

    Andrew J. Edelman; John L. Koprowski; Jennifer L. Edelman

    2005-01-01

    We used remote photography to assess the frequency of inter- and intra-specific kleptoparasitism and species richness at Mt. Graham red squirrel (Tamiasciurus hudsonicus grahamensis) middens. Remote cameras and conifer cones were placed at occupied and unoccupied middens, and random sites. Species richness of small mammals was higher at red squirrel...

  3. Microrefugia and Shifts of Hippophae tibetana (Elaeagnaceae) on the north side of Mt. Qomolangma (Mt. Everest) during the last 25000 years.

    PubMed

    Xu, Lu; Wang, Hao; La, Qiong; Lu, Fan; Sun, Kun; Fang, Yang; Yang, Mei; Zhong, Yang; Wu, Qianhong; Chen, Jiakuan; Birks, H John B; Zhang, Wenju

    2014-01-01

    Microrefugia at high altitudes or high latitudes are thought to play an important role in the post-glacial colonization of species. However, how populations in such microrefugia have responded to climate changes in alternating cold glacial and warm interglacial stages remain unclear. Here we present evidence to indicate the Rongbuk Valley of the Mt. Qomolangma (Mt. Everest) area, the highest region on earth, had microrefugia for Hippophae tibetana and discuss how this low shrub was adapted to the extreme climate fluctuations of the last 25,000 years by shifts. By integrating geological, glaciological, meteorological, and genetic information, we found that the Rongbuk Valley was not only a glacial microrefugium but also an interglacial microrefugium for H. tibetana: the former was located on the riverbank below 4800 m above sea level (asl) or lower area and the latter at ∼ 5000 m asl. Our results show that after the Last Glacial Maximum (LGM), H. tibetana in the valley has undergone upward and downward migrations around ∼ 5000 m driven by climate fluctuations and the population in the glacial microrefugium has suffered extinction or extreme contraction. Moreover, with the rise of temperature in the last four decades, the upper limit of H. tibetana has shifted at least 30 m upward. Combining population history and recent range shift of this species is important in predicting the fate of this endemic species to future climate changes.

  4. Microrefugia and Shifts of Hippophae tibetana (Elaeagnaceae) on the North Side of Mt. Qomolangma (Mt. Everest) during the Last 25000 Years

    PubMed Central

    Lu, Fan; Sun, Kun; Fang, Yang; Yang, Mei; Zhong, Yang; Wu, Qianhong; Chen, Jiakuan; Birks, H. John B.; Zhang, Wenju

    2014-01-01

    Microrefugia at high altitudes or high latitudes are thought to play an important role in the post-glacial colonization of species. However, how populations in such microrefugia have responded to climate changes in alternating cold glacial and warm interglacial stages remain unclear. Here we present evidence to indicate the Rongbuk Valley of the Mt. Qomolangma (Mt. Everest) area, the highest region on earth, had microrefugia for Hippophae tibetana and discuss how this low shrub was adapted to the extreme climate fluctuations of the last 25,000 years by shifts. By integrating geological, glaciological, meteorological, and genetic information, we found that the Rongbuk Valley was not only a glacial microrefugium but also an interglacial microrefugium for H. tibetana: the former was located on the riverbank below 4800 m above sea level (asl) or lower area and the latter at ∼5000 m asl. Our results show that after the Last Glacial Maximum (LGM), H. tibetana in the valley has undergone upward and downward migrations around ∼5000 m driven by climate fluctuations and the population in the glacial microrefugium has suffered extinction or extreme contraction. Moreover, with the rise of temperature in the last four decades, the upper limit of H. tibetana has shifted at least 30 m upward. Combining population history and recent range shift of this species is important in predicting the fate of this endemic species to future climate changes. PMID:24841004

  5. The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

    PubMed

    Noda, Aoi; Yonesaka, Riku; Sasazaki, Shinji; Mannen, Hideyuki

    2018-01-01

    Aurochs (Bos primigenius) were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E) have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle. We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region. We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181). Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity.

  6. Germ line insertion of mtDNA at the breakpoint junction of a reciprocal constitutional translocation.

    PubMed

    Willett-Brozick, J E; Savul, S A; Richey, L E; Baysal, B E

    2001-08-01

    Constitutional chromosomal translocations are relatively common causes of human morbidity, yet the DNA double-strand break (DSB) repair mechanisms that generate them are incompletely understood. We cloned, sequenced and analyzed the breakpoint junctions of a familial constitutional reciprocal translocation t(9;11)(p24;q23). Within the 10-kb region flanking the breakpoints, chromosome 11 had 25% repeat elements, whereas chromosome 9 had 98% repeats, 95% of which were L1-type LINE elements. The breakpoints occurred within an L1-type repeat element at 9p24 and at the 3'-end of an Alu sequence at 11q23. At the breakpoint junction of derivative chromosome 9, we discovered an unusually large 41-bp insertion, which showed 100% identity to 12S mitochondrial DNA (mtDNA) between nucleotides 896 and 936 of the mtDNA sequence. Analysis of the human genome failed to show the preexistence of the inserted sequence at normal chromosomes 9 and 11 breakpoint junctions or elsewhere in the genome, strongly suggesting that the insertion was derived from human mtDNA and captured into the junction during the DSB repair process. To our knowledge, these findings represent the first observation of spontaneous germ line insertion of modern human mtDNA sequences and suggest that DSB repair may play a role in inter-organellar gene transfer in vivo. Our findings also provide evidence for a previously unrecognized insertional mechanism in human, by which non-mobile extra-chromosomal fragments can be inserted into the genome at DSB repair junctions.

  7. The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

    PubMed Central

    Noda, Aoi; Yonesaka, Riku; Sasazaki, Shinji

    2018-01-01

    Background Aurochs (Bos primigenius) were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E) have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle. Methodology We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region. Conclusions We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181). Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity. PMID:29304129

  8. Evolution of the lithospheric mantle beneath Mt. Baekdu (Changbaishan)

    NASA Astrophysics Data System (ADS)

    Choi, S. H.; Park, K.; Cho, M.; Lee, D. C.

    2017-12-01

    Major and trace element compositions of minerals as well as Sr-Nd-Hf isotopic compositions of clinopyroxenes from spinel peridotite xenoliths entrained in Late Cenozoic trachybasalt from Mt. Baekdu (Changbaishan) were used to elucidate lithospheric mantle formation and evolution in the eastern North China Craton (NCC). The analyzed peridotites were mainly spinel lherzolites with rare harzburgites. They consisted of olivine, enstatite, diopside and spinel. Plots of the Cr# in spinel against the Mg# in coexisting olivine or spinel suggested an affinity with abyssal peridotites. Comparisons of Cr# and TiO2 in spinel were also compatible with an abyssal peridotite-like composition; however, harzburgites were slightly enriched in TiO2 because of the reaction with MORB-like melt. Temperatures estimated using two-pyroxene thermometry ranged from 750 to 1,010°C, reflecting their lithospheric mantle origin. The REE patterns in clinopyroxenes of the peridotites varied from LREE-depleted to spoon shaped to LREE-enriched, reflecting secondary overprinting effects of metasomatic melts or fluids on the residues from primordial melting. The calculated trace element pattern of metasomatic melt equilibrated with clinopyroxene in Mt. Baekdu peridotite showed strong enrichment in LILEs, Th and U together with slight fractionation in HREEs and considerable depletion in Nb and Ti. The Sr-Nd-Hf isotopic compositions of clinopyroxenes separated from the peridotites varied from more depleted than present-day MORB to bulk Earth values. However, some clinopyroxene showed a decoupling between Nd and Sr isotopes, deviating from the mantle array with a high 87Sr/86Sr ratio. This sample also showed a significant Nd-Hf isotope decoupling lying well above the mantle array. The Lu-Hf and Sm-Nd model ages of residual clinopyroxenes yielded Early Proterozoic to Phanerozoic ages. No signature of Archean cratonic mantle was present. Therefore, Mt. Baekdu peridotite is residual lithospheric mantle

  9. Hazard connected to tunnel construction in Mt Stena karstic area (Rosandra Valley, Classical Karst)

    NASA Astrophysics Data System (ADS)

    Cucchi, F.; Boschin, W.; Visintin, L.; Zini, L.

    2009-04-01

    Rosandra Valley -a unique geomorphological environment- is located in the western side of the Classical Karst plateau. This deep limestone gorge is crossed by a stream that is fed by a large basin located in Slovenia. Rosandra Valley is the only example of Classical Karst river valley with surface hydrography; the torrent digs a deep gully into the rock, rich in rapids, swirl holes, small waterfalls, enclosed meanders and basins; here, the first seepage phenomena occur, and part of the water feeds the underground aquifer. Rosandra Valley is theatre to complex structural situation; the NE slope culminates in the structure of Mt Stena, a limestone tectonic scale located between two faults and firmly rooted in the karst platform. Tectonics is quite important for the development of deep karst in this area; Mt Stena, in particular, hosts a comprehensive net of articulated and diversely shaped caves, basically organised on several levels, which stretches over a total of 9,000 metres, bearing testimony to ancient geological and hydrogeological origins. The deepest areas of the system reach a suspended aquifer that is probably sustained by an overthrust and placed about 100 meters above Rosandra torrent underground aquifer. During feasibility studies about Trieste-Divača high velocity railway link, interaction between project and karst features was examined; in fact the proximity of proposal project and Mt Stena karst system suggest to improve the knowledge related to karst and hydrogeological aspects of the massif. Compatibly with the project requirements, risk of voids intersection and water contamination were analyzed. In fact the Mt Stena suspended aquifer partially feeds Rosandra torrent which flows in a protected natural area. Karst features were represented in a 3D model in order to better understand the spatial relationship between railway project and karst system.

  10. Cenozoic exhumation history of South China: A case study from the Xuefeng Mt. Range

    NASA Astrophysics Data System (ADS)

    Wang, Yannan; Zhang, Jin; Zhang, Beihang; Zhao, Heng

    2018-01-01

    New apatite fission track (AFT) dating was applied to the Xuefeng Mt. Range and Yuanma Basin to constrain the Cenozoic exhumation process of the southeastern Yangtze Block, South China. The analyzed samples in this study have AFT ages ranging from 27.9 ± 2.5 to 61.5 ± 5.9 Ma, which are younger than the deposition or crystallization ages of the host rocks. The AFT analysis and thermal history modeling indicate that both the Xuefeng Mt. Range and the Yuanma Basin underwent significant exhumation during the early Cenozoic (ca. 60-40 Ma). These samples were rapidly exhumed to near the surface during this period. Our results suggest that an important tectonic event occurred along or near regional fault zones (e.g., the Qinhang Fault) in South China during the early Cenozoic (ca. 60-40 Ma). However, it is difficult to relate this event to the Eastern Sichuan fold belt, which is much older and is characterized by large-scale folding and thrusting. Combined with fieldwork in the Yuanma, Xupu, and Xinning basins, we refute the Cretaceous "Pan-Yangtze Basin" that was proposed to have been separated by the uplifted Xuefeng Mt. Range after the Late Cretaceous. The exhumation stage from ca. 60 Ma to 40 Ma was an important period during which plate movements across the eastern Asian and Pacific regions were reorganized. The early Cenozoic tectonothermal event in South China can be attributed to a change in the direction and speed of the subduction of the Pacific Plate beneath the Eurasian Plate. An Oligocene-Miocene cooling event was also recorded in the eastern Xuefeng Mt. Range, which we tentatively attribute to the activity of dextral faults in this area as a far-field effect of the collision between the Indian and Eurasian plates.

  11. Depletion of atmospheric gaseous elemental mercury by plant uptake at Mt. Changbai, Northeast China

    NASA Astrophysics Data System (ADS)

    Fu, Xuewu; Zhu, Wei; Zhang, Hui; Sommar, Jonas; Yu, Ben; Yang, Xu; Wang, Xun; Lin, Che-Jen; Feng, Xinbin

    2016-10-01

    There exists observational evidence that gaseous elemental mercury (GEM) can be readily removed from the atmosphere via chemical oxidation followed by deposition in the polar and sub-polar regions, free troposphere, lower stratosphere, and marine boundary layer under specific environmental conditions. Here we report GEM depletions in a temperate mixed forest at Mt. Changbai, Northeast China. The strong depletions occurred predominantly at night during the leaf-growing season and in the absence of gaseous oxidized mercury (GOM) enrichment (GOM < 3 pg m-3). Vertical gradients of decreasing GEM concentrations from layers above to under forest canopy suggest in situ loss of GEM to forest canopy at Mt. Changbai. Foliar GEM flux measurements showed that the foliage of two predominant tree species is a net sink of GEM at night, with a mean flux of -1.8 ± 0.3 ng m2 h-1 over Fraxinus mandshurica (deciduous tree species) and -0.1 ± 0.2 ng m2 h-1 over Pinus Koraiensis (evergreen tree species). Daily integrated GEM δ202Hg, Δ199Hg, and Δ200Hg at Mt. Changbai during 8-18 July 2013 ranged from -0.34 to 0.91 ‰, from -0.11 to -0.04 ‰ and from -0.06 to 0.01 ‰, respectively. A large positive shift in GEM δ202Hg occurred during the strong GEM depletion events, whereas Δ199Hg and Δ200Hg remained essentially unchanged. The observational findings and box model results show that uptake of GEM by forest canopy plays a predominant role in the GEM depletion at Mt. Changbai forest. Such depletion events of GEM are likely to be a widespread phenomenon, suggesting that the forest ecosystem represents one of the largest sinks ( ˜ 1930 Mg) of atmospheric Hg on a global scale.

  12. 75 FR 58430 - Notice of Inventory Completion: University of Montana, Missoula, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... DEPARTMENT OF THE INTERIOR National Park Service Notice of Inventory Completion: University of... University of Montana, Missoula, MT. The human remains and associated funerary object were removed from a... made by University of Montana, Department of Anthropology, professional staff in consultation with...

  13. Aerosol ionic components at Mt. Heng in central southern China: abundances, size distribution, and impacts of long-range transport.

    PubMed

    Gao, Xiaomei; Xue, Likun; Wang, Xinfeng; Wang, Tao; Yuan, Chao; Gao, Rui; Zhou, Yang; Nie, Wei; Zhang, Qingzhu; Wang, Wenxing

    2012-09-01

    Water-soluble ions in PM(2.5) were continuously measured, along with the measurements of many other species and collection of size-resolved aerosol samples, at the summit of Mt. Heng in the spring of 2009, to understand the sources of aerosols in rural central southern China. The mean concentrations of SO(4)(2-), NH(4)(+) and NO(3)(-) in PM(2.5) were 8.02, 2.94 and 1.47 μg/m(3), indicating a moderate aerosol pollution level at Mt. Heng. Water-soluble ions composed approximately 40% of the PM(2.5) mass on average. PM(2.5) was weakly acidic with about 66% of the samples being acidic. SO(4)(2-), NO(3)(-) and NH(4)(+) exhibited similar diurnal patterns with a broad afternoon maximum. SO(4)(2-) and NH(4)(+) were mainly present in the fine aerosols with a peak in the droplet mode of 0.56-1 μm, suggesting the important role of cloud processing in the formation of aerosol sulfate. NO(3)(-) was largely distributed in the coarse particles with a predominant peak in the size-bin of 3.2-5.6 μm. Long-distance transport of processed air masses, dust aerosols, and cloud/fog processes were the major factors determining the variations of fine aerosol at Mt. Heng. The results at Mt. Heng were compared with those obtained from our previous study at Mt. Tai in north China. The comparison revealed large differences in the aerosol characteristics and processes between southern and northern China. Backward trajectories indicated extensive transport of anthropogenic pollution from the coastal regions of eastern/northern China and the Pearl River Delta (PRD) to Mt. Heng in spring, highlighting the need for regionally coordinated control measures for the secondary pollutants. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. An ice core record of net snow accumulation and seasonal snow chemistry at Mt. Waddington, southwest British Columbia, Canada

    NASA Astrophysics Data System (ADS)

    Neff, P. D.; Steig, E. J.; Clark, D. H.; McConnell, J. R.; Pettit, E. C.; Menounos, B.

    2011-12-01

    We recovered a 141 m ice core from Combatant Col (51.39°N, 125.22°W, 3000 m asl) on the flank of Mt. Waddington, southern Coast Mountains, British Columbia, Canada. Aerosols and other impurities in the ice show unambiguous seasonal variations, allowing for annual dating of the core. Clustered melt layers, originating from summer surface heating, also aid in the dating of the core. Seasonality in water stable isotopes is preserved throughout the record, showing little evidence of diffusion at depth, and serves as an independent verification of the timescale. The annual signal of deuterium excess is especially well preserved. The record of lead deposition in the core agrees with those of ice cores from Mt. Logan and from Greenland, with a sharp drop-off in concentration in the 1970s and early 1980s, further validating the timescales. Despite significant summertime melt at this mid-latitude site, these data collectively reveal a continuous and annually resolved 36-year record of snow accumulation. We derived an accumulation time series from the Mt. Waddington ice core, after correcting for ice flow. Years of anomalously high or low snow accumulation in the core correspond with extremes in precipitation data and geopotential height anomalies from reanalysis data that make physical sense. Specifically, anomalously high accumulation years at Mt. Waddington correlate with years where "Pineapple Express" atmospheric river events bring large amounts of moisture from the tropical Pacific to western North America. The Mt. Waddington accumulation record thus reflects regional-scale climate. These results demonstrate the potential of ice core records from temperate glaciers to provide meaningful paleoclimate information. A longer core to bedrock (250-300 m) at the Mt. Waddington site could yield ice with an age of several hundred to 1000 years.

  15. Y-Chromosome and mtDNA Genetics Reveal Significant Contrasts in Affinities of Modern Middle Eastern Populations with European and African Populations

    PubMed Central

    Badro, Danielle A.; Youhanna, Sonia C.; Salloum, Angélique; Ghassibe-Sabbagh, Michella; Johnsrud, Brian; Khazen, Georges; Matisoo-Smith, Elizabeth; Soria-Hernanz, David F.; Wells, R. Spencer; Tyler-Smith, Chris; Platt, Daniel E.; Zalloua, Pierre A.

    2013-01-01

    The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of FST's, RST's, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations. PMID:23382925

  16. Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis

    PubMed Central

    Remacle, Albert G; Cieplak, Piotr; Hyun, Dong Nam; Shiryaev, Sergey A; Ge, Xin; Strongin, Alex Y

    2017-01-01

    The invasion-promoting MT1-MMP is a cell surface-associated collagenase with a plethora of critical cellular functions. There is a consensus that MT1-MMP is a key protease in aberrant pericellular proteolysis in migrating cancer cells and, accordingly, a promising drug target. Because of high homology in the MMP family and a limited success in the design of selective small-molecule inhibitors, it became evident that the inhibitor specificity is required for selective and successful MT1-MMP therapies. Using the human Fab antibody library (over 1.25×109 individual variants) that exhibited the extended, 23-27 residue long, VH CDR-H3 segments, we isolated a panel of the inhibitory antibody fragments, from which the 3A2 Fab outperformed others as a specific and potent, low nanomolar range, inhibitor of MT1-MMP. Here, we report the in-depth characterization of the 3A2 antibody. Our multiple in vitro and cell-based tests and assays, and extensive structural modeling of the antibody/protease interactions suggest that the antibody epitope involves the residues proximal to the protease catalytic site and that, in contrast with tissue inhibitor-2 of MMPs (TIMP-2), the 3A2 Fab inactivates the protease functionality by binding to the catalytic domain outside the active site cavity. In agreement with the studies in metastasis by others, our animal studies in acute pulmonary melanoma metastasis support a key role of MT1-MMP in metastatic process. Conversely, the selective anti-MT1-MMP monotherapy significantly alleviated melanoma metastatic burden. It is likely that further affinity maturation of the 3A2 Fab will result in the lead inhibitor and a proof-of-concept for MT1-MMP targeting in metastatic cancers. PMID:27835863

  17. Y-chromosome and mtDNA genetics reveal significant contrasts in affinities of modern Middle Eastern populations with European and African populations.

    PubMed

    Badro, Danielle A; Douaihy, Bouchra; Haber, Marc; Youhanna, Sonia C; Salloum, Angélique; Ghassibe-Sabbagh, Michella; Johnsrud, Brian; Khazen, Georges; Matisoo-Smith, Elizabeth; Soria-Hernanz, David F; Wells, R Spencer; Tyler-Smith, Chris; Platt, Daniel E; Zalloua, Pierre A

    2013-01-01

    The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

  18. Structural and Functional Studies of a Phosphatidic Acid-Binding Antifungal Plant Defensin MtDef4: Identification of an RGFRRR Motif Governing Fungal Cell Entry

    PubMed Central

    Buchko, Garry W.; Berg, Howard R.; Kaur, Jagdeep; Pandurangi, Raghu S.; Smith, Thomas J.; Shah, Dilip M.

    2013-01-01

    MtDef4 is a 47-amino acid cysteine-rich evolutionary conserved defensin from a model legume Medicago truncatula. It is an apoplast-localized plant defense protein that inhibits the growth of the ascomycetous fungal pathogen Fusarium graminearum in vitro at micromolar concentrations. Little is known about the mechanisms by which MtDef4 mediates its antifungal activity. In this study, we show that MtDef4 rapidly permeabilizes fungal plasma membrane and is internalized by the fungal cells where it accumulates in the cytoplasm. Furthermore, analysis of the structure of MtDef4 reveals the presence of a positively charged γ-core motif composed of β2 and β3 strands connected by a positively charged RGFRRR loop. Replacement of the RGFRRR sequence with AAAARR or RGFRAA abolishes the ability of MtDef4 to enter fungal cells, suggesting that the RGFRRR loop is a translocation signal required for the internalization of the protein. MtDef4 binds to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Amino acid substitutions in the RGFRRR sequence which abolish the ability of MtDef4 to enter fungal cells also impair its ability to bind PA. These findings suggest that MtDef4 is a novel antifungal plant defensin capable of entering into fungal cells and affecting intracellular targets and that these processes are mediated by the highly conserved cationic RGFRRR loop via its interaction with PA. PMID:24324798

  19. Mitochondrial proteome disruption in the diabetic heart through targeted epigenetic regulation at the mitochondrial heat shock protein 70 (mtHsp70) nuclear locus.

    PubMed

    Shepherd, Danielle L; Hathaway, Quincy A; Nichols, Cody E; Durr, Andrya J; Pinti, Mark V; Hughes, Kristen M; Kunovac, Amina; Stine, Seth M; Hollander, John M

    2018-06-01

    >99% of the mitochondrial proteome is nuclear-encoded. The mitochondrion relies on a coordinated multi-complex process for nuclear genome-encoded mitochondrial protein import. Mitochondrial heat shock protein 70 (mtHsp70) is a key component of this process and a central constituent of the protein import motor. Type 2 diabetes mellitus (T2DM) disrupts mitochondrial proteomic signature which is associated with decreased protein import efficiency. The goal of this study was to manipulate the mitochondrial protein import process through targeted restoration of mtHsp70, in an effort to restore proteomic signature and mitochondrial function in the T2DM heart. A novel line of cardiac-specific mtHsp70 transgenic mice on the db/db background were generated and cardiac mitochondrial subpopulations were isolated with proteomic evaluation and mitochondrial function assessed. MicroRNA and epigenetic regulation of the mtHsp70 gene during T2DM were also evaluated. MtHsp70 overexpression restored cardiac function and nuclear-encoded mitochondrial protein import, contributing to a beneficial impact on proteome signature and enhanced mitochondrial function during T2DM. Further, transcriptional repression at the mtHsp70 genomic locus through increased localization of H3K27me3 during T2DM insult was observed. Our results suggest that restoration of a key protein import constituent, mtHsp70, provides therapeutic benefit through attenuation of mitochondrial and contractile dysfunction in T2DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. RiArsB and RiMT-11: Two novel genes induced by arsenate in arbuscular mycorrhiza.

    PubMed

    Maldonado-Mendoza, Ignacio E; Harrison, Maria J

    Plants associated with arbuscular mycorrhizal fungi (AMF) increase their tolerance to arsenic-polluted soils. This study aims to investigate the genes involved in the AMF molecular response to arsenic pollution. Genes encoding proteins involved in arsenic metabolism were identified and their expression assessed by PCR or RT-qPCR. The As-inducible gene GiArsA (R. irregularis ABC ATPase component of the ArsAB arsenite efflux pump) and two new genes, an arsenate/arsenite permease component of ArsAB (RiArsB) and a methyltransferase type 11 (RiMT-11) were induced when arsenate was added to two-compartment in vitro monoxenic cultures of R. irregularis-transformed carrot roots. RiArsB and RiMT-11 expression in extraradical hyphae in response to arsenate displayed maximum induction 4-6 h after addition of 350 μM arsenate. Their expression was also detected in colonized root tissues grown in pots, or in the root-fungus compartment of two-compartment in vitro systems. We used a Medicago truncatula double mutant (mtpt4/mtpt8) to demonstrate that RiMT-11 and RiArsB transcripts accumulate in response to the addition of arsenate but not in response to phosphate. These results suggest that these genes respond to arsenate addition regardless of non-functional Pi symbiotic transport, and that RiMT-11 may be involved in arsenate detoxification by methylation in AMF-colonized tissues. Copyright © 2017 British Mycological Society. All rights reserved.

  1. MT1-MMP regulates the turnover and endocytosis of extracellular matrix fibronectin

    PubMed Central

    Shi, Feng; Sottile, Jane

    2011-01-01

    The extracellular matrix (ECM) is dynamically remodeled by cells during development, normal tissue homeostasis and in a variety of disease processes. We previously showed that fibronectin is an important regulator of ECM remodeling. The deposition and/or polymerization of fibronectin into the ECM controls the deposition and stability of other ECM molecules. In addition, agents that inhibit fibronectin polymerization promote the turnover of fibronectin fibrils and enhance ECM fibronectin endocytosis and intracellular degradation. Endocytosis of ECM fibronectin is regulated by β1 integrins, including α5β1 integrin. We have examined the role of extracellular proteases in regulating ECM fibronectin turnover. Our data show that membrane type matrix metalloproteinase 1 (MT1-MMP; also known as MMP14) is a crucial regulator of fibronectin turnover. Cells lacking MT1-MMP show reduced turnover and endocytosis of ECM fibronectin. MT1-MMP regulates ECM fibronectin remodeling by promoting extracellular cleavage of fibronectin and by regulating α5β1-integrin endocytosis. Our data also show that fibronectin polymerization stabilizes fibronectin fibrils and inhibits ECM fibronectin endocytosis by inhibiting α5β1-integrin endocytosis. These data are the first to show that an ECM protein and its modifying enzyme can regulate integrin endocytosis. These data also show that integrin trafficking plays a major role in modulating ECM fibronectin remodeling. The dual dependence of ECM fibronectin turnover on extracellular proteolysis and endocytosis highlights the complex regulatory mechanisms that control ECM remodeling to ensure maintenance of proper tissue function. PMID:22159414

  2. Land use and nutrient inputs affect priming in Andosols of Mt. Kilimanjaro

    NASA Astrophysics Data System (ADS)

    Mganga, Kevin; Kuzyakov, Yakov

    2015-04-01

    Organic C and nutrients additions in soil can accelerate mineralisation of soil organic matter i.e. priming effects. However, only very few studies have been conducted to investigate the priming effects phenomenon in tropical Andosols. Nutrients (N, P, N+P) and 14C labelled glucose were added to Andosols from six natural and intensively used ecosystems at Mt. Kilimanjaro i.e. (1) savannah, (2) maize fields, (3) lower montane forest, (4) coffee plantation, (5) grasslands and (6) Chagga homegardens. Carbon-dioxide emissions were monitored over a 60 days incubation period. Mineralisation of glucose to 14CO2 was highest in coffee plantation and lowest in Chagga homegarden soils. Maximal and minimal mineralisation rates immediately after glucose additions were observed in lower montane forest with N+P fertilisation (9.1% ± 0.83 d -1) and in savannah with N fertilisation (0.9% ± 0.17 d -1), respectively. Glucose and nutrient additions accelerated native soil organic matter mineralisation i.e. positive priming. Chagga homegarden soils had the lowest 14CO2 emissions and incorporated the highest percent of glucose into microbial biomass. 50-60% of the 14C input was retained in soil. We attribute this mainly to the high surface area of non-crystalline constituents i.e. allophanes, present in Andosols and having very high sorption capacity for organic C. The allophanic nature of Andosols of Mt. Kilimanjaro especially under traditional Chagga homegarden agroforestry system shows great potential for providing essential environmental services, notably C sequestration. Key words: Priming Effects, Andosols, Land Use Changes, Mt. Kilimanjaro, Allophanes, Tropical Agroforestry

  3. Manipulating the content of dynamic natural scenes to characterize response in human MT/MST.

    PubMed

    Durant, Szonya; Wall, Matthew B; Zanker, Johannes M

    2011-09-09

    Optic flow is one of the most important sources of information for enabling human navigation through the world. A striking finding from single-cell studies in monkeys is the rapid saturation of response of MT/MST areas with the density of optic flow type motion information. These results are reflected psychophysically in human perception in the saturation of motion aftereffects. We began by comparing responses to natural optic flow scenes in human visual brain areas to responses to the same scenes with inverted contrast (photo negative). This changes scene familiarity while preserving local motion signals. This manipulation had no effect; however, the response was only correlated with the density of local motion (calculated by a motion correlation model) in V1, not in MT/MST. To further investigate this, we manipulated the visible proportion of natural dynamic scenes and found that areas MT and MST did not increase in response over a 16-fold increase in the amount of information presented, i.e., response had saturated. This makes sense in light of the sparseness of motion information in natural scenes, suggesting that the human brain is well adapted to exploit a small amount of dynamic signal and extract information important for survival.

  4. Bone Marrow Stromal Cells Stimulate an Angiogenic Program that Requires Endothelial MT1-MMP

    PubMed Central

    Kachgal, Suraj; Carrion, Bita; Janson, Isaac A.; Putnam, Andrew J.

    2012-01-01

    Bone marrow-derived stromal/stem cells (BMSCs) have recently been characterized as mediators of tissue regeneration after injury. In addition to preventing fibrosis at the wound site, BMSCs elicit an angiogenic response within the fibrin matrix. The mechanistic interactions between BMSCs and invading endothelial cells (ECs) during this process are not fully understood. Using a three-dimensional, fibrin-based angiogenesis model, we sought to investigate the proteolytic mechanisms by which BMSCs promote vessel morphogenesis. We find that BMSC-mediated vessel formation depends on the proteolytic ability of membrane type 1-matrix metalloproteinase (MT1-MMP). Knockdown of the protease results in a small network of vessels with enlarged lumens. Contrastingly, vessel morphogenesis is unaffected by the knockdown of MMP-2 and MMP-9. Furthermore, we find that BMSC-mediated vessel morphogenesis in vivo follows mechanisms similar to what we observe in vitro. Subcutaneous, cellular fibrin implants in C.B-17/SCID mice form aberrant vasculature when MMPs are inhibited with a broad spectrum chemical inhibitor, and a very minimal amount of vessels when MT1-MMP proteolytic activity is interrupted in ECs. Other studies have debated the necessity of MT1-MMP in the context of vessel invasion in fibrin, but this study clearly demonstrates its requirement in BMSC-mediated angiogenesis. PMID:22262018

  5. Clustered metallothionein genes are co-regulated in rice and ectopic expression of OsMT1e-P confers multiple abiotic stress tolerance in tobacco via ROS scavenging

    PubMed Central

    2012-01-01

    Background Metallothioneins (MT) are low molecular weight, cysteine rich metal binding proteins, found across genera and species, but their function(s) in abiotic stress tolerance are not well documented. Results We have characterized a rice MT gene, OsMT1e-P, isolated from a subtractive library generated from a stressed salinity tolerant rice genotype, Pokkali. Bioinformatics analysis of the rice genome sequence revealed that this gene belongs to a multigenic family, which consists of 13 genes with 15 protein products. OsMT1e-P is located on chromosome XI, away from the majority of other type I genes that are clustered on chromosome XII. Various members of this MT gene cluster showed a tight co-regulation pattern under several abiotic stresses. Sequence analysis revealed the presence of conserved cysteine residues in OsMT1e-P protein. Salinity stress was found to regulate the transcript abundance of OsMT1e-P in a developmental and organ specific manner. Using transgenic approach, we found a positive correlation between ectopic expression of OsMT1e-P and stress tolerance. Our experiments further suggest ROS scavenging to be the possible mechanism for multiple stress tolerance conferred by OsMT1e-P. Conclusion We present an overview of MTs, describing their gene structure, genome localization and expression patterns under salinity and development in rice. We have found that ectopic expression of OsMT1e-P enhances tolerance towards multiple abiotic stresses in transgenic tobacco and the resultant plants could survive and set viable seeds under saline conditions. Taken together, the experiments presented here have indicated that ectopic expression of OsMT1e-P protects against oxidative stress primarily through efficient scavenging of reactive oxygen species. PMID:22780875

  6. Clustered metallothionein genes are co-regulated in rice and ectopic expression of OsMT1e-P confers multiple abiotic stress tolerance in tobacco via ROS scavenging.

    PubMed

    Kumar, Gautam; Kushwaha, Hemant Ritturaj; Panjabi-Sabharwal, Vaishali; Kumari, Sumita; Joshi, Rohit; Karan, Ratna; Mittal, Shweta; Pareek, Sneh L Singla; Pareek, Ashwani

    2012-07-10

    Metallothioneins (MT) are low molecular weight, cysteine rich metal binding proteins, found across genera and species, but their function(s) in abiotic stress tolerance are not well documented. We have characterized a rice MT gene, OsMT1e-P, isolated from a subtractive library generated from a stressed salinity tolerant rice genotype, Pokkali. Bioinformatics analysis of the rice genome sequence revealed that this gene belongs to a multigenic family, which consists of 13 genes with 15 protein products. OsMT1e-P is located on chromosome XI, away from the majority of other type I genes that are clustered on chromosome XII. Various members of this MT gene cluster showed a tight co-regulation pattern under several abiotic stresses. Sequence analysis revealed the presence of conserved cysteine residues in OsMT1e-P protein. Salinity stress was found to regulate the transcript abundance of OsMT1e-P in a developmental and organ specific manner. Using transgenic approach, we found a positive correlation between ectopic expression of OsMT1e-P and stress tolerance. Our experiments further suggest ROS scavenging to be the possible mechanism for multiple stress tolerance conferred by OsMT1e-P. We present an overview of MTs, describing their gene structure, genome localization and expression patterns under salinity and development in rice. We have found that ectopic expression of OsMT1e-P enhances tolerance towards multiple abiotic stresses in transgenic tobacco and the resultant plants could survive and set viable seeds under saline conditions. Taken together, the experiments presented here have indicated that ectopic expression of OsMT1e-P protects against oxidative stress primarily through efficient scavenging of reactive oxygen species.

  7. A melting pot of multicontinental mtDNA lineages in admixed Venezuelans.

    PubMed

    Gómez-Carballa, Alberto; Ignacio-Veiga, Ana; Alvarez-Iglesias, Vanesa; Pastoriza-Mourelle, Ana; Ruíz, Yarimar; Pineda, Lennie; Carracedo, Angel; Salas, Antonio

    2012-01-01

    The arrival of Europeans in Colonial and post-Colonial times coupled with the forced introduction of sub-Saharan Africans have dramatically changed the genetic background of Venezuela. The main aim of the present study was to evaluate, through the study of mitochondrial DNA (mtDNA) variation, the extent of admixture and the characterization of the most likely continental ancestral sources of present-day urban Venezuelans. We analyzed two admixed populations that have experienced different demographic histories, namely, Caracas (n = 131) and Pueblo Llano (n = 219). The native American component of admixed Venezuelans accounted for 80% (46% haplogroup [hg] A2, 7% hg B2, 21% hg C1, and 6% hg D1) of all mtDNAs; while the sub-Saharan and European contributions made up ∼10% each, indicating that Trans-Atlantic immigrants have only partially erased the native American nature of Venezuelans. A Bayesian-based model allowed the different contributions of European countries to admixed Venezuelans to be disentangled (Spain: ∼38.4%, Portugal: ∼35.5%, Italy: ∼27.0%), in good agreement with the documented history. Seventeen entire mtDNA genomes were sequenced, which allowed five new native American branches to be discovered. B2j and B2k, are supported by two different haplotypes and control region data, and their coalescence ages are 3.9 k.y. (95% C.I. 0-7.8) and 2.6 k.y. (95% C.I. 0.1-5.2), respectively. The other clades were exclusively observed in Pueblo Llano and they show the fingerprint of strong recent genetic drift coupled with severe historical consanguinity episodes that might explain the high prevalence of certain Mendelian and complex multi-factorial diseases in this region. Copyright © 2011 Wiley Periodicals, Inc.

  8. Relationships between environmental factors and hemlock distribution at Mt. Ascutney, Vermont

    Treesearch

    Richard L. Boyce

    2000-01-01

    In order to quantify relationships between environmental factors and the distribution of eastern hemlock (Tsuga canadensis (L.) Carr.) and other tree species, sites were established every 100 m along four contour lines, lying at 455 m (1500'), 610 m (2000'), 760 m (2500') and 915 m (3000') on Mt. Ascutney, a monadnock in the...

  9. Interpretation of Historical Eruptions of Mt. Baekdu Volcano, Korea

    NASA Astrophysics Data System (ADS)

    Yun, S. H.; Cho, E.; Yang, I. S.

    2014-12-01

    This study is performed to find out the eruptive events of the historical period recorded in literature, which have been recognized and regarded as ones from Mt. Baekdusan, and to make volcanological interpretations of the eruptive events. Since the Millennium eruption, more than 31 eruptive events have been discovered, most of which are Plinian eruptions with volcanic ash that dispersed into the regions in the vicinity of the volcano. The minimum volume of erupted materials in 1702 is estimated to be 1.2 km3when calculated with an empirical formula using an isopach line obtained from two points 140 km away from the vent. The 1702 eruption was a paroxysmal one with VEI of 5. The historical record described a deposition of wind-modified fallout ash by movement of hot ash cloud. The 1903 record includes the event of the phreatomagmatic or vulcanian eruption that occurred within the Cheonji caldera lake. Based on the eruption records of the historical period and the 2002 precursor unrest to volcanic eruptions, Mt. Baekdusan has been evaluated and regarded as an active volcano that has the potential to erupt in the future. This research was supported by a grant [NEMA-BAEKDUSAN-2012-1-2] from the Volcanic Disaster Preparedness Research Center sponsored by National Emergency Management Agency of Korea. T

  10. The Qartaba Structure: An Active Backthrust In Central Mt-Lebanon.

    NASA Astrophysics Data System (ADS)

    Elias, Ata Richard

    2016-04-01

    The Qartaba structure in central Mt-Lebanon is a 15x5km box fold running parallel to the restraining bend of the sinsitral Yammouneh Fault, the main fault of the central segment of the Dead Sea Transform. The Qartaba structure has long been described as a "horst" and associated with Mesozoic normal faulting. However, the Qartaba anticline is suitably oriented with the direction of maximum compression along the restraining bend. Jurassic carbonate rocks form the core of this anticline culminating at ~1953m asl to the east, of the highest structural elevation of the Mt-Lebanon range indicating important tectonic uplift rate. The fold is asymmetric. The western limb is steep and bordered by the Lebanese Flexure, a prominent continuous monocline of Upper Jurassic to Mid Cretaceous rocks, running along the western flank of Mt-Lebanon. The eastern limb of the anticline has a very steep dip, and forms a 200m high cliff well marked in the topography. Its Jurassic layers are almost vertical and end up overhanging Lower Cretaceous beds. Our study suggest that the Qartaba structure is a growing anticline, built by active thrusting over a west dipping thrust fault that cuts the surface at the base of the eastern limb of the anticline. The fault plane can be seen dipping 30-35 degrees to the west. At depth, this thrust is likely to connect with the blind thrust ramp of the Mt-Lebanon Flexure. The Qartaba backthrust with a dip to the west, is opposite to the general vergence of similar structures in the area. On some of the segments of the steep cliff forming the faulted eastern limb, a fresh scarp with smooth and polished surfaces bearing vertical slickensides can be followed over ~700m along the base of the cliff. It corresponds with the location of the thrust fault tip. Talus accumulation over the steep eastern limb covers most of the cliff base, and may be masking further extent of this scarp. We interpret this scarp as the freeface of a co-seismic rupture on the underlying

  11. Vulnerability of settlements around Mt. Cameroon volcano, Cameroon

    NASA Astrophysics Data System (ADS)

    Zogning, Appolinaire; Spinetti, Claudia; Ngouanet, Chretien; Tchoudam, David; Kouokam, Emmanuel; Thierry, Pierre; Bignami, Christian; Fabrizia Buongiorno, Maria; Ilaria Pannaccione Apa, Maria

    2010-05-01

    Located at the bottom of the Gulf of Guinea, Cameroon is exposed to a large variety of natural hazards, including volcanism. Most of the hazard are concentrated around the active volcano Mt. Cameroon which combines effusive and explosive types of activity. The threatened stakes are numerous and different exposed: people, settlements, industrial plantations, petrol refinery and many other factories and infrastructures. Until 2005, no risk management plans has been available. In 2006, the French Embassy in Cameroon, within the framework of a financial convention between Cameroon and France, put in place the GRINP (Management of Natural Risks and Civil Protection) project whose objective was to reinforce the capacity of Cameroon's civil protection department and thus, contribute to the improvement of the security of the population faced with catastrophes. The objective was to realize a Risk Prevention Plan at a local council scale, and taking into consideration the specific natural risks of each zone. The general objective of the RPP was to clearly draw land use maps for risks zones, showing the overlay of stakes with risk of different intensities. In 2008 European Commission funded the Mia-Vita project (Mitigating and Assessing Volcanic Impacts on Terrain and human Activities). The aim of the project is to improve the crisis management capabilities based on monitoring and early warning systems and secure communications; reduction of people's vulnerability and development of recovering capabilities after an event occurs for both local communities and ecological systems. Keyword: natural hazards, Mt. Cameroon, vulnerability, risk prevention plan

  12. Microevolution in prehistoric Andean populations: chronologic mtDNA variation in the desert valleys of northern Chile.

    PubMed

    Moraga, Mauricio; Santoro, Calogero M; Standen, Vivien G; Carvallo, Pilar; Rothhammer, Francisco

    2005-06-01

    Archeological evidence suggests that the iconographic and technological developments that took place in the highlands around Lake Titicaca in the Central Andean region had an influence on the cultural elaborations of the human groups in the valleys and the Pacific coast of northern Chile. In a previous communication, we were able to show, by means of a distance analysis, that a craniofacial differentiation accompanied the process of cultural evolution in the valleys (Rothhammer and Santoro [2001] Lat. Am. Antiq. 12:59-66). Recently, numerous South Amerindian mtDNA studies were published, and more accurate molecular techniques to study ancient mtDNA are available. In view of these recent developments, we decided 1) to study chronological changes of ancient mtDNA haplogroup frequencies in the nearby Lluta, Azapa, and Camarones Valleys, 2) to identify microevolutionary forces responsible for such changes, and 3) to compare ancient mtDNA haplogroup frequencies with previous data in order to validate craniometrical results and to reconstruct the biological history of the prehistoric valley groups in the context of their interaction with culturally more developed highland populations. From a total of 97 samples from 83 individuals, 68 samples (61 individuals) yielded amplifications for the fragments that harbor classical mtDNA markers. The haplogroup distribution among the total sample was as follows: 26.2%, haplogroup A; 34.4%, haplogroup B; 14.8%, haplogroup C; 3.3%, haplogroup D; and 21.3%, other haplogroups. Haplogroup B tended to increase, and haplogroup A to decrease during a 3,900-year time interval. The sequence data are congruent with the haplogroup analysis. In fact, the sequencing of hypervariable region I of 30 prehistoric individuals revealed 43 polymorphic sites. Sequence alignment and subsequent phylogenetic tree construction showed two major clusters associated with the most common restriction haplogroups. Individuals belonging to haplogroups C and D

  13. Myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications associated with a novel m.5513G>A mutation in the MT-TW gene.

    PubMed

    Cardaioli, Elena; Mignarri, Andrea; Cantisani, Teresa Anna; Malandrini, Alessandro; Nesti, Claudia; Rubegni, Anna; Funel, Niccola; Federico, Antonio; Santorelli, Filippo Maria; Dotti, Maria Teresa

    2018-06-02

    We sequenced the mitochondrial genome from a 40-year-old woman with myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications. Histological and biochemical features of mitochondrial respiratory chain dysfunction were present. Direct sequencing showed a novel heteroplasmic mutation at nucleotide 5513 in the MT-TW gene that encodes tRNA Trp . Restriction Fragment Length Polymorphism analysis confirmed that about 80% of muscle mtDNA harboured the mutation while it was present in minor percentages in mtDNA from other tissues. The mutation is predicted to disrupt a highly conserved base pair within the aminoacyl acceptor stem of the tRNA. This is the 17° mutation in MT-TW gene and expands the known causes of late-onset mitochondrial diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Measurements of IN and BIO-IN with the fast ice nucleus chamber FINCH at Mt. Zugspitze, Mt. Puy de Dôme and Jungfraujoch during fall and winter

    NASA Astrophysics Data System (ADS)

    Nillius, B.; Frank, F.; Bingemer, H.; Curtius, J.; Bundke, U.

    2013-05-01

    In this work we present IN measurements at Mt. Zugspitze, Germany, 2650 m.a.s.l., Mt. Puy de Dôme, France, 1464 m.a.s.l. and Jungfraujoch, Switzerland, 3580 m a.s.l during fall and winter 2012 with the instrument FINCH HALO (Fast Ice Nucleus Chamber for the High Altitude and LOng range research aircraft HALO). In this device the temperature and super saturation for activation of Ice Nuclei (IN) and the growth to ice crystals is obtained by mixing three gas flows of different temperatures and moisture. After the growth of IN and Cloud Condensation Nuclei (CCN) to macroscopic ice crystals and super-cooled water droplets in the development chamber, they are counted using an optical detector. The discrimination between ice and water is made by measuring the circular depolarization ratio of the backscattered laser light of each individual particle. IN are classified as biological particles by measuring their individual intrinsic-fluorescence during the winter campaigns in average 30-40 % of the IN show an intrinsic fluorescence and are supposed to be of biological origin.

  15. Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats.

    PubMed

    Mehus, Aaron A; Picklo, Matthew J

    2017-10-19

    Metallothioneins (MTs) perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER) and dietary n -3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n -3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO) that is α-linolenic acid (ALA; 18:3 n -3) sufficient or corn oil (CO; ALA-deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs ( Mt1-3 ) and modulators of MT expression including glucocorticoid receptors ( Nr3c1 and Nr3c2 ) and several mediators of thyroid hormone regulation ( Dio1-3 , Mct8 , Oatp1c1 , Thra , and Thrb ) were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral cortex (23%). In liver, a reduction in dietary n -3 PUFA reduced Mt1 , Mt2 , Nr3c1 , Mct8 , and Thrb . ER elevated Nr3c1 , Dio1 , and Thrb and reduced Thra in the liver. Given MT's role in cellular protection, further studies are needed to evaluate whether ER or n -3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors.

  16. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

    PubMed

    Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2010-03-09

    Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  17. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

    PubMed Central

    2010-01-01

    Background Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt. PMID:20214782

  18. Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans

    PubMed Central

    Metspalu, Mait; Kivisild, Toomas; Metspalu, Ene; Parik, Jüri; Hudjashov, Georgi; Kaldma, Katrin; Serk, Piia; Karmin, Monika; Behar, Doron M; Gilbert, M Thomas P; Endicott, Phillip; Mastana, Sarabjit; Papiha, Surinder S; Skorecki, Karl; Torroni, Antonio; Villems, Richard

    2004-01-01

    Background Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia. Results Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades. Conclusions Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent. PMID:15339343

  19. Positive selection of AS3MT to arsenic water in Andean populations

    PubMed Central

    Eichstaedt, Christina A.; Antao, Tiago; Cardona, Alexia; Pagani, Luca; Kivisild, Toomas; Mormina, Maru

    2016-01-01

    Arsenic is a carcinogen associated with skin lesions and cardiovascular diseases. The Colla population from the Puna region in Northwest Argentinean is exposed to levels of arsenic in drinking water exceeding the recommended maximum by a factor of 20. Yet, they thrive in this challenging environment since thousands of years and therefore we hypothesize strong selection signatures in genes involved in arsenic metabolism. We analyzed genome-wide genotype data for 730,000 loci in 25 Collas, considering 24 individuals of the neighbouring Calchaquíes and 24 Wichí from the Gran Chaco region in the Argentine province of Salta as control groups. We identified a strong signal of positive selection in the main arsenic methyltransferase AS3MT gene, which has been previously associated with lower concentrations of the most toxic product of arsenic metabolism monomethylarsonic acid. This study confirms recent studies reporting selection signals in the AS3MT gene albeit using different samples, tests and control populations. PMID:26366667

  20. Hazard assessment in geothermal exploration: The case of Mt. Parker, Southern Philippines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Delfin, F.G. Jr.; Salonga, N.D.; Bayon, F.E.B.

    1996-12-31

    Hazard assessment of the Mt. Parker geothermal prospect, conducted in parallel with the surface exploration from 1992 to 1994, was undertaken to determine the long-term suitability of the prospect for development. By comparison with other acidic magmatic-hydrothermal systems in the Philippines, the geochemical data indicated minimal input of acidic magmatic fluids into Mt. Parker`s hydrothermal system. This system was regarded to be a neutral-pH and high-enthalpy chloride reservoir with temperature of at least 200-250{degrees}C. These favorable geochemical indications contrasted sharply with the C-14 and volcanological data indicating a shallow magmatic body with a potential for future eruption. This hazard ledmore » PNOC EDC to discontinue the survey and abandon the prospect by late 1994. On September 6, 1995, a flashflood of non-volcanic origin from the caldera lake killed nearly 100 people on the volcano`s northwestern flank.« less