Novel approach of wavelet analysis for nonlinear ultrasonic measurements and fatigue assessment of jet engine components

NASA Astrophysics Data System (ADS)

Bunget, Gheorghe; Tilmon, Brevin; Yee, Andrew; Stewart, Dylan; Rogers, James; Webster, Matthew; Farinholt, Kevin; Friedersdorf, Fritz; Pepi, Marc; Ghoshal, Anindya

2018-04-01

Widespread damage in aging aircraft is becoming an increasing concern as both civil and military fleet operators are extending the service lifetime of their aircraft. Metallic components undergoing variable cyclic loadings eventually fatigue and form dislocations as precursors to ultimate failure. In order to characterize the progression of fatigue damage precursors (DP), the acoustic nonlinearity parameter is measured as the primary indicator. However, using proven standard ultrasonic technology for nonlinear measurements presents limitations for settings outside of the laboratory environment. This paper presents an approach for ultrasonic inspection through automated immersion scanning of hot section engine components where mature ultrasonic technology is used during periodic inspections. Nonlinear ultrasonic measurements were analyzed using wavelet analysis to extract multiple harmonics from the received signals. Measurements indicated strong correlations of nonlinearity coefficients and levels of fatigue in aluminum and Ni-based superalloys. This novel wavelet cross-correlation (WCC) algorithm is a potential technique to scan for fatigue damage precursors and identify critical locations for remaining life prediction.

Cell size control and a cell-intrinsic maturation program in proliferating oligodendrocyte precursor cells.

PubMed

Gao, F B; Raff, M

1997-09-22

We have used clonal analysis and time-lapse video recording to study the proliferative behavior of purified oligodendrocyte precursor cells isolated from the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from precursor cells isolated from postnatal day 7 (P7) or P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the precursor cells, just like single-celled eucaryotes, have to reach a threshold size before they can divide. These and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic events occurring in G1 proposed by "transition probability" models, may explain the random variability of cell cycle times seen within clonal cell lines in culture.

Cell Size Control and a Cell-intrinsic Maturation Program in Proliferating Oligodendrocyte Precursor Cells

PubMed Central

Gao, Fen-Biao; Raff, Martin

1997-01-01

We have used clonal analysis and time-lapse video recording to study the proliferative behavior of purified oligodendrocyte precursor cells isolated from the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from precursor cells isolated from postnatal day 7 (P7) or P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the precursor cells, just like single-celled eucaryotes, have to reach a threshold size before they can divide. These and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic events occurring in G1 proposed by “transition probability” models, may explain the random variability of cell cycle times seen within clonal cell lines in culture. PMID:9298991

Effect of precursor solutions stirring on deep level defects concentration and spatial distribution in low temperature aqueous chemical synthesis of zinc oxide nanorods

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

Alnoor, Hatim, E-mail: hatim.alnoor@liu.se; Chey, Chan Oeurn; Pozina, Galia

Hexagonal c-axis oriented zinc oxide (ZnO) nanorods (NRs) with 120-300 nm diameters are synthesized via the low temperature aqueous chemical route at 80 °C on silver-coated glass substrates. The influence of varying the precursor solutions stirring durations on the concentration and spatial distributions of deep level defects in ZnO NRs is investigated. Room temperature micro-photoluminesnce (μ-PL) spectra were collected for all samples. Cathodoluminescence (CL) spectra of the as-synthesized NRs reveal a significant change in the intensity ratio of the near band edge emission (NBE) to the deep-level emission (DLE) peaks with increasing stirring durations. This is attributed to the variation inmore » the concentration of the oxygen-deficiency with increasing stirring durations as suggested from the X-ray photoelectron spectroscopy analysis. Spatially resolved CL spectra taken along individual NRs revealed that stirring the precursor solutions for relatively short duration (1-3 h), which likely induced high super saturation under thermodynamic equilibrium during the synthesis process, is observed to favor the formation of point defects moving towards the tip of the NRs. In contrary, stirring for longer duration (5-15 h) will induce low super saturation favoring the formation of point defects located at the bottom of the NRs. These findings demonstrate that it is possible to control the concentration and spatial distribution of deep level defects in ZnO NRs by varying the stirring durations of the precursor solutions.« less

Expression of amyloid-β protein and amyloid-β precursor protein after primary brain-stem injury in rats.

PubMed

Yang, Shudong; Sun, Rongchao; Zhou, Zhiyi; Zhou, Jing; Liang, Jiabei; Mu, Huijun

2014-09-01

Amyloid-β (Aβ) protein and its precursor, amyloid-β precursor protein (β-APP), have traditionally been used in the diagnosis of Alzheimer disease. Their use in diagnosis of traumatic brain injury by forensic analysis is becoming more widespread. However, to date, no reliable small animal model exists to evaluate these brain injury indicators. To address this, we have studied primary brain-stem injury in rats to assess the appearance of diffuse axonal injury in brain sections and correlate these findings with appearance of Aβ and relative β-APP mRNA levels. Using an EnVision 2-step immunohistochemical staining method to measure axon diameter, we found that there was significant difference in axon diameters within the medulla oblongata and several time points after brain injury, ranging from 3 to 24 hours. In addition, mRNA expression levels of β-APP increased following brain injury, peaking 3 hours following injury and decreasing back to baseline levels by 24 hours after injury. These results suggest that using immunohistochemistry and reverse transcription-polymerase chain reaction to detect changes in Aβ-associated axonal changes and β-APP mRNA levels, respectively, can be useful for the diagnosis of diffuse axonal injury during autopsy at early time points following fatal brain injury.

Effect of precursor on epitaxially grown of ZnO thin film on p-GaN/sapphire (0 0 0 1) substrate by hydrothermal technique

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

Sahoo, Trilochan; Ju, Jin-Woo; Kannan, V.

2008-03-04

Single crystalline ZnO thin film on p-GaN/sapphire (0 0 0 1) substrate, using two different precursors by hydrothermal route at a temperature of 90 deg. C were successfully grown. The effect of starting precursor on crystalline nature, surface morphology and optical emission of the films were studied. ZnO thin films were grown in aqueous solution of zinc acetate and zinc nitrate. X-ray diffraction analysis revealed that all the thin films were single crystalline in nature and exhibited wurtzite symmetry and c-axis orientation. The thin films obtained with zinc nitrate had a more pitted rough surface morphology compared to the filmmore » grown in zinc acetate. However the thickness of the films remained unaffected by the nature of the starting precursor. Sharp luminescence peaks were observed from the thin films almost at identical energies but deep level emission was slightly prominent for the thin film grown in zinc nitrate.« less

Multi-omics analysis provides insight to the Ignicoccus hospitalis - Nanoarchaeum equitans association

DOE PAGES

Rawle, Rachel A.; Hamerly, Timothy; Tripet, Brian P.; ...

2017-06-04

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted ‘omics’ analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized usingmore » interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis–N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. In conclusion, this multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis–N. equitans association. This study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies.« less

Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association.

PubMed

Rawle, Rachel A; Hamerly, Timothy; Tripet, Brian P; Giannone, Richard J; Wurch, Louie; Hettich, Robert L; Podar, Mircea; Copié, Valerie; Bothner, Brian

2017-09-01

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted 'omics' analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized using interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis-N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. This multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis-N. equitans association. Our study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Rawle, Rachel A.; Hamerly, Timothy; Tripet, Brian P.

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted ‘omics’ analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized usingmore » interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis–N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. In conclusion, this multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis–N. equitans association. This study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies.« less

Functional Analyses and Treatment of Precursor Behavior

PubMed Central

Najdowski, Adel C; Wallace, Michele D; Ellsworth, Carrie L; MacAleese, Alicia N; Cleveland, Jackie M

2008-01-01

Functional analysis has been demonstrated to be an effective method to identify environmental variables that maintain problem behavior. However, there are cases when conducting functional analyses of severe problem behavior may be contraindicated. The current study applied functional analysis procedures to a class of behavior that preceded severe problem behavior (precursor behavior) and evaluated treatments based on the outcomes of the functional analyses of precursor behavior. Responding for all participants was differentiated during the functional analyses, and individualized treatments eliminated precursor behavior. These results suggest that functional analysis of precursor behavior may offer an alternative, indirect method to assess the operant function of severe problem behavior. PMID:18468282

Phylogenetic appearance of Neuropeptide S precursor proteins in tetrapods

PubMed Central

Reinscheid, Rainer K.

2007-01-01

Sleep and emotional behavior are two hallmarks of vertebrate animal behavior, implying that specialized neuronal circuits and dedicated neurochemical messengers may have been developed during evolution to regulate such complex behaviors. Neuropeptide S (NPS) is a newly identified peptide transmitter that activates a typical G protein-coupled receptor. Central administration of NPS produces profound arousal, enhances wakefulness and suppresses all stages of sleep. In addition, NPS can alleviate behavioral responses to stress by producing anxiolytic-like effects. A bioinformatic analysis of current genome databases revealed that the NPS peptide precursor gene is present in all vertebrates with the exception of fish. A high level of sequence conservation, especially of aminoterminal structures was detected, indicating stringent requirements for agonist-induced receptor activation. Duplication of the NPS precursor gene was only found in one out of two marsupial species with sufficient genome coverage (Monodelphis domestica; opossum), indicating that the duplicated opossum NPS sequence might have arisen as an isolated event. Pharmacological analysis of both Monodelphis NPS peptides revealed that only the closely related NPS peptide retained agonistic activity at NPS receptors. The duplicated precursor might be either a pseudogene or could have evolved different receptor selectivity. Together, these data show that NPS is a relatively recent gene in vertebrate evolution whose appearance might coincide with its specialized physiological functions in terrestrial vertebrates. PMID:17293003

Progressing from Identification and Functional Analysis of Precursor Behavior to Treatment of Self-Injurious Behavior

ERIC Educational Resources Information Center

Dracobly, Joseph D.; Smith, Richard G.

2012-01-01

This multiple-study experiment evaluated the utility of assessing and treating severe self-injurious behavior (SIB) based on the outcomes of a functional analysis of precursor behavior. In Study 1, a precursor to SIB was identified using descriptive assessment and conditional probability analyses. In Study 2, a functional analysis of precursor…

High resolution biogeochemistry in the Upper Cenomanian black shales of the Umbria-Marche Basin (central Italy)

NASA Astrophysics Data System (ADS)

Bombardiere, L.; Farrimond, P.; Tyson, R. V.; Forster, A.; Sinninghe-Damsté, J.

2003-04-01

The uppermost Cenomanian "anoxic event" (i.e. OAE2) in the Umbria-Marche Basin is recorded by a 0.7-1.2 metre thick interval (the Bonarelli Level) consisting of black, organic-rich laminated mudstones ("black shales"), radiolarian layers and grey-greenish, organic-poor claystones. The occurrence of the radiolarian layers and the organic-poor claystones defines three lithological sub-units which can be correlated at basin scale. In addition, a number of thin black shales ("Bonarelli precursors") has been observed in the limestones underlying the Bonarelli Level; their occurrence appears to be tuned with Milankovitch cycles. This study investigates palaeoproductivity and preservation in the Bonarelli Level and in the precursors using a high resolution molecular biomarker analysis. The onset of the Bonarelli deposition (i.e. the lower sub-unit) is characterized by a drastic increase in the relative abundance of compounds associated with algal precursors (e.g. steranes and phytane). Equally, the same interval shows an increase in the biomarker proxies related to the intensity of oxygen depletion (e.g. homohopane index). The other two Bonarelli sub-units also reflect fluctuations in oxic-anoxic conditions and palaeoproductivity. As the molecular compounds thought to reflect qualitative changes in palaeoproductivity and anoxia do not exhibit any significant differencies between the precursor black shales and the Bonarelli Level, the palaeoenvironmental conditions leading to organic-rich sediments were presumably similar. The results from the Italian sites have been compared with two other OAE2 localities, both characterized by proximal depositional settings: Oued Bahloul (Tunisia) and Tarfaya (Morocco). This work is supported by the European Community's Improving Human Potential Programme under contract HPRN-CT-1999-00055, C/T-NET.

Water quality following extensive beetle-induced tree mortality: Interplay of aromatic carbon loading, disinfection byproducts, and hydrologic drivers.

PubMed

Brouillard, Brent M; Dickenson, Eric R V; Mikkelson, Kristin M; Sharp, Jonathan O

2016-12-01

The recent bark beetle epidemic across western North America may impact water quality as a result of elevated organic carbon release and hydrologic shifts associated with extensive tree dieback. Analysis of quarterly municipal monitoring data from 2004 to 2014 with discretization of six water treatment facilities in the Rocky Mountains by extent of beetle impact revealed a significant increasing trend in total organic carbon (TOC) and total trihalomethane (TTHM) production within high (≳50% areal infestation) beetle-impacted watersheds while no or insignificant trends were found in watersheds with lower impact levels. Alarmingly, the TTHM concentration trend in the high impact sites exceeded regulatory maximum contaminant levels during the most recent two years of analysis (2013-14). To evaluate seasonal differences, explore the interplay of water quality and hydrologic processes, and eliminate variability associated with municipal reporting, these treatment facilities were targeted for more detailed surface water sampling and characterization. Surface water samples collected from high impact watersheds exhibited significantly higher TOC, aromatic signatures, and disinfection byproduct (DBP) formation potential than watersheds with lower infestation levels. Spectroscopic analyses of surface water samples indicated that these heightened DBP precursor levels are a function of both elevated TOC loading and increased aromatic character. This association was heightened during precipitation and runoff events in high impact sites, supporting the hypothesis that altered hydrologic flow paths resulting from tree mortality mobilize organic carbon and elevate DBP formation potential for several months after runoff ceases. The historical trends found here likely underestimate the full extent of TTHM shifts due to monitoring biases with the extended seasonal release of DBP precursors increasing the potential for human exposure. Collectively, our analysis suggests that while water quality impacts continue to rise nearly one decade after infestation, significant increases in TOC mobilization and DBP precursors are limited to watersheds that experience extensive tree mortality. Copyright © 2016 Elsevier B.V. All rights reserved.

Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A.

PubMed

Disertori, Marcello; Quintarelli, Silvia; Grasso, Maurizia; Pilotto, Andrea; Narula, Nupoor; Favalli, Valentina; Canclini, Camilla; Diegoli, Marta; Mazzola, Silvia; Marini, Massimiliano; Del Greco, Maurizio; Bonmassari, Roberto; Masè, Michela; Ravelli, Flavia; Specchia, Claudia; Arbustini, Eloisa

2013-02-01

Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

PubMed Central

Zuurbier, Linda; Gutierrez, Alejandro; Mullighan, Charles G.; Canté-Barrett, Kirsten; Gevaert, A. Olivier; de Rooi, Johan; Li, Yunlei; Smits, Willem K.; Buijs-Gladdines, Jessica G.C.A.M.; Sonneveld, Edwin; Look, A. Thomas; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2014-01-01

Three distinct immature T-cell acute lymphoblastic leukemia entities have been described including cases that express an early T-cell precursor immunophenotype or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic leukemia cluster cases based on gene expression analysis (immature cluster) and cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute lymphoblastic leukemia cases exclusively overlap with immature cluster samples based on the expression of early T-cell precursor acute lymphoblastic leukemia signature genes, indicating that both are featuring a single disease entity. Patients lacking TRG@ rearrangements represent only 40% of immature cluster cases, but no further evidence was found to suggest that cases with absence of bi-allelic TRG@ deletions reflect a distinct and even more immature disease entity. Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are strongly enriched for genes expressed in hematopoietic stem cells as well as genes expressed in normal early thymocyte progenitor or double negative-2A T-cell subsets. Identification of early T-cell precursor acute lymphoblastic leukemia cases solely by defined immunophenotypic criteria strongly underestimates the number of cases that have a corresponding gene signature. However, early T-cell precursor acute lymphoblastic leukemia samples correlate best with a CD1 negative, CD4 and CD8 double negative immunophenotype with expression of CD34 and/or myeloid markers CD13 or CD33. Unlike various other studies, immature cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on the COALL-97 protocol did not have an overall inferior outcome, and demonstrated equal sensitivity levels to most conventional therapeutic drugs compared to other pediatric T-cell acute lymphoblastic leukemia patients. PMID:23975177

Cluster self-organization of TR-containing germanate systems: Suprapolyhedral precursors and self-assembly of the crystal structures of the LiNdGeO{sub 4} and CeGeO{sub 4} compounds

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

Ilyushin, G. D., E-mail: ilyushin@nc.cryst.ras.ru; Dem'yanets, L. N.

2007-07-15

A combinatorial-topological analysis of the orthogermanates LiNdGeO{sub 4} (space group Pbcn) and CeGeO{sub 4} (space group I 4{sub 1}/a, the scheelite structure type), which have MT frameworks composed of polyhedral structural units in the form of M dodecahedra (NdO{sub 8} and CeO{sub 8}) and T tetrahedra (GeO{sub 4}), is performed using the method of coordination sequences with the TOPOS program package. It is established that the structures of both orthogermanates are characterized by equivalent crystal-forming nets 4444. The cluster precursors of the M{sub 2}T{sub 2} cyclic type are identified by the method of two-color decomposition. The local symmetry of four-polyhedralmore » clusters corresponds to the point group 2. In the precursor of the LiNdGeO{sub 4} orthogermanate, the Li atom is located above the M{sub 2}T{sub 2} ring. The number of Li-O bonds in this precursor is 4. The cluster precursors M{sub 2}T{sub 2} and LiM{sub 2}T{sub 2} are responsible for the formation of crystal-forming clusters of a higher level according to the mechanism of matrix self-assembly. The coordination numbers of the cluster precursors in two-dimensional nets for these structures are found to be equal to 4. The equivalent bilayer TR,Ge stacks that consist of eight cluster precursors are revealed in the structures under investigation. It is demonstrated that there exist three types of translational interlayer arrangements of cluster precursors upon the formation of macrostructures of the orthogermanates.« less

Production of highly efficient activated carbons from industrial wastes for the removal of pharmaceuticals from water-A full factorial design.

PubMed

Jaria, Guilaine; Silva, Carla Patrícia; Oliveira, João A B P; Santos, Sérgio M; Gil, María Victoria; Otero, Marta; Calisto, Vânia; Esteves, Valdemar I

2018-02-26

The wide occurrence of pharmaceuticals in aquatic environments urges the development of cost-effective solutions for their removal from water. In a circular economy context, primary paper mill sludge (PS) was used to produce activated carbon (AC) aiming the adsorptive removal of these contaminants. The use of low-cost precursors for the preparation of ACs capable of competing with commercial ACs continues to be a challenge. A full factorial design of four factors (pyrolysis temperature, residence time, precursor/activating agent ratio, and type of activating agent) at two levels was applied to the production of AC using PS as precursor. The responses analysed were the yield of production, percentage of adsorption for three pharmaceuticals (sulfamethoxazole, carbamazepine, and paroxetine), specific surface area (S BET ), and total organic carbon (TOC). Statistical analysis was performed to evaluate influencing factors in the responses and to determine the most favourable production conditions. Four ACs presented very good responses, namely on the adsorption of the pharmaceuticals under study (average adsorption percentage around 78%, which is above that of commercial AC), and S BET between 1389 and 1627 m 2  g -1 . A desirability analysis pointed out 800 °C for 60 min and a precursor/KOH ratio of 1:1 (w/w) as the optimal production conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased KPI containing amyloid precursor protein in experimental autoimmune encephalomyelitis brains.

PubMed

Beilin, Orit; Karussis, Dimitrios M; Korczyn, Amos D; Gurwitz, David; Aronovich, Ramona; Mizrachi-Kol, Rachel; Chapman, Joab

2007-04-16

Amyloid precursor protein can be translated from three alternatively spliced mRNAs. We measured levels of amyloid precursor protein isoforms containing the Kunitz protease inhibitor domain (KPIAPP), and amyloid precursor protein without the Kunitz protease inhibitor domain (KPIAPP) in brain homogenates of acute experimental autoimmune encephalomyelitis mice. At the preclinical phase of the disease, both KPIAPP and KPIAPP levels were significantly higher in homogenates from brains of autoimmune encephalomyelitis mice, whereas at the acute phase of the disease only KPIAPP remained significantly elevated compared with controls. At the recovery phase, no differences were observed between the groups. The early and isoform-specific elevation of KPIAPP in autoimmune encephalomyelitis mice suggests a possible role for amyloid precursor protein in the immune response mediating the disease.

Cu-Doped ZnO Thin Films Deposited by a Sol-Gel Process Using Two Copper Precursors: Gas-Sensing Performance in a Propane Atmosphere.

PubMed

Gómez-Pozos, Heberto; Arredondo, Emma Julia Luna; Maldonado Álvarez, Arturo; Biswal, Rajesh; Kudriavtsev, Yuriy; Pérez, Jaime Vega; Casallas-Moreno, Yenny Lucero; Olvera Amador, María de la Luz

2016-01-29

A study on the propane gas-sensing properties of Cu-doped ZnO thin films is presented in this work. The films were deposited on glass substrates by sol-gel and dip coating methods, using zinc acetate as a zinc precursor, copper acetate and copper chloride as precursors for doping. For higher sensitivity values, two film thickness values are controlled by the six and eight dippings, whereas for doping, three dippings were used, irrespective of the Cu precursor. The film structure was analyzed by X-ray diffractometry, and the analysis of the surface morphology and film composition was made through scanning electron microscopy (SEM) and secondary ion mass spectroscopy (SIMS), respectively. The sensing properties of Cu-doped ZnO thin films were then characterized in a propane atmosphere, C₃H₈, at different concentration levels and different operation temperatures of 100, 200 and 300 °C. Cu-doped ZnO films doped with copper chloride presented the highest sensitivity of approximately 6 × 10⁴, confirming a strong dependence on the dopant precursor type. The results obtained in this work show that the use of Cu as a dopant in ZnO films processed by sol-gel produces excellent catalysts for sensing C₃H₈ gas.

XPS study of thermal and electron-induced decomposition of Ni and Co acetylacetonate thin films for metal deposition

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

Weiss, Theodor; Warneke, Jonas; Zielasek, Volkmar, E-mail: zielasek@uni-bremen.de

2016-07-15

Optimizing thin metal film deposition techniques from metal-organic precursors such as atomic layer deposition, chemical vapor deposition (CVD), or electron beam-induced deposition (EBID) with the help of surface science analysis tools in ultrahigh vacuum requires a contamination-free precursor delivery technique, especially in the case of the less volatile precursors. For this purpose, the preparation of layers of undecomposed Ni(acac){sub 2} and Co(acac){sub 2} was tried via pulsed spray evaporation of a liquid solution of the precursors in ethanol into a flow of nitrogen on a CVD reactor. Solvent-free layers of intact precursor molecules were obtained when the substrate was heldmore » at a temperature of 115 °C. A qualitative comparison of thermally initiated and electron-induced precursor decomposition and metal center reduction was carried out. All deposited films were analyzed with respect to chemical composition quasi in situ by x-ray photoelectron spectroscopy. Thermally initiated decomposition yielded higher metal-to-metal oxide ratios in the deposit than the electron-induced process for which ratios of 60:40 and 20:80 were achieved for Ni and Co, resp. Compared to continuous EBID processes, all deposits showed low levels of carbon impurities of ∼10 at. %. Therefore, postdeposition irradiation of metal acetylacetonate layers by a focused electron beam and subsequent removal of intact precursor by dissolution in ethanol or by heating is proposed as electron beam lithography technique on the laboratory scale for the production of the metal nanostructures.« less

Anticipating flash-floods: Multi-scale aspects of the social response

NASA Astrophysics Data System (ADS)

Lutoff, Céline; Creutin, Jean-Dominique; Ruin, Isabelle; Borga, Marco

2016-10-01

This paper aims at exploring the anticipation phase before a flash flood, corresponding to the time between the first climatic signs and the peak-flow. We focus the analysis on people's behaviors observing how they use this period to organize themselves for facing the event. The analysis is made through the definition of three specific scales: the timeliness scale, an analytical scale of anticipatory actions and the scale of human response network. Using a cross-scale and cross level analysis enables to define different phases in the anticipation period where different kind of environmental precursors are mobilized by the actors in order to make sense of the situation and adapt. Three main points deserve attention at the end: firstly, the concepts of timeliness, anticipatory actions and crisis network scales enable to understand differently what happens both physically and socially during an extreme event; secondly, analyzing the precursors shows that each level of crisis network uses different kinds of signs for estimating the situation, organizing and reacting; thirdly, there is a potential for improvement in observation on both social and physical processes at different scales, for verifying the theory of the anticipatory phases.

Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient.

PubMed

Miyata, T; van Ypersele de Strihou, C; Imasawa, T; Yoshino, A; Ueda, Y; Ogura, H; Kominami, K; Onogi, H; Inagi, R; Nangaku, M; Kurokawa, K

2001-12-01

Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.

Generation of amyloid-β is reduced by the interaction of calreticulin with amyloid precursor protein, presenilin and nicastrin.

PubMed

Stemmer, Nina; Strekalova, Elena; Djogo, Nevena; Plöger, Frank; Loers, Gabriele; Lutz, David; Buck, Friedrich; Michalak, Marek; Schachner, Melitta; Kleene, Ralf

2013-01-01

Dysregulation of the proteolytic processing of amyloid precursor protein by γ-secretase and the ensuing generation of amyloid-β is associated with the pathogenesis of Alzheimer's disease. Thus, the identification of amyloid precursor protein binding proteins involved in regulating processing of amyloid precursor protein by the γ-secretase complex is essential for understanding the mechanisms underlying the molecular pathology of the disease. We identified calreticulin as novel amyloid precursor protein interaction partner that binds to the γ-secretase cleavage site within amyloid precursor protein and showed that this Ca(2+)- and N-glycan-independent interaction is mediated by amino acids 330-344 in the C-terminal C-domain of calreticulin. Co-immunoprecipitation confirmed that calreticulin is not only associated with amyloid precursor protein but also with the γ-secretase complex members presenilin and nicastrin. Calreticulin was detected at the cell surface by surface biotinylation of cells overexpressing amyloid precursor protein and was co-localized by immunostaining with amyloid precursor protein and presenilin at the cell surface of hippocampal neurons. The P-domain of calreticulin located between the N-terminal N-domain and the C-domain interacts with presenilin, the catalytic subunit of the γ-secretase complex. The P- and C-domains also interact with nicastrin, another functionally important subunit of this complex. Transfection of amyloid precursor protein overexpressing cells with full-length calreticulin leads to a decrease in amyloid-β42 levels in culture supernatants, while transfection with the P-domain increases amyloid-β40 levels. Similarly, application of the recombinant P- or C-domains and of a synthetic calreticulin peptide comprising amino acid 330-344 to amyloid precursor protein overexpressing cells result in elevated amyloid-β40 and amyloid-β42 levels, respectively. These findings indicate that the interaction of calreticulin with amyloid precursor protein and the γ-secretase complex regulates the proteolytic processing of amyloid precursor protein by the γ-secretase complex, pointing to calreticulin as a potential target for therapy in Alzheimer's disease.

Condensation of the isoprenoid and amino precursors in the biosynthesis of domoic acid.

PubMed

Savage, Thomas J; Smith, G Jason; Clark, Amy T; Saucedo, Portia N

2012-01-01

Understanding how environmental signals regulate production of domoic acid in blooms of Pseudo-nitzschia spp. at a molecular level requires description of the biochemical pathway to this kainoid neurotoxin. Precursor feeding studies have suggested domoic acid arises from the condensation of the C(10) isoprenoid geranyl diphosphate with glutamate, but the specific reactions leading to domoic acid from these precursors remain undescribed. Here, we develop a method to derivatize domoic acid with propyl chloroformate that enables gas chromatography-mass spectrometry (GC-MS) analysis to measure incorporation of stable isotopes into domoic acid generated in cultures incubated with isotopically-labeled substrates. We apply this method to demonstrate that both (2)H from [1-(2)H(2)]geraniol are incorporated into domoic acid, suggesting that the condensation of geranyl diphosphate with an amino group occurs by nucleophilic substitution of the diphosphate rather than by oxidation of geraniol to the aldehyde before reaction with an amino group to form an imine. Ultimately, these and similar studies will facilitate the identification of DA biosynthetic enzymes and genes which will enable the study of how environmental factors regulate DA biosynthesis at the molecular level. Copyright © 2011 Elsevier Ltd. All rights reserved.

Using GPS radio occultation data in the study of tropical cyclogenesis

NASA Astrophysics Data System (ADS)

Didlake, A. C., Jr.; Kuo, Y. B.; Metcalfe, T.

2005-12-01

Numerous studies have examined atmospheric conditions and patterns in tropical cyclogenesis. Although much has been accomplished, a complete understanding of tropical cyclogenesis is hindered by the lack of data in the regions where formation occurs. The GPS (Global Positioning System) radio occultation technique can provide valuable data in key areas. In GPS radio occultation, GPS satellites emit radio signals through the atmosphere that are received by another satellite in a low Earth orbit. Various atmospheric properties are calculated based on the alteration of the signal. This study assessed the value of GPS radio occultation data in the study of tropical cyclogenesis by examining storms of the 2002 Western North Pacific typhoon season. The signature of precursor disturbances to tropical cyclogenesis was determined by analyzing composites of data from the NCEP Aviation (AVN) analysis over four days. Similar composites of GPS radio occultation data were produced. The AVN analysis showed strong signals of precursor disturbances in the low-level wind fields and atmospheric refractivity. The GPS radio occultation data detected similarly increased refractivity values in corresponding regions, but had sizeable measurement differences with the AVN analysis. These differences were attributed to AVN analysis error due to the lack of input observational data and the high accuracy of GPS radio occultation measurements. Further comparisons showed that with the limited quantity of data currently available, GPS radio occultation by itself was not sufficient to detect precursor disturbances. It can best be used in data assimilation to improve the analysis and forecasts of tropical storms.

Functional Analysis of Precursors for Serious Problem Behavior and Related Intervention

ERIC Educational Resources Information Center

Langdon, Nancy A.; Carr, Edward G.; Owen-DeSchryver, Jamie S.

2008-01-01

Precursor behaviors are innocuous behaviors that reliably precede the occurrence of problem behavior. Intervention efforts applied to precursors might prevent the occurrence of severe problem behavior. We examined the relationship between precursor behavior and problem behavior in three individuals with developmental disabilities. First, a…

Ophthalmic acid is a marker of oxidative stress in plants as in animals.

PubMed

Servillo, Luigi; Castaldo, Domenico; Giovane, Alfonso; Casale, Rosario; D'Onofrio, Nunzia; Cautela, Domenico; Balestrieri, Maria Luisa

2018-04-01

Ophthalmic acid (OPH), γ-glutamyl-L-2-aminobutyryl-glycine, a tripeptide analogue of glutathione (GSH), has recently captured considerable attention as a biomarker of oxidative stress in animals. The OPH and GSH biosynthesis, as well as some biochemical behaviors, are very similar. Here, we sought to investigate the presence of OPH in plants and its possible relationship with GSH, known to possess multiple functions in the plant development, growth and response to environmental changes. HPLC-ESI-MS/MS analysis was used to examine the occurrence of OPH in leaves from various plant species, and flours from several plant seeds. Different types of oxidative stress, i.e., water, dark, paraquat, and cadmium stress, were induced in rye, barley, oat, and winter wheat leaves to evaluate the effects on the levels of OPH and its metabolic precursors. OPH and its dipeptide precursor, γ-glutamyl-2-aminobutyric acid, were found to occur in phylogenetically distant plants. Interestingly, the levels of OPH were tightly associated with the oxidative stress tested. Levels of OPH precursors, γ-glutamyl-2-aminobutyric acid and 2-aminobutyric acid, the latter efficiently formed in plants via biosynthetic pathways absent in the animal kingdom, were also found to increase during oxidative stress. OPH occurs in plants and its levels are tightly associated with oxidative stress. OPH behaves as an oxidative stress marker and its biogenesis might occur through a biochemical pathway common to many living organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

[Analysis of perfluoroalkyl substances precursors in human milk from 12 provinces of China].

PubMed

Yang, Lin; Yu, Xinping; Wang, Meng; Li, Jingguang; Wang, Yuxin; Zhao, Yunfeng; Wu, Yongning

2015-06-01

To explore the level of perfluoroalkyl substances (PFASs) precursors in Chinese human milk samples. The human milk samples were collected during the performance of Stockholm convention on survey of human milk in China in 2007. Based on the geographical location and dietary habits, China was divided into the south area and north area which 6 provinces were chosen from each area and there were 12 provinces in all. In each province, one urban site and two rural sites were selected to collect 80-110 samples. Mothers were randomly selected in each site to collect their breast milk. There were 1 237 individual human milk samples in all. For each province, the individual samples from the urban areas and the rural areas were pooled separately resulting in 24 pooled human milk samples. 11 PFAS precursors were measured in pooled samples by ultra-high performance liquid chromatography-tandem quadruple mass spectrometry (UPLC-MS/MS). The dietary exposure assessment of newborns was made. Three PFAS precursors were found above the detection limits, namely, 6:2 FTS, FHUEA, and 6:2 diPAP. Their concentration ranges were < Limit of determination (LOD) -47.46 pg/ml, < LOD -70.68 pg/ml and < LOD -35.08 pg/ml, respectively. The highest total PFAS precursor concentration 77.70 pg/ml was found in urban area samples from Shannxi Province. Rural area samples from Hubei had the lowest total PFAS precursor concentration, which was below the LOD. There were significant differences between rural and urban areas in many provinces, such as Shannxi (rural: 1.51 pg/ml; urban: 77.70 pg/ml), Shanghai (rural: 1.13 pg/ml; urban: 71.88 pg/ml), Jiangxi (rural: 65.39 pg/ml; urban: 0.55 pg/ml) and so on. The ranges estimated daily intake of 6:2 FTS, FHUEA and 6:2 diPAP of the samples from 12 provinces were 0.05-4.51, 1.13-6.72 and 1.15-3.34 ng · kg⁻¹ · d⁻¹. The results suggested the human exposure of PFAS precursors in China and the potential health impact of postnatal exposure through breastfeeding to infants. The level of PFAS precursors showed differences in regions, rural and urban places.

Probing de novo sphingolipid metabolism in mammalian cells utilizing mass spectrometry.

PubMed

Snider, Justin M; Snider, Ashley J; Obeid, Lina M; Luberto, Chiara; Hannun, Yusuf A

2018-06-01

Sphingolipids constitute a dynamic metabolic network that interconnects several bioactive molecules, including ceramide (Cer), sphingosine (Sph), Sph 1-phosphate, and Cer 1-phosphate. The interconversion of these metabolites is controlled by a cohort of at least 40 enzymes, many of which respond to endogenous or exogenous stimuli. Typical probing of the sphingolipid pathway relies on sphingolipid mass levels or determination of the activity of individual enzymes. Either approach is unable to provide a complete analysis of flux through sphingolipid metabolism, which, given the interconnectivity of the sphingolipid pathway, is critical information to identify nodes of regulation. Here, we present a one-step in situ assay that comprehensively probes the flux through de novo sphingolipid synthesis, post serine palmitoyltransferase, by monitoring the incorporation and metabolism of the 17 carbon dihydrosphingosine precursor with LC/MS. Pulse labeling and analysis of precursor metabolism identified sequential well-defined phases of sphingolipid synthesis, corresponding to the activity of different enzymes in the pathway, further confirmed by the use of specific inhibitors and modulators of sphingolipid metabolism. This work establishes precursor pulse labeling as a practical tool for comprehensively studying metabolic flux through de novo sphingolipid synthesis and complex sphingolipid generation.

Multipurpose Dissociation Cell for Enhanced ETD of Intact Protein Species

PubMed Central

Rose, Christopher M.; Russell, Jason D.; Ledvina, Aaron R.; McAlister, Graeme C.; Westphall, Michael S.; Griep-Raming, Jens; Schwartz, Jae C.; Coon, Joshua J.; Syka, John E.P.

2013-01-01

We describe and characterize an improved implementation of ETD on a modified hybrid linear ion trap-Orbitrap instrument. Instead of performing ETD in the mass-analyzing quadrupole linear ion trap (A-QLT), the instrument collision cell was modified to enable ETD. We partitioned the collision cell into a multi-section RF ion storage and transfer device to enable injection and simultaneous separate storage of precursor and reagent ions. Application of a secondary (axial) confinement voltage to the cell end lens electrodes enables charge-sign independent trapping for ion-ion reactions. The approximately two-fold higher quadrupole field frequency of this cell relative to that of the A-QLT, enables higher reagent ion densities and correspondingly faster ETD reactions, and, with the collision cell’s longer axial dimensions, larger populations of precursor ions may be reacted. The higher ion capacity of the collision cell permits the accumulation and reaction of multiple full loads of precursor ions from the A-QLT followed by FT Orbitrap m/z analysis of the ETD product ions. This extends the intra-scan dynamic range by increasing the maximum number of product ions in a single MS/MS event. For analyses of large peptide/small protein precursor cations, this reduces or eliminates the need for spectral averaging to achieve acceptable ETD product ion signal-to-noise levels. Using larger ion populations, we demonstrate improvements in protein sequence coverage and aggregate protein identifications in LC-MS/MS analysis of intact protein species as compared to the standard ETD implementation. PMID:23609185

Cu-Doped ZnO Thin Films Deposited by a Sol-Gel Process Using Two Copper Precursors: Gas-Sensing Performance in a Propane Atmosphere

PubMed Central

Gómez-Pozos, Heberto; Arredondo, Emma Julia Luna; Maldonado Álvarez, Arturo; Biswal, Rajesh; Kudriavtsev, Yuriy; Pérez, Jaime Vega; Casallas-Moreno, Yenny Lucero; Olvera Amador, María de la Luz

2016-01-01

A study on the propane gas-sensing properties of Cu-doped ZnO thin films is presented in this work. The films were deposited on glass substrates by sol-gel and dip coating methods, using zinc acetate as a zinc precursor, copper acetate and copper chloride as precursors for doping. For higher sensitivity values, two film thickness values are controlled by the six and eight dippings, whereas for doping, three dippings were used, irrespective of the Cu precursor. The film structure was analyzed by X-ray diffractometry, and the analysis of the surface morphology and film composition was made through scanning electron microscopy (SEM) and secondary ion mass spectroscopy (SIMS), respectively. The sensing properties of Cu-doped ZnO thin films were then characterized in a propane atmosphere, C3H8, at different concentration levels and different operation temperatures of 100, 200 and 300 °C. Cu-doped ZnO films doped with copper chloride presented the highest sensitivity of approximately 6 × 104, confirming a strong dependence on the dopant precursor type. The results obtained in this work show that the use of Cu as a dopant in ZnO films processed by sol-gel produces excellent catalysts for sensing C3H8 gas. PMID:28787885

On the level of skill in predicting maximum sunspot number - A comparative study of single variate and bivariate precursor techniques

NASA Technical Reports Server (NTRS)

Wilson, Robert M.

1990-01-01

The level of skill in predicting the size of the sunspot cycle is investigated for the two types of precursor techniques, single variate and bivariate fits, both applied to cycle 22. The present level of growth in solar activity is compared to the mean level of growth (cycles 10-21) and to the predictions based on the precursor techniques. It is shown that, for cycle 22, both single variate methods (based on geomagnetic data) and bivariate methods suggest a maximum amplitude smaller than that observed for cycle 19, and possibly for cycle 21. Compared to the mean cycle, cycle 22 is presently behaving as if it were a +2.6 sigma cycle (maximum amplitude of about 225), which means that either it will be the first cycle not to be reliably predicted by the combined precursor techniques or its deviation relative to the mean cycle will substantially decrease over the next 18 months.

Folding of Cu/Zn superoxide dismutase suggests structural hotspots for gain of neurotoxic function in ALS: Parallels to precursors in amyloid disease

PubMed Central

Nordlund, Anna; Oliveberg, Mikael

2006-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to misfolding of the ubiquitous enzyme Cu/Zn superoxide dismutase (SOD). In contrast to other protein-misfolding disorders with similar neuropathogenesis, ALS is not always associated with the in vivo deposition of protein aggregates. Thus, under the assumption that all protein-misfolding disorders share at primary level a similar disease mechanism, ALS constitutes an interesting disease model for identifying the yet-mysterious precursor states from which the cytotoxic pathway emerges. In this study, we have mapped out the conformational repertoire of the apoSOD monomer through analysis of its folding behavior. The results allow us to target the regions of the SOD structure that are most susceptible to unfolding locally under physiological conditions, leading to the exposure of structurally promiscuous interfaces that are normally hidden in the protein’s interior. The structure of this putative ALS precursor is strikingly similar to those implicated in amyloid disease. PMID:16798882

Urban sprawl and air quality in large US cities.

PubMed

Stone, Brian

2008-03-01

This study presents the results of a paper of urban spatial structure and exceedances of the 8-h national ambient air quality standard for ozone in 45 large US metropolitan regions. Through the integration of a published index of sprawl with metropolitan level data on annual ozone exceedances, precursor emissions, and regional climate over a 13-year period, the association between the extent of urban decentralization and the average number of ozone exceedances per year, while controlling for precursor emissions and temperature, is measured. The results of this analysis support the hypothesis that large metropolitan regions ranking highly on a quantitative index of sprawl experience a greater number of ozone exceedances than more spatially compact metropolitan regions. Importantly, this relationship was found to hold when controlling for population size, average ozone season temperatures, and regional emissions of nitrogen oxides and volatile organic compounds, suggesting that urban spatial structure may have effects on ozone formation that are independent of its effects on precursor emissions from transportation, industry, and power generation facilities.

Differentially regulated splice variants and systems biology analysis of Kaposi's sarcoma-associated herpesvirus-infected lymphatic endothelial cells.

PubMed

Chang, Ting-Yu; Wu, Yu-Hsuan; Cheng, Cheng-Chung; Wang, Hsei-Wei

2011-09-01

Alternative RNA splicing greatly increases proteome diversity, and the possibility of studying genome-wide alternative splicing (AS) events becomes available with the advent of high-throughput genomics tools devoted to this issue. Kaposi's sarcoma associated herpesvirus (KSHV) is the etiological agent of KS, a tumor of lymphatic endothelial cell (LEC) lineage, but little is known about the AS variations induced by KSHV. We analyzed KSHV-controlled AS using high-density microarrays capable of detecting all exons in the human genome. Splicing variants and altered exon-intron usage in infected LEC were found, and these correlated with protein domain modification. The different 3'-UTR used in new transcripts also help isoforms to escape microRNA-mediated surveillance. Exome-level analysis further revealed information that cannot be disclosed using classical gene-level profiling: a significant exon usage difference existed between LEC and CD34(+) precursor cells, and KSHV infection resulted in LEC-to-precursor, dedifferentiation-like exon level reprogramming. Our results demonstrate the application of exon arrays in systems biology research, and suggest the regulatory effects of AS in endothelial cells are far more complex than previously observed. This extra layer of molecular diversity helps to account for various aspects of endothelial biology, KSHV life cycle and disease pathogenesis that until now have been unexplored.

A Comparative Study on Ozone Photochemical Formation in the Megacities of Tianjin and Shanghai, China

NASA Astrophysics Data System (ADS)

Ran, L.; Zhao, C.; Xu, W.; Geng, F.; Lu, X.; Han, M.; Lin, W.; Xu, X.

2011-12-01

As one of the most widespread and stubborn environmental issues, the ozone problem has been of particular concern for many years, given the potential adverse effects of high ozone concentrations on public health and agricultural productivity. In the past decades, rapid urbanization and industrialization have given rise to a significant increase in ozone precursor emissions in many regions of China, especially in the densely populated megacities. Due to the highly nonlinear impacts of ozone precursors including nitrogen oxides (NOx) and various volatile organic compounds (VOCs) on ozone photochemistry, formation of ozone affected by different precursor emission patterns in those megacities has exhibited different characteristics. A comparative analysis of ozone photochemical production in the megacities of Tianjin and Shanghai has thus been carried out, using the data sets of surface ozone and its precursors measured respectively at an urban and a suburban site of the two megacities during the summertime. Observation-based analysis indicated an elevated ozone daily peak under photochemistry dominant conditions from the urban center to the suburb in both regions, nevertheless bearing different reasons. Ozone production was generally sensitive to VOCs in the Tianjin region, leading to a relatively higher level of ozone in the suburb where reactive VOCs were abundantly released from a number of industrial facilities, whereas a sensitivity of ozone production to NOx was found in Shanghai. The high level of NOx emitted mainly by motor vehicles in urban Shanghai largely inhibited ozone formation and resulted in a much more rapid decrease in ozone concentrations after reaching the daily maximum around midday compared with the other three areas. Ozone pollution in the megacity of Tianjin was more representative of the regional condition, implying that combined efforts would be needed to bring the ozone problem under control within this region. Improved understanding of ozone formation in the two megacities would be quite imperative and critical to provide a solid scientific basis for designing effective ozone control strategies.

Measurements of ozone and its precursors in Beijing in summer

NASA Astrophysics Data System (ADS)

Lee, J. D.; Squires, F. A.; Dunmore, R.; Hamilton, J. F.; Hopkins, J. R.; Rickard, A. R.

2017-12-01

Over the past few years there have been substantial reductions in emission of primary pollutants (e.g. PM, NOx) in Beijing. However, levels of ozone (O3), which is produced from VOCs and NOxin the presence of sunlight, frequently break recommended exposure limits in Beijing and other large conurbations in China. In fact, it is suggested that ozone is likely to become the major air pollutant effecting human health in Beijing over the next 5-10 years. For 5 weeks in May and June 2017 O3 was measured, along with NOx, CO and a large range of VOCs (C2 - C13) at the Institute of Atmospheric Physics of the Chinese Academy of Sciences site, close to the 4th ring road in central Beijing. Elevated levels of O3 were regularly observed, with maximum concentrations of 180 ppbv. On 75% of days during this period, O3 breached the recommended WHO 8 hour exposure limit of 60 ppbv. Data will be presented showing the effect of different levels of precursor species and photolysis rates on O3. The peak concentration of O3 on each day seemed to have little correlation with NOx. Typically NO concentrations were elevated during the morning but often decreased to below <0.05 ppbv during the afternoon hours when the O3 concentrations peaked. The highest levels of O3 were observed on days when CO, VOC and SO2 concentrations were highest, showing the potential importance of industrial emissions of precursor VOCs for O3 formation. Temperatures often peaked at >35oC meaning biogenic emissions also influenced the chemistry at the site, with several ppbv of isoprene measured during the afternoons. The importance of different VOCs for in-situ O3 formation is investigated using a simple steady state analysis of OH reactivity, along with a more detailed analysis using the Master Chemical Mechanism.

Child maltreatment, attention networks, and potential precursors to borderline personality disorder

PubMed Central

ROGOSCH, FRED A.; CICCHETTI, DANTE

2006-01-01

Potential precursors to borderline personality disorder (BPD) were investigated in a sample of 185 maltreated and 175 nonmaltreated school-aged children attending a summer camp research program. Self-report, peer-report, and counselor-report measures were utilized to assess developmental constructs conceptualized to constitute vulnerability for later emerging BPD. These areas, including personality features, representational models of self, parent, and peers, interpersonal relationship difficulties with peers and adults, and suicidal/self-harm behavior, were used to develop a BPD precursors composite. Additionally, the efficiency of three attention networks was assessed with a computerized task. Maltreated children had higher mean scores on the BPD precursors composite, and children classified as having high levels of these precursors were more prevalent in the maltreatment group. No maltreatment group differences were found for the efficiency of the three attention networks; however, children with high levels of BPD precursors evinced less efficient processing of the conflict attention network, comparable to findings observed among adult patients with BPD. Child maltreatment and efficiency of the conflict attention network independently predicted scores on the BPD precursors composite. Experiential and biological contributions to risk for BPD and recommendations for prevention and intervention are discussed. PMID:16613431

Identification, by molecular cloning, of a novel type of I2-superfamily conotoxin precursor and two novel I2-conotoxins from the worm-hunter snail Conus spurius from the Gulf of México.

PubMed

Zamora-Bustillos, Roberto; Aguilar, Manuel B; Falcón, Andrés

2010-03-01

cDNA was prepared from the venom duct of a single Conus spurius specimen collected near the coast of Campeche, México. From it, PCR products were generated aiming to clone I-conotoxin precursors. Thirty clones were sequenced and predicted to encode ten distinct precursors: seven of I(2)-conotoxins and three of I(2)-like-conotoxins. These precursors contain three different, mature toxins, sr11a, sr11b and sr11c, of which two are novel and one (sr11a) has been previously purified and characterized from the venom of this species. The precursors include a 26- (I(2)) or 23- residue signal peptide (I(2)-like), a 31-residue "pro" region (I(2)-like), and a 32-residue mature toxin region (I(2) and I(2)-like). In addition, all the precursors have a 13-residue "post" region which contains a gamma-carboxylation recognition sequence that directs the gamma-carboxylation of Glu-9 and Glu-10 of toxin sr11a and, possibly, Glu-13 of toxin sr11b and Glu-9 of toxin sr11c. This is the first time that a "post" region has been found in precursors of I-conotoxins that also contain a "pro" region. The "post" peptide is enzymatically processed to yield the amidated mature toxin sr11a, which implies that gamma-carboxylation occurs before amidation. Phylogenetic analysis at the whole precursor level indicates that the I(2)-like-conotoxins of C. spurius are more related to I(2)-conotoxins than to I(1)- and I(3)-conotoxins from other species, and that they might represent a new subgroup of the I(2)-superfamily. The three I-conotoxins from C. spurius have charge differences at seven to nine positions, suggesting that they might have different molecular target types or subtypes. (c) 2009 Elsevier Inc. All rights reserved.

Fate of grape flavor precursors during storage on yeast lees.

PubMed

Loscos, Natalia; Hernández-Orte, Purificación; Cacho, Juan; Ferreira, Vicente

2009-06-24

The effect of the addition of a grape flavor precursor extract to a grape juice, before or after fermentation with three different Saccharomyces cerevisiae yeast strains, on the evolution of the wine aroma composition during a 9-month aging period on yeast lees has been studied. Wine aroma compounds were determined by gas chromatography-mass spectrometry after alcoholic fermentation and after 3 and 9 months of storage. The aging of wine on lees caused important changes in the aroma profiles of wines, making the concentrations of three terpenes, norisoprenoids (except beta-damascenone and beta-ionone), 4-allyl-2,6-dimethoxyphenol, ethyl vanillate, syringaldehyde, and ethyl cinnamate increase, whereas the concentrations of most of the rest of compounds tended to decrease. Lees are responsible for the observed increasing trends, except for linalool and alpha-terpineol, and also for a large part of the observed decrements. As expected, the addition of precursors brings about an increment in the levels of most terpenes, norisoprenoids, vanillins, and ethyl cinnamate, and it is after an aging time when differences linked to the level of precursors in the must become more evident. The timing of the addition of precursors has a minor influence, except for beta-damascenone, vanillin, and syringaldehyde, for which supplementation after fermentation is more effective. It has also been observed that the precursor fraction makes the levels of vinylphenols decrease. Finally, it has also been found that lees from different yeast strains may have a slightly different abilities to release volatile compounds derived from precursors.

Increased neuronal beta-amyloid precursor protein expression in human temporal lobe epilepsy: association with interleukin-1 alpha immunoreactivity.

PubMed

Sheng, J G; Boop, F A; Mrak, R E; Griffin, W S

1994-11-01

Levels of immunoreactive beta-amyloid precursor protein and interleukin-1 alpha were found to be elevated in surgically resected human temporal lobe tissue from patients with intractable epilepsy compared with postmortem tissue from neurologically unaffected patients (controls). In tissue from epileptics, the levels of the 135-kDa beta-amyloid precursor protein isoform were elevated to fourfold (p < 0.05) those of controls and those of the 130-kDa isoform to threefold (p < 0.05), whereas those of the 120-kDa isoform (p > 0.05) were not different from control values. beta-Amyloid precursor protein-immunoreactive neurons were 16 times more numerous, and their cytoplasm and proximal processes were more intensely immunoreactive in tissue sections from epileptics than controls (133 +/- 12 vs. 8 +/- 3/mm2; p < 0.001). However, neither beta-amyloid precursor protein-immunoreactive dystrophic neurites nor beta-amyloid deposits were found in this tissue. Interleukin-1 alpha-immunoreactive cells (microglia) were three times more numerous in epileptics than in controls (80 +/- 8 vs. 25 +/- 5/mm2; p < 0.001), and these cells were often found adjacent to beta-amyloid precursor protein-immunoreactive neuronal cell bodies. Our findings, together with functions established in vitro for interleukin-1, suggest that increased expression of this protein contributes to the increased levels of beta-amyloid precursor protein in epileptics, thus indicating a potential role for both of these proteins in the neuronal dysfunctions, e.g., hyperexcitability, characteristic of epilepsy.

Transcription Analysis of the Beta-Glucosidase Precursor in Wild-Type and l-4i Mutant Bombyx mori (Lepidoptera: Bombycidae).

PubMed

Kang, Lequn; Huang, Fei; Wu, Fan; Zhao, Qiaoling

2015-01-01

Lethal fourth-instar larvae (l-4i) mutant of Bombyx mori, a recently discovered novel mutant, die from energy depletion due to genetic mutation. Beta-glucosidase is a common digestive enzyme that hydrolyzes cellulose in the diet to provide energy. In this study, the mRNA expression profiles of B. mori beta-glucosidase precursor (BmpreBG) were characterized by reverse transcription polymerase chain reaction and quantitative real-time polymerase chain reaction. The transcription level of BmpreBG varied in different tissues and developmental stages, except in the pupa and moth, which are the no-diet period. Remarkably, the mRNA expression level of BmpreBG was sharply reduced in l-4i but not in the wild type, which suggested that the digestive function of the mutant was severely damaged. This was consistent with the l-4i phenotypic traits of not eating mulberries, lack of energy, and ultimate death. 5'-rapid amplification of cDNA ends showed, for the first time, that BmpreBG has a 160-bp 5'-untranslated region. These findings suggested that B. mori β-glucosidase precursor was involved in the death process of l-4i mutant larvae. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Protein-expression profiles in mouse blood-plasma following acute whole-body exposure to (137)Cs gamma rays.

PubMed

Rithidech, Kanokporn Noy; Honikel, Louise; Rieger, Robert; Xie, Weiping; Fischer, Thomas; Simon, Sanford R

2009-05-01

To compare the pattern of protein-expression profiles in blood-plasma after exposure of CBA/CaJ mice to 0 or 3 Gy of (137)Cs gamma rays. Two-dimensional electrophoresis gel coupled with mass spectrometry was used to analyze blood-samples collected at days 2 and 7 post-irradiation. At each sacrifice-time, alterations in expression-level of protein spots between control- and exposed-groups were analyzed statistically by the PDQuest software using Student's t-test (at the significance level of p < 0.05). Mass spectrometry was used to identify the identity of protein-spots with significantly altered expression-level. At day 2, 18 proteins were significantly up-regulated in exposed-mice. These included: alpha-2-Heremans-Schmid (HS)-glycoprotein, apolipoprotein (Apo)-AII-precursor, Apo-E, beta-2-glycoprotein-I, clusterin, fibrinogen-alpha-chain, fibrinogen-gamma-polypeptide, fetuin-B, haptoglobin, high-molecular-weight (HMW)-kininogen (Kng), low-MW-Kng, Kng1-precursor, liver-carboxylesterase-I-precursor, major-urinary-protein-6-precursor, mannose-binding-protein-C-precursor, mannose-binding-lectin-C, and prothrombin-precursor. Gelsolin was detected in control-mice only. At day 7, high expression-levels of 14 proteins were detected in control-mice (i.e., alpha-1-antitrypsin-precursor, carboxylesterase-N, cholesterol-7-alpha-hydroxylase, contraspin, coagulation-factor-II, coagulation-factor-XIII, gelsolin, immunoglobulin-G-heavy-chain, neurexin, prothrombin-precursor, protein-phosphatase, putative-calcium-influx-channel, vitamin-D-binding-protein, and 1110018G07Rik); while 15 proteins were highly expressed in exposed-mice. These included: alpha-1-acid-glycoprotein, alpha-2-HS-glycoprotein, alpha-1-protease-inhibitor-2, ApoA-IV, ApoC-I, ApoH, beta-1-globin, clusterin, complement-component-3, fibrinogen-beta-chain, HMW-Kng, major-histocompatibility-complex-class-Ia-H2-K, serine-(cysteine)-proteinase-inhibitor, retinoblastoma-associated-protein-140, and vascular-cell-adhesion-molecule-1. Although different proteins (mostly involved in inflammatory responses) were detected in exposed-mice, alterations in expression-levels of clusterin, gelsolin, kininogen, and alpha-2-HS-glycoproteins were found at both times. Despite the need for validation, the results suggested that alterations in expression-levels of specific proteins may be indicative of radiation-exposure. The results also provided the important step in an eventual establishment of blood-based biomarkers of radiation-exposure in vivo.

Synthesis, characterization, microstructure, optical and magnetic properties of strontium cobalt carbonate precursor and Sr2Co2O5 oxide material

NASA Astrophysics Data System (ADS)

Agilandeswari, K.; Ruban Kumar, A.

2014-04-01

Sr2Co2O5 ceramic synthesized by the coprecipitation of strontium cobalt carbonate method. XRD analysis shows the single phase strontianite precursor and decomposed oxide product as orthorhombic structure of Sr2Co2O5. Thermal analysis proves the Sr2Co2O5 phase formation temperature of 800 °C. SEM image indicates crystalline rod shaped carbonate precursor transformed to oxide as porous diffused sphere shape particles. Optical band gap it reveals the strontium cobalt carbonate precursor as insulating material and the Sr2Co2O5 as semiconducting nature. The room temperature magnetic study indicates the carbonate precursor as paramagnetic but its oxide Sr2Co2O5 as superparamagnetic behavior.

Quantitative analysis of indigo and indigo precursors in leaves of Isatis spp. and Polygonum tinctorium.

PubMed

Gilbert, Kerry G; Maule, Hamish G; Rudolph, Bernd; Lewis, Mervyn; Vandenburg, Harold; Sales, Ester; Tozzi, Sabrina; Cooke, David T

2004-01-01

Analysis of extracts from two woad species (Isatis tinctoria and Isatis indigotica) and Polygonum tinctorium revealed that only one indigo precursor (indican) was present in Polygonum, but two precursors were found in Isatis spp. This was done using high performance liquid chromatography (HPLC), coupled to an evaporative light scattering detector (ELSD). In Isatis spp., the indigo precursors indican and a fraction representing isatan B were identified. The proportion of indican and isatan B was different between the two Isatis spp. tested. For the first time, it was possible to quantify the precursors in woad plant species, and the results were found to be in good agreement with those made from total indigo quantification using two different spectrophotometric methods or a derivatization technique.

N-nitrosamine formation by monochloramine, free chlorine, and peracetic acid disinfection with presence of amine precursors in drinking water system.

PubMed

West, Danielle M; Wu, Qihua; Donovan, Ariel; Shi, Honglan; Ma, Yinfa; Jiang, Hua; Wang, Jianmin

2016-06-01

In this study, the formation of eight N-nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, N-nitrosomethylamine, N-nitrosodi-n-propylamine, N-nitrosodi-n-butylamine, N-Nitrosopiperidine, N-Nitrosopyrrolidine, N-Nitrosomorpholine, were systematically evaluated with respect to seven N-nitrosamine precursors (dimethylamine, trimethylamine, 3-(dimethylaminomethyl)indole, 4-dimethylaminoantipyrine, ethylmethylamine, diethylamine, dipropylamine) and three disinfectants (monochloramine, free chlorine, peracetic acid) under variable dosages, exposure times, and pH in a drinking water system. Without the presence of the seven selected N-nitrosamine precursors N-nitrosamine formation was not observed under any tested condition except very low levels of N-Nitrosopyrrolidine under some conditions. With selected N-nitrosamine precursors present N-nitrosamines formed at different levels under different conditions. The highest N-nitrosamine formation was NDMA with a maximum concentration of 1180 ng/L by monochloramine disinfection with precursors present; much lower levels of N-nitrosamines were formed by free chlorine disinfection; and no detectable level of N-nitrosamines were observed by peracetic acid disinfection except low level of N-Nitrosodi-n-propylamine under some conditions. NDMA formation was not affected by pH while four other N-nitrosamine formations were slightly affected by sample pH tested between 7 and 9, with formation decreasing with increasing pH. Monochloramine exposure time study displayed fast formation of N-nitrosamines, largely formed in four hours of exposure and maximized after seven days. This was a systematic study on the N-nitrosamine formation with the seven major N-nitrosamine precursors presence and absence under different conditions, including peracetic acid disinfection which has not been studied elsewhere. Copyright © 2016 Elsevier Ltd. All rights reserved.

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals.

PubMed

Heng, Eng Chee; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Abdul Hamid, Noor Aini; Hamid, Zalina; Wan Ngah, Wan Zurinah

2013-10-01

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups. Subjects were divided into two age groups-32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78% tocotrienol and 22% tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting. Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression. TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.

A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus.

PubMed Central

Bahnsen, U; Oosting, P; Swaab, D F; Nahke, P; Richter, D; Schmale, H

1992-01-01

Familial neurohypophyseal diabetes insipidus in humans is a rare disease transmitted as an autosomal dominant trait. Affected individuals have very low or undetectable levels of circulating vasopressin and suffer from polydipsia and polyuria. An obvious candidate gene for the disease is the vasopressin-neurophysin (AVP-NP) precursor gene on human chromosome 20. The 2 kb gene with three exons encodes a composite precursor protein consisting of the neuropeptide vasopressin and two associated proteins, neurophysin and a glycopeptide. Cloning and nucleotide sequence analysis of both alleles of the AVP-NP gene present in a Dutch ADNDI family reveals a point mutation in one allele of the affected family members. Comparison of the nucleotide sequences shows a G----T transversion within the neurophysin-encoding exon B. This missense mutation converts a highly conserved glycine (Gly17 of neurophysin) to a valine residue. RFLP analysis of six related family members indicates cosegregation of the mutant allele with the DI phenotype. The mutation is not present in 96 chromosomes of an unrelated control group. These data suggest that a single amino acid exchange within a highly conserved domain of the human vasopressin-associated neurophysin is the primary cause of one form of ADNDI. Images PMID:1740104

[Factors related to nurses' patient identification behavior and the moderating effect of person-organization value congruence climate within nursing units].

PubMed

Kim, Young Mee; Kang, Seung Wan; Kim, Se Young

2014-04-01

This research was an empirical study designed to identify precursors and interaction effects related to nurses' patient identification behavior. A multilevel analysis methodology was used. A self-report survey was administered to registered nurses (RNs) of a university hospital in South Korea. Of the questionnaires, 1114 were analyzed. The individual-level factors that had a significantly positive association with patient identification behavior were person-organization value congruence, organizational commitment, occupational commitment, tenure at the hospital, and tenure at the unit. Significantly negative group-level precursors of patient identification behavior were burnout climate and the number of RNs. Two interaction effects of the person-organization value congruence climate were identified. The first was a group-level moderating effect in which the negative relationship between the number of RNs and patient identification behavior was weaker when the nursing unit's value congruence climate was high. The second was a cross-level moderating effect in which the positive relationship between tenure at the unit and patient identification behavior was weaker when value congruence climate was high. This study simultaneously tested both individual-level and group-level factors that potentially influence patient identification behavior and identified the moderating role of person-organization value congruence climate. Implications of these results are discussed.

Perceived discrimination and sexual precursor behaviors in Mexican American preadolescent girls: The role of psychological distress, sexual attitudes, and marianismo beliefs.

PubMed

Sanchez, Delida; Whittaker, Tiffany A; Hamilton, Emma; Zayas, Luis H

2016-07-01

This study explored the relation between perceived discrimination and sexual precursor behaviors among 205 Mexican American preadolescent middle school girls. In addition, this study examined whether psychological distress and sexual attitudes mediated and whether marianismo beliefs moderated this relation. A categorical confirmatory factor analysis (CCFA) of the Marianismo Beliefs Scale (MBS) was conducted to test the factor structure with a preadolescent Mexican American population (ages 11-14). A path analysis of analytic models was then performed to examine the hypothesized relations between perceived discrimination, psychological distress, sexual attitudes, marianismo beliefs, and sexual precursor behaviors. Results of the CCFA did not support the original 5-factor structure of the MBS for preadolescent Latina girls. However, a revised version of the MBS indicated an acceptable model fit, and findings from the path analysis indicated that perceived discrimination was both directly and indirectly linked to sexual precursor behaviors via psychological distress. Marianismo was not found to moderate the relation between perceived discrimination and sexual risk behaviors, however certain marianismo pillars were significantly negatively linked with sexual attitudes and precursor behaviors. This study underscores the importance of psychological distress in the perceived discrimination and sexual precursor link as well as the compensatory aspects of marianismo against sexual precursor behaviors in Mexican American preadolescent girls. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Experimental analysis of precursors to severe problem behavior.

PubMed

Fritz, Jennifer N; Iwata, Brian A; Hammond, Jennifer L; Bloom, Sarah E

2013-01-01

Some individuals engage in both mild and severe forms of problem behavior. Research has shown that when mild behaviors precede severe behaviors (i.e., the mild behaviors serve as precursors), they can (a) be maintained by the same source of reinforcement as severe behavior and (b) reduce rates of severe behavior observed during assessment. In Study 1, we developed an objective checklist to identify precursors via videotaped trials for 16 subjects who engaged in problem behavior and identified at least 1 precursor for every subject. In Study 2, we conducted separate functional analyses of precursor and severe problem behaviors for 8 subjects, and obtained correspondence between outcomes in 7 cases. In Study 3, we evaluated noncontingent reinforcement schedule thinning plus differential reinforcement of alternative behavior to reduce precursors, increase appropriate behavior, and maintain low rates of severe behavior during 3 treatment analyses for 2 subjects. Results showed that this treatment strategy was effective for behaviors maintained by positive and negative reinforcement. © Society for the Experimental Analysis of Behavior.

Spatial distribution and importance of potential perfluoroalkyl acid precursors in urban rivers and sewage treatment plant effluent--case study of Tama River, Japan.

PubMed

Ye, Feng; Tokumura, Masahiro; Islam, Md Saiful; Zushi, Yasuyuki; Oh, Jungkeun; Masunaga, Shigeki

2014-12-15

Production and use of perfluorooctane sulfonate (PFOS) is regulated worldwide. However, numerous potential precursors that eventually decompose into PFOS and other perfluoroalkyl acids (PFAAs) such as perfluorooctanoic acid (PFOA) are still being used and have not been studied in detail. Therefore, knowledge about the levels and sources of the precursors is essential. We investigated the total concentration of potential PFAA precursors in the Tama River, which is one of the major rivers flowing into the Tokyo Bay, by converting all the perfluorinated carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA) precursors into PFCAs by chemical oxidation. The importance of controlling PFAA precursors was determined by calculating the ratios of PFCAs formed by oxidation to the PFAAs originally present (ΣΔ[PFCAC4-C12]/Σ[PFAAs]before oxidation) (average = 0.28 and 0.69 for main and tributary branch rivers, respectively). Higher total concentrations of Δ[PFCAs] were found in sewage treatment plant (STP) effluents. However, the ratios found in the effluents were lower (average = 0.21) than those found in the river water samples, which implies the decomposition of some precursors into PFAAs during the treatment process. On the other hand, higher ratios were observed in the upstream water samples and the existence of emission sources other than the STP effluents was indicated. This study showed that although the treatment process converting a part of the PFAA precursors into PFAAs, STPs were important sources of precursors to the Tama River. To reduce the levels of PFAAs in the aquatic environment, it is necessary to reduce the emission of the PFAA precursors as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

Source Attribution of Tropospheric Ozone using a Global Model

NASA Astrophysics Data System (ADS)

Coates, J.; Lupascu, A.; Butler, T. M.; Zhu, S.

2016-12-01

Tropospheric ozone is both a short-lived climate forcing pollutant and a radiatively active greenhouse gas. Ozone is not directly emitted into the troposphere but photochemically produced from chemical reactions involving nitrogen oxides (NOx) and volatile organic compounds (VOCs). Emissions of ozone precursors (NOx and VOCs) have both natural and anthropogenic sources and may be transported away from their sources to produce ozone downwind. Also, transport of ozone from the stratosphere into the troposphere also influences tropospheric ozone levels in some regions. Attributing ozone concentrations to the contributions from different sources would indicate the effects of locally emitted or transported precursors on ozone levels in specific regions. This information could be used to inform the emission reduction strategies of ozone precursors by indicating which emission sources could be targeted for effective reductions thus reducing the burden of ozone pollution. We use a "tagging" approach within the CESM global model to attribute ozone levels to their source emissions. We use different tags to quantify the impact from natural (soils, lightning, stratospheric transport) and anthropogenic (aircraft, biomass burning) sources of NOx and VOCs (including methane) on ozone levels. These source sectors of different global regions are assigned based on the global emissions specified by HTAPv2.2. Using these results, we develop a transboundary source-receptor relationship of ozone concentration to its precursor emission regions. Additionally, the transport of ozone precursors from regional anthropogenic sources is analysed to illustrate the extent to which mitigation strategies of regional emissions aid in mitigating global ozone levels.

A precursor system analysis of automated construction, maintenance, and operational requirements : resource materials

DOT National Transportation Integrated Search

1995-03-01

This report documents work performed by the University of California at Davis in collaboration with the California Department of Transportation (Caltrans) in relationship to a Precursor System Analysis dealing with a study of automated construction, ...

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli: Production of Jet Fuel Precursor Monoterpenoids

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

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP productionmore » but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes.« less

TGFbeta regulation of membrane mucin Muc4 via proteosome degradation.

PubMed

Lomako, Wieslawa M; Lomako, Joseph; Soto, Pedro; Carraway, Coralie A Carothers; Carraway, Kermit L

2009-07-01

Muc4 is a heterodimeric membrane mucin implicated in epithelial differentiation and tumor progression. It is expressed from a single gene as a 300 kDa precursor protein which is cleaved in the endoplasmic reticulum to its two subunits. Our previous work has shown that Muc4 is regulated by TGFbeta, which represses the precursor cleavage. Working with Muc4-transfected A375 tumor cells, we now show that Muc4 undergoes proteosomal degradation. Proteosome inhibitors prolong the life of the precursor, shunt the Muc4 into cytoplasmic aggresomes, increase the level of Muc4 associated with the endoplasmic reticulum chaperones calnexin and calreticulin and increase the levels of ubiquitinated Muc4. Most importantly, proteosome inhibitors repress the TGFbeta inhibition of Muc4 expression. These results suggest a model in which TGFbeta inhibits precursor cleavage, shunting the precursor into the proteosomal degradation pathway. Thus, the cells have evolved a mechanism to use the quality control pathway for glycoproteins to control the quantity of the protein produced. 2009 Wiley-Liss, Inc.

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli: Production of Jet Fuel Precursor Monoterpenoids

DOE PAGES

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun; ...

2017-05-18

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP productionmore » but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes.« less

Four-way regulation of mosquito yolk protein precursor genes by juvenile hormone-, ecdysone-, nutrient-, and insulin-like peptide signaling pathways.

PubMed

Hansen, Immo A; Attardo, Geoffrey M; Rodriguez, Stacy D; Drake, Lisa L

2014-01-01

Anautogenous mosquito females require a meal of vertebrate blood in order to initiate the production of yolk protein precursors by the fat body. Yolk protein precursor gene expression is tightly repressed in a state-of-arrest before blood meal-related signals activate it and expression levels rise rapidly. The best understood example of yolk protein precursor gene regulation is the vitellogenin-A gene (vg) of the yellow fever mosquito Aedes aegypti. Vg-A is regulated by (1) juvenile hormone signaling, (2) the ecdysone-signaling cascade, (3) the nutrient sensitive target-of-rapamycin signaling pathway, and (4) the insulin-like peptide (ILP) signaling pathway. A plethora of new studies have refined our understanding of the regulation of yolk protein precursor genes since the last review on this topic in 2005 (Attardo et al., 2005). This review summarizes the role of these four signaling pathways in the regulation of vg-A and focuses upon new findings regarding the interplay between them on an organismal level.

Neuropeptides encoded by the genomes of the Akoya pearl oyster Pinctata fucata and Pacific oyster Crassostrea gigas: a bioinformatic and peptidomic survey.

PubMed

Stewart, Michael J; Favrel, Pascal; Rotgans, Bronwyn A; Wang, Tianfang; Zhao, Min; Sohail, Manzar; O'Connor, Wayne A; Elizur, Abigail; Henry, Joel; Cummins, Scott F

2014-10-02

Oysters impart significant socio-ecological benefits from primary production of food supply, to estuarine ecosystems via reduction of water column nutrients, plankton and seston biomass. Little though is known at the molecular level of what genes are responsible for how oysters reproduce, filter nutrients, survive stressful physiological events and form reef communities. Neuropeptides represent a diverse class of chemical messengers, instrumental in orchestrating these complex physiological events in other species. By a combination of in silico data mining and peptide analysis of ganglia, 74 putative neuropeptide genes were identified from genome and transcriptome databases of the Akoya pearl oyster, Pinctata fucata and the Pacific oyster, Crassostrea gigas, encoding precursors for over 300 predicted bioactive peptide products, including three newly identified neuropeptide precursors PFGx8amide, RxIamide and Wx3Yamide. Our findings also include a gene for the gonadotropin-releasing hormone (GnRH) and two egg-laying hormones (ELH) which were identified from both oysters. Multiple sequence alignments and phylogenetic analysis supports similar global organization of these mature peptides. Computer-based peptide modeling of the molecular tertiary structures of ELH highlights the structural homologies within ELH family, which may facilitate ELH activity leading to the release of gametes. Our analysis demonstrates that oysters possess conserved molluscan neuropeptide domains and overall precursor organization whilst highlighting many previously unrecognized bivalve idiosyncrasies. This genomic analysis provides a solid foundation from which further studies aimed at the functional characterization of these molluscan neuropeptides can be conducted to further stimulate advances in understanding the ecology and cultivation of oysters.

Ethyl Carbamate Formation Regulated by Lactic Acid Bacteria and Nonconventional Yeasts in Solid-State Fermentation of Chinese Moutai-Flavor Liquor.

PubMed

Du, Hai; Song, Zhewei; Xu, Yan

2018-01-10

This study aimed to identify specific microorganisms related to the formation of precursors of EC (ethyl carbamate) in the solid-state fermentation of Chinese Moutai-flavor liquor. The EC content was significantly correlated with the urea content during the fermentation process (R 2 = 0.772, P < 0.01). Differences in urea production and degradation were found at both species and functional gene levels by metatranscriptomic sequencing and culture-dependent analysis. Lactobacillus spp. could competitively degrade arginine through the arginine deiminase pathway with yeasts, and most Lactobacillus species were capable of degrading urea. Some dominant nonconventional yeasts, such as Pichia, Schizosaccharomyces, and Zygosaccharomyces species, were shown to produce low amounts of urea relative to Saccharomyces cerevisiae. Moreover, unusual urea degradation pathways (urea carboxylase, allophanate hydrolase, and ATP-independent urease) were identified. Our results indicate that EC precursor levels in the solid-state fermentation can be controlled using lactic acid bacteria and nonconventional yeasts.

NASA's Accident Precursor Analysis Process and the International Space Station

NASA Technical Reports Server (NTRS)

Groen, Frank; Lutomski, Michael

2010-01-01

This viewgraph presentation reviews the implementation of Accident Precursor Analysis (APA), as well as the evaluation of In-Flight Investigations (IFI) and Problem Reporting and Corrective Action (PRACA) data for the identification of unrecognized accident potentials on the International Space Station.

A Functional Interplay between Human Immunodeficiency Virus Type 1 Protease Residues 77 and 93 Involved in Differential Regulation of Precursor Autoprocessing and Mature Protease Activity

PubMed Central

Counts, Christopher J.; Ho, P. Shing; Donlin, Maureen J.; Tavis, John E.; Chen, Chaoping

2015-01-01

HIV-1 protease (PR) is a viral enzyme vital to the production of infectious virions. It is initially synthesized as part of the Gag-Pol polyprotein precursor in the infected cell. The free mature PR is liberated as a result of precursor autoprocessing upon virion release. We previously described a model system to examine autoprocessing in transfected mammalian cells. Here, we report that a covariance analysis of miniprecursor (p6*-PR) sequences derived from drug naïve patients identified a series of amino acid pairs that vary together across independent viral isolates. These covariance pairs were used to build the first topology map of the miniprecursor that suggests high levels of interaction between the p6* peptide and the mature PR. Additionally, several PR-PR covariance pairs are located far from each other (>12 Å Cα to Cα) relative to their positions in the mature PR structure. Biochemical characterization of one such covariance pair (77–93) revealed that each residue shows distinct preference for one of three alkyl amino acids (V, I, and L) and that a polar or charged amino acid at either of these two positions abolishes precursor autoprocessing. The most commonly observed 77V is preferred by the most commonly observed 93I, but the 77I variant is preferred by other 93 variances (L, V, or M) in supporting precursor autoprocessing. Furthermore, the 77I93V covariant enhanced precursor autoprocessing and Gag polyprotein processing but decreased the mature PR activity. Therefore, both covariance and biochemical analyses support a functional association between residues 77 and 93, which are spatially distant from each other in the mature PR structure. Our data also suggests that these covariance pairs differentially regulate precursor autoprocessing and the mature protease activity. PMID:25893662

The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels

PubMed Central

Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Moir, Robert D.; Xia, Weiming; Marcantonio, Edward R.; Culley, Deborah J.; Crosby, Gregory; Tanzi, Rudolph E.; Xie, Zhongcong

2009-01-01

Objective: To assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and β-amyloid protein (Aβ) levels in vitro and in vivo. Subjects: Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein. Interventions: Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% sevoflurane for 6 hours. Mice received 2.5% sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and Aβ levels were assessed. Results: Sevoflurane induced apoptosis and elevated levels of β-site amyloid precursor protein-cleaving enzyme and Aβ in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of sevoflurane on apoptosis and Aβ. Sevoflurane-induced caspase-3 activation was attenuated by the γ-secretase inhibitor L-685,458 and was potentiated by Aβ. These results suggest that sevoflurane induces caspase activation which, in turn, enhances β-site amyloid precursor protein–cleaving enzyme and Aβ levels. Increased Aβ levels then induce further rounds of apoptosis. Conclusions: These results suggest that inhalational anesthetic sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral Aβ. PMID:19433662

Level 3 material characterization of NARC HRPF, HRHU, HRHF, and HRPU

NASA Technical Reports Server (NTRS)

Tobias, Mark E.

1993-01-01

The North American Rayon Corporation (NARC) precursor was developed, qualified, and characterized for Space Shuttle nozzle carbon-cloth phenolic ablative materials in three distinct phases. The characterization phase includes thermal and structural material property analysis and comparisons. This report documents the thermal and structural material property characterization performed by Southern Research Institute (SRI) on the two NARC baseline and two crossover materials.

On-fiber furan formation from volatile precursors: a critical example of artefact formation during Solid-Phase Microextraction.

PubMed

Adams, An; Van Lancker, Fien; De Meulenaer, Bruno; Owczarek-Fendor, Agnieszka; De Kimpe, Norbert

2012-05-15

For the analysis of furan, a possible carcinogen formed during thermal treatment of food, Solid-Phase Microextraction (SPME) is a preferred and validated sampling method. However, when volatile furan precursors are adsorbed on the carboxen/PDMS fiber, additional amounts of furan can be formed on the fiber during thermal desorption, as shown here for 2-butenal and furfural. No significant increase in furan amounts was found upon heating the furan precursor 2-butenal, indicating that the furan amounts formed during precursor heating experiments are negligible as compared to the additional amounts of furan formed during fiber desorption. This artefactual furan formation increased with increasing desorption time, but especially with increasing desorption temperature. Although this effect was most pronounced on the Carboxen/PDMS SPME-fiber, it was also noted on two other SPME-fibers tested (PDMS and DVB/Carboxen/PDMS). The general impact on furan data from food and model systems in literature will depend on the amounts of volatile precursors present, but will probably remain limited. However, considering the importance of this worldwide food contaminant, special care has to be taken during SPME-analysis of furan. Especially when performing precursor studies, static headspace sampling should preferably be applied for furan analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Photochemically consumed hydrocarbons and their relationship with ozone formation in two megacities of China

NASA Astrophysics Data System (ADS)

Chang, C.; Wang, J.; Liu, S.; Shao, M.; Zhang, Y.; Zhu, T.; Shiu, C.; Lai, C.

2010-12-01

Two on-site continuous measurements of ozone and its precursors in two megacities of China were carried out in an urban site of Beijing and a suburban site near Guangzhou in the Pearl River Delta (PRD) to estimate precursor consumption and to assess its relationship with oxidant (O3+NO2) formation level. An observation-based method (OBM) with the precursor consumption concept was adopted to assess the relationship between oxidant production and amounts of photochemically consumed non-methane hydrocarbons (NMHCs). In this approach, the ratio of ethylbenzene to m,p-xylenes was used to estimate the degree of photochemical processing, as well as the amounts of photochemically consumed NMHCs by reacting with OH. By trying to correlate the observed oxidant with the observed NMHC concentration, the two areas both revealed nearly no to low correlation between them. However, it existed fair to good correlations (R2=0.68 for Beijing, 0.53 for PRD) between the observed oxidant level and the degree of photochemical processing (ethylbenzene/m,p-xylenes). Furthermore, after taking the approach of consumption to estimate the consumed amounts of NMHCs, an interesting finding reveals that the definite correlation existed between the observed oxidant level and the total consumed NMHCs. The good correlations (R2=0.83 for Beijing, 0.81 for PRD) implies that the ambient oxidant level correlated to the amount of consumed NMHCs. The results of the two megacities in China by using the OBM with the precursor consumption concept can provide another pathway to explore the relationship between photochemically produced oxidant and consumed precursors, and will be helpful to validate model results and to reduce uncertainty of model predictions. However, the method has some room for uncertainty, as injection of fresh precursor emissions and additional boundary ozone involved, etc. could affect the estimation of consumed NMHCs and observed oxidant levels. Assistance of approaches in assessing the influence of the interfering factors would be helpful to acquire more reliable inferences of relationship between oxidant formation and precursor consumption.

Preparing for Humans at Mars, MPPG Updates to Strategic Knowledge Gaps and Collaboration with Science Missions

NASA Technical Reports Server (NTRS)

Baker, John; Wargo, Michael J.; Beaty, David

2013-01-01

The Mars Program Planning Group (MPPG) was an agency wide effort, chartered in March 2012 by the NASA Associate Administrator for Science, in collaboration with NASA's Associate Administrator for Human Exploration and Operations, the Chief Scientist, and the Chief Technologist. NASA tasked the MPPG to develop foundations for a program-level architecture for robotic exploration of Mars that is consistent with the President's challenge of sending humans to the Mars system in the decade of the 2030s and responsive to the primary scientific goals of the 2011 NRC Decadal Survey for Planetary Science. The Mars Exploration Program Analysis Group (MEPAG) also sponsored a Precursor measurement Strategy Analysis Group (P-SAG) to revisit prior assessments of required precursor measurements for the human exploration of Mars. This paper will discuss the key results of the MPPG and P-SAG efforts to update and refine our understanding of the Strategic Knowledge Gaps (SKGs) required to successfully conduct human Mars missions.

Confirmatory Factor Analysis of the Trinity Inventory of Precursors to Suicide (TIPS) and Its Relationship to Hopelessness and Depression

ERIC Educational Resources Information Center

Smyth, Caroline L.; MacLachlan, Malcolm

2005-01-01

Numerous existing measures assess attitudes toward suicide yet fail to account for contextual factors. The Trinity Inventory of Precursors to Suicide (TIPS) is presented as an alternative, with implications for the development of prevention programs. Having previously reported exploratory analysis of the TIPS; confirmatory factor analysis and…

Pseudo-Capacitors: SPPS Deposition and Electrochemical Analysis of α-MoO3 and Mo2N Coatings

NASA Astrophysics Data System (ADS)

Golozar, Mehdi; Chien, Ken; Lian, Keryn; Coyle, Thomas W.

2013-06-01

Solution precursor plasma spraying (SPPS) is a novel thermal spray process in which a solution precursor is injected into the high-temperature zone of a DC-arc plasma jet to allow solvent evaporation from the precursor droplets, solute precipitation, and precipitate pyrolysis prior to substrate impact. This investigation explored the potential of SPPS to fabricate α-MoO3 coatings with fine grain sizes, high porosity levels, and high surface area: characteristics needed for application as pseudo-capacitor electrodes. Since molybdenum nitride has shown a larger electrochemical stability window and higher specific area capacitance, the α-MoO3 deposits were subsequently converted into molybdenum nitride. A multistep heat-treatment procedure resulted in a topotactic phase-transformation mechanism, which retained the high surface area lath-shaped features of the original α-MoO3. The electrochemical behaviors of molybdenum oxide and molybdenum nitride deposits formed under different deposition conditions were studied using cyclic voltammetry to assess the influence of the resulting microstructure on the charge storage behavior and potential for use in pseudo-capacitors.

Temporal Characterisation of Ground-level Ozone Concentration in Klang Valley

NASA Astrophysics Data System (ADS)

Izzah Mohamad Hashim, Nur; Noor, Norazian Mohamed; Yasina Yusof, Sara

2018-03-01

In Malaysia, ground-level ozone (O3) is one of the most significant air pollutants due to the increasing sources of ozone precursors. Hence, the surface O3 concentration should have received substantial attention because of its negative effects to human health, vegetation and the environment. In this study, hourly air pollutants dataset (i.e O3, Carbon monoxide (CO), Nitrogen dioxide (NO2), Particulate matter (PM10), Non-methane hydrocarbon (NmHC), Sulphur dioxide (SO2)) and weather parameters (i.e. wind speed (WS), wind direction (WD), temperature (T), ultraviolet B (UVB)) for ten years period (2003-2012) in Klang Valley were selected for analysis in this study. Two monitoring stations were selected that are Petaling Jaya and Shah Alam. The aim of the study is to determine the diurnal variations of O3 concentrations according to the seasonal monsoon and the correlation between the ground-level O3 concentration and others parameter. A high concentration of ground-level O3 was observed during the first transition (April to May) for both of the stations. While at a low surface, O3 concentration was found out during the southwest monsoon within June to September. Pearson correlation was used to find the correlation between the O3 concentration and all other pollutants and weather parameters. Most of the relationship between O3concentrationswas positively correlated with NO2 and negative relationship was found out with NMHC. These results were expected since these pollutants are known as the O3 precursors. Besides that, O3 concentration and its precursors show a positive significant correlation with all meteorological factors except for relative humidity.

Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis

PubMed Central

Auchtung, Jennifer; Brown, Aaron; Boonma, Prapaporn; Oezguen, Numan; Ross, Caná L.; Luna, Ruth Ann; Runge, Jessica; Versalovic, James; Peniche, Alex; Dann, Sara M.; Britton, Robert A.; Haag, Anthony; Savidge, Tor C.

2017-01-01

ABSTRACT Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials. PMID:28760934

Determination of 14 nitrosamines at nanogram per liter levels in drinking water.

PubMed

Qian, Yichao; Wu, Minghuo; Wang, Wei; Chen, Beibei; Zheng, Hao; Krasner, Stuart W; Hrudey, Steve E; Li, Xing-Fang

2015-01-20

N-Nitrosamines, probable human carcinogens, are a group of disinfection byproducts under consideration for drinking water regulation. Currently, no method can determine trace levels of alkyl and tobacco-specific nitrosamines (TSNAs) of varying physical and chemical properties in water by a single analysis. To tackle this difficulty, we developed a single solid-phase extraction (SPE) method with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of 14 nitrosamines of health concern with widely differing properties. We made a cartridge composed of a vinyl/divinylbenzene polymer that efficiently concentrated the 14 nitrosamines in 100 mL of water (in contrast to 500 mL in other methods). This single SPE-HPLC-MS/MS technique provided calculated method detection limits of 0.01-2.7 ng/L and recoveries of 53-93% for the 14 nitrosamines. We have successfully demonstrated that this method can determine the presence or absence of the 14 nitrosamines in drinking water systems (eight were evaluated in Canada and the U.S.), with occurrence similar to that in other surveys. N-Nitrosodimethylamine (NDMA), N-nitrosodiphenylamine, and the TSNA 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were identified and quantified in authentic drinking water. Formation potential (FP) tests demonstrated that NDMA and TSNA precursors were present in (1) water samples in which tobacco was leached and (2) wastewater-impacted drinking water. Our results showed that prechlorination or ozonation destroyed most of the nitrosamine precursors in water. Our new single method determination of alkylnitrosamines and TSNAs significantly reduced the time and resource demands of analysis and will enable other studies to more efficiently study precursor sources, formation mechanisms, and removal techniques. It will be useful for human exposure and health risk assessments of nitrosamines in drinking water.

Eye pigments in wild-type and eye-color mutant strains of the African malaria vector Anopheles gambiae.

PubMed

Beard, C B; Benedict, M Q; Primus, J P; Finnerty, V; Collins, F H

1995-01-01

Chromatographic analysis of pigments extracted from wild-type eyes of the mosquito Anopheles gambiae reveals the presence of the ommatin precursor 3-hydroxykynurenine, its transamination derivative xanthurenic acid, and a dark, red-brown pigment spot that probably is composed of two or more low mobility xanthommatins. No colored or fluorescent pteridines are evident. Mosquitoes homozygous for an autosomal recessive mutation at the red-eye (r) locus have a brick-red eye color in larvae, pupae, and young adults, in contrast to the almost black color of the wild eye. Mosquitoes homozygous for this mutant allele have levels of ommochrome precursors that are indistinguishable from the wild-type, but the low-mobility xanthommatin spot is ochre-brown in color rather than red-brown as in the wild-type. Mosquitoes with two different mutant alleles at the X-linked pink-eye locus (p, which confers a pink eye color, and pw, which confers a white eye phenotype in homozygotes or hemizygous males) have normal levels of ommochrome precursors but no detectable xanthommatins. Mosquitoes homozygous for both the r and p mutant alleles have apricot-colored eyes and show no detectable xanthommatins. Both the pink-eye and red-eye mutations appear to involve defects in the transport into or assembly of pigments in the membrane-bound pigment granules rather then defects in ommochrome synthesis.

Electron-Beam-Induced Deposition as a Technique for Analysis of Precursor Molecule Diffusion Barriers and Prefactors.

PubMed

Cullen, Jared; Lobo, Charlene J; Ford, Michael J; Toth, Milos

2015-09-30

Electron-beam-induced deposition (EBID) is a direct-write chemical vapor deposition technique in which an electron beam is used for precursor dissociation. Here we show that Arrhenius analysis of the deposition rates of nanostructures grown by EBID can be used to deduce the diffusion energies and corresponding preexponential factors of EBID precursor molecules. We explain the limitations of this approach, define growth conditions needed to minimize errors, and explain why the errors increase systematically as EBID parameters diverge from ideal growth conditions. Under suitable deposition conditions, EBID can be used as a localized technique for analysis of adsorption barriers and prefactors.

Precursors of Professionalism in Senior-Level Undergraduate Business Students and the Implications of These Precursors for Business Education and the Profession

ERIC Educational Resources Information Center

Nino, Lana Sami

2012-01-01

Understanding the professional identity of senior-level undergraduate business students may shed light on the rampant unethical acts of business managers in industry. Business education is the largest segment of undergraduate majors, constituting more than 20% of students in four-year institutions, year after year. To explain the professional…

Exogenous Supply of Pantoyl Lactone to Excised Leaves Increases their Pantothenate Levels

PubMed Central

RATHINASABAPATHI, BALA; RAMAN, SURESH BABU

2005-01-01

• Background and Aims All plants synthesize pantothenate but its synthesis and regulation are not well understood. The aim of this work is to study the effect of exogenous supply of precursor compounds on pantothenate levels in leaves. • Methods Precursor compounds were supplied in solution to excised leaves and the pantothenate content was measured using a microbial method. • Key Results Pantothenate levels in excised leaves of Limonium latifolium, tomato (Lycopersicon esculentum), bean (Phaseolus vulgaris) and grapefruit (Citrus × paradisi) were examined following an exogenous supply of the precursor compounds pantoyl lactone or β-alanine. Significantly higher levels of extractable pantothenate were found when pantoyl lactone was supplied, but not when β-alanine was supplied despite a measurable uptake of β-alanine into the leaf. • Conclusions The results suggested that the pantoate supply may be rate-limiting or regulating pantothenate synthesis in leaves. PMID:15767268

Metabolic assessment of E. coli as a Biofactory for commercial products.

PubMed

Zhang, Xiaolin; Tervo, Christopher J; Reed, Jennifer L

2016-05-01

Metabolic engineering uses microorganisms to synthesize chemicals from renewable resources. Given the thousands of known metabolites, it is unclear what valuable chemicals could be produced by a microorganism and what native and heterologous reactions are needed for their synthesis. To answer these questions, a systematic computational assessment of Escherichia coli's potential ability to produce different chemicals was performed using an integrated metabolic model that included native E.coli reactions and known heterologous reactions. By adding heterologous reactions, a total of 1777 non-native products could theoretically be produced in E. coli under glucose minimal medium conditions, of which 279 non-native products have commercial applications. Synthesis pathways involving native and heterologous reactions were identified from eight central metabolic precursors to the 279 non-native commercial products. These pathways were used to evaluate the dependence on, and diversity of, native and heterologous reactions to produce each non-native commercial product, as well as to identify each product׳s closest central metabolic precursor. Analysis of the synthesis pathways (with 5 or fewer reaction steps) to non-native commercial products revealed that isopentenyl diphosphate, pyruvate, and oxaloacetate are the closest central metabolic precursors to the most non-native commercial products. Additionally, 4-hydroxybenzoate, tyrosine, and phenylalanine were found to be common precursors to a large number of non-native commercial products. Strains capable of producing high levels of these precursors could be further engineered to create strains capable of producing a variety of commercial non-native chemicals. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Four-way regulation of mosquito yolk protein precursor genes by juvenile hormone-, ecdysone-, nutrient-, and insulin-like peptide signaling pathways

PubMed Central

Hansen, Immo A.; Attardo, Geoffrey M.; Rodriguez, Stacy D.; Drake, Lisa L.

2014-01-01

Anautogenous mosquito females require a meal of vertebrate blood in order to initiate the production of yolk protein precursors by the fat body. Yolk protein precursor gene expression is tightly repressed in a state-of-arrest before blood meal-related signals activate it and expression levels rise rapidly. The best understood example of yolk protein precursor gene regulation is the vitellogenin-A gene (vg) of the yellow fever mosquito Aedes aegypti. Vg-A is regulated by (1) juvenile hormone signaling, (2) the ecdysone-signaling cascade, (3) the nutrient sensitive target-of-rapamycin signaling pathway, and (4) the insulin-like peptide (ILP) signaling pathway. A plethora of new studies have refined our understanding of the regulation of yolk protein precursor genes since the last review on this topic in 2005 (Attardo et al., 2005). This review summarizes the role of these four signaling pathways in the regulation of vg-A and focuses upon new findings regarding the interplay between them on an organismal level. PMID:24688471

Material State Awareness for Composites Part I: Precursor Damage Analysis Using Ultrasonic Guided Coda Wave Interferometry (CWI).

PubMed

Patra, Subir; Banerjee, Sourav

2017-12-16

Detection of precursor damage followed by the quantification of the degraded material properties could lead to more accurate progressive failure models for composite materials. However, such information is not readily available. In composite materials, the precursor damages-for example matrix cracking, microcracks, voids, interlaminar pre-delamination crack joining matrix cracks, fiber micro-buckling, local fiber breakage, local debonding, etc.-are insensitive to the low-frequency ultrasonic guided-wave-based online nondestructive evaluation (NDE) or Structural Health Monitoring (SHM) (~100-~500 kHz) systems. Overcoming this barrier, in this article, an online ultrasonic technique is proposed using the coda part of the guided wave signal, which is often neglected. Although the first-arrival wave packets that contain the fundamental guided Lamb wave modes are unaltered, the coda wave packets however carry significant information about the precursor events with predictable phase shifts. The Taylor-series-based modified Coda Wave Interferometry (CWI) technique is proposed to quantify the stretch parameter to compensate the phase shifts in the coda wave as a result of precursor damage in composites. The CWI analysis was performed on five woven composite-fiber-reinforced-laminate specimens, and the precursor events were identified. Next, the precursor damage states were verified using high-frequency Scanning Acoustic Microscopy (SAM) and optical microscopy imaging.

Enhancement of cordyceps polysaccharide production via biosynthetic pathway analysis in Hirsutella sinensis.

PubMed

Lin, Shan; Liu, Zhi-Qiang; Baker, Peter James; Yi, Ming; Wu, Hui; Xu, Feng; Teng, Yi; Zheng, Yu-Guo

2016-11-01

The addition of various sulfates for enhanced cordyceps polysaccharide (CP) production in submerged cultivation of H. sinensis was investigated, and manganese sulfate was found the most effective. 2mM of manganese sulfate on 0day (d) was investigated as the optimal adding condition, and the CP production reached optimum with 5.33%, increasing by 93.3% compared with the control. Furthermore, the consumption of three main precursors of CP was studied over cultivation under two conditions. Intracellular mannose content decreased by 43.1% throughout 6days cultivation, which corresponded to CP accumulation rate sharply increased from 0 d to 6 d, and mannose was considered as the most preferred precursor for generating CP. Subsequently, mannose biosynthetic pathway was constructed and verified for the first time in H. sinensis, which constituted the important part of CP biosynthesis, and transcriptional levels of the biosynthetic genes were studied. Transcriptional level of gene cpsA was significantly up-regulated 5.35-fold and it was a key gene involved both in mannose and CP biosynthesis. This study demonstrated that manganese sulfate addition is an efficient and simple way to improve CP production. Transcriptional analysis based on biosynthetic pathway was helpful to find key genes and better understand CP biosynthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

PubMed

Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

2015-09-01

The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype. Copyright © 2015 Elsevier B.V. All rights reserved.

Gamma-Ray Burst Precursor Activity as Observed with BATSE

NASA Technical Reports Server (NTRS)

Koshut, Thomas M.; Kouveliotou, Chryssa; Paciesas, William S.; vanParadijs, Jan; Pendleton, Geoffrey N.; Briggs, Michael S.; Fishman, Gerald J.; Meegan, Charles A.

1995-01-01

Gamma-ray burst time histories often consist of multiple episodes of emission with the count rate dropping to the background level between adjacent episodes. We define precursor activity as any case in which the first episode (referred to as the precursor episode) has a lower peak intensity than that of the remaining emission (referred to as the main episode) and is separated from the remaining burst emission by a background interval that is at least as long as the remaining emission. We find that approx. 3% of the bursts observed with the Burst and Transient Source Experiment (BATSE) on Compton Gamma Ray Observatory (CGRO) satisfy this definition. We present the results of a study of the properties of these events. The spatial distribution of these sources is consistent with that of the larger set of all BATSE gamma-ray bursts: inhomogeneous and isotropic. A correlation between the duration of the precursor emission and the duration of the main episode emission is observed at about the 3 sigma confidence level. We find no meaningful significant correlations between or among any of the other characteristics of the precursor or main episode emission. It appears that the characteristics of the main episode emission are independent of the existence of the precursor emission.

Optical Precursor with Four-Wave Mixing and Storage Based on a Cold-Atom Ensemble

NASA Astrophysics Data System (ADS)

Ding, Dong-Sheng; Jiang, Yun Kun; Zhang, Wei; Zhou, Zhi-Yuan; Shi, Bao-Sen; Guo, Guang-Can

2015-03-01

We observed optical precursors in four-wave mixing based on a cold-atom gas. Optical precursors appear at the edges of pulses of the generated optical field, and propagate through the atomic medium without absorption. Theoretical analysis suggests that these precursors correspond to high-frequency components of the signal pulse, which means the atoms cannot respond quickly to rapid changes in the electromagnetic field. In contrast, the low-frequency signal components are absorbed by the atoms during transmission. We also showed experimentally that the backward precursor can be stored using a Raman transition of the atomic ensemble and retrieved later.

Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

PubMed

Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

2012-05-01

In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD. Copyright © 2012 American Association for the Study of Liver Diseases.

Chemical Evolution of Ozone and Its Precursors in Asian Pacific Rim Outflow During TRACE-P

NASA Astrophysics Data System (ADS)

Hamlin, A.; Crawford, J.; Olson, J.; Pippin, M.; Avery, M.; Sachse, G.; Barrick, J.; Blake, D.; Tan, D.; Sandholm, S.; Kondo, Y.; Singh, H.; Eisele, F.; Zondlo, M.; Flocke, F.; Talbot, R.

2002-12-01

During NASA's GTE/TRACE-P (Transport and Chemical Evolution over the Pacific) mission, a widespread stagnant pollution layer was observed between 2 and 4 km over the central Pacific. In this region, high levels of O3 (70~ppbv), CO (210~ppbv), and NOx (130~pptv) were observed. Back trajectories suggest this airmass had been rapidly transported from the Asian coast near the Yellow Sea to the central Pacific where it underwent subsidence. The chemical evolution of ozone and its precursors for this airmass is examined using lagrangian photochemical box model calculations. Simulations are conducted along trajectories which intersect the flight path where predicted mixing ratios are compared to measurements. An analysis of the photochemical processes controlling the cycling of nitrogen oxides and ozone production and destruction during transport will be presented.

Major Accidents (Gray Swans) Likelihood Modeling Using Accident Precursors and Approximate Reasoning.

PubMed

Khakzad, Nima; Khan, Faisal; Amyotte, Paul

2015-07-01

Compared to the remarkable progress in risk analysis of normal accidents, the risk analysis of major accidents has not been so well-established, partly due to the complexity of such accidents and partly due to low probabilities involved. The issue of low probabilities normally arises from the scarcity of major accidents' relevant data since such accidents are few and far between. In this work, knowing that major accidents are frequently preceded by accident precursors, a novel precursor-based methodology has been developed for likelihood modeling of major accidents in critical infrastructures based on a unique combination of accident precursor data, information theory, and approximate reasoning. For this purpose, we have introduced an innovative application of information analysis to identify the most informative near accident of a major accident. The observed data of the near accident were then used to establish predictive scenarios to foresee the occurrence of the major accident. We verified the methodology using offshore blowouts in the Gulf of Mexico, and then demonstrated its application to dam breaches in the United Sates. © 2015 Society for Risk Analysis.

Modeling of Regional Climate Change Effects on Ground-Level Ozone and Childhood Asthma

PubMed Central

Sheffield, Perry E.; Knowlton, Kim; Carr, Jessie L.; Kinney, Patrick L.

2011-01-01

Background The adverse respiratory effects of ground-level ozone are well-established. Ozone is the air pollutant most consistently projected to increase under future climate change. Purpose To project future pediatric asthma emergency department visits associated with ground-level ozone changes, comparing 1990s to 2020s. Methods This study assessed future numbers of asthma emergency department visits for children aged 0–17 years using (1) baseline New York City metropolitan area emergency department rates, (2) a dose–response relationship between ozone levels and pediatric asthma emergency department visits, and (3) projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by a global-to-regional climate change and atmospheric chemistry model. Sensitivity analyses included population projections and ozone precursor changes. This analysis occurred in 2010. Results In this model, climate change could cause an increase in regional summer ozone-related asthma emergency department visits for children aged 0–17 years of 7.3% across the New York City metropolitan region by the 2020s. This effect diminished with inclusion of ozone precursor changes. When population growth is included, the projections of morbidity related to ozone are even larger. Conclusions The results of this analysis demonstrate that the use of regional climate and atmospheric chemistry models make possible the projection of local climate change health effects for specific age groups and specific disease outcomes – such as emergency department visits for asthma. Efforts should be made to improve on this type of modeling to inform local and wider-scale climate change mitigation and adaptation policy. PMID:21855738

A novel chlorophyll a/b binding (Cab) protein gene from petunia which encodes the lower molecular weight Cab precursor protein.

PubMed

Stayton, M M; Black, M; Bedbrook, J; Dunsmuir, P

1986-12-22

The 16 petunia Cab genes which have been characterized are all closely related at the nucleotide sequence level and they encode Cab precursor polypeptides which are similar in sequence and length. Here we describe a novel petunia Cab gene which encodes a unique Cab precursor protein. This protein is a member of the smallest class of Cab precursor proteins for which no gene has previously been assigned in petunia or any other species. The features of this Cab precursor protein are that it is shorter by 2-3 amino acids than the formerly characterized Cab precursors, its transit peptide sequence is unrelated, and the mature polypeptide is significantly diverged at the functionally important N terminus from other petunia Cab proteins. Gene structure also discriminates this gene which is the only intron containing Cab gene in petunia genomic DNA.

The impacts of precursor reduction and meteorology on ground-level ozone in the Greater Toronto Area

NASA Astrophysics Data System (ADS)

Pugliese, S. C.; Murphy, J. G.; Geddes, J. A.; Wang, J. M.

2014-08-01

Tropospheric ozone (O3) is a major component of photochemical smog and is a known human health hazard, as well as a damaging factor for vegetation. Its precursor compounds, nitrogen oxides (NOx) and volatile organic compounds (VOCs), have a variety of anthropogenic and biogenic sources and exhibit non-linear effects on ozone production. As an update to previous studies on ground-level ozone in the Greater Toronto Area (GTA), we present an analysis of NO2, VOC and O3 data from federal and provincial governmental monitoring sites in the GTA from 2000 to 2012. We show that, over the study period, summertime 24 h VOC reactivity and NO2 midday (11:00-15:00) concentrations at all sites decreased significantly; since 2000, all sites experienced a decrease in NO2 of 28-62% and in measured VOC reactivity of at least 53-71%. Comparing 2002-2003 to 2011-2012, the summed reactivity of OH towards NO2 and a suite of measured VOCs decreased from 8.6 to 4.6 s-1. Ratios of reactive VOC pairs indicate that the effective OH concentration experienced by primary pollutants in the GTA has increased significantly over the study period. Despite the continuous decrease in precursor levels, ozone concentrations are not following the same pattern at all stations; it was found that the Canada-wide Standard for ozone continues to be exceeded at all monitoring stations. Additionally, while the years 2008-2011 had consistently lower ozone levels than previous years, 2012 experienced one of the highest recorded summertime ozone concentrations and a large number of smog episodes. We demonstrate that these high ozone observations in 2012 may be a result of the number of days with high solar radiation, the number of stagnant periods and the transport of high ozone levels from upwind regions.

The impacts of precursor reduction and meteorology on ground-level ozone in the Greater Toronto Area

NASA Astrophysics Data System (ADS)

Pugliese, S. C.; Murphy, J. G.; Geddes, J. A.; Wang, J. M.

2014-04-01

Tropospheric ozone (O3) is a major component of photochemical smog and is a known human health hazard as well as a damaging factor for vegetation. Its precursor compounds, nitrogen oxides (NOx) and volatile organic compounds (VOCs), have a variety of anthropogenic and biogenic sources and exhibit non-linear effects on ozone production. As an update to previous studies on ground-level ozone in the GTA, we present an analysis of NO2, VOC and O3 data from federal and provincial governmental monitoring sites in the GTA from 2000-2012. We show that over the study period, summertime 24 h VOC reactivity and NO2 midday (11:00-15:00) concentrations at all sites decreased significantly; since 2000, all sites experienced a decrease in NO2 of 28-62% and in measured VOC reactivity of at least 53-71%. Comparing 2002/2003 to 2011/2012, the summed reactivity of OH towards NO2 and a suite of measured VOCs decreased from 8.6 to 4.6 s-1. Ratios of reactive VOC pairs indicate that the effective OH concentration experienced by primary pollutants in the GTA has increased significantly over the study period. Despite the continuous decrease in precursor levels, ozone concentrations are not following the same pattern at all stations; it was found that the Canada-Wide Standard for ozone continues to be exceeded at all monitoring stations. Additionally, while the years 2008-2011 had consistently lower ozone levels than previous years, 2012 experienced one of the highest recorded summertime ozone concentrations and a large number of smog episodes. We demonstrate that these high ozone observations in 2012 may be a result of the number of days with high solar radiation, the number of stagnant periods and the transport of high ozone levels from upwind regions.

Cross-correlation earthquake precursors in the hydrogeochemical and geoacoustic signals for the Kamchatka peninsula

NASA Astrophysics Data System (ADS)

Ryabinin, Gennadiy; Gavrilov, Valeriy; Polyakov, Yuriy; Timashev, Serge

2012-06-01

We propose a new type of earthquake precursor based on the analysis of correlation dynamics between geophysical signals of different nature. The precursor is found using a two-parameter cross-correlation function introduced within the framework of flicker-noise spectroscopy, a general statistical physics approach to the analysis of time series. We consider an example of cross-correlation analysis for water salinity time series, an integral characteristic of the chemical composition of groundwater, and geoacoustic emissions recorded at the G-1 borehole on the Kamchatka peninsula in the time frame from 2001 to 2003, which is characterized by a sequence of three groups of significant seismic events. We found that cross-correlation precursors took place 27, 31, and 35 days ahead of the strongest earthquakes for each group of seismic events, respectively. At the same time, precursory anomalies in the signals themselves were observed only in the geoacoustic emissions for one group of earthquakes.

Effect of precursors condition on the structural morphology of synthesized GaN

NASA Astrophysics Data System (ADS)

Muzammil, P.; Basha, S. Munawar; Muhammad, G. Shakil

2018-05-01

GaN nanostructures were synthesized using different mole concentration of precursor composing of gallium nitrate and PVP by sol-gel method. The structural analysis using X-ray diffraction shows the wurtzite form of GaN nanostructure, also it observed that the concentration of precursor play a vital role in structural quality as FWHM increase for higher concentration. From the SEM image it observed that for 0.25 and 0.5 M concentration the honey bee and nanorod structure were obtained. The micro-Raman analysis shows a strong E2H peak of GaN nanostructure.

The effect of pre-oxidation on NDMA formation and the influence of pH.

PubMed

Selbes, Meric; Kim, Daekyun; Karanfil, Tanju

2014-12-01

N-nitrosodimethylamine (NDMA), a probable human carcinogen, is a disinfection by-product that has been detected in chloraminated drinking water systems. Pre-oxidation of the NDMA precursors prior to chloramination can be a viable approach for water utilities to control the NDMA levels. This study examined the effects of (i) commonly used oxidants (i.e., chlorine, chlorine dioxide and ozone) in water treatment, (ii) oxidant concentration and contact time (CT), and (iii) pre-oxidation pH on the formation of NDMA from subsequent chloramination. Fifteen model precursors with NDMA molar yields ranging from approximately 0.1%-90% were examined. Pre-chlorination reduced NDMA formation from most precursors by 10%-50% except quaternary amine polymers (i.e., PolyDADMAC, PolyACRYL, PolyAMINE). Pre-oxidation with chlorine dioxide and ozone achieved the same or higher deactivation of NDMA precursors (e.g., ranitidine) while increasing NDMA formation for some other precursors (e.g., daminozid). The increases with chlorine dioxide exposure were attributed to the release of oxidation products with dimethylamine (DMA) moiety, which may form more NDMA upon chloramination than the unoxidizied parent compound. On the other hand, chlorine dioxide was effective, if a precursors NDMA yield were higher than DMA. The ozone-triggered increases could be related to direct NDMA formation from DMA which are released by ozonation of amines with DMA moiety, amides or hydrazines. However, hydroxyl radicals formed from the decomposition of ozone would be also involved in decomposition of formed NDMA, reducing the overall NDMA levels at longer contact times. pH conditions influenced significantly the effectiveness of deactivation of precursors depending on the type of precursor and oxidant used. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

PubMed

Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

2013-11-01

Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

Degradation of SO 2, NO 2 and NH 3 leading to formation of secondary inorganic aerosols: An environmental chamber study

NASA Astrophysics Data System (ADS)

Behera, Sailesh N.; Sharma, Mukesh

2011-08-01

We have examined the interactions of gaseous pollutants and primary aerosols that can produce secondary inorganic aerosols. The specific objective was to estimate degradation rates of precursor gases (NH 3, NO 2 and SO 2) responsible for formation of secondary inorganic aerosols. A Teflon-based outdoor environmental chamber facility (volume 12.5 m 3) was built and checked for wall losses, leaks, solar transparency and ability to simulate photochemical reactions. The chamber was equipped with state-of-the-art instrumentation to monitor concentration-time profiles of precursor gases, ozone, and aerosol. A total of 14 experimental runs were carried out for estimating the degradation of precursor gases. The following initial conditions were maintained in the chamber: NO 2 = 246 ± 104 ppb(v), NH 3 = 548 ± 83 ppb(v), SO 2 = 238 ± 107 ppb(v), O 3 = 50 ± 11 ppb(v), PM 2.5 aerosol = 283438 ± 60524 No./litre. The concentration-time profile of gases followed first-order decay and were used for estimating degradation rates (NO 2 = 0.26 ± 0.15 h -1, SO 2 = 0.31 ± 0.17 h -1, NH 3 = 0.35 ± 0.21 h -1). We observed that degradation rates showed a statistical significant positive correlation (at 5% level of significance) with the initial PM 2.5 levels in the chamber (coefficient of correlation: 0.63 for NO 2; 0.62 for NH 3 and 0.51 for SO 2), suggesting that the existing surface of the aerosol could play a significant role in degradation of precursor gases. One or more gaseous species can be adsorbed on to the existing particles and these may undergo heterogeneous or homogeneous chemical transformation to produce secondary inorganic aerosols. Through correlation analysis, we have observed that degradation rates of precursor gases were dependent on initial molar ratio of (NH 3)/(NO 2 + SO 2), indicative of ammonia-rich and ammonia-poor situations for eventual production of ammonium salts.

Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution

PubMed Central

Semmens, Dean C.; Mirabeau, Olivier; Moghul, Ismail; Pancholi, Mahesh R.; Wurm, Yannick; Elphick, Maurice R.

2016-01-01

Neuropeptides are evolutionarily ancient mediators of neuronal signalling in nervous systems. With recent advances in genomics/transcriptomics, an increasingly wide range of species has become accessible for molecular analysis. The deuterostomian invertebrates are of particular interest in this regard because they occupy an ‘intermediate' position in animal phylogeny, bridging the gap between the well-studied model protostomian invertebrates (e.g. Drosophila melanogaster, Caenorhabditis elegans) and the vertebrates. Here we have identified 40 neuropeptide precursors in the starfish Asterias rubens, a deuterostomian invertebrate from the phylum Echinodermata. Importantly, these include kisspeptin-type and melanin-concentrating hormone-type precursors, which are the first to be discovered in a non-chordate species. Starfish tachykinin-type, somatostatin-type, pigment-dispersing factor-type and corticotropin-releasing hormone-type precursors are the first to be discovered in the echinoderm/ambulacrarian clade of the animal kingdom. Other precursors identified include vasopressin/oxytocin-type, gonadotropin-releasing hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin-type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone-type, bursicon-type, relaxin-type and insulin-like growth factor-type precursors. This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuropeptide signalling systems. Furthermore, these data provide a basis for experimental analysis of neuropeptide function in the unique context of the decentralized, pentaradial echinoderm bauplan. PMID:26865025

Amyloid-β Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease.

PubMed

Barrera-Ocampo, Alvaro; Arlt, Sönke; Matschke, Jakob; Hartmann, Ursula; Puig, Berta; Ferrer, Isidre; Zürbig, Petra; Glatzel, Markus; Sepulveda-Falla, Diego; Jahn, Holger

2016-09-01

The mechanisms leading to amyloid-β (Aβ) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with Aβ plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant Aβ precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced Aβ40 and Aβ42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor Aβ accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of Aβ species. © 2016 Oxford University Press OR American Association of Neuropathologists.

Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

NASA Astrophysics Data System (ADS)

Pizzarello, Sandra

1998-10-01

Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

NASA Technical Reports Server (NTRS)

Pizzarello, Sandra

1998-01-01

Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

Transient changes in oxygen tension inhibit osteogenic differentiation and Runx2 expression in osteoblasts.

PubMed

Salim, Ali; Nacamuli, Randall P; Morgan, Elise F; Giaccia, Amato J; Longaker, Michael T

2004-09-17

Vascular disruption following bony injury results in a hypoxic gradient within the wound microenvironment. Nevertheless, the effects of low oxygen tension on osteogenic precursors remain to be fully elucidated. In the present study, we investigated in vitro osteoblast and mesenchymal stem cell differentiation following exposure to 21% O(2) (ambient oxygen), 2% O(2) (hypoxia), and <0.02% O(2) (anoxia). Hypoxia had little effect on osteogenic differentiation. In contrast, short-term anoxic treatment of primary osteoblasts and mesenchymal precursors inhibited in vitro bone nodule formation and extracellular calcium deposition. Cell viability assays revealed that this effect was not caused by immediate or delayed cell death. Microarray profiling implicated down-regulation of the key osteogenic transcription factor Runx2 as a potential mechanism for the anoxic inhibition of differentiation. Subsequent analysis revealed not only a short-term differential regulation of Runx2 and its targets by anoxia and hypoxia, but a long-term inhibition of Runx2 transcriptional and protein levels after only 12-24 h of anoxic insult. Furthermore, we present evidence that Runx2 inhibition may, at least in part, be because of anoxic repression of BMP2, and that restoring Runx2 levels during anoxia by pretreatment with recombinant BMP2 rescued the anoxic inhibition of differentiation. Taken together, our findings indicate that brief exposure to anoxia (but not 2% hypoxia) down-regulated BMP2 and Runx2 expression, thus inhibiting critical steps in the osteogenic differentiation of pluripotent mesenchymal precursors and committed osteoblasts.

High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation

PubMed Central

2013-01-01

Background The fatty acid mixture of human milk is ideal for the newborn but little is known about its composition in the first few weeks of lactation. Of special interest are the levels of long-chain PUFAs (LCPUFAs), since these are essential for the newborn’s development. Additionally, the LCPUFAs arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are precursors for lipid mediators which regulate inflammation. Methods We determined the composition of 94 human milk samples from 30 mothers over the first month of lactation for fatty acids using GC-MS and quantified lipid mediators using HPLC-MS/MS. Results Over the four weeks period, DHA levels decreased, while levels of γC18:3 and αC18:3 steadily increased. Intriguingly, we found high concentrations of lipid mediators and their hydroxy fatty acid precursors in human milk, including pro-inflammatory leukotriene B4 (LTB4) and anti-inflammatory and pro-resolving lipoxin A4 (LXA4), resolvin D1 (RvD1) and resolvin E1 (RvE1). Lipid mediator levels were stable with the exception of two direct precursors. Conclusions Elevated levels of DHA right after birth might represent higher requirements of the newborn and the high content of anti-inflammatory and pro-resolving lipid mediators and their precursors may indicate their role in neonatal immunity and may be one of the reasons for the advantage of human milk over infant formula. PMID:23767972

Effects of Low Level Radiation exposure on Neurogenesis and Cognitive Function: Mechanisms and Prevention

DTIC Science & Technology

2005-09-01

precursor cells in culture with uX-lipoic acid reverses the density dependent changes observed in culture; this compound may provide an effective means...inhibited growth of precursor cells in vitro; - Antioxidant treatment of neural precursor cells in culture with a-lipoic acid (ALA) reverses the...with a single lO-Gy dose, and tissues avidin-biotinylated pemxidase complex; GFAP, glial fibrillary acidic protein; DAB, 3,3’- were collected from 6 to

Redundancy and divergence in the amyloid precursor protein family.

PubMed

Shariati, S Ali M; De Strooper, Bart

2013-06-27

Gene duplication provides genetic material required for functional diversification. An interesting example is the amyloid precursor protein (APP) protein family. The APP gene family has experienced both expansion and contraction during evolution. The three mammalian members have been studied quite extensively in combined knock out models. The underlying assumption is that APP, amyloid precursor like protein 1 and 2 (APLP1, APLP2) are functionally redundant. This assumption is primarily supported by the similarities in biochemical processing of APP and APLPs and on the fact that the different APP genes appear to genetically interact at the level of the phenotype in combined knockout mice. However, unique features in each member of the APP family possibly contribute to specification of their function. In the current review, we discuss the evolution and the biology of the APP protein family with special attention to the distinct properties of each homologue. We propose that the functions of APP, APLP1 and APLP2 have diverged after duplication to contribute distinctly to different neuronal events. Our analysis reveals that APLP2 is significantly diverged from APP and APLP1. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Two ways of legumin-precursor processing in conifers. Characterization and evolutionary relationships of Metasequoia cDNAs representing two divergent legumin gene subfamilies.

PubMed

Häger, K P; Wind, C

1997-06-15

Subunit monomers and oligomers of crystalloid-type legumins are major components of SDS-soluble fractions from Metasequoia glyptostroboides (Dawn redwood, Taxodiaceae) seed proteins. The subunits are made up of disulfide linked alpha-polypeptides and beta-polypeptides with molecular masses of 33 kDa and 23-25 kDa, respectively. Unusually for legumins, those from Metasequoia are glycosylated and the carbohydrate moieties are residing in the C-terminal region of the respective beta-polypeptides. A Metasequoia endosperm cDNA library has been constructed and legumin-encoding transcripts representing two divergent gene subfamilies have been characterized. Intersubfamily comparisons reveal 75% identity at the amino acid level and the values range from 53-35% when the legumin precursors deduced were compared with those from angiosperms. The predicted sequences together with data from amino acid sequencing prove that post-translational processing of Metasequoia prolegumins is directed to two different processing sites, each of them specific for one of the legumin subfamilies. The sites involved differ in their relative position and in the junction to be cleaved: Metasequoia legumin precursors MgLeg18 and MgLeg26 contain the conventional post-translational Asn-Gly processing site, which is generally regarded as highly conserved. In contrast, the MgLeg4 precursor is lacking this site and post-translational cleavage is directed to an unusual Asn-Thr processing site located in its hypervariable region, causing N-terminal extension of the beta-polypeptide relative to those hitherto known. Evidence is given that the unusual variant of processing also occurs in other conifers. Phylogenetic analysis reveals the precursors concerned as representatives of a distinct legumin subfamily, originating from duplication of an ancestral gene prior to or at the beginning of Taxodiaceae diversification.

Perfluoroalkyl Acids (PFAAs) and Selected Precursors in the Baltic Sea Environment: Do Precursors Play a Role in Food Web Accumulation of PFAAs?

PubMed

Gebbink, Wouter A; Bignert, Anders; Berger, Urs

2016-06-21

The present study examined the presence of perfluoroalkyl acids (PFAAs) and selected precursors in the Baltic Sea abiotic environment and guillemot food web, and investigated the relative importance of precursors in food web accumulation of PFAAs. Sediment, water, zooplankton, herring, sprat, and guillemot eggs were analyzed for perfluoroalkane sulfonic acids (PFSAs; C4,6,8,10) and perfluoroalkyl carboxylic acids (PFCAs; C6-15) along with six perfluoro-octane sulfonic acid (PFOS) precursors and 11 polyfluoroalkyl phosphoric acid diesters (diPAPs). FOSA, FOSAA and its methyl and ethyl derivatives (Me- and EtFOSAA), and 6:2/6:2 diPAP were detected in sediment and water. While FOSA and the three FOSAAs were detected in all biota, a total of nine diPAPs were only detected in zooplankton. Concentrations of PFOS precursors and diPAPs exceeded PFOS and PFCA concentrations, respectively, in zooplankton, but not in fish and guillemot eggs. Although PFOS precursors were present at all trophic levels, they appear to play a minor role in food web accumulation of PFOS based on PFOS precursor/PFOS ratios and PFOS and FOSA isomer patterns. The PFCA pattern in fish could not be explained by the intake pattern based on PFCAs and analyzed precursors, that is, diPAPs. Exposure to additional precursors might therefore be a dominant exposure pathway compared to direct PFCA exposure for fish.

Ovary-derived precursor gibberellin A9 is essential for female flower development in cucumber.

PubMed

Pimenta Lange, Maria João; Lange, Theo

2016-12-01

Gibberellins (GAs) are hormones that control many aspects of plant development, including flowering. It is well known that stamen is the source of GAs that regulate male and bisexual flower development. However, little is known about the role of GAs in female flower development. In cucumber, high levels of GA precursors are present in ovaries and high levels of bioactive GA 4 are identified in sepals/petals, reflecting the expression of GA 20-oxidase and 3-oxidase in these organs, respectively. Here, we show that the biologically inactive precursor GA 9 moves from ovaries to sepal/petal tissues where it is converted to the bioactive GA 4 necessary for female flower development. Transient expression of a catabolic GA 2-oxidase from pumpkin in cucumber ovaries decreases GA 9 and GA 4 levels and arrests the development of female flowers, and this can be restored by application of GA 9 to petals thus confirming its function. Given that bioactive GAs can promote sex reversion of female flowers, movement of biologically inactive precursors, instead of the hormone itself, might help to maintain floral organ identity, ensuring fruit and seed production. © 2016. Published by The Company of Biologists Ltd.

Natural cotton as precursor for the refractory boron carbide—a hydrothermal synthesis and characterization

NASA Astrophysics Data System (ADS)

Saritha Devi, H. V.; Swapna, M. S.; Raj, Vimal; Ambadas, G.; Sankararaman, S.

2018-01-01

Boron carbide (B4C) is an excellent covalent carbide that finds applications in industries and nuclear power plants. The present synthesis methods of boron carbide are expensive and involve the use of toxic chemicals that adversely affect environment. In the present work, we report for the first time the use of the hydrothermal method for converting the cellulose from cotton as the carbon precursor for B4C. The carbon precursor is converted into functionalized porous carbonaceous material by hydrothermal treatment followed by sodium borohydride. It is further treated with boric acid to make it a B4C precursor. The precursor is characterized by UV-visible diffuse reflectance, Raman, Fourier transform infrared, photoluminescent and energy dispersive spectroscopy. The morphology and structure analysis is carried out using field emission scanning electron microscopy and x-ray diffraction techniques. The results of structural and optical characterization of the sample synthesized are compared with the commercial B4C. The thermal stability of the sample is studied by thermogravimetric analysis. The sample annealed at 700 °C is found to be B4C devoid of amorphous carbon with a yield of 44.7%. The analysis reveals the formation of boron carbide from the sample.

Precursor uptake assays and metabolic analyses in isolated tomato fruit chromoplasts

PubMed Central

2012-01-01

Background Carotenoids are the most widespread group of pigments found in nature. In addition to their role in the physiology of the plant, carotenoids also have nutritional relevance as their incorporation in the human diet provides health benefits. In non-photosynthetic tissues, carotenoids are synthesized and stored in specialized plastids called chromoplasts. At present very little is known about the origin of the metabolic precursors and cofactors required to sustain the high rate of carotenoid biosynthesis in these plastids. Recent proteomic data have revealed a number of biochemical and metabolic processes potentially operating in fruit chromoplasts. However, considering that chloroplast to chromoplast differentiation is a very rapid process during fruit ripening, there is the possibility that some of the proteins identified in the proteomic analysis could represent remnants no longer having a functional role in chromoplasts. Therefore, experimental validation is necessary to prove whether these predicted processes are actually operative in chromoplasts. Results A method has been established for high-yield purification of tomato fruit chromoplasts suitable for metabolic studies. Radiolabeled precursors were efficiently incorporated and further metabolized in isolated chromoplast. Analysis of labeled lipophilic compounds has revealed that lipid biosynthesis is a very efficient process in chromoplasts, while the relatively low incorporation levels found in carotenoids suggest that lipid production may represent a competing pathway for carotenoid biosynthesis. Malate and pyruvate are efficiently converted into acetyl-CoA, in agreement with the active operation of the malic enzyme and the pyruvate dehydrogenase complex in the chromoplast. Our results have also shown that isolated chromoplasts can actively sustain anabolic processes without the exogenous supply of ATP, thus suggesting that these organelles may generate this energetic cofactor in an autonomous way. Conclusions We have set up a method for high yield purification of intact tomato fruit chromoplasts suitable for precursor uptake assays and metabolic analyses. Using targeted radiolabeled precursors we have been able to unravel novel biochemical and metabolic aspects related with carotenoid and lipid biosynthesis in tomato fruit chromoplasts. The reported chromoplast system could represent a valuable platform to address the validation and characterization of functional processes predicted from recent transcriptomic and proteomic data. PMID:22243738

Precursor uptake assays and metabolic analyses in isolated tomato fruit chromoplasts.

PubMed

Angaman, Djédoux Maxime; Petrizzo, Rocco; Hernández-Gras, Francesc; Romero-Segura, Carmen; Pateraki, Irene; Busquets, Montserrat; Boronat, Albert

2012-01-13

Carotenoids are the most widespread group of pigments found in nature. In addition to their role in the physiology of the plant, carotenoids also have nutritional relevance as their incorporation in the human diet provides health benefits. In non-photosynthetic tissues, carotenoids are synthesized and stored in specialized plastids called chromoplasts. At present very little is known about the origin of the metabolic precursors and cofactors required to sustain the high rate of carotenoid biosynthesis in these plastids. Recent proteomic data have revealed a number of biochemical and metabolic processes potentially operating in fruit chromoplasts. However, considering that chloroplast to chromoplast differentiation is a very rapid process during fruit ripening, there is the possibility that some of the proteins identified in the proteomic analysis could represent remnants no longer having a functional role in chromoplasts. Therefore, experimental validation is necessary to prove whether these predicted processes are actually operative in chromoplasts. A method has been established for high-yield purification of tomato fruit chromoplasts suitable for metabolic studies. Radiolabeled precursors were efficiently incorporated and further metabolized in isolated chromoplast. Analysis of labeled lipophilic compounds has revealed that lipid biosynthesis is a very efficient process in chromoplasts, while the relatively low incorporation levels found in carotenoids suggest that lipid production may represent a competing pathway for carotenoid biosynthesis. Malate and pyruvate are efficiently converted into acetyl-CoA, in agreement with the active operation of the malic enzyme and the pyruvate dehydrogenase complex in the chromoplast. Our results have also shown that isolated chromoplasts can actively sustain anabolic processes without the exogenous supply of ATP, thus suggesting that these organelles may generate this energetic cofactor in an autonomous way. We have set up a method for high yield purification of intact tomato fruit chromoplasts suitable for precursor uptake assays and metabolic analyses. Using targeted radiolabeled precursors we have been able to unravel novel biochemical and metabolic aspects related with carotenoid and lipid biosynthesis in tomato fruit chromoplasts. The reported chromoplast system could represent a valuable platform to address the validation and characterization of functional processes predicted from recent transcriptomic and proteomic data.

Precursor Lesions of Urologic Malignancies.

PubMed

Khani, Francesca; Robinson, Brian D

2017-12-01

- Precursor lesions of urologic malignancies are established histopathologic entities, which are important not only to recognize for clinical purposes, but also to further investigate at the molecular level in order to gain a better understanding of the pathogenesis of these malignancies. - To provide a brief overview of precursor lesions to the most common malignancies that develop within the genitourinary tract with a focus on their clinical implications, histologic features, and molecular characteristics. - Literature review from PubMed, urologic pathology textbooks, and the 4th edition of the World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. All photomicrographs were taken from cases seen at Weill Cornell Medicine or from the authors' personal slide collections. - The clinical importance and histologic criteria are well established for the known precursor lesions of the most common malignancies throughout the genitourinary tract, but further investigation is warranted at the molecular level to better understand the pathogenesis of these lesions. Such investigation may lead to better risk stratification of patients and potentially novel treatments.

Analysis of Precursor Properties of mixed Al/Alumel Cylindrical Wire Arrays*

NASA Astrophysics Data System (ADS)

Stafford, A.; Safronova, A. S.; Kantsyrev, V. L.; Esaulov, A. A.; Weller, M. E.; Shrestha, I.; Osborne, G. C.; Shlyaptseva, V. V.; Keim, S. F.; Coverdale, C. A.; Chuvatin, A. S.

2012-10-01

Previous studies of mid-Z (Cu and Ni) cylindrical wire arrays (CWAs) on Zebra have found precursors with high electron temperatures of >300 eV. However, past experiments with Al CWAs did not find the same high temperature precursors. New precursor experiments using mixed Al/Alumel (Ni 95%, Si 2%, and Al 2%) cylindrical wire arrays have been performed to understand how the properties of L-shell Ni precursor will change and whether Al precursor will be observed. Time gated spectra and pinholes are used to determine precursor plasma conditions for comparison with previous Alumel precursor experiments. A full diagnostic set which included more than ten different beam-lines was implemented. Future work in this direction is discussed. [4pt] *This work was supported by NNSA under DOE Cooperative Agreements DE-FC52-06NA27588, and in part by DE-FC52-06NA27586, and DE-FC52-06NA27616. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under Contract DE-AC04-94AL85000.

Comparative analysis of 1-phenyl-2-propanone (P2P), an amphetamine-type stimulant precursor, using stable isotope ratio mass spectrometry: presented in part as a poster at the 2nd meeting of the Joint European Stable Isotope User Meeting (JESIUM), Giens, France, September 2008.

PubMed

Schneiders, S; Holdermann, T; Dahlenburg, R

2009-06-01

The isotope ratios of amphetamine type stimulants (ATS) depend as well on the precursor as the synthetic pathway. For clandestine production of amphetamine and methamphetamine, 1-phenyl-2-propanone (P2P, benzylmethylketone) is a commonly used precursor. Our aim was to determine the variation of the isotope ratios within precursor samples of one manufacturer and to compare seized samples of unknown sources to these values. delta13C(V-PDB), delta2H(V-SMOW) and delta118O(V-SMOW) isotope ratios were determined using elemental analysis (EA) and gas chromatography (GC) coupled toan isotope ratio mass spectrometer (IRMS). The comparison of all seized samples to the data of the samples of one manufacturer revealed considerable differences. The results show that IRMS provides a high potential in differentiating between precursors from different manufacturers for the clandestine production of ATS and identifying corresponding sources.

Distribution and urban-suburban differences in ground-level ozone and its precursors over Shenyang, China

NASA Astrophysics Data System (ADS)

Liu, Ningwei; Ren, Wanhui; Li, Xiaolan; Ma, Xiaogang; Zhang, Yunhai; Li, Bingkun

2018-03-01

Hourly mixing ratio data of ground-level ozone and its main precursors at ambient air quality monitoring sites in Shenyang during 2013-2015 were used to survey spatiotemporal variations in ozone. Then, the transport of ozone and its precursors among urban, suburban, and rural sites was examined. The correlations between ozone and some key meteorological factors were also investigated. Ozone and O x mixing ratios in Shenyang were higher during warm seasons and lower during cold ones, while ozone precursors followed the opposite cycle. Ozone mixing ratios reached maximum and minimum values in the afternoon and morning, respectively, reflecting the significant influence of photochemical production during daytime and depletion via titration during nighttime. Compared to those in downtown Shenyang, ozone mixing ratios were higher and the occurrence of peak values were later in suburban and rural areas downwind of the prevailing wind. The differences were most significant in summer, when the ozone mixing ratios at one suburban downwind site reached a maximum value of 35.6 ppb higher than those at the downtown site. This suggests that photochemical production processes were significant during the transport of ozone precursors, particularly in warm seasons with sufficient sunlight. Temperature, total radiation, and wind speed all displayed positive correlations with ozone concentration, reflecting their important role in accelerating ozone formation. Generally, the correlations between ozone and meteorological factors were slightly stronger at suburban sites than in urban areas, indicating that ozone levels in suburban areas were more sensitive to these meteorological factors.

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

PubMed Central

Ivanovitch, Kenzo; Temiño, Susana

2017-01-01

During vertebrate heart development, two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development. PMID:29202929

Atmospheric new particle formation at the research station Melpitz, Germany: connection with gaseous precursors and meteorological parameters

NASA Astrophysics Data System (ADS)

Größ, Johannes; Hamed, Amar; Sonntag, André; Spindler, Gerald; Elina Manninen, Hanna; Nieminen, Tuomo; Kulmala, Markku; Hõrrak, Urmas; Plass-Dülmer, Christian; Wiedensohler, Alfred; Birmili, Wolfram

2018-02-01

This paper revisits the atmospheric new particle formation (NPF) process in the polluted Central European troposphere, focusing on the connection with gas-phase precursors and meteorological parameters. Observations were made at the research station Melpitz (former East Germany) between 2008 and 2011 involving a neutral cluster and air ion spectrometer (NAIS). Particle formation events were classified by a new automated method based on the convolution integral of particle number concentration in the diameter interval 2-20 nm. To study the relevance of gaseous sulfuric acid as a precursor for nucleation, a proxy was derived on the basis of direct measurements during a 1-month campaign in May 2008. As a major result, the number concentration of freshly produced particles correlated significantly with the concentration of sulfur dioxide as the main precursor of sulfuric acid. The condensation sink, a factor potentially inhibiting NPF events, played a subordinate role only. The same held for experimentally determined ammonia concentrations. The analysis of meteorological parameters confirmed the absolute need for solar radiation to induce NPF events and demonstrated the presence of significant turbulence during those events. Due to its tight correlation with solar radiation, however, an independent effect of turbulence for NPF could not be established. Based on the diurnal evolution of aerosol, gas-phase, and meteorological parameters near the ground, we further conclude that the particle formation process is likely to start in elevated parts of the boundary layer rather than near ground level.

Investigation of phase evolution of CaCu3Ti4O12 (CCTO) by in situ synchrotron high-temperature powder diffraction

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Huang, Saifang; Zhang, Weijun; Cao, Peng; Huang, Zhaohui; Gao, Wei

2014-03-01

In situ synchrotron X-ray powder diffraction was used to study the high-temperature phase evolution of CaCu3Ti4O12 (CCTO) precursors prepared via solid-state and sol-gel methods. After the precursors are heated to 1225 °C, the CCTO phase is the main phase observed in the calcined powder, with the presence of some minor impurities. Comparing the two precursors, we found that the onset temperature for the CCTO phase formation is 800 °C in the sol-gel precursor, lower than that in the solid-state precursor (875 °C). Intermediate phases were only observed in the sol-gel precursor. Both precursors are able to be calcined to sub-micrometric sized powders. Based on the synchrotron data along with differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA), the phase formation sequence and mechanism during calcination are proposed in this study.

Processing of the precursor of protamine P2 in mouse. Peptide mapping and N-terminal sequence analysis of intermediates.

PubMed Central

Carré-Eusèbe, D; Lederer, F; Lê, K H; Elsevier, S M

1991-01-01

Protamine P2, the major basic chromosomal protein of mouse spermatozoa, is synthesized as a precursor almost twice as long as the mature protein, its extra length arising from an N-terminal extension of 44 amino acid residues. This precursor is integrated into chromatin of spermatids, and the extension is processed during chromatin condensation in the haploid cells. We have studied processing in the mouse and have identified two intermediates generated by proteolytic cleavage of the precursor. H.p.l.c. separated protamine P2 from four other spermatid proteins, including the precursor and three proteins known to possess physiological characteristics expected of processing intermediates. Peptide mapping indicated that all of these proteins were structurally similar. Two major proteins were further purified by PAGE, transferred to poly(vinylidene difluoride) membranes and submitted to automated N-terminal sequence analysis. Both sequences were found within the deduced sequence of the precursor extension. The N-terminus of the larger intermediate, PP2C, was Gly-12, whereas the N-terminus of the smaller, PP2D, was His-21. Both processing sites involved a peptide bond in which the carbonyl function was contributed by an acidic amino acid. Images Fig. 1. Fig. 3. Fig. 4. PMID:1854346

Discovery of novel representatives of bilaterian neuropeptide families and reconstruction of neuropeptide precursor evolution in ophiuroid echinoderms

PubMed Central

Abylkassimova, Nikara; Hugall, Andrew F.; O'Hara, Timothy D.; Elphick, Maurice R.

2017-01-01

Neuropeptides are a diverse class of intercellular signalling molecules that mediate neuronal regulation of many physiological and behavioural processes. Recent advances in genome/transcriptome sequencing are enabling identification of neuropeptide precursor proteins in species from a growing variety of animal taxa, providing new insights into the evolution of neuropeptide signalling. Here, detailed analysis of transcriptome sequence data from three brittle star species, Ophionotus victoriae, Amphiura filiformis and Ophiopsila aranea, has enabled the first comprehensive identification of neuropeptide precursors in the class Ophiuroidea of the phylum Echinodermata. Representatives of over 30 bilaterian neuropeptide precursor families were identified, some of which occur as paralogues. Furthermore, homologues of endothelin/CCHamide, eclosion hormone, neuropeptide-F/Y and nucleobinin/nesfatin were discovered here in a deuterostome/echinoderm for the first time. The majority of ophiuroid neuropeptide precursors contain a single copy of a neuropeptide, but several precursors comprise multiple copies of identical or non-identical, but structurally related, neuropeptides. Here, we performed an unprecedented investigation of the evolution of neuropeptide copy number over a period of approximately 270 Myr by analysing sequence data from over 50 ophiuroid species, with reference to a robust phylogeny. Our analysis indicates that the composition of neuropeptide ‘cocktails’ is functionally important, but with plasticity over long evolutionary time scales. PMID:28878039

Synthesis, Dielectric, Electrical and Optical characterization of ZnO synthesized by chemical route using polymer precursors

NASA Astrophysics Data System (ADS)

Mishra, Raman; Bajpai, P. K.

2011-11-01

Nano-size ZnO (particle size 7.8 nm) have been prepared from a versatile, efficient and technically simple polymer matrix based precursor solution. The precursor solution constituted of zinc nitrates with polymer PVA in presence of mono-/disaccharides. Annealing the precursor mass at 900 °C single phase zinc oxide nano-particles are obtained. X-ray diffraction analysis confirms hexagonal crystal structure with lattice parameter a = b = 3.261 A0, c = 5.220 A0. The estimated average particle size obtained from XRD data is ≈7.8 nm. The impedance analysis reveals that the grain resistance decreases with increase in temperature as expected for a semi-conducting material. The relaxation is polydispersive and conduction is mainly through grains. Optical properties and AC/DC conduction activation energies are estimated from Arrhenius plots and conduction mechanism is discussed.

Effect of Human Auditory Efferent Feedback on Cochlear Gain and Compression

PubMed Central

Drga, Vit; Plack, Christopher J.

2014-01-01

The mammalian auditory system includes a brainstem-mediated efferent pathway from the superior olivary complex by way of the medial olivocochlear system, which reduces the cochlear response to sound (Warr and Guinan, 1979; Liberman et al., 1996). The human medial olivocochlear response has an onset delay of between 25 and 40 ms and rise and decay constants in the region of 280 and 160 ms, respectively (Backus and Guinan, 2006). Physiological studies with nonhuman mammals indicate that onset and decay characteristics of efferent activation are dependent on the temporal and level characteristics of the auditory stimulus (Bacon and Smith, 1991; Guinan and Stankovic, 1996). This study uses a novel psychoacoustical masking technique using a precursor sound to obtain a measure of the efferent effect in humans. This technique avoids confounds currently associated with other psychoacoustical measures. Both temporal and level dependency of the efferent effect was measured, providing a comprehensive measure of the effect of human auditory efferents on cochlear gain and compression. Results indicate that a precursor (>20 dB SPL) induced efferent activation, resulting in a decrease in both maximum gain and maximum compression, with linearization of the compressive function for input sound levels between 50 and 70 dB SPL. Estimated gain decreased as precursor level increased, and increased as the silent interval between the precursor and combined masker-signal stimulus increased, consistent with a decay of the efferent effect. Human auditory efferent activation linearizes the cochlear response for mid-level sounds while reducing maximum gain. PMID:25392499

Production of volatiles in fresh-cut apple: effect of applying alginate coatings containing linoleic acid or isoleucine.

PubMed

Maya-Meraz, Irma O; Espino-Díaz, Miguel; Molina-Corral, Francisco J; González-Aguilar, Gustavo A; Jacobo-Cuellar, Juan L; Sepulveda, David R; Olivas, Guadalupe I

2014-11-01

One of the main quality parameters in apples is aroma, its main precursors are fatty acids (FA) and amino acids (AA). In this study, alginate edible coatings were used as carriers of linoleic acid or isoleucine to serve as precursors for the production of aroma in cut apples. Apple wedges were immersed in a CaCl2 solution and coated with one of the following formulations: alginate solution (Alg-Ca), Alg-Ca-low-level linoleic acid (0.61 g/Lt), (LFA), Alg-Ca-high-level linoleic acid (2.44 g/L; HFA), Alg-Ca-low-level isoleucine (0.61 g/L; LAA), and Alg-Ca-high-level isoleucine (2.44 g/L; HAA). Apple wedges were stored at 3 °C and 85% relative humidity for 21 d and key volatiles were studied during storage. Addition of precursors, mainly isoleucine, showed to increase the production of some key volatiles on coated fresh-cut apples during storage. The concentration of 2-methyl-1-butanol was 4 times higher from day 12 to day 21 in HAA, while 2-methyl butyl acetate increased from day 12 to day 21 in HAA. After 21 d, HAA-apples presented a 40-fold value of 2-methyl-butyl acetate, compared to Alg-Ca cut apples. Values of hexanal increased during cut apple storage when the coating carried linoleic acid, mainly on HFA, from 3 to 12 d. The ability of apples to metabolize AA and FA depends on the concentration of precursors, but also depends on key enzymes, previous apple storage, among others. Further studies should be done to better clarify the behavior of fresh-cut apples as living tissue to metabolize precursors contained in edible coatings for the production of volatiles. © 2014 Institute of Food Technologists®

Human proinsulin C-peptide from a precursor overexpressed in Pichia pastoris.

PubMed

Huang, Yang-Bin; Li, Jiang; Gao, Xin; Sun, Jiu-Ru; Lu, Yi; Feng, Tao; Fei, Jian; Cui, Da-Fu; Xia, Qi-Chang; Ren, Jun; Zhang, You-Shang

2006-08-01

In this article we report the production of human proinsulin C-peptide with 31 amino acid residues from a precursor overexpressed in Pichia pastoris. A C-peptide precursor expression plasmid containing nine C-peptide genes in tandem was constructed and used to transform P. pastoris. Transformants with a high copy number of the C-peptide precursor gene integrated into the chromosome of P. pastoris were selected. In high-density fermentation in a 300 liter fermentor using a simple culture medium composed mainly of salt and methanol, the C-peptide precursor was overexpressed to a level of 2.28 g per liter. A simple procedure was established to purify the expression product from the culture medium. The purified C-peptide precursor was converted into C-peptide by trypsin and carboxypeptidase B joint digestion. The yield of C-peptide with a purity of 96% was 730 mg per liter of culture. The purified C-peptide was characterized by mass spectrometry, N- and C-terminal amino acid sequencing, and sodium dodecylsulfate-polyacrylamide gel electrophoresis.

Obtaining aluminas from the thermal decomposition of their different precursors: An {sup 27}Al MAS NMR and X-ray powder diffraction studies

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

Chagas, L.H.; De Carvalho, G.S.G.; San Gil, R.A.S.

2014-01-01

Graphical abstract: - Highlights: • We synthesized three precursors of alumina from different methods. • The calcination of the precursors generated several alumina polymorphs. • XRD and NMR were used for structural investigation of the polymorphs. • The synthesis route determines the structural and textural properties of the solids. - Abstract: A commercial sample of Boehmite was used as precursor of alumina polymorphs. For comparison, three other precursors were synthesized from different methods. Particularly, the use of excess of urea promoted a very crystalline form of basic aluminum carbonate. The characteristics of the four precursors were investigated by thermal, vibrationalmore » and X-ray powder diffraction (XRD) analysis. Additionally, the nuclear magnetic resonance, with magic angle spinning ({sup 27}Al MAS NMR), was used to verify the coordination of aluminum cations. Each precursor was calcined at various temperatures generating alumina polymorphs, which were structurally analyzed by XRD and {sup 27}Al MAS NMR. Due to interest in catalysis supports, special attention was given to the γ-Al{sub 2}O{sub 3} phase, which in addition to structural investigation was subjected to textural analysis. The results showed that, from different synthesis procedures and common route of calcination, one can obtain materials with the same composition but with different structural and textural properties, which in turn can significantly influence the performance of a supported catalyst.« less

Preliminary Analysis of Aircraft Loss of Control Accidents: Worst Case Precursor Combinations and Temporal Sequencing

NASA Technical Reports Server (NTRS)

Belcastro, Christine M.; Groff, Loren; Newman, Richard L.; Foster, John V.; Crider, Dennis H.; Klyde, David H.; Huston, A. McCall

2014-01-01

Aircraft loss of control (LOC) is a leading cause of fatal accidents across all transport airplane and operational classes, and can result from a wide spectrum of hazards, often occurring in combination. Technologies developed for LOC prevention and recovery must therefore be effective under a wide variety of conditions and uncertainties, including multiple hazards, and their validation must provide a means of assessing system effectiveness and coverage of these hazards. This requires the definition of a comprehensive set of LOC test scenarios based on accident and incident data as well as future risks. This paper defines a comprehensive set of accidents and incidents over a recent 15 year period, and presents preliminary analysis results to identify worst-case combinations of causal and contributing factors (i.e., accident precursors) and how they sequence in time. Such analyses can provide insight in developing effective solutions for LOC, and form the basis for developing test scenarios that can be used in evaluating them. Preliminary findings based on the results of this paper indicate that system failures or malfunctions, crew actions or inactions, vehicle impairment conditions, and vehicle upsets contributed the most to accidents and fatalities, followed by inclement weather or atmospheric disturbances and poor visibility. Follow-on research will include finalizing the analysis through a team consensus process, defining future risks, and developing a comprehensive set of test scenarios with correlation to the accidents, incidents, and future risks. Since enhanced engineering simulations are required for batch and piloted evaluations under realistic LOC precursor conditions, these test scenarios can also serve as a high-level requirement for defining the engineering simulation enhancements needed for generating them.

Toward a reliable distinction between patients with mild cognitive impairment and Alzheimer-type dementia versus major depression.

PubMed

Post, Anke; Ackl, Nibal; Rücker, Monika; Schreiber, Yvonne; Binder, Elisabeth B; Ising, Marcus; Sonntag, Annette; Holsboer, Florian; Almeida, Osborne F X

2006-05-01

Cerebrospinal fluid (CSF) levels of soluble amyloid precursor protein (sAPP) and its alpha-secreted form (alpha-sAPP) were investigated as a means to distinguish between individuals with mild cognitive impairment (MCI) and Alzheimer-type dementia (DAT) and those with major depressive episode (MDE) showing secondary memory deficits. Twenty-seven patients with MCI, 32 with probable DAT, and 24 with MDE attending a memory clinic were studied. Cerebrospinal fluid levels of sAPP/amyloid precursor-like protein 2 (APLP2) and alpha-sAPP were detected by Western blotting. Patients with MDE had the highest CSF levels of total sAPP/APLP2 as compared with MCI and DAT patients (p < .001); sAPP/APLP2 levels were higher in MCI than in DAT subjects. Whereas alpha-sAPP levels did not differ between the MCI and DAT groups, median levels of this peptide were significantly lower in MCI and DAT versus MDE patients. Soluble amyloid precursor protein/APLP2 and alpha-sAPP concentrations in CSF can differentiate between DAT and MCI versus MDE, facilitating early ameliorative interventions and appropriate treatment regimens.

Acrylamide formation in almonds (Prunus dulcis): influences of roasting time and temperature, precursors, varietal selection, and storage.

PubMed

Zhang, Gong; Huang, Guangwei; Xiao, Lu; Seiber, James; Mitchell, Alyson E

2011-08-10

Acrylamide is a probable human carcinogen that is found in many roasted and baked foods. This paper describes two sensitive and reliable LC-(ESI)MS/MS methods for the analysis of (1) acrylamide and (2) common acrylamide precursors (i.e., glucose, fructose, asparagine, and glutamine) in raw and roasted almonds. These methods were used to evaluate the impact of roasting temperatures (between 129 and 182 °C) and times on acrylamide formation. Controlling the roasting temperature at or below 146 °C resulted in acrylamide levels below 200 ppb at all roasting times evaluated. Six varieties of almonds collected in various regions of California over two harvest years and roasted at 138 °C for 22 min had acrylamide levels ranging from 117 ± 5 μg/kg (Sonora) to 221 ± 95 μg/kg (Butte) with an average of 187 ± 71 μg/kg. A weak correlation between asparagine content in raw almonds and acrylamide formation was observed (R(2) = 0.6787). No statistical relationship was found between acrylamide formation and almond variety, orchard region, or harvest year. Stability studies on roasted almonds indicated that acrylamide levels decreased by 12.9-68.5% (average of 50.2%) after 3 days of storage at 60 °C. Short-term elevated temperature storage may be another approach for mitigating acrylamide levels in roasted almonds.

Extremely High Expression of Antisense RNA for Wilms' Tumor 1 in Active Osteoclasts: Suppression of Wilms' Tumor 1 Protein Expression during Osteoclastogenesis.

PubMed

Li, Yin-Ji; Kukita, Akiko; Kyumoto-Nakamura, Yukari; Kukita, Toshio

2016-09-01

Wilms' tumor 1 (WT1), a zinc-finger transcription regulator of the early growth response family, identified as the product of a tumor suppressor gene of Wilms' tumors, bears potential ability to induce macrophage differentiation in blood cell differentiation. Herein, we examined the involvement of WT1 in the regulation of osteoclastogenesis. We detected a high level of WT1 protein expression in osteoclast precursors; however, WT1 expression was markedly suppressed during osteoclastogenesis. We examined expression of WT1 transcripts in bone tissue by RNA in situ hybridization. We found a high level of antisense transcripts in osteoclasts actively resorbing bone in mandible of newborn rats. Expression of antisense WT1 RNA in mandible was also confirmed by Northern blot analysis and strand-specific RT-PCR. Overexpression of antisense WT1 RNA in RAW-D cells, an osteoclast precursor cell line, resulted in a marked enhancement of osteoclastogenesis, suggesting that antisense WT1 RNA functions to suppress expression of WT1 protein in osteoclastogenesis. High level expression of antisense WT1 RNA may contribute to commitment to osteoclastogenesis, and may allow osteoclasts to maintain or stabilize their differentiation state. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Future heat waves and surface ozone

NASA Astrophysics Data System (ADS)

Meehl, Gerald A.; Tebaldi, Claudia; Tilmes, Simone; Lamarque, Jean-Francois; Bates, Susan; Pendergrass, Angeline; Lombardozzi, Danica

2018-06-01

A global Earth system model is used to study the relationship between heat waves and surface ozone levels over land areas around the world that could experience either large decreases or little change in future ozone precursor emissions. The model is driven by emissions of greenhouse gases and ozone precursors from a medium-high emission scenario (Representative Concentration Pathway 6.0–RCP6.0) and is compared to an experiment with anthropogenic ozone precursor emissions fixed at 2005 levels. With ongoing increases in greenhouse gases and corresponding increases in average temperature in both experiments, heat waves are projected to become more intense over most global land areas (greater maximum temperatures during heat waves). However, surface ozone concentrations on future heat wave days decrease proportionately more than on non-heat wave days in areas where ozone precursors are prescribed to decrease in RCP6.0 (e.g. most of North America and Europe), while surface ozone concentrations in heat waves increase in areas where ozone precursors either increase or have little change (e.g. central Asia, the Mideast, northern Africa). In the stabilized ozone precursor experiment, surface ozone concentrations increase on future heat wave days compared to non-heat wave days in most regions except in areas where there is ozone suppression that contributes to decreases in ozone in future heat waves. This is likely associated with effects of changes in isoprene emissions at high temperatures (e.g. west coast and southeastern North America, eastern Europe).

Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae

PubMed Central

2011-01-01

Background The expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations to high-level expression of active viral surface glycoproteins in yeast are not well understood. To identify possible bottlenecks we performed a detailed study on overexpression of recombinant mumps hemagglutinin-neuraminidase (MuHN) and measles hemagglutinin (MeH) in yeast Saccharomyces cerevisiae, combining the analysis of recombinant proteins with a proteomic approach. Results Overexpressed recombinant MuHN and MeH proteins were present in large aggregates, were inactive and totally insoluble under native conditions. Moreover, the majority of recombinant protein was found in immature form of non-glycosylated precursors. Fractionation of yeast lysates revealed that the core of viral surface protein aggregates consists of MuHN or MeH disulfide-linked multimers involving eukaryotic translation elongation factor 1A (eEF1A) and is closely associated with small heat shock proteins (sHsps) that can be removed only under denaturing conditions. Complexes of large Hsps seem to be bound to aggregate core peripherally as they can be easily removed at high salt concentrations. Proteomic analysis revealed that the accumulation of unglycosylated viral protein precursors results in specific cytosolic unfolded protein response (UPR-Cyto) in yeast cells, characterized by different action and regulation of small Hsps versus large chaperones of Hsp70, Hsp90 and Hsp110 families. In contrast to most environmental stresses, in the response to synthesis of recombinant MuHN and MeH, only the large Hsps were upregulated whereas sHsps were not. Interestingly, the amount of eEF1A was also increased during this stress response. Conclusions Inefficient translocation of MuHN and MeH precursors through ER membrane is a bottleneck for high-level expression in yeast. Overexpression of these recombinant proteins induces the UPR's cytosolic counterpart, the UPR-Cyto, which represent a subset of proteins involved in the heat-shock response. The involvement of eEF1A may explain the mechanism by which only large chaperones, but not small Hsps are upregulated during this stress response. Our study highlights important differences between viral surface protein expression in yeast and mammalian cells at the first stage of secretory pathway. PMID:21595909

Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta.

PubMed

Shimojo, Masafumi; Sahara, Naruhiko; Mizoroki, Tatsuya; Funamoto, Satoru; Morishima-Kawashima, Maho; Kudo, Takashi; Takeda, Masatoshi; Ihara, Yasuo; Ichinose, Hiroshi; Takashima, Akihiko

2008-06-13

Presenilin (PS)/gamma-secretase-mediated intramembranous proteolysis of amyloid precursor protein produces amyloid beta (Abeta) peptides in which Abeta species of different lengths are generated through multiple cleavages at the gamma-, zeta-, and epsilon-sites. An increased Abeta42/Abeta40 ratio is a common characteristic of most cases of familial Alzheimer disease (FAD)-linked PS mutations. However, the molecular mechanisms underlying amyloid precursor protein proteolysis leading to increased Abeta42/Abeta40 ratios still remain unclear. Here, we report our findings on the enzymatic analysis of gamma-secretase derived from I213T mutant PS1-expressing PS1/PS2-deficient (PS(-/-)) cells and from the brains of I213T mutant PS1 knock-in mice. Kinetics analyses revealed that the FAD mutation reduced de novo Abeta generation, suggesting that mutation impairs the total catalytic rate of gamma-secretase. Analysis of each Abeta species revealed that the FAD mutation specifically reduced Abeta40 levels more drastically than Abeta42 levels, leading to an increased Abeta42/Abeta40 ratio. By contrast, the FAD mutation increased the generation of longer Abeta species such as Abeta43, Abeta45, and >Abeta46. These results were confirmed by analyses of gamma-secretase derived from I213T knock-in mouse brains, in which the reduction of de novo Abeta generation was mutant allele dose-dependent. Our findings clearly indicate that the mechanism underlying the increased Abeta42/Abeta40 ratio observed in cases of FAD mutations is related to the differential inhibition of gamma-site cleavage reactions, in which the reaction producing Abeta40 is subject to more inhibition than that producing Abeta42. Our results also provide novel insight into how enhancing the generation of longer Abetas may contribute to Alzheimer disease onset.

Contribution of the Antibiotic Chloramphenicol and Its Analogues as Precursors of Dichloroacetamide and Other Disinfection Byproducts in Drinking Water.

PubMed

Chu, Wenhai; Krasner, Stuart W; Gao, Naiyun; Templeton, Michael R; Yin, Daqiang

2016-01-05

Dichloroacetamide (DCAcAm), a disinfection byproduct, has been detected in drinking water. Previous research showed that amino acids may be DCAcAm precursors. However, other precursors may be present. This study explored the contribution of the antibiotic chloramphenicol (CAP) and two of its analogues (thiamphenicol, TAP; florfenicol, FF) (referred to collectively as CAPs), which occur in wastewater-impacted source waters, to the formation of DCAcAm. Their formation yields were compared to free and combined amino acids, and they were investigated in filtered waters from drinking-water-treatment plants, heavily wastewater-impacted natural waters, and secondary effluents from wastewater treatment plants. CAPs had greater DCAcAm formation potential than two representative amino acid precursors. However, in drinking waters with ng/L levels of CAPs, they will not contribute as much to DCAcAm formation as the μg/L levels of amino acids. Also, the effect of advanced oxidation processes (AOPs) on DCAcAm formation from CAPs in real water samples during subsequent chlorination was evaluated. Preoxidation of CAPs with AOPs reduced the formation of DCAcAm during postchlorination. The results of this study suggest that CAPs should be considered as possible precursors of DCAcAm, especially in heavily wastewater-impacted waters.

Investigation of phase evolution of CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) by in situ synchrotron high-temperature powder diffraction

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

Ouyang, Xin; Huang, Saifang; School of Materials Science and Technology, China University of Geosciences

2014-03-15

In situ synchrotron X-ray powder diffraction was used to study the high-temperature phase evolution of CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) precursors prepared via solid-state and sol–gel methods. After the precursors are heated to 1225 °C, the CCTO phase is the main phase observed in the calcined powder, with the presence of some minor impurities. Comparing the two precursors, we found that the onset temperature for the CCTO phase formation is 800 °C in the sol–gel precursor, lower than that in the solid-state precursor (875 °C). Intermediate phases were only observed in the sol–gel precursor. Both precursors are able to bemore » calcined to sub-micrometric sized powders. Based on the synchrotron data along with differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA), the phase formation sequence and mechanism during calcination are proposed in this study. -- Graphical abstract: The in situ synchrotron HT-XRD patterns of CCTO sol–gel and solid-state precursor. Highlights: • Phase formation sequence/mechanism in two CCTO precursors has been established. • Formation temperature of CCTO via sol–gel method is lower than solid-state method. • Intermediate phases are only observed in the sol–gel precursor. • Both precursors are able to be calcined into sub-micrometric sized powders.« less

Total N-nitrosamine Precursor Adsorption with Carbon Nanotubes: Elucidating Controlling Physiochemical Properties and Developing a Size-Resolved Precursor Surrogate

NASA Astrophysics Data System (ADS)

Needham, Erin Michelle

As drinking water sources become increasingly impaired with nutrients and wastewater treatment plant (WWTP) effluent, formation of disinfection byproducts (DBPs)--such as trihalomethanes (THMs), dihaloacetonitriles (DHANs), and N-nitrosamines--during water treatment may also increase. N-nitrosamines may comprise the bulk of the chronic toxicity in treated drinking waters despite forming at low ng/L levels. This research seeks to elucidate physicochemical properties of carbon nanotubes (CNTs) for removal of DBP precursors, with an emphasis on total N-nitrosamines (TONO). Batch experiments with CNTs were completed to assess adsorption of THM, DHAN, and TONO precursors; physiochemical properties of CNTs were quantified through gas adsorption isotherms and x-ray photoelectron spectroscopy. Numerical modeling was used to elucidate characteristics of CNTs controlling DBP precursor adsorption. Multivariate models developed with unmodified CNTs revealed that surface carboxyl groups and, for TONO precursors, cumulative pore volume (CPV), controlled DBP precursor adsorption. Models developed with modified CNTs revealed that specific surface area controlled adsorption of THM and DHAN precursors while CPV and surface oxygen content were significant for adsorption of TONO precursors. While surrogates of THM and DHAN precursors leverage metrics from UV absorbance and fluorescence spectroscopy, a TONO precursor surrogate has proved elusive. This is important as measurements of TONO formation potential (TONOFP) require large sample volumes and long processing times, which impairs development of treatment processes. TONO precursor surrogates were developed using samples that had undergone oxidative or sorption treatments. Precursors were analyzed with asymmetric flow field-flow fractionation (AF4) with inline fluorescence detection (FLD) and whole water fluorescence excitation-emission matrices (EEMs). TONO precursor surrogates were discovered, capable of predicting changes in TONOFP in WWTP samples that have undergone oxidation (R2 = 0.996) and sorption (R2 = 0.576). Importantly, both surrogates only require just 2 mL of sample volume to measure and take only 1 hour. Application of the sorption precursor surrogate revealed that DBP precursor adsorption was feasible with freeform CNT microstructures with various dimensions and surface chemistries, establishing a framework for development of this novel CNT application for drinking water treatment.

Influence of calcium precursors on the morphology and crystallinity of sol gel-derived hydroxyapatite nanoparticles

NASA Astrophysics Data System (ADS)

Vijayalakshmi Natarajan, U.; Rajeswari, S.

2008-10-01

Nanosized hydroxyapatite (HAP) particles were prepared by sol-gel method from the water-based solution of calcium and phosphorus precursor. In this study, two calcium precursors such as calcium nitrate tetrahydrate and calcium acetate were chosen as calcium precursors. The influence of aging period, pH, viscosity and sintering temperature on crystallinity and morphology of the HAP particles were investigated for the two calcium precursors with triethyl phosphate precursor. The morphology of nano-HAP towards phosphorous precursor was dependent on the type of calcium precursor used. The HAP prepared from calcium nitrate and triethyl phosphate was spherically shaped whereas the one from calcium acetate was found to be fibrous in structure. Both HAPs were stable up to 1200 °C and their crystallinity increased with respect to the sintering temperature. The obtained sample was characterized through X-ray diffraction (XRD), P 31 nuclear magnetic resonance (NMR), scanning electronic microscopy (SEM) and TEM analysis. The sol derived from the optimized aging period for the two different calcium precursors was coated on 316L stainless-steel (SS) implant and its corrosion resistivity during long-term implantation was studied by cyclic polarization in Ringer's solution. Both HAPs have their own desirable qualities and were found to be corrosion resistive.

Analysis and identification of astaxanthin and its carotenoid precursors from Xanthophyllomyces dendrorhous by high-performance liquid chromatography.

PubMed

Lu, Mingbo; Zhang, Yang'e; Zhao, Chunfang; Zhou, Pengpeng; Yu, Longjiang

2010-01-01

This study presents an HPLC method for simultaneous analysis of astaxanthin and its carotenoid precursors from Xanthophyllomyces dendrorhous. The HPLC method is accomplished by employing a C18 column and the mobile phase methanol/water/acetonitrile/ dichloromethane (70:4:13:13, v/v/v/v). Astaxanthin is quantified by detection at 480 nm. The carotenoid precursors are identified by LC-APCI-MS and UV-vis absorption spectra. Peaks showed in the HPLC chromatogram are identified as carotenoids in the monocyclic biosynthetic pathway or their derivatives. In the monocyclic carotenoid pathway, 3,3'-dihydroxy-beta,psi-carotene-4,4'-dione (DCD) is produced through gamma-carotene and torulene.

Factors dominating 3-dimensional ozone distribution during high tropospheric ozone period.

PubMed

Chen, Xiaoyang; Liu, Yiming; Lai, Anqi; Han, Shuangshuang; Fan, Qi; Wang, Xuemei; Ling, Zhenhao; Huang, Fuxiang; Fan, Shaojia

2018-01-01

Data from an in situ monitoring network and five ozone sondes are analysed during August of 2012, and a high tropospheric ozone episode is observed around the 8th of AUG. The Community Multi-scale Air Quality (CMAQ) model and its process analysis tool were used to study factors and mechanisms for high ozone mixing ratio at different levels of ozone vertical profiles. A sensitive scenario without chemical initial and boundary conditions (ICBCs) from MOZART4-GEOS5 was applied to study the impact of stratosphere-troposphere exchange (STE) on vertical ozone. The simulation results indicated that the first high ozone peak near the tropopause was dominated by STE. Results from process analysis showed that: in the urban area, the second peak at approximately 2 km above ground height was mainly caused by local photochemical production. The third peak (near surface) was mainly caused by the upwind transportation from the suburban/rural areas; in the suburban/rural areas, local photochemical production of ozone dominated the high ozone mixing ratio from the surface to approximately 3 km height. Furthermore, the capability of indicators to distinguish O 3 -precursor sensitivity along the vertical O 3 profiles was investigated. Two sensitive scenarios, which had cut 30% anthropogenic NO X or VOC emissions, showed that O 3 -precursor indicators, specifically the ratios of O 3 /NOy, H 2 O 2 /HNO 3 or H 2 O 2 /NO Z , could partly distinguish the O 3 -precursor sensitivity between VOCs-sensitive and NOx-sensitive along the vertical profiles. In urban area, the O 3 -precursor relationship transferred from VOCs-sensitive within the boundary layer to NOx-sensitive at approximately 1-3 km above ground height, further confirming the dominant roles of transportation and photochemical production in high O 3 peaks at the near-ground layer and 2 km above ground height, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of scientific findings from major ozone field studies in North America and Europe

NASA Astrophysics Data System (ADS)

Solomon, Paul; Cowling, Ellis; Hidy, George; Furiness, Cari

During the past decade, nearly 600 million dollars were invested in more than 30 major field studies in North America and Europe examining tropospheric ozone chemistry, meteorology, precursor emissions, and modeling. Most of these studies were undertaken to provide new or refined knowledge about ozone accumulation and to assist in the development of economical and effective emissions management practices for ozone. In this paper, we describe a selection of field research programs conducted under a wide range of geographical and climatological conditions in North America and Europe. The designs of these studies were generally similar, employing a combination of ground-based observation networks, upper-air sampling, and meteorological observations. Analysis and interpretation of the resulting data were combined with improved inventories of ozone precursor emissions and air quality modeling to develop new or enhanced knowledge about photochemical processes under various tropospheric conditions. The scientific results from these studies contained few surprises; in fact, they generally affirmed the conclusions in the review by the US National Research Council (NRC, 1999). Key findings include: (1) reaffirmation that tropospheric ozone is a multi-scale phenomenon extending to continental boundaries; (2) aerometric conditions aloft are important to ground-level ozone; (3) biogenic sources make important contributions to VOC and NO x emissions in parts of eastern North America and southern Europe; (4) emissions estimates are among the more uncertain components of predictive models for ozone; (5) recirculating flow over complex terrain and large water bodies are universally important factors affecting accumulation of ozone at the ground; (6) nonlinearities in ozone response to precursor changes create important degrees of freedom in management strategies - VOC and NO x sensitivities vary extensively in urban and rural areas, making decisions about emissions management complicated; (7) measurement methods for many precursors, intermediates, and products of photochemical reactions have improved greatly; and (8) additional analysis and interpretation of existing data from many of these field studies should pay handsome dividends at relatively modest cost.

Traffic congestion and ozone precursor emissions in Bilbao, Spain.

PubMed

Ibarra-Berastegi, Gabriel; Madariaga, Imanol

2003-01-01

In urban environments, the measured levels of ozone are the result of the interaction between emissions of precursors (mainly VOCs and NOx) and meteorological effects. In this work, time series of daily values of ozone, measured at three locations in Bilbao (Spain), have been built. Then, after removing meteorological effects from them, ozone and traffic data have been analyzed jointly. The goal was to identify traffic situations and link them to ozone levels in the area of Bilbao. To remove meteorological effects from the selected ozone time series, the technique developed by Rao and Zurbenko was used. This is a widely used technique and, after its application, the fraction obtained from a given ozone time series represents an ozone forming capability attributable to emissions of precursors. This fraction is devoid of any meteorological influence and includes only the apportion of periodicities above 1.7 years. In the case of Bilbao, the ozone fractions obtained at three locations have been compared on that time scale with traffic data from the area. For the 1993-1996 period, a regression analysis of the ozone and traffic fractions due to periodicities above 1.7 years (long-term fractions), shows that traffic is the main explanatory factor for ozone with R2 ranging from 0.916 to 0.996 at the three locations studied. Analysis of these longterm fractions has made it possible to identify two traffic regimes for the whole area, associated to different profiles of ozone forming capability. The first one favors low ozone forming capability, and is associated with a situation of fluent traffic. The second one shows high ozone forming capability and represents congestion. Joint analysis of raw data of ozone and traffic do not show any clear pattern due to the strong masking effects that seasonal-meteorological effects (mainly radiation) have on the measured ozone signal. If only immission data of ozone are available, as in this case, a comparison between ozone and traffic can only be made on the long-term time scale, since that is the only fraction embedded in the ozone time series that can exclusively be attributed to emissions of precursors. This fact stresses the need to study the different fractions embedded in the time series of ozone measured levels separately. Though the coefficients obtained in the regression are only valid for the 1993-1996 period, these traffic regimes represent long-term targets (congestion or fluent traffic) that can inspire policies for a joint management of the traffic and pollution by ozone in the area of Bilbao beyond that period. The results of this work show the need of a joint management of ozone and traffic in Bilbao. Since an accurate knowledge of traffic was not available, the use of emission factors to relate traffic and actual ozone levels has not been possible. For this reason, this study has focused on the long-term fractions of traffic and ozone. In the future, if a more accurate knowledge of traffic is available, it will be possible to find relationships between traffic and ozone on all time scales.

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes.

PubMed

Braidy, Nady; Berg, Jade; Clement, James; Khorshidi, Fatemeh; Poljak, Anne; Jayasena, Tharusha; Grant, Ross; Sachdev, Perminder

2018-05-11

Nicotinamide adenine dinucleotide (NAD + ) is an essential pyridine nucleotide that serves as an essential cofactor and substrate for a number of critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions. NAD + depletion may occur in response to either excessive DNA damage due to free radical or ultraviolet attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation and a high turnover and subsequent depletion of NAD + , and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decline in NAD + levels. Recent studies have shown that enhancing NAD + levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, promotion of intracellular NAD + anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general, and is essential to the effective realization of multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD + synthesis pathway in mammalian cells. NAD + can also be produced by the NAD + salvage pathway. Recent Advances: In this review, we describe and discuss recent insights regarding the efficacy and benefits of the NAD + precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), in attenuating NAD + decline in degenerative disease states and physiological aging. Results obtained in recent years have shown that NAD + precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD + synthesis via their location in the NAD + anabolic pathway. Increased synthesis of NAD + promotes protective cell responses, further demonstrating that NAD + is a regulatory molecule associated with several biochemical pathways. In the next few years, the refinement of personalized therapy for the use of NAD + precursors and improved detection methodologies allowing the administration of specific NAD + precursors in the context of patients' NAD + levels will lead to a better understanding of the therapeutic role of NAD + precursors in human diseases. Antioxid. Redox Signal. 00, 000-000.

Response of rats fed diets low in glucose and glucose precursors to low levels of glucose, starch and chemically modified starch.

PubMed

Chen, S C; Tsai, S; Nesheim, M C

1980-05-01

Several levels of glucose or starches were added to a basal diet that was free of available carbohydrate and low in carbohydrate precursors and fed to male, weanling rats. Rats fed such diets were highly responsive to dietary carbohydrate in growth rate, blood glucose levels and blood ketone bodies. There were no significant differences in the activities of pancreatic amylase, liver glucokinase, glucose-6-phosphatase and fructose-1,6-diphosphatase when dietary carbohydrate varied from 1.5 to 6% of the diet. Under these feeding conditions, a minimum of 6% by weight or 5.8% of the dietary calories has to be provided by carbohydrate to allow the rat an optimum rate of growth. Such diets that are low in glucose precursors were employed as an assay system for glucose availability from chemically cross-bonded starches with various degrees of phosphate crosslinkage. The data showed that introducing low levels of phosphate crosslinkages into the starch had little effect on the glucose availability from the starch.

Immune responses to epstein-barr virus in atomic bomb survivors: Study of precursor frequency of cytotoxic lymphocytes and titer levels of anti-Epstein-Barr virus-related antibodies

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

Kusunoki, Yoichiro; Kyoizumi, Seishi; Saito, Mayumi

Precursor frequencies of cytotoxic lymphocytes to autologous Epstein-Barr virus-transformed B cells and serum titers of anti-Epstein-Barr virus-related antibodies were measured in 68 atomic bomb survivors to clarify the immune mechanism controlling Epstein-Barr virus infection. The precursor frequency was negatively correlated with the titer of anti-early antigen lgG, which is probably produced at the stage of viral reactivation. A positive correlation between the precursor frequency and titer of anti-Epstein-Barr virus-associated nuclear antigen antibody was also observed, indicating that the precursor frequency reflects the degree of in vivo destruction by T cells of the virus-infected cells. These results suggest that T-cell memorymore » specific to Epstein-Barr virus keeps the virus under control and that the precursor frequency assay is useful for the evaluation of immune responses to Epstein-Barr virus. However, no significant effect of atomic bomb radiation on the precursor frequency was observed in the present study, probably due to the limited number of participants. 24 refs., 4 figs., 2 tabs.« less

Electrical and optical evaluation of n-type doping in In x Ga(1-x)P nanowires.

PubMed

Zeng, Xulu; Mourão, Renato T; Otnes, Gaute; Hultin, Olof; Dagytė, Vilgailė; Heurlin, Magnus; Borgström, Magnus T

2018-06-22

To harvest the benefits of III-V nanowires in optoelectronic devices, the development of ternary materials with controlled doping is needed. In this work, we performed a systematic study of n-type dopant incorporation in dense In x Ga (1-x) P nanowire arrays using tetraethyl tin (TESn) and hydrogen sulfide (H 2 S) as dopant precursors. The morphology, crystal structure and material composition of the nanowires were characterized by use of scanning electron microscopy, transmission electron microscopy and energy dispersive x-ray analysis. To investigate the electrical properties, the nanowires were broken off from the substrate and mechanically transferred to thermally oxidized silicon substrates, after which electron beam lithography and metal evaporation were used to define electrical contacts to selected nanowires. Electrical characterization, including four-probe resistivity and Hall effect, as well as back-gated field effect measurements, is combined with photoluminescence spectroscopy to achieve a comprehensive evaluation of the carrier concentration in the doped nanowires. We measure a carrier concentration of ∼1 × 10 16 cm -3 in nominally intrinsic nanowires, and the maximum doping level achieved by use of TESn and H 2 S as dopant precursors using our parameters is measured to be ∼2 × 10 18 cm -3 , and ∼1 × 10 19 cm -3 , respectively (by Hall effect measurements). Hence, both TESn and H 2 S are suitable precursors for a wide range of n-doping levels in In x Ga (1-x) P nanowires needed for optoelectronic devices, grown via the vapor-liquid-solid mode.

Electrical and optical evaluation of n-type doping in In x Ga(1‑x)P nanowires

NASA Astrophysics Data System (ADS)

Zeng, Xulu; Mourão, Renato T.; Otnes, Gaute; Hultin, Olof; Dagytė, Vilgailė; Heurlin, Magnus; Borgström, Magnus T.

2018-06-01

To harvest the benefits of III–V nanowires in optoelectronic devices, the development of ternary materials with controlled doping is needed. In this work, we performed a systematic study of n-type dopant incorporation in dense In x Ga(1‑x)P nanowire arrays using tetraethyl tin (TESn) and hydrogen sulfide (H2S) as dopant precursors. The morphology, crystal structure and material composition of the nanowires were characterized by use of scanning electron microscopy, transmission electron microscopy and energy dispersive x-ray analysis. To investigate the electrical properties, the nanowires were broken off from the substrate and mechanically transferred to thermally oxidized silicon substrates, after which electron beam lithography and metal evaporation were used to define electrical contacts to selected nanowires. Electrical characterization, including four-probe resistivity and Hall effect, as well as back-gated field effect measurements, is combined with photoluminescence spectroscopy to achieve a comprehensive evaluation of the carrier concentration in the doped nanowires. We measure a carrier concentration of ∼1 × 1016 cm‑3 in nominally intrinsic nanowires, and the maximum doping level achieved by use of TESn and H2S as dopant precursors using our parameters is measured to be ∼2 × 1018 cm‑3, and ∼1 × 1019 cm‑3, respectively (by Hall effect measurements). Hence, both TESn and H2S are suitable precursors for a wide range of n-doping levels in In x Ga(1‑x)P nanowires needed for optoelectronic devices, grown via the vapor–liquid–solid mode.

Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiae

PubMed Central

Henry, Susan A.; Kohlwein, Sepp D.; Carman, George M.

2012-01-01

Due to its genetic tractability and increasing wealth of accessible data, the yeast Saccharomyces cerevisiae is a model system of choice for the study of the genetics, biochemistry, and cell biology of eukaryotic lipid metabolism. Glycerolipids (e.g., phospholipids and triacylglycerol) and their precursors are synthesized and metabolized by enzymes associated with the cytosol and membranous organelles, including endoplasmic reticulum, mitochondria, and lipid droplets. Genetic and biochemical analyses have revealed that glycerolipids play important roles in cell signaling, membrane trafficking, and anchoring of membrane proteins in addition to membrane structure. The expression of glycerolipid enzymes is controlled by a variety of conditions including growth stage and nutrient availability. Much of this regulation occurs at the transcriptional level and involves the Ino2–Ino4 activation complex and the Opi1 repressor, which interacts with Ino2 to attenuate transcriptional activation of UASINO-containing glycerolipid biosynthetic genes. Cellular levels of phosphatidic acid, precursor to all membrane phospholipids and the storage lipid triacylglycerol, regulates transcription of UASINO-containing genes by tethering Opi1 to the nuclear/endoplasmic reticulum membrane and controlling its translocation into the nucleus, a mechanism largely controlled by inositol availability. The transcriptional activator Zap1 controls the expression of some phospholipid synthesis genes in response to zinc availability. Regulatory mechanisms also include control of catalytic activity of glycerolipid enzymes by water-soluble precursors, products and lipids, and covalent modification of phosphorylation, while in vivo function of some enzymes is governed by their subcellular location. Genome-wide genetic analysis indicates coordinate regulation between glycerolipid metabolism and a broad spectrum of metabolic pathways. PMID:22345606

Efficient production of reactive oxygen species in neural precursor cells after exposure to 250 MeV protons.

PubMed

Giedzinski, Erich; Rola, Radoslaw; Fike, John R; Limoli, Charles L

2005-10-01

The space radiation environment is composed of highly energetic ions, dominated by protons, that pose a range of potential health risks to astronauts. Traversals of these particles through certain tissues may compromise the viability and/or function of sensitive cells, including neural precursors found within the dentate subgranular zone of the hippocampus. Irradiation has been shown to deplete these cells in vivo, and reductions of these critical cells are believed to impair neurogenesis and cognition. To more fully understand the mechanisms underlying the behavior of these precursor cells after irradiation, we have developed an in vitro neural precursor cell system and used it to assess acute (0-48 h) changes in ROS and mitochondrial end points after exposure to Bragg-peak protons of 250 MeV. Relative ROS levels were increased at nearly all doses (1-10 Gy) and postirradiation times (6-24 h) compared to unirradiated controls. The increase in ROS after proton irradiation was more rapid than that observed with X rays and showed a well-defined dose response at 6 and 24 h, increasing approximately 10% and 3% per gray, respectively. However, by 48 h postirradiation, ROS levels fell below controls and coincided with minor reductions in mitochondrial content. Use of the antioxidant alpha-lipoic acid (before or after irradiation) was shown to eliminate the radiation-induced rise in ROS levels. Our results corroborate earlier studies using X rays and provide further evidence that elevated ROS are integral to the radioresponse of neural precursor cells.

The role of chloramine species in NDMA formation.

PubMed

Selbes, Meric; Beita-Sandí, Wilson; Kim, Daekyun; Karanfil, Tanju

2018-09-01

N-nitrosodimethylamine (NDMA), a probable human carcinogen disinfection by-product, has been detected in chloraminated drinking water systems. Understanding its formation over time is important to control NDMA levels in distribution systems. The main objectives of this study were to investigate the role of chloramine species (i.e., monochloramine and dichloramine); and the factors such as pH, sulfate, and natural organic matter (NOM) influencing the formation of NDMA. Five NDMA precursors (i.e., dimethylamine (DMA), trimethylamine (TMA), N,N-dimethylisopropylamine (DMiPA), N,N-dimethylbenzylamine (DMBzA), and ranitidine (RNTD)) were carefully selected based on their chemical structures and exposed to varying ratios of monochloramine and dichloramine. All amine precursors reacted relatively fast to form NDMA and reached their maximum NDMA yields within 24 h in the presence of excess levels of chloramines (both mono- and dichloramine) or excess levels of dichloramine conditions (with limited monochloramine). When the formation of dichloramine was suppressed (i.e., only monochloramine existed in the system) over the 5 day contact time, NDMA formation from DMA, TMA, and DMiPA was drastically reduced (∼0%). Under monochloramine abundant conditions, however, DMBzA and RNTD showed 40% and 90% NDMA conversions at the end of 5 day contact time, respectively, with slow formation rates, indicating that while these amine precursors react preferentially with dichloramine to form NDMA, they can also react with monochloramine in the absence of dichloramine. NOM and pH influenced dichloramine levels that affected NDMA yields. NOM had an adverse effect on NDMA formation as it created a competition with NDMA precursors for dichloramine. Sulfate did not increase the NDMA formation from the two selected NDMA precursors. pH played a key role as it influenced both chloramine speciation and protonation state of amine precursors and the highest NDMA formation was observed at the pH range where dichloramine and deprotonated amines coexisted. In selected natural water and wastewater samples, dichloramine led to the formation of more NDMA than monochloramine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impacts of changes in precursor emissions from the San Francisco Bay Area on ozone in the North Central Coast and San Joaquin Valley air basins. Final report

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

Douglas, S.G.; Stoeckenius, T.E.; Austin, B.S.

1991-02-01

The study examined the effect of emissions reductions in the San Francisco Bay Area (SFBA) on ozone levels in the North Central Coast (NCC) and San Joaquin Valley (SJV) air basins. It included an emissions trends analysis for the SFBA, NCC, and SJV air basins; identification of possible transport days and an analysis of ozone trends in both the source and receptor basins on transport and no-transport days; and calculation of interbasin pollutant fluxes using air-quality modeling results. The emissions trends analysis indicated that the SFBA achieved large decreases in emissions of reactive organic gases (ROG) and oxides of nitrogenmore » (NOx) between 1979 and 1988. Despite the large decreases in emissions no significant ozone trends were observed on either transport or no-transport days. Ozone concentrations at the downwind monitors were higher on transport days. Results of the flux plane calculations indicate that elimination of SFBA emissions would significantly reduce ozone concentrations in the NCC and SJV during meteorological conditions conducive to transport and that the lower concentrations in the downwind air basins would be due primarily to a reduction in the amount of precursor pollutants that are transport from the SFBA to the receptor basins.« less

The construction and partial characterization of plasmids containing complementary DNA sequences to human calcitonin precursor polyprotein.

PubMed Central

Allison, J; Hall, L; MacIntyre, I; Craig, R K

1981-01-01

(1) Total poly(A)-containing RNA isolated from human thyroid medullary carcinoma tissue was shown to direct the synthesis in the wheat germ cell-free system of a major (Mr 21000) and several minor forms of human calcitonin precursor polyproteins. Evidence for processing of these precursor(s) by the wheat germ cell-free system is also presented. (2) A small complementary DNA (cDNA) plasmid library has been constructed in the PstI site of the plasmid pAT153, using total human thyroid medullary carcinoma poly(A)-containing RNA as the starting material. (3) Plasmids containing abundant cDNA sequences were selected by hybridization in situ, and two of these (ph T-B3 and phT-B6) were characterized by hybridization--translation and restriction analysis. Each was shown to contain human calcitonin precursor polyprotein cDNA sequences. (4) RNA blotting techniques demonstrate that the human calcitonin precursor polyprotein is encoded within a mRNA containing 1000 bases. (5) The results demonstrate that human calcitonin is synthesized as a precursor polyprotein. Images Fig. 1. Fig. 2. Fig. 3. PMID:6896146

[Separation and identification of 5 glycosidic flavor precursors in tobacco by ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry].

PubMed

Wu, Xinhua; Zhu, Ruizhi; Ren, Zhuoying; Wang, Kai; Mou, Dingrong; Wei, Wanzhi; Miao, Mingming

2009-11-01

A qualitative method for the identification of 5 main glycosidic flavor precursors in tobacco was developed by using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS) and gas chromatography-mass spectrometry (GC-MS). The glycosidic flavor precursors in tobacco were extracted with methanol, cleaned up with an XAD-2 column. The aglycones were later released by enzyme-mediated hydrolysis under the condition of pH 5. The 5 volatile aglycone moieties were identified by GC-MS standard spectra library. The precursor ions of glycosides were determined by using electrospray ionization mass spectrometry in negative ion mode, then the 5 glycosidic flavor precursors were identified by using product ion scan (MS2) finally, using UPLC-ESI MS/MS, separation and identification of 5 glycosidic flavor precursors were accomplished on an RP-C,8 column in the multiple reaction monitoring (MRM) mode by using methanol and acetic acid-ammonium acetate aqueous solution as eluent. This work lays a foundation for the analysis of glycosidic flavor precursors without the standards by using liquid chromatography-mass spectrometry.

Extracting the distribution of laser damage precursors on fused silica surfaces for 351 nm, 3 ns laser pulses at high fluences (20-150 J/cm2).

PubMed

Laurence, Ted A; Bude, Jeff D; Ly, Sonny; Shen, Nan; Feit, Michael D

2012-05-07

Surface laser damage limits the lifetime of optics for systems guiding high fluence pulses, particularly damage in silica optics used for inertial confinement fusion-class lasers (nanosecond-scale high energy pulses at 355 nm/3.5 eV). The density of damage precursors at low fluence has been measured using large beams (1-3 cm); higher fluences cannot be measured easily since the high density of resulting damage initiation sites results in clustering. We developed automated experiments and analysis that allow us to damage test thousands of sites with small beams (10-30 µm), and automatically image the test sites to determine if laser damage occurred. We developed an analysis method that provides a rigorous connection between these small beam damage test results of damage probability versus laser pulse energy and the large beam damage results of damage precursor densities versus fluence. We find that for uncoated and coated fused silica samples, the distribution of precursors nearly flattens at very high fluences, up to 150 J/cm2, providing important constraints on the physical distribution and nature of these precursors.

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli.

PubMed

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun; Molinas, Margaux; Baidoo, Edward E K; Wang, George; Chan, Leanne J G; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek S

2017-08-01

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

PubMed

Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

2015-01-01

Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF1

PubMed Central

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-01-01

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years. PMID:18633461

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

PubMed

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-07-01

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

The auditory enhancement effect is not reflected in the 80-Hz auditory steady-state response.

PubMed

Carcagno, Samuele; Plack, Christopher J; Portron, Arthur; Semal, Catherine; Demany, Laurent

2014-08-01

The perceptual salience of a target tone presented in a multitone background is increased by the presentation of a precursor sound consisting of the multitone background alone. It has been proposed that this "enhancement" phenomenon results from an effective amplification of the neural response to the target tone. In this study, we tested this hypothesis in humans, by comparing the auditory steady-state response (ASSR) to a target tone that was enhanced by a precursor sound with the ASSR to a target tone that was not enhanced. In order to record neural responses originating in the brainstem, the ASSR was elicited by amplitude modulating the target tone at a frequency close to 80 Hz. The results did not show evidence of an amplified neural response to enhanced tones. In a control condition, we measured the ASSR to a target tone that, instead of being perceptually enhanced by a precursor sound, was acoustically increased in level. This level increase matched the magnitude of enhancement estimated psychophysically with a forward masking paradigm in a previous experimental phase. We found that the ASSR to the tone acoustically increased in level was significantly greater than the ASSR to the tone enhanced by the precursor sound. Overall, our results suggest that the enhancement effect cannot be explained by an amplified neural response at the level of the brainstem. However, an alternative possibility is that brainstem neurons with enhanced responses do not contribute to the scalp-recorded ASSR.

Kinetic and Surface Study of Single-Walled Aluminosilicate Nanotubes and Their Precursors

PubMed Central

Arancibia-Miranda, Nicolás; Escudey, Mauricio; Molina, Mauricio; García-González, María Teresa

2013-01-01

The structural and surface changes undergone by the different precursors that are produced during the synthesis of imogolite are reported. The surface changes that occur during the synthesis of imogolite were determined by electrophoretic migration (EM) measurements, which enabled the identification of the time at which the critical precursor of the nanoparticles was generated. A critical parameter for understanding the evolution of these precursors is the isoelectric point (IEP), of which variation revealed that the precursors modify the number of active ≡Al-OH and ≡Si-OH sites during the formation of imogolite. We also found that the IEP is displaced to a higher pH level as a consequence of the surface differentiation that occurs during the synthesis. At the same time, we established that the pH of the reaction (pHrx) decreases with the evolution and condensation of the precursors during aging. Integration of all of the obtained results related to the structural and surface properties allows an overall understanding of the different processes that occur and the products that are formed during the synthesis of imogolite. PMID:28348326

Nanoscale liposomal formulation of a SYK P-site inhibitor against B-precursor leukemia

PubMed Central

Qazi, Sanjive; Cely, Ingrid; Sahin, Kazim; Shahidzadeh, Anoush; Ozercan, Ibrahim; Yin, Qian; Gaynon, Paul; Termuhlen, Amanda; Cheng, Jianjun

2013-01-01

We report preclinical proof of principle for effective treatment of B-precursor acute lymphoblastic leukemia (ALL) by targeting the spleen tyrosine kinase (SYK)–dependent antiapoptotic blast cell survival machinery with a unique nanoscale pharmaceutical composition. This nanoscale liposomal formulation (NLF) contains the pentapeptide mimic 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C61) as the first and only selective inhibitor of the substrate binding P-site of SYK. The C61 NLF exhibited a very favorable pharmacokinetic and safety profile in mice, induced apoptosis in primary B-precursor ALL blast cells taken directly from patients as well as in vivo clonogenic ALL xenograft cells, destroyed the in vivo clonogenic fraction of ALL blast cells, and, at nontoxic dose levels, exhibited potent in vivo antileukemic activity against patient-derived ALL cells in xenograft models of aggressive B-precursor ALL. Our findings establish SYK as an attractive molecular target for therapy of B-precursor ALL. Further development of the C61 NLF may provide the foundation for therapeutic innovation against therapy-refractory B-precursor ALL. PMID:23568490

Kinetic and Surface Study of Single-Walled Aluminosilicate Nanotubes and Their Precursors.

PubMed

Arancibia-Miranda, Nicolás; Escudey, Mauricio; Molina, Mauricio; García-González, María Teresa

2013-03-01

The structural and surface changes undergone by the different precursors that are produced during the synthesis of imogolite are reported. The surface changes that occur during the synthesis of imogolite were determined by electrophoretic migration (EM) measurements, which enabled the identification of the time at which the critical precursor of the nanoparticles was generated. A critical parameter for understanding the evolution of these precursors is the isoelectric point (IEP), of which variation revealed that the precursors modify the number of active ≡Al-OH and ≡Si-OH sites during the formation of imogolite. We also found that the IEP is displaced to a higher pH level as a consequence of the surface differentiation that occurs during the synthesis. At the same time, we established that the pH of the reaction (pH rx ) decreases with the evolution and condensation of the precursors during aging. Integration of all of the obtained results related to the structural and surface properties allows an overall understanding of the different processes that occur and the products that are formed during the synthesis of imogolite.

Precursor Selection for Property Optimization in Biomorphic SiC Ceramics

NASA Technical Reports Server (NTRS)

Varela-Feria, F. M.; Lopez-Robledo, M. J.; Martinez-Fernandez, J.; deArellano-Lopez, A. R.; Singh, M.; Gray, Hugh R. (Technical Monitor)

2002-01-01

Biomorphic SiC ceramics have been fabricated using different wood precursors. The evolution of volume, density and microstructure of the woods, carbon performs, and final SiC products are systematically studied in order to establish experimental guidelines that allow materials selection. The wood density is a critical characteristic, which results in a particular final SiC density, and the level of anisotropy in mechanical properties in directions parallel (axial) and perpendicular (radial) to the growth of the wood. The purpose of this work is to explore experimental laws that can help choose a type of wood as precursor for a final SiC product, with a given microstructure, density and level of anisotropy. Preliminary studies of physical properties suggest that not only mechanical properties are strongly anisotropic, but also electrical conductivity and gas permeability, which have great technological importance.

Accelerated Evolution of the Pituitary Adenylate Cyclase-Activating Polypeptide Precursor Gene During Human Origin

PubMed Central

Wang, Yin-qiu; Qian, Ya-ping; Yang, Su; Shi, Hong; Liao, Cheng-hong; Zheng, Hong-Kun; Wang, Jun; Lin, Alice A.; Cavalli-Sforza, L. Luca; Underhill, Peter A.; Chakraborty, Ranajit; Jin, Li; Su, Bing

2005-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition. PMID:15834139

Characterization of Fine Particulate Matter (PM) and Secondary PM Precursor Gases in the Mexico City Metropolitan Area

DOE R&D Accomplishments Database

Molina, Luisa T.; Volkamer, Rainer; de Foy, Benjamin; Lei, Wenfang; Zavala, Miguel; Velasco, Erik; Molina; Mario J.

2008-10-31

This project was one of three collaborating grants funded by DOE/ASP to characterize the fine particulate matter (PM) and secondary PM precursors in the Mexico City Metropolitan Area (MCMA) during the MILAGRO Campaign. The overall effort of MCMA-2006, one of the four components, focused on i) examination of the primary emissions of fine particles and precursor gases leading to photochemical production of atmospheric oxidants and secondary aerosol particles; ii) measurement and analysis of secondary oxidants and secondary fine PM production, with particular emphasis on secondary organic aerosol (SOA), and iii) evaluation of the photochemical and meteorological processes characteristic of the Mexico City Basin. The collaborative teams pursued the goals through three main tasks: i) analyses of fine PM and secondary PM precursor gaseous species data taken during the MCMA-2002/2003 campaigns and preparation of publications; ii) planning of the MILAGRO Campaign and deployment of the instrument around the MCMA; and iii) analysis of MCMA-2006 data and publication preparation.

Variability in ozone and its precursor gases over the Bay of Bengal during post-monsoon

NASA Astrophysics Data System (ADS)

Mallik, Chinmay; Lal, Shyam; Venkataramani, Sethuram; Naja, Manish; Ojha, Narendra

2013-04-01

O3 and precursor gases were measured during a ship campaign over the Bay of Bengal (BoB) during 28 October -17 November, 2010. The measurements revealed the large spatial heterogeneity in trace gas levels over the BoB during post-monsoon months. The heterogeneity was attributed to unique transport patterns over north and south BoB during this period. Four distinct types of air-masses influenced by heavy pollution from nearby source regions (49% time over North-West Myanmar, East Bangladesh and North-East India), mixed type (25% time over Myanmar, Thailand and Vietnam and 75% time over East BoB), affected by long-range transport of pollutants (59% time over continental South Myanmar, Vietnam and Hong-Kong region of China) and pristine marine (99% time over oceanic regions) were identified. Among these, the continental air masses were fresher compared to marine air masses. High O3 and CO levels were observed in air masses coming from South-East Asia. O3, C4H10 and alkenes were highest in air masses arriving from eastern IGP, Bangladesh, Myanmar via the North BoB. The C2H2 to CO slope of 0.004 and C3H8 to CO slope of 0.003 indicated predominance of biofuel/biomass burning in air masses from South-East Asia. The i-C4H10 to n- C4H10 value of 0.62 indicated contributions of urban/industrial sources in air masses arriving from Bangladesh, India and North-West Myanmar. 'Potential Source Contribution Function' analysis indicated fire impacted South of Myanmar and Thailand regions as potential contributors to high CO levels above 260 ppbv measured on 14 November. Observed enhancements in surface CO during 2-3 November were attributed to the faster transport of continental pollutants associated with cyclonic winds. The O3 e-fold time of 2.3 days indicated the higher rate of O3 destruction over the BoB due to higher precursor levels. Principle component analysis indicated that transport from continental source regions played a major role in determining the chemical composition of the air masses during the campaign and presence of regional sources of NOx. Diurnal variations of surface O3 revealed effects of advection, entrainment and photochemistry. Chemical box model simulations of O3 diurnal variations over the BoB were found to be very sensitive to background O3 and NO2 levels as well as dilution.

Mitotic position and morphology of committed precursor cells in the zebrafish retina adapt to architectural changes upon tissue maturation.

PubMed

Weber, Isabell P; Ramos, Ana P; Strzyz, Paulina J; Leung, Louis C; Young, Stephen; Norden, Caren

2014-04-24

The development of complex neuronal tissues like the vertebrate retina requires the tight orchestration of cell proliferation and differentiation. Although the complexity of transcription factors and signaling pathways involved in retinogenesis has been studied extensively, the influence of tissue maturation itself has not yet been systematically explored. Here, we present a quantitative analysis of mitotic events during zebrafish retinogenesis that reveals three types of committed neuronal precursors in addition to the previously known apical progenitors. The identified precursor types present at distinct developmental stages and exhibit different mitotic location (apical versus nonapical), cleavage plane orientation, and morphology. Interestingly, the emergence of nonapically dividing committed bipolar cell precursors can be linked to an increase in apical crowding caused by the developing photoreceptor cell layer. Furthermore, genetic interference with neuronal subset specification induces ectopic divisions of committed precursors, underlining the finding that progressing morphogenesis can effect precursor division position. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Increased Secreted Amyloid Precursor Protein-α (sAPPα) in Severe Autism: Proposal of a Specific, Anabolic Pathway and Putative Biomarker

PubMed Central

Sokol, Deborah K.; Lahiri, Debomoy K.

2011-01-01

Autism is a neurodevelopmental disorder characterized by deficits in verbal communication, social interactions, and the presence of repetitive, stereotyped and compulsive behaviors. Excessive early brain growth is found commonly in some patients and may contribute to disease phenotype. Reports of increased levels of brain-derived neurotrophic factor (BDNF) and other neurotrophic-like factors in autistic neonates suggest that enhanced anabolic activity in CNS mediates this overgrowth effect. We have shown previously that in a subset of patients with severe autism and aggression, plasma levels of the secreted amyloid-β (Aβ) precursor protein-alpha form (sAPPα) were significantly elevated relative to controls and patients with mild-to-moderate autism. Here we further tested the hypothesis that levels of sAPPα and sAPPβ (proteolytic cleavage products of APP by α- and β-secretase, respectively) are deranged in autism and may contribute to an anabolic environment leading to brain overgrowth. We measured plasma levels of sAPPα, sAPPβ, Aβ peptides and BDNF by corresponding ELISA in a well characterized set of subjects. We included for analysis 18 control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We have observed that sAPPα levels are increased and BDNF levels decreased in the plasma of patients with severe autism as compared to controls. Further, we show that Aβ1-40, Aβ1-42, and sAPPβ levels are significantly decreased in the plasma of patients with severe autism. These findings do not extend to patients with mild-to-moderate autism, providing a biochemical correlate of phenotypic severity. Taken together, this study provides evidence that sAPPα levels are generally elevated in severe autism and suggests that these patients may have aberrant non-amyloidogenic processing of APP. PMID:21731612

Probing Coagulation Behavior of Individual Aluminum Species for Removing Corresponding Disinfection Byproduct Precursors: The Role of Specific Ultraviolet Absorbance

PubMed Central

Zhao, He; Hu, Chengzhi; Zhang, Di; Liu, Huijuan; Qu, Jiuhui

2016-01-01

Coagulation behavior of aluminum chloride and polyaluminum chloride (PACl) for removing corresponding disinfection byproduct (DBP) precursors was discussed in this paper. CHCl3, bromine trihalomethanes (THM-Br), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) formation potential yields were correlated with specific ultraviolet absorbance (SUVA) values in different molecular weight (MW) fractions of humic substances (HS), respectively. Correlation analyses and principal component analysis were performed to examine the relationships between SUVA and different DBP precursors. To acquire more structural characters of DBP precursors and aluminum speciation, freeze-dried precipitates were analyzed by fourier transform infrared (FTIR) and C 1s, Al 2p X-ray photoelectron spectroscopy (XPS). The results indicated that TCAA precursors (no MW limits), DCAA and CHCl3 precursors in low MW fractions (MW<30 kDa) had a relatively good relations with SUVA values. These DBP precursors were coagulated more easily by in situ Al13 of AlCl3 at pH 5.0. Due to relatively low aromatic content and more aliphatic structures, THM-Br precursors (no MW limits) and CHCl3 precursors in high MW fractions (MW>30 kDa) were preferentially removed by PACl coagulation with preformed Al13 species at pH 5.0. Additionally, for DCAA precursors in high MW fractions (MW>30 kDa) with relatively low aromatic content and more carboxylic structures, the greatest removal occurred at pH 6.0 through PACl coagulation with aggregated Al13 species. PMID:26824243

Analysis of L-serine-O-phosphate in cerebrospinal spinal fluid by derivatization-liquid chromatography/mass spectrometry.

PubMed

McNaney, Colleen A; Benitex, Yulia; Luchetti, David; Labasi, Jeffrey M; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

2014-05-01

L-serine-O-phosphate (L-SOP), the precursor of L-serine, is a potent agonist against the group III metabotropic glutamate receptors (mGluRs) and, thus, is of interest as a potential biomarker for monitoring modulation of neurotransmitter release. So far, no reports are available on the analysis of L-SOP in cerebrospinal fluid (CSF). Here a novel method is presented to determine L-SOP levels in CSF employing precolumn derivatization with (5-N-succinimidoxy-5-oxopentyl)triphenylphosphonium bromide (SPTPP) coupled to liquid chromatography/mass spectrometry (derivatization-LC/MS, d-LC/MS). Copyright © 2014 Elsevier Inc. All rights reserved.

KINETICS OF LOW SOURCE REACTOR STARTUPS. PART II

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

hurwitz, H. Jr.; MacMillan, D.B.; Smith, J.H.

1962-06-01

A computational technique is described for computation of the probability distribution of power level for a low source reactor startup. The technique uses a mathematical model, for the time-dependent probability distribution of neutron and precursor concentration, having finite neutron lifetime, one group of delayed neutron precursors, and no spatial dependence. Results obtained by the technique are given. (auth)

The Genetic Precursors and the Advantageous and Disadvantageous Sequelae of Inhibited Temperament: An Evolutionary Perspective

ERIC Educational Resources Information Center

Davies, Patrick T.; Cicchetti, Dante; Hentges, Rochelle F.; Sturge-Apple, Melissa L.

2013-01-01

Guided by evolutionary game theory (Korte, Koolhaas, Wingfield, & McEwen, 2005), this study aimed to identify the genetic precursors and the psychosocial sequelae of inhibited temperament in a sociodemographically disadvantaged and racially diverse sample (N = 201) of 2-year-old children who experienced elevated levels of domestic violence.…

Comparison of PFASs contamination in the freshwater and terrestrial environments by analysis of eggs from osprey (Pandion haliaetus), tawny owl (Strix aluco), and common kestrel (Falco tinnunculus)

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

Eriksson, Ulrika, E-mail: ulrika.eriksson@oru.se; Roos, Anna; Lind, Ylva

The level of PFAS (per- and polyfluorinated alkyl substances) contamination in freshwater and terrestrial Swedish environments in 2013/2014 was assessed by analyzing a range of perfluorinated alkyl acids, fluorotelomer acids, sulfonamides, sulfonamidoethanols and polyfluoralkyl phosphate diesters (diPAPs) in predator bird eggs. Stable isotopes ({sup 13}C and {sup 15}N) were analyzed to elucidate the dietary source. The tawny owl (Strix aluco, n=10) and common kestrel (Falco tinnunculus, n=40), two terrestrial species, and the osprey (Pandion haliaetus, n=30), a freshwater specie were included. In addition, a temporal trend (1997–2001, 2008–2009, 2013) in osprey was studied as well. The PFAS profile was dominatedmore » by perfluorooctane sulfonic acid (PFOS) in eggs from osprey and tawny owl, while for common kestrel perfluorinated carboxylic acids (∑PFCA) exceeded the level of PFOS. PFOS concentration in osprey eggs remained at the same level between 1997 and 2001 and 2013. For the long-chained PFCAs, there were a significant increase in concentrations in osprey eggs between 1997 and 2001 and 2008–2009. The levels of PFOS and PFCAs were about 10 and five times higher, respectively, in osprey compared to tawny owl and common kestrel. Evidence of direct exposure from PFCA precursor compounds to birds in both freshwater and terrestrial environment was observed. Low levels of diPAPs were detected in a few samples of osprey (<0.02–2.4 ng/g) and common kestrel (<0.02–0.16 ng/g) eggs, and 6:2 FTSA was detected in a majority of the osprey eggs (<6.3–52 ng/g). One saturated telomer acid (7:3 FTCA), which is a transformation marker from precursor exposure, was detected in all species (<0.24–2.7 ng/g). The {sup 15}N data showed higher levels in osprey eggs compared to tawny owl and common kestrel, indicating that they feed on a 2–3 times higher trophic level. We conclude that ospreys are continuously exposed to PFAS at levels where adverse toxic effects have been observed in birds. - Highlights: • Levels in the freshwater environment exceeded those of the terrestrial environment. • Birds in both freshwater and terrestrial environment are exposed to PFCA precursors. • No significant change of PFOS level in osprey eggs between 1997 and 2001 and 2013. • PFAS levels pose a risk to birds in the freshwater environment.« less

Effects of Residual Lithium in the precursors of Li[Ni1/3Co1/3Mn1/3]O2 on their lithium-ion battery performance

NASA Astrophysics Data System (ADS)

Jo, Minsang; Ku, Heesuk; Park, Sanghyuk; Song, Junho; Kwon, Kyungjung

2018-07-01

Li[Ni1/3Co1/3Mn1/3]O2 cathode active materials are synthesized from co-precipitated hydroxide precursors Lix[Ni1/3Co1/3Mn1/3]1-x(OH)2, and the effect of residual Li in the precursors on the lithium-ion battery (LIB) performance of their corresponding cathode active materials is investigated. Three kinds of precursors that contain different amounts of Li are selected depending on different conditions of the solution composition for the co-precipitation and washing process. It is confirmed that the introduction of Li to the precursors reduces the degree of structural perfection by X-ray diffraction analysis. Undesirable cation mixing occurs with the increasing Li content of the precursors, which is inferred from a decline in lattice parameters and the calculated intensity ratio of (003) and (104) peaks. In the voltage range of 3.0-4.3 V, the initial charge/discharge capacities and the rate capability of the cathode active materials are aggravated when Li exists in the precursors. Therefore, it could be concluded that the strict control of Li in a solution for co-precipitation of precursors is necessary in the resynthesis of cathode active materials from spent LIBs.

Situation awareness and documentation of changes that affect patient outcomes in progress notes.

PubMed

Tower, Marion; Chaboyer, Wendy

2014-05-01

To report on registered nurses' situation awareness as a precursor to decision-making when recording changes in patients' conditions. Progress notes are important to communicate patients' progress and detail changes in patients' conditions. However, documentation is often poorly completed. There is little work that examines nurses' decision-making during documentation. This study focused on describing situation awareness as a precursor to decision-making during documentation. This study used Endsley's (Situation Awareness Analysis and Measurement, 2000, Lawrence Erlbaum Associates, NJ) work on situation awareness to guide and conceptualise information. The study was situated in a naturalistic paradigm to provide an interpretation of nurses' decision-making. Think-aloud research methods and semi-structured interviews were employed to illuminate decision-making processes. Audio recordings and interview texts were individually examined for evidence of cues, informed by Endsley's (Situation Awareness Analysis and Measurement, 2000, Lawrence Erlbaum Associates, NJ) descriptions of situation awareness. As patients' conditions changed, nurses used complex mental models and pattern-matching of information, drawing on all 3 levels of situation awareness during documentation. Level 1 situation awareness provided context, level 2 situation awareness signified a change in condition and its significance for the patient, and level 3 situation awareness was evident when nurses thought aloud about what this information indicated. Three themes associated with changes in patients' conditions emerged: deterioration in condition, not responding to prescribed treatments as expected and issues related to professional practice that impacted on patients' conditions. Nurses used a complex mental model for decision-making, drawing on 3 levels of situation awareness. Hamm's cognitive continuum theory, when related to situation awareness, is a useful decision-making theory to provide a platform on which to draw together components of situation awareness and provide a framework on which to base decision-making regarding documentation. Understanding how RNs employ situation awareness and providing a framework for decision-making during documentation may assist effective documentation about changes in patients' conditions. © 2013 John Wiley & Sons Ltd.

A Joint Prosodic Origin of Language and Music

PubMed Central

Brown, Steven

2017-01-01

Vocal theories of the origin of language rarely make a case for the precursor functions that underlay the evolution of speech. The vocal expression of emotion is unquestionably the best candidate for such a precursor, although most evolutionary models of both language and speech ignore emotion and prosody altogether. I present here a model for a joint prosodic precursor of language and music in which ritualized group-level vocalizations served as the ancestral state. This precursor combined not only affective and intonational aspects of prosody, but also holistic and combinatorial mechanisms of phrase generation. From this common stage, there was a bifurcation to form language and music as separate, though homologous, specializations. This separation of language and music was accompanied by their (re)unification in songs with words. PMID:29163276

Contribution of citrulline to the formation of ethyl carbamate during Chinese rice wine production.

PubMed

Wang, Peihong; Sun, Junyong; Li, Xiaomin; Wu, Dianhui; Li, Tong; Lu, Jian; Chen, Jian; Xie, Guangfa

2014-04-01

Ethyl carbamate is a well-known carcinogen and widely occurs in Chinese rice wine. To provide more clues to minimise ethyl carbamate accumulation, the levels of possible precursors of ethyl carbamate in Chinese rice wine were investigated by HPLC. Studies of the possible precursors of ethyl carbamate in Chinese raw rice wine with various additives and treatments indicated that significant amounts of urea can account for ethyl carbamate formation. It was also recognised that citrulline is another important precursor that significantly affects ethyl carbamate production during the boiling procedure used in the Chinese rice wine manufacturing process. Besides urea and citrulline, arginine was also found to be an indirect ethyl carbamate precursor due to its ability to form urea and citrulline by microorganism metabolism.

Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis.

PubMed

Somogyi, Aleksandra; Petcherski, Anton; Beckert, Benedikt; Huebecker, Mylene; Priestman, David A; Banning, Antje; Cotman, Susan L; Platt, Frances M; Ruonala, Mika O; Tikkanen, Ritva

2018-02-22

Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model ( Cln3 Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3 Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4- N -acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3 Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis.

Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis

PubMed Central

Somogyi, Aleksandra; Petcherski, Anton; Beckert, Benedikt; Huebecker, Mylene; Priestman, David A.; Banning, Antje; Cotman, Susan L.; Platt, Frances M.; Ruonala, Mika O.

2018-01-01

Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis. PMID:29470438

Effect of chain length on thermal conversion of alkoxy-substituted copper phthalocyanine precursors.

PubMed

Fukuda, Takamitsu; Kikukawa, Yuu; Tsuruya, Ryota; Fuyuhiro, Akira; Ishikawa, Naoto; Kobayashi, Nagao

2011-11-21

A series of dialkoxy-substituted copper phthalocyanine (CuPc) precursors (4a-4d) have been prepared by treating phthalonitrile with the corresponding lithium alkoxide under mild conditions. The precursors exhibited high solubilities in common organic solvents, including acetone, toluene, tetrahydrofuran (THF), CH(2)Cl(2), and CHCl(3). Elongation of the alkoxy chains improved the solubilities of the precursors effectively, and accordingly, the butoxy-substituted derivative (4d) showed the highest solubility among 4a-4d. X-ray crystallography clarified that the conjugated skeletons of 4a-4d are all isostructural, and have two alkoxy groups in a syn-conformation fashion, leading to highly bent structures. Thermal conversions of the precursors examined by thermogravimetry (TG) and differential thermal analysis (DTA) demonstrate that 4a was converted into CuPc via two distinct exothermic processes in the 200-250 °C temperature range, while 4d exhibits only one exothermic signal in the DTA. In the field emission scanning electron microscopy (FESEM) images of 4a, the presence of two types of distinct crystal morphology (prismatic and plate-like crystals) can be recognized, implying that the two observed exothermic processes in the DTA can be attributed to the different crystal morphologies of the samples rather than the step-by-step elimination of the alkoxy groups. The thermal formation of CuPc from the precursors has been unambiguously confirmed by X-ray powder diffraction, UV-vis spectroscopy, and elemental analysis. The precursors were converted into CuPc at lower temperature with increasing chain length, presumably because of the increased void volume in the crystals. Thermal conversion performed in the solution phase results in a bright blue-colored solution with prominent absorption bands in the 650-700 nm region, strongly supporting the formation of CuPc.

Precursors, consequences and implications for stability and change in pre-adolescent antisocial behaviors.

PubMed

Pevalin, David J; Wade, Terrance J; Brannigan, Augustine

2003-06-01

Although much of the evidence stresses the stability of dysfunctional behavior throughout the life cycle, other evidence suggests that stability of antisocial behavior is a matter of degree. In this work we determine the degree of stability of such behavior in preadolescence and how this is influenced by age, gender, social structures, and family processes. Also, we explore whether change in the level of antisocial behavior impacts upon other important developmental regimes such as health and educational performance. We use a large, 2 wave, nationally representative sample of preadolescent children, and focus on children 4-9 years of age at wave 1 (n=6,846). We employ a cluster analysis across a series of behavioral variables to determine levels of antisocial behavior and then examine the stability of antisocial behavior over time and identify the precursors and consequences associated with movement into and out of these behavioral clusters. Antisocial behavior is more stable in boys and older children. Structural factors--age of the mother, number of children in the household, and having a single parent--along with family factors--hostile parenting and maternal depression--raise the likelihood of increases in and lower the likelihood of decreases in antisocial behavior, although there are notable differences by gender of the child and initial level of antisocial behavior. Consequences of change in antisocial behavior include scholastic performance, high levels of school mobility, school-parent contacts, and health perceptions. The implications of these findings for prevention and intervention programs are discussed.

Role of Elemental Sulfur in Forming Latent Precursors of H2S in Wine.

PubMed

Jastrzembski, Jillian A; Allison, Rachel B; Friedberg, Elle; Sacks, Gavin L

2017-12-06

The level of hydrogen sulfide (H 2 S) can increase during abiotic storage of wines, and potential latent sources of H 2 S are still under investigation. We demonstrate that elemental sulfur (S 0 ) residues on grapes not only can produce H 2 S during fermentation but also can form precursors capable of generating additional H 2 S after bottle storage for 3 months. H 2 S could be released from S 0 -derived precursors by addition of a reducing agent (TCEP), but not by addition of strong brine to induce release of H 2 S from metal sulfide complexes. The size of the TCEP-releasable pool varied among yeast strains. Using the TCEP assay, multiple polar S 0 -derived precursors were detected following normal-phase preparative chromatography. Using reversed-phase liquid chromatography and high-resolution mass spectrometry, we detected an increase in the levels of diglutathione trisulfane (GSSSG) and glutathione disulfide (GSSG) in S 0 -fermented red wine and an increase in the levels of glutathione S-sulfonate (GSSO 3 - ) and tetrathionate (S 4 O 6 2- ) in S 0 -fermented white wine as compared to controls. GSSSG, but not S 4 O 6 2- , was shown to evolve H 2 S in the presence of TCEP. Pathways for the formation of GSSSG, GSSG, GSSO 3 - , and S 4 O 6 2- from S 0 are proposed.

Status of Cycle 23 Forecasts

NASA Technical Reports Server (NTRS)

Hathaway, D. H.

2000-01-01

A number of techniques for predicting solar activity on a solar cycle time scale are identified, described, and tested with historical data. Some techniques, e.g,, regression and curve-fitting, work well as solar activity approaches maximum and provide a month- by-month description of future activity, while others, e.g., geomagnetic precursors, work well near solar minimum but provide an estimate only of the amplitude of the cycle. A synthesis of different techniques is shown to provide a more accurate and useful forecast of solar cycle activity levels. A combination of two uncorrelated geomagnetic precursor techniques provides the most accurate prediction for the amplitude of a solar activity cycle at a time well before activity minimum. This precursor method gave a smoothed sunspot number maximum of 154+21 for cycle 23. A mathematical function dependent upon the time of cycle initiation and the cycle amplitude then describes the level of solar activity for the complete cycle. As the time of cycle maximum approaches a better estimate of the cycle activity is obtained by including the fit between recent activity levels and this function. This Combined Solar Cycle Activity Forecast now gives a smoothed sunspot maximum of 140+20 for cycle 23. The success of the geomagnetic precursors in predicting future solar activity suggests that solar magnetic phenomena at latitudes above the sunspot activity belts are linked to solar activity, which occurs many years later in the lower latitudes.

Material quality frontiers of MOVPE grown AlGaAs for minority carrier devices

NASA Astrophysics Data System (ADS)

Heckelmann, S.; Lackner, D.; Dimroth, F.; Bett, A. W.

2017-04-01

In this study, secondary ion mass spectroscopy of oxygen, deep level transient spectroscopy and power dependent relative photoluminescence are compared regarding their ability to resolve differences in AlxGa1-xAs material quality. AlxGa1-xAs samples grown with two different trimethylaluminum sources showing low and high levels of oxygen contamination are compared. As tested in the growth of minority carrier devices, i.e. AlxGa1-xAs solar cells, the two precursors clearly lead to different device characteristics. It is shown that secondary ion mass spectroscopy could not resolve the difference in oxygen concentration, whereas deep level transient spectroscopy and photoluminescence based measurements indicate the influence of the precursor oxygen level on the material quality.

Preparation of TiO2-SiO2 via sol-gel method: Effect of Silica precursor on Catalytic and Photocatalytic properties

NASA Astrophysics Data System (ADS)

Fatimah, I.

2017-02-01

TiO2-SiO2have been synthesized by the sol-gel method from titanium isopropoxide and varied silica precursors: tetraethyl orthosilicate and tetra methyl ortho silicate. To study the effect of the precursor, prepared materials were characterized by X-ray diffraction, scanning electron microscopy, Diffuse Reflectance UV-vis optical absorption, and also gas sorption analysis. XRD patterns showed the formation of TiO2 anatase in the TiO2-SiO2 composite with different crystallite size from different silica precursor as well as the different surface morphology. The DRUV-vis absorption spectra exhibit similar band gap energy correspond to 3.21eV value while the surface area, pore volume and pore radius of the materials seems to be affected by the precursor. The higher specific surface area contributes to give the enhanced activity in phenol hydroxylation and methylene blue photodegradation.

Novel technological strategies to enhance tropical thiol precursors in winemaking by-products.

PubMed

Román Villegas, Tomás; Tonidandel, Loris; Fedrizzi, Bruno; Larcher, Roberto; Nicolini, Giorgio

2016-09-15

Grape pomace is a winemaking by-product that can be used to extract oenological tannins. Recently, some grape skin tannins were shown to contain very high amounts of two polyfunctional thiol precursors (3-S-glutathionylhexan-1-ol, 3-S-cysteinylhexan-1-ol) whose free forms are responsible for appreciated tropical-like flavours. This study shows that an oxidative treatment (no SO2) of white grape pomace and the presence of grape leaves and stems can increase the content of the above mentioned precursors. Moreover, it shows significant differences between Sauvignon Blanc, Gewuerztraminer and Mueller-Thurgau grape pomace for the 3-mercaptohexan-1-ol precursors and 4-S-cysteinyl-4-methylpentan-2-one. The grape cultivar is crucial, but the technological ability of enhancing the level of the volatile thiol precursors simply by treating the grape marc in different ways is a promising and powerful tool for the production of potentially flavouring tannins intended for food and beverage industry. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in Dissolved Organic Matter Composition and Disinfection Byproduct Precursors in Advanced Drinking Water Treatment Processes.

PubMed

Phungsai, Phanwatt; Kurisu, Futoshi; Kasuga, Ikuro; Furumai, Hiroaki

2018-03-20

Molecular changes in dissolved organic matter (DOM) from treatment processes at two drinking water treatment plants in Japan were investigated using unknown screening analysis by Orbitrap mass spectrometry. DOM formulas with carbon, hydrogen and oxygen (CHO-DOM) were the most abundant class in water samples, and over half of them were commonly found at both plants. Among the treatment processes, ozonation induced the most drastic changes to DOM. Mass peak intensities of less saturated CHO-DOM (positive (oxygen subtracted double bond equivalent per carbon (DBE-O)/C)) decreased by ozonation, while more saturated oxidation byproducts (negative (DBE-O)/C) increased and new oxidation byproducts (OBPs) were detected. By Kendrick mass analysis, ozone reactions preferred less saturated CHO-DOM in the same alkylation families and produced more saturated alkylation families of OBPs. Following ozonation, biological activated carbon filtration effectively removed <300 Da CHO-DOM, including OBPs. Following chlorination, over 50 chlorinated formulas of disinfection byproducts (DBPs) were found in chlorinated water samples where at least half were unknown. Putative precursors of these DBPs were determined based on electrophilic substitutions and addition reactions. Ozonation demonstrated better decomposition of addition reaction-type precursors than electrophilic substitution-type precursors; over half of both precursor types decreased during biological activated carbon filtration.

SEARCH FOR PRECURSOR ERUPTIONS AMONG TYPE IIB SUPERNOVAE

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

Strotjohann, Nora L.; Ofek, Eran O.; Gal-Yam, Avishay

2015-10-01

The progenitor stars of several Type IIb supernovae (SNe) show indications of extended hydrogen envelopes. These envelopes might be the outcome of luminous energetic pre-explosion events, so-called precursor eruptions. We use the Palomar Transient Factory (PTF) pre-explosion observations of a sample of 27 nearby SNe IIb to look for such precursors during the final years prior to the SN explosion. No precursors are found when combining the observations in 15-day bins, and we calculate the absolute-magnitude-dependent upper limit on the precursor rate. At the 90% confidence level, SNe IIb have on average <0.86 precursors as bright as an absolute R-bandmore » magnitude of −14 in the final 3.5 years before the explosion and <0.56 events over the final year. In contrast, precursors among SNe IIn have a ≳5 times higher rate. The kinetic energy required to unbind a low-mass stellar envelope is comparable to the radiated energy of a few-weeks-long precursor that would be detectable for the closest SNe in our sample. Therefore, mass ejections, if they are common in such SNe, are radiatively inefficient or have durations longer than months. Indeed, when using 60-day bins, a faint precursor candidate is detected prior to SN 2012cs (∼2% false-alarm probability). We also report the detection of the progenitor of SN 2011dh that does not show detectable variability over the final two years before the explosion. The suggested progenitor of SN 2012P is still present, and hence is likely a compact star cluster or an unrelated object.« less

Applying the polarity rapid assessment method to characterize nitrosamine precursors and to understand their removal by drinking water treatment processes.

PubMed

Liao, Xiaobin; Bei, Er; Li, Shixiang; Ouyang, Yueying; Wang, Jun; Chen, Chao; Zhang, Xiaojian; Krasner, Stuart W; Suffet, I H Mel

2015-12-15

Some N-nitrosamines (NAs) have been identified as emerging disinfection by-products during water treatment. Thus, it is essential to understand the characteristics of the NA precursors. In this study, the polarity rapid assessment method (PRAM) and the classical resin fractionation method were studied as methods to fractionate the NA precursors during drinking water treatment. The results showed that PRAM has much higher selectivity for NA precursors than the resin approach. The normalized N-nitrosodimethylamine formation potential (NDMA FP) and N-nitrosodiethylamine (NDEA) FP of four resin fractions was at the same level as the average yield of the bulk organic matter whereas that of the cationic fraction by PRAM showed 50 times the average. Thus, the cationic fraction was shown to be the most important NDMA precursor contributor. The PRAM method also helped understand which portions of the NA precursor were removed by different water treatment processes. Activated carbon (AC) adsorption removed over 90% of the non-polar PRAM fraction (that sorbs onto the C18 solid phase extraction [SPE] cartridge) of NDMA and NDEA precursors. Bio-treatment removed 80-90% of the cationic fraction of PRAM (that is retained on the cation exchange SPE cartridge) and 40-60% of the non-cationic fractions. Ozonation removed 50-60% of the non-polar PRAM fraction of NA precursors and transformed part of them into the polar fraction. Coagulation and sedimentation had very limited removal of various PRAM fractions of NA precursors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile.

PubMed

Bartoszyk, G D; Van Amsterdam, C; Greiner, H E; Rautenberg, W; Russ, H; Seyfried, C A

2004-02-01

Sarizotan exhibited high affinities only to serotonin 5-HT1A receptors and dopamine DA D4>D3>D2 receptors with the profile of a 5-HT1A agonist and DA antagonist demonstrated by the inhibition of cAMP-stimulation and guinea pig ileum contraction, decreased accumulation of the 5-HT precursor 5-hydroxytryptophan and increased levels of 5-HT metabolites, increased accumulation of DA precursor dihydroxyphenylalanine (DOPA) and the reduced levels of DA metabolites in intact rats. However, sarizotan at higher doses decreased DA precursor accumulation in reserpinized rats and induced contralateral rotational behavior in unilaterally substantia nigra lesioned rats, indicating some intrinsic dopaminergic activity; at D2 receptors sarizotan may act as a partial agonist, depending on the dopaminergic impulse flow. Sarizotan represents a new approach for the treatment of extrapyramidal motor complications such as l-DOPA-induced dyskinesia in Parkinson's disease.

Analysis and Chemistry of Novel Protein Oxidation Markers in Vivo.

PubMed

Henning, Christian; Liehr, Kristin; Girndt, Matthias; Ulrich, Christof; Glomb, Marcus A

2018-05-09

Proteins continually undergo spontaneous oxidation reactions, which lead to changes in structure and function. The quantitative assessment of protein oxidation adducts provides information on the level of exposure to reactive precursor compounds with a high oxidizing potential and reactive oxygen species (ROS). In the present work, we introduce N 6 -(2-hydroxyethyl)lysine as a novel marker based on the ratio of glycolaldehyde and its oxidized form glyoxal. The high analytical potential was proven with a first set of patients undergoing hemodialysis versus healthy controls, in comparison with well-established parameters for oxidative stress. In vitro experiments with N 1 - t-BOC-lysine and N 1 - t-BOC-arginine enlightened the mechanistic relationship of glycolaldehyde and glyoxal. Oxidation was strongly dependent on the catalytic action of the ε-amino moiety of lysine. Investigations on the formation of N 6 -carboxymethyl lysine revealed glycolaldehyde-imine as the more reactive precursor, even though an additional oxidative step is required. As a result, a novel and very effective alternative mechanism was unraveled.

Identification of a plastidial phenylalanine exporter that influences flux distribution through the phenylalanine biosynthetic network

PubMed Central

Widhalm, Joshua R.; Gutensohn, Michael; Yoo, Heejin; Adebesin, Funmilayo; Qian, Yichun; Guo, Longyun; Jaini, Rohit; Lynch, Joseph H.; McCoy, Rachel M.; Shreve, Jacob T.; Thimmapuram, Jyothi; Rhodes, David; Morgan, John A.; Dudareva, Natalia

2015-01-01

In addition to proteins, L-phenylalanine is a versatile precursor for thousands of plant metabolites. Production of phenylalanine-derived compounds is a complex multi-compartmental process using phenylalanine synthesized predominantly in plastids as precursor. The transporter(s) exporting phenylalanine from plastids, however, remains unknown. Here, a gene encoding a Petunia hybrida plastidial cationic amino-acid transporter (PhpCAT) functioning in plastidial phenylalanine export is identified based on homology to an Escherichia coli phenylalanine transporter and co-expression with phenylalanine metabolic genes. Radiolabel transport assays show that PhpCAT exports all three aromatic amino acids. PhpCAT downregulation and overexpression result in decreased and increased levels, respectively, of phenylalanine-derived volatiles, as well as phenylalanine, tyrosine and their biosynthetic intermediates. Metabolic flux analysis reveals that flux through the plastidial phenylalanine biosynthetic pathway is reduced in PhpCAT RNAi lines, suggesting that the rate of phenylalanine export from plastids contributes to regulating flux through the aromatic amino-acid network. PMID:26356302

Identification of a plastidial phenylalanine exporter that influences flux distribution through the phenylalanine biosynthetic network

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

Widhalm, Joshua R.; Gutensohn, Michael; Yoo, Heejin

In addition to proteins, L-phenylalanine is a versatile precursor for thousands of plant metabolites. Production of phenylalanine-derived compounds is a complex multi-compartmental process using phenylalanine synthesized predominantly in plastids as precursor. The transporter(s) exporting phenylalanine from plastids, however, remains unknown. Here, a gene encoding a Petunia hybrida plastidial cationic amino-acid transporter (PhpCAT) functioning in plastidial phenylalanine export is identified based on homology to an Escherichia coli phenylalanine transporter and co-expression with phenylalanine metabolic genes. Radiolabel transport assays show that PhpCAT exports all three aromatic amino acids. PhpCAT downregulation and overexpression result in decreased and increased levels, respectively, of phenylalanine-derived volatiles,more » as well as phenylalanine, tyrosine and their biosynthetic intermediates. Metabolic flux analysis reveals that flux through the plastidial phenylalanine biosynthetic pathway is reduced in PhpCAT RNAi lines, suggesting that the rate of phenylalanine export from plastids contributes to regulating flux through the aromatic amino-acid network.« less

The importance of non-quasigeostrophic forcing during the development of a blocking anticyclone

NASA Technical Reports Server (NTRS)

Tsou, Chih-Hua; Smith, Phillip J.

1990-01-01

This study examines the impact of non-quasigeostrophic (NQG) processes during the development of a blocking anticyclone (January 21, 1979 over the southern tip of Greenland) and a precursor, upstream intense cyclone (January 18, 1979). Energy quantities and height tendencies determined from quasigeostrophic estimates are compared with the same quantities obtained from more general formulations. GLA FGGE Level III-b analysis on a 4 deg lat by 5 deg long grid was used to obtain energetics results. It is concluded that NQG processes strengthened the intensity of the block and a precursor explosive cyclone and that a portion of this increase resulted from enhanced baroclinic conversion of eddy potential to eddy kinetic energy and reduced barotropic energy conversion from eddy to zonal flow. It is suggested that NQG vorticity advection, instead of moderating wave developments, enhanced the block development, and it is also suggested that QG forcing might not have been adequate to produce the observed block development.

Identification of a plastidial phenylalanine exporter that influences flux distribution through the phenylalanine biosynthetic network

DOE PAGES

Widhalm, Joshua R.; Gutensohn, Michael; Yoo, Heejin; ...

2015-09-10

In addition to proteins, L-phenylalanine is a versatile precursor for thousands of plant metabolites. Production of phenylalanine-derived compounds is a complex multi-compartmental process using phenylalanine synthesized predominantly in plastids as precursor. The transporter(s) exporting phenylalanine from plastids, however, remains unknown. Here, a gene encoding a Petunia hybrida plastidial cationic amino-acid transporter (PhpCAT) functioning in plastidial phenylalanine export is identified based on homology to an Escherichia coli phenylalanine transporter and co-expression with phenylalanine metabolic genes. Radiolabel transport assays show that PhpCAT exports all three aromatic amino acids. PhpCAT downregulation and overexpression result in decreased and increased levels, respectively, of phenylalanine-derived volatiles,more » as well as phenylalanine, tyrosine and their biosynthetic intermediates. Metabolic flux analysis reveals that flux through the plastidial phenylalanine biosynthetic pathway is reduced in PhpCAT RNAi lines, suggesting that the rate of phenylalanine export from plastids contributes to regulating flux through the aromatic amino-acid network.« less

Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse.

PubMed

Orejana, Lourdes; Barros-Miñones, Lucía; Jordan, Joaquin; Cedazo-Minguez, Angel; Tordera, Rosa M; Aguirre, Norberto; Puerta, Elena

2015-06-01

The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features of Alzheimer's disease. Cognitive impairments and increased levels of hyperphosphorylated tau are found in the hippocampus of SAMP8 mice along with an increased β-secretase activity and amyloid-β (Aβ) depositions that increase in number and extent with age. Based on a previous study from our laboratory showing an amelioration of cognitive impairments and tau pathology by sildenafil, in this study we tested whether this drug could also modulate the amyloid precursor protein amyloidogenic processing in this mouse model. Our results show that the protein levels of the β-secretases β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated learning and memory impairments shown by SAMP8 mice in the passive avoidance test. The increased expression of β-site amyloid precursor protein cleaving enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the activities of two β-site amyloid precursor protein cleaving enzyme 1 modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly, sildenafil enhanced both Akt and glycogen synthase kinase-3β (ser9) phosphorylation, which could be mediating the reduction in cathepsin B levels found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced reduction in β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B expression in SAMP8 mice was associated with a decrease in hippocampal Aβ42 levels which, in turn, could mediate the parallel decline in glial fibrillary acidic protein expression observed in these animals. These findings highlight the therapeutic potential of sildenafil in Alzheimer's disease pathogenesis. © The Author 2014. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Radiation-Induced Processing of Hydrocarbons in Environments Relevant to Pluto

DTIC Science & Technology

2001-05-07

energetic’ (characterized by high levels of electrical and geothermal activity) liquid water environment, are capable of generating significant prebiotic ...synthesis of biogenic molecules (Chyba & Sagan 1992). In this light, a potential cometary source of prebiotic organics (the precursors of biological...precursors for prebiotic molecules. This exogenous source of prebiotic organics on early Earth could provide an alternative method of accounting for

Microglia modulate hippocampal neural precursor activity in response to exercise and aging.

PubMed

Vukovic, Jana; Colditz, Michael J; Blackmore, Daniel G; Ruitenberg, Marc J; Bartlett, Perry F

2012-05-09

Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may have the ability to differentially instruct neurogenesis in the adult brain. Here, we used transgenic Csf1r-GFP mice to investigate whether hippocampal microglia directly influence the activation of neural precursor cells. Our results revealed that an exercise-induced increase in neural precursor cell activity was mediated via endogenous microglia and abolished when these cells were selectively removed from hippocampal cultures. Conversely, microglia from the hippocampi of animals that had exercised were able to activate latent neural precursor cells when added to neurosphere preparations from sedentary mice. We also investigated the role of CX(3)CL1, a chemokine that is known to provide a more neuroprotective microglial phenotype. Intraparenchymal infusion of a blocking antibody against the CX(3)CL1 receptor, CX(3)CR1, but not control IgG, dramatically reduced the neurosphere formation frequency in mice that had exercised. While an increase in soluble CX(3)CL1 was observed following running, reduced levels of this chemokine were found in the aged brain. Lower levels of CX(3)CL1 with advancing age correlated with the natural decline in neural precursor cell activity, a state that could be partially alleviated through removal of microglia. These findings provide the first direct evidence that endogenous microglia can exert a dual and opposing influence on neural precursor cell activity within the hippocampus, and that signaling through the CX(3)CL1-CX(3)CR1 axis critically contributes toward this process.

3D analysis of high ozone production rates observed during the ESCOMPTE campaign

NASA Astrophysics Data System (ADS)

Coll, Isabelle; Pinceloup, Stéphanie; Perros, Pascal E.; Laverdet, Gérard; Le Bras, Georges

2005-03-01

The development of environmental policies to reduce the ozone levels around large agglomerations requires a good understanding of the development of ozone episodes. In particular, it is necessary to know the location and photochemical activity of the plume where ozone is formed. Measurement campaigns make it possible not only to characterize the concentration fields of ozone and its precursors but also to identify the zones of strong ozone production, by means of specific measurements and kinetic calculations. The combination of the observation-based data with numerical simulations allows to better characterize photochemical pollution. This paper presents a study carried out within the ESCOMPTE program and based on the determination of ozone production rates by experimental and numerical methods: ground measurements of peroxy radicals, NO x at a rural site, airborne measurements of NO X and O 3, Eulerian modeling. The reported case is of particular interest since it corresponds to an episode with very different photochemical situations. The diurnal variations of the peroxy radical concentration are analyzed in relation to those of ozone and its precursors. Ozone production rates— P(O 3)-are studied over one particular day. The results show particularly high concentrations of RO 2+HO 2 at ground level (up to 200 pptv) under the influence of the urban and industrial plume, but also highlight very high production rates of ozone (60 to 80 ppbv h -1) a few tens of kilometers from the sources. The results show satisfactory agreement between the various approaches. Modeling provides a four-dimensional (4D) description of the plumes, in particular the relation between the ozone precursor concentrations and P(O 3) on the ground.

The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

PubMed

Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa; Bastianelli, Daniela; Maroder, Marella; Ragona, Giuseppe; Roussel, Pascal; Thiry, Marc; Mercola, Dan; Calogero, Antonella

2014-01-01

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

Effect of Temperature, Precursor Type and Dripping Time on the Crystallite Size of Nano ZnO Obtained by One-Pot Synthesis: 2 k Full Factorial Design Analysis.

PubMed

Machado, Morgana de Medeiros; Savi, Bruna Martinello; Perucchi, Mariana Borges; Benedetti, Alessandro; Oliveira, Luis Felipe Silva; Bernardin, Adriano Michael

2018-06-01

The aim of this work was to determine the effect of temperature, precursor and dripping time on the crystallite size of ZnO nanoparticles synthesized by controlled precipitation according a 2k full factorial design. ZnCl2, Zn(NO3)2 and NaOH were used as precursors. After synthesis, the nano crystalline powder was characterized by XRD (Cu Kα), UV-Vis, and HR-TEM. The nano ZnO particles presented a crystallite size between 210 and 260 Å (HR-TEM and XRD). The results show that the crystallite size depends on the type of precursor and temperature of synthesis, but not on the dripping time.

Increasing CNS norepinephrine levels by the precursor L-DOPS facilitates beam-walking recovery after sensorimotor cortex ablation in rats.

PubMed

Kikuchi, K; Nishino, K; Ohyu, H

2000-03-31

The present investigation was conducted to document a role of L-threo-3,4-dihydroxyphenylserine (L-DOPS), precursor of L-norepinephrine (NE), in the functional recovery from beam-walking performance deficits in rats after unilateral sensorimotor cortex ablation. L-DOPS was administered simultaneously with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor), and the regional contents of NE in the cerebral cortex, hippocampus, and cerebellum were assayed. Behavioral recovery was demonstrated by the rats treated with L-DOPS and BSZ, and the rate of recovery was significantly different from that of either BSZ-treated or vehicle-treated control rats. The NE tissue levels in the three discrete regions of the rat brain were significantly elevated in the experimental rats receiving both L-DOPS and BSZ. The present studies indicate that increasing NE levels by the precursor L-DOPS may be responsible for facilitating behavioral recovery from beam-walking performance deficits in rats, and further suggest that L-DOPS may become one of the candidate compounds for further clinical human trials promoting functional recovery after injuries to the cerebral cortex.

Stoichiometry for binding and transport by the twin arginine translocation system.

PubMed

Celedon, Jose M; Cline, Kenneth

2012-05-14

Twin arginine translocation (Tat) systems transport large folded proteins across sealed membranes. Tat systems accomplish this feat with three membrane components organized in two complexes. In thylakoid membranes, cpTatC and Hcf106 comprise a large receptor complex containing an estimated eight cpTatC-Hcf106 pairs. Protein transport occurs when Tha4 joins the receptor complex as an oligomer of uncertain size that is thought to form the protein-conducting structure. Here, binding analyses with intact membranes or purified complexes indicate that each receptor complex could bind eight precursor proteins. Kinetic analysis of translocation showed that each precursor-bound site was independently functional for transport, and, with sufficient Tha4, all sites were concurrently active for transport. Tha4 titration determined that ∼26 Tha4 protomers were required for transport of each OE17 (oxygen-evolving complex subunit of 17 kD) precursor protein. Our results suggest that, when fully saturated with precursor proteins and Tha4, the Tat translocase is an ∼2.2-megadalton complex that can individually transport eight precursor proteins or cooperatively transport multimeric precursors.

Can Ni phosphides become viable hydroprocessing catalysts?

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

Soled, S.; Miseo, S.; Baumgartner, J.

2015-05-15

We prepared higher surface area nickel phosphides than are normally found by reducing nickel phosphate. To do this, we hydrothermally synthesized Ni hydroxy phosphite precursors with low levels of molybdenum substitution. The molybdenum substitution increases the surface area of these precursors. During pretreatment in a sulfiding atmosphere (such as H2S/H2) dispersed islands of MoS2 segregate from the precursor and provide a pathway for H2 dissociation that allows reduction of the phosphite precursor to nickel phosphide at substantially lower temperatures than in the absence of MoS2. The results reported here show that to create nickel phosphides with comparable activity to conventionalmore » supported sulfide catalysts, one would have to synthesize the phosphide with surface areas exceeding 400 m2/g (i.e. with nanoparticles less than 30 Å in lateral dimension).« less

An ozone episode over the Pearl River Delta in October 2008

NASA Astrophysics Data System (ADS)

Shen, Jin; Zhang, Yuanhang; Wang, Xuesong; Li, Jinfeng; Chen, Hao; Liu, Run; Zhong, Liuju; Jiang, Ming; Yue, Dingli; Chen, Duohong; Lv, Wei

2015-12-01

The north and east Pearl River Delta (PRD) is usually a clean, upwind area in autumn. Serious ozone pollution there in mid-late October 2008 was first discovered and then analyzed. Trajectory analysis, process analysis, ozone source apportionment technology, and sensitivity analysis were used to study this episode. Under the influence of a weak south wind, the precursors emitted in Guangzhou and Foshan were transported to the north and northeast PRD and formed ozone there, which resulted in high ozone concentration (>100 ppb). As the wind direction later transited to northerly, the precursors in the northeast PRD that originated from the central and west PRD were transported to the south, and caused severe ozone pollution in the southeast PRD. The ozone contributed by chemical processes reached >20 ppb/h in Jinguowan. More than 40 ppb ozone was contributed by the precursor emission in the central and west PRD during the episode. The ozone concentration was highly sensitive to the precursor emission in the PRD region in the high-ozone situations. This episode showed the complexity of regional pollution in the PRD. When the PRD is controlled by a low air pressure system and then cold air moves from northern China to the south, the risk of ozone pollution in the north and southeast PRD increases.

Discovery and characterization of miRNA genes in atlantic salmon (Salmo salar) by use of a deep sequencing approach

PubMed Central

2013-01-01

Background MicroRNAs (miRNAs) are an abundant class of endogenous small RNA molecules that downregulate gene expression at the posttranscriptional level. They play important roles in multiple biological processes by regulating genes that control developmental timing, growth, stem cell division and apoptosis by binding to the mRNA of target genes. Despite the position Atlantic salmon (Salmo salar) has as an economically important domesticated animal, there has been little research on miRNAs in this species. Knowledge about miRNAs and their target genes may be used to control health and to improve performance of economically important traits. However, before their biological function can be unravelled they must be identified and annotated. The aims of this study were to identify and characterize miRNA genes in Atlantic salmon by deep sequencing analysis of small RNA libraries from nine different tissues. Results A total of 180 distinct mature miRNAs belonging to 106 families of evolutionary conserved miRNAs, and 13 distinct novel mature miRNAs were discovered and characterized. The mature miRNAs corresponded to 521 putative precursor sequences located at unique genome locations. About 40% of these precursors were part of gene clusters, and the majority of the Salmo salar gene clusters discovered were conserved across species. Comparison of expression levels in samples from different tissues applying DESeq indicated that there were tissue specific expression differences in three conserved and one novel miRNA. Ssa-miR 736 was detected in heart tissue only, while two other clustered miRNAs (ssa-miR 212 and132) seems to be at a higher expression level in brain tissue. These observations correlate well with their expected functions as regulators of signal pathways in cardiac and neuronal cells, respectively. Ssa-miR 8163 is one of the novel miRNAs discovered and its function remains unknown. However, differential expression analysis using DESeq suggests that this miRNA is enriched in liver tissue and the precursor was mapped to intron 7 of the transferrin gene. Conclusions The identification and annotation of evolutionary conserved and novel Salmo salar miRNAs as well as the characterization of miRNA gene clusters provide biological knowledge that will greatly facilitate further functional studies on miRNAs in this species. PMID:23865519

Analysis of Novel Prostate Cancer Biomarkers and their Predictive Utility in an Active Surveillance Protocol

DTIC Science & Technology

2014-05-01

Shock Protein, Annexin A3, Sorbitol Dehydrogenase, Fibrinogen Beta Chain Precursor, Creatine Kinase B-Type, Annexin A1, Cystatin B, and AZI. We have...Shock Protein, Annexin A3, Sorbitol Dehydrogenase, Fibrinogen Beta Chain Precursor, and Creatine Kinase B-Type. After testing these candidates with

Mechanically activated synthesis of PZT and its electromechanical properties

NASA Astrophysics Data System (ADS)

Liu, X.; Akdogan, E. K.; Safari, A.; Riman, R. E.

2005-08-01

Mechanical activation was successfully used to synthesize nanostructured phase-pure Pb(Zr0.7Ti0.3)O3 (PZT) powders. Lead zirconium titanium (PbZrTi) hydrous oxide precursor, synthesized from chemical co-precipitation, was mechanically activated in a NaCl matrix. The synthesized PZT particles were characterized by using X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, laser-light diffraction, and nitrogen adsorption. Thermogravimetric analysis and differential thermal analysis were used to monitor dehydration and phase transformation of PbZrTi hydrous oxide precursor during mechanical activation. The best mechanical activation conditions corresponded to mechanically activating PbZrTi hydrous oxide precursor in a NaCl matrix with a NaCl/precursor weight ratio of 4:1 for 8 h. These conditions resulted in a dispersible phase-pure PZT powder with a median secondary-particle size of ˜110 nm. The properties of PZT 70/30 from mechanically activated powder, as measured on discs sintered at 1150 °C for 2 h, were found to be in close conformity to those obtained by a conventional mixed oxide solid state reaction route.

Natural Organochlorines as Precursors of 3-Monochloropropanediol Esters in Vegetable Oils.

PubMed

Tiong, Soon Huat; Saparin, Norliza; Teh, Huey Fang; Ng, Theresa Lee Mei; Md Zain, Mohd Zairey Bin; Neoh, Bee Keat; Md Noor, Ahmadilfitri; Tan, Chin Ping; Lai, Oi Ming; Appleton, David Ross

2018-01-31

During high-temperature refining of vegetable oils, 3-monochloropropanediol (3-MCPD) esters, possible carcinogens, are formed from acylglycerol in the presence of a chlorine source. To investigate organochlorine compounds in vegetable oils as possible precursors for 3-MCPD esters, we tested crude palm, soybean, rapeseed, sunflower, corn, coconut, and olive oils for the presence of organochlorine compounds. Having found them in all vegetable oils tested, we focused subsequent study on oil palm products. Analysis of the chlorine isotope mass pattern exhibited in high-resolution mass spectrometry enabled organochlorine compound identification in crude palm oils as constituents of wax esters, fatty acid, diacylglycerols, and sphingolipids, which are produced endogenously in oil palm mesocarp throughout ripening. Analysis of thermal decomposition and changes during refining suggested that these naturally present organochlorine compounds in palm oils and perhaps in other vegetable oils are precursors of 3-MCPD esters. Enrichment and dose-response showed a linear relationship to 3-MCPD ester formation and indicated that the sphingolipid-based organochlorine compounds are the most active precursors of 3-MCPD esters.

A survey on levels and seasonal changes of assimilable organic carbon (AOC) and its precursors in drinking water.

PubMed

Ohkouchi, Yumiko; Ly, Bich Thuy; Ishikawa, Suguru; Aoki, Yusuke; Echigo, Shinya; Itoh, Sadahiko

2011-10-01

In Japan, customers' concerns about chlorinous odour in drinking water have been increasing. One promising approach for reducing chlorinous odour is the minimization of residual chlorine in water distribution, which requires stricter control of organics to maintain biological stability in water supply systems. In this investigation, the levels and seasonal changes of assimilable organic carbon (AOC) and its precursors in drinking water were surveyed to accumulate information on organics in terms of biological stability. In tap water samples purified through rapid sand filtration processes, the average AOC concentration was 174 microgC/L in winter and 60 microgC/L in summer. This difference seemed to reflect the seasonal changes of AOC in the natural aquatic environment. On the other hand, very little or no AOC could be removed after use of an ozonation-biological activated carbon (BAC) process. Especially in winter, waterworks should pay attention to BAC operating conditions to improve AOC removal. The storage of BAC effluent with residual chlorine at 0.05-0.15 mgCl2/L increased AOC drastically. This result indicated the possibility that abundant AOC precursors remaining in the finished water could contribute to newly AOC formation during water distribution with minimized residual chlorine. Combined amino acids, which remained at roughly equivalent to AOC in finished water, were identified as major AOC precursors. Prior to minimization of residual chlorine, enhancement of the removal abilities for both AOC and its precursors would be necessary.

FGF-2 and Anosmin-1 are selectively expressed in different types of multiple sclerosis lesions.

PubMed

Clemente, Diego; Ortega, María Cristina; Arenzana, Francisco Javier; de Castro, Fernando

2011-10-19

Multiple sclerosis is a demyelinating disease that affects ≈ 2,000,000 people worldwide. In the advanced stages of the disease, endogenous oligodendrocyte precursors cannot colonize the lesions or differentiate into myelinating oligodendrocytes. During development, both FGF-2 and Anosmin-1 participate in oligodendrocyte precursor cell migration, acting via the FGF receptor 1 (FGFR1). Hence, we performed a histopathological and molecular analysis of these developmental modulators in postmortem tissue blocks from multiple sclerosis patients. Accordingly, we demonstrate that the distribution of FGF-2 and Anosmin-1 varies between the different types of multiple sclerosis lesions: FGF-2 is expressed only within active lesions and in the periplaque of chronic lesions, whereas Anosmin-1 is upregulated within chronic lesions and is totally absent in active lesions. We show that the endogenous oligodendrocyte precursor cells recruited toward chronic-active lesions express FGFR1, possibly in response to the FGF-2 produced by microglial cells in the periplaque. Also in human tissue, FGF-2 is upregulated in perivascular astrocytes in regions of the normal-appearing gray matter, where the integrity of the blood-brain barrier is compromised. In culture, FGF-2 and Anosmin-1 influence adult mouse oligodendrocyte precursor cell migration in the same manner as at embryonic stages, providing an explanation for the histopathological observations: FGF-2 attracts/enhances its migration, which is hindered by Anosmin-1. We propose that FGF-2 and Anosmin-1 are markers for the histopathological type and the level of inflammation of multiple sclerosis lesions, and that they may serve as novel pharmacogenetic targets to design future therapies that favor effective remyelination and protect the blood-brain barrier.

Simultaneous Measurement of Thirteen Steroid Hormones in Women with Polycystic Ovary Syndrome and Control Women Using Liquid Chromatography-Tandem Mass Spectrometry

PubMed Central

Zhang, Ke; Clarke, Nigel; Welt, Corrine K.

2014-01-01

Background The measurement of adrenal and ovarian androgens in women with PCOS has been difficult based on poor specificity and sensitivity of assays in the female range. Methods Women with PCOS (NIH criteria; n = 52) and control subjects with 25–35 day menstrual cycles, no evidence of hyperandrogenism and matched for BMI (n = 42) underwent morning blood sampling. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to simultaneously measure 13 steroids from a single blood sample to measure adrenal and ovarian steroids. Androgen and progesterone results were compared in the same samples using RIA. Results Testosterone, androstenedione, progesterone and 17OH progesterone levels were higher when measured using RIA compared to LC-MS/MS, although the testosterone RIA demonstrated the best agreement with the LC-MS/MS using a Bland-Altman analysis. Results using LC-MS/MS demonstrated that the concentration of androgens and their precursors were higher in women with PCOS than controls [median (2.5, 97.5th %ile); 1607 (638, 3085) vs. 1143 (511, 4784) ng/dL; p = 0.03]. Women with PCOS had higher testosterone [49 (16, 125) vs. 24 (10, 59) ng/dL], androstenedione [203 (98, 476) vs. 106 (69, 223) ng/dL] and 17OH progesterone levels [80 (17, 176) vs. 44 (17, 142) ng/dL] compared to controls (all P<0.02), but no differences in serum concentrations of the adrenal steroids DHEAS, cortisol, corticosterone and their 11 deoxy precursors. Women with PCOS also had an increase in the product:precursor ratio for 3β-hydroxysteroid dehydrogenase [22% (6, 92) vs. 20% (4, 43); p = 0.009]. Conclusion LC-MS/MS was superior to RIA in measuring androstenedione, progesterone and 17OH progesterone levels, while testosterone measurements were better matched in the two assays. Androgen levels were higher in women with PCOS in the absence of a difference in adrenal-predominant steroids. These data support previous findings that the ovary is an important source for the androgen excess in women with PCOS. PMID:24713888

A phase coherence approach to identifying co-located earthquakes and tremor

NASA Astrophysics Data System (ADS)

Hawthorne, J. C.; Ampuero, J.-P.

2018-05-01

We present and use a phase coherence approach to identify seismic signals that have similar path effects but different source time functions: co-located earthquakes and tremor. The method used is a phase coherence-based implementation of empirical matched field processing, modified to suit tremor analysis. It works by comparing the frequency-domain phases of waveforms generated by two sources recorded at multiple stations. We first cross-correlate the records of the two sources at a single station. If the sources are co-located, this cross-correlation eliminates the phases of the Green's function. It leaves the relative phases of the source time functions, which should be the same across all stations so long as the spatial extent of the sources are small compared with the seismic wavelength. We therefore search for cross-correlation phases that are consistent across stations as an indication of co-located sources. We also introduce a method to obtain relative locations between the two sources, based on back-projection of interstation phase coherence. We apply this technique to analyse two tremor-like signals that are thought to be composed of a number of earthquakes. First, we analyse a 20 s long seismic precursor to a M 3.9 earthquake in central Alaska. The analysis locates the precursor to within 2 km of the mainshock, and it identifies several bursts of energy—potentially foreshocks or groups of foreshocks—within the precursor. Second, we examine several minutes of volcanic tremor prior to an eruption at Redoubt Volcano. We confirm that the tremor source is located close to repeating earthquakes identified earlier in the tremor sequence. The amplitude of the tremor diminishes about 30 s before the eruption, but the phase coherence results suggest that the tremor may persist at some level through this final interval.

Theoretical modeling of the urinary supersaturation of calcium salts in healthy individuals and kidney stone patients: Precursors, speciation and therapeutic protocols for decreasing its value

NASA Astrophysics Data System (ADS)

Rodgers, Allen L.; Allie-Hamdulay, Shameez; Jackson, Graham E.; Durbach, Ian

2013-11-01

BackgroundSupersaturation (SS) of urinary salts has been extensively invoked for assessing the risk of renal stone formation, but precursors have often been ignored. Our objectives were to establish by computer modeling, which urinary components are essential for calculating reliable SS values, to investigate whether unique equilibrium processes occur in the urine of stone formers (SF) which might account for their higher SS levels relative to healthy controls (N), to determine the relative efficacies of three different, widely-used protocols for lowering urinary SS of calcium salts and to examine the influence of precursors.

Quality degradation: Implications for DBP formation

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

Krasner, S.W.; Sclimenti, M.J.; Means, E.G.

1994-06-01

During development of the draft Disinfectants-Disinfection By-products (D-DBP) Rule, the issue of watershed management for DBP precursor control was discussed but not included in the rule. This article focuses on a major California watershed, describing examples of the types of studies that utilities can use to determine precursor sources and develop solutions for control. In addition, a chlorination and ozonation study of a five-by-five matrix of total organic carbon and bromide levels--which spanned a wide range of concentrations that can be expected in many US waters--provided insights into the effects of organic and inorganic precursors and disinfectants in DBP formation.

Functional characterization of a second pedal peptide/orcokinin‐type neuropeptide signaling system in the starfish Asterias rubens

PubMed Central

Lin, Ming; Egertová, Michaela; Zampronio, Cleidiane G.; Jones, Alexandra M.

2017-01-01

Abstract Molluscan pedal peptides (PPs) and arthropod orcokinins (OKs) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK‐type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK‐type precursors: an SMP‐type precursor (A. rubens PP‐like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2). We reported previously a detailed analysis of ArPPLNP1 expression in A. rubens and here we report the first functional characterization ArPPLNP2‐derived neuropeptides. Sequencing of a cDNA encoding ArPPLNP2 revealed that it comprises eleven related neuropeptides (ArPPLN2a‐k), the structures of several of which were confirmed using mass spectrometry. Analysis of the expression of ArPPLNP2 and neuropeptides derived from this precursor using mRNA in situ hybridization and immunohistochemistry revealed a widespread distribution, including expression in radial nerve cords, circumoral nerve ring, digestive system, tube feet and innervation of interossicular muscles. In vitro pharmacology revealed that the ArPPLNP2‐derived neuropeptide ArPPLN2h has no effect on the contractility of tube feet or the body wall‐associated apical muscle, contrasting with the relaxing effect of ArPPLN1b (ArSMP) on these preparations. ArPPLN2h does, however, cause dose‐dependent relaxation of cardiac stomach preparations, with greater potency/efficacy than ArPPLN1b and with similar potency/efficacy to the SALMFamide neuropeptide S2. In conclusion, there are similarities in the expression patterns of ArPPLNP1 and ArPPLNP2 but our data also indicate specialization in the roles of neuropeptides derived from these two PP/OK‐type precursors in starfish. PMID:29218721

Functional characterization of a second pedal peptide/orcokinin-type neuropeptide signaling system in the starfish Asterias rubens.

PubMed

Lin, Ming; Egertová, Michaela; Zampronio, Cleidiane G; Jones, Alexandra M; Elphick, Maurice R

2018-04-01

Molluscan pedal peptides (PPs) and arthropod orcokinins (OKs) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK-type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK-type precursors: an SMP-type precursor (A. rubens PP-like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2). We reported previously a detailed analysis of ArPPLNP1 expression in A. rubens and here we report the first functional characterization ArPPLNP2-derived neuropeptides. Sequencing of a cDNA encoding ArPPLNP2 revealed that it comprises eleven related neuropeptides (ArPPLN2a-k), the structures of several of which were confirmed using mass spectrometry. Analysis of the expression of ArPPLNP2 and neuropeptides derived from this precursor using mRNA in situ hybridization and immunohistochemistry revealed a widespread distribution, including expression in radial nerve cords, circumoral nerve ring, digestive system, tube feet and innervation of interossicular muscles. In vitro pharmacology revealed that the ArPPLNP2-derived neuropeptide ArPPLN2h has no effect on the contractility of tube feet or the body wall-associated apical muscle, contrasting with the relaxing effect of ArPPLN1b (ArSMP) on these preparations. ArPPLN2h does, however, cause dose-dependent relaxation of cardiac stomach preparations, with greater potency/efficacy than ArPPLN1b and with similar potency/efficacy to the SALMFamide neuropeptide S2. In conclusion, there are similarities in the expression patterns of ArPPLNP1 and ArPPLNP2 but our data also indicate specialization in the roles of neuropeptides derived from these two PP/OK-type precursors in starfish. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Investigation of relationship between precursor of miRNA-944 and its mature form in lung squamous-cell carcinoma - the diagnostic value.

PubMed

Powrózek, Tomasz; Mlak, Radosław; Dziedzic, Marcin; Małecka-Massalska, Teresa; Sagan, Dariusz

2018-03-01

MicroRNA (miRNA) are attractive markers of lung cancer, due to their regulatory role in cell cycle. However, we know more about function of miRNA in cancer development, there is still little known about role of their precursors (primary miRNA; pri-miRNA) in tumorgenesis. In present study we investigated potential role of miRNA-944 and its precursor pri-miRNA-944 in development of squamous-cell lung cancer (SCC) and explored interdependence between miRNA precursor and its mature form. This is a first available literature report analyzing pri-miRNA as a cancer diagnostic marker. Expression of miRNA-944 and its precursor was analyzed in 58 fresh-frozen tissues of non-small cell lung cancer and corresponding adjacent non-cancerous tissues using qRT-PCR. Expression of pri-miRNA-944 was correlated with TP63 and miRNA-944. Using ROC analysis diagnostic accuracy of studied markers was evaluated. miRNA-944 and its precursor were significantly overexspressed in SCC compared to adenocarcinoma (AC) and non-cancerous tissue. pri-miRNA-944 strongly and positively correlated with TP63 (r = 0.739, p < 0.001) and with mature miRNA-944 expression (r = 0.691, p < 0.001). Also, TP63 expression significantly correlated with mature miRNA (r = 0.785, p < 0.001). Combined analysis of pri-miRNA-944 and mature miRNA-944 allowed to distinguish SCC tissue form AC with sensitivity of 93.3% and specificity of 100% (AUC = 0.978), and SCC from non-cancerous tissue with 92.9% sensitivity and 100% specificity (AUC = 0.992). We assumed that pri-miRNA-944 and miRNA-944 may be involved in early squamous-type differentiation of lung tumors. Moreover, analysis of both markers provided high diagnostic accuracy for SCC detection. Copyright © 2018 Elsevier GmbH. All rights reserved.

The Role of the Progressive Ankylosis Protein (ANK) in Adipogenic/Osteogenic Fate Decision of Precursor Cells

PubMed Central

Minashima, Takeshi; Quirno, Martin; Lee, You Jin; Kirsch, Thorsten

2017-01-01

The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu. In this study we show increased fatty degeneration of the bone marrow of adult ank/ank mice, which lack a functional ANK protein. In addition, isolated bone marrow stromal cells (BMSCs) isolated from ank/ank mice showed a decreased proliferation rate and osteogenic differentiation potential, and an increased adipogenic differentiation potential compared to BMSCs isolated from wild type (WT) littermates. Wnt signaling pathway PCR array analysis revealed that Wnt ligands, Wnt receptors and Wnt signaling proteins that stimulate osteoblast differentiation were expressed at markedly lower levels in ank/ank BMSCs than in WT BMSCs. Lack of ANK function also resulted in impaired bone fracture healing, as indicated by a smaller callus formed and delayed bone formation in the callus site. Whereas 5 weeks after fracture, the fractured bone in WT mice was further remodeled and restored to original shape, the fractured bone in ank/ank mice was not fully restored and remodeled to original shape. In conclusion, our study provides evidence that ANK plays a critical role in the adipogenic/osteogenic fate decision of adult mesenchymal precursor cells. ANK functions in precursor cells are required for osteogenic differentiation of these cells during adult bone homeostasis and repair, whereas lack of ANK functions favors adipogenic differentiation. PMID:28286238

Using Groundwater physiochemical properties for assessing potential earthquake precursor

NASA Astrophysics Data System (ADS)

Inbar, Nimrod; Reuveni, Yuval; Anker, Yaakov; Guttman, Joseph

2017-04-01

Worldwide studies reports pre-seismic, co-seismic and post-seismic reaction of groundwater to earthquakes. The unique hydrological and geological situation in Israel resulted in relatively deep water wells which are located close to seismically active tectonic plate boundary. Moreover, the Israeli experience show that anomalies may occurs 60-90 minutes prior to the seismic event (Guttman et al., 2005; Anker et al., 2016). Here, we try to assess the possible connection between changes in physiochemical parameters of groundwater and earthquakes along the Dead Sea Transform (DST) region. A designated network of monitoring stations was installed in MEKOROT abandoned deep water wells, continuously measuring water table, conductivity and temperature at a sampling rate of 1 minute. Preliminary analysis compares changes in the measured parameters with rain events, tidal effects and earthquake occurrences of all measured magnitudes (>2.5Md) at monitoring area surroundings. The acquired data set over one year recorded simultaneous abrupt changes in several wells which seems disconnected from standard hydrological occurrences such as precipitation, abstraction or tidal effects. At this stage, our research aims to determine and rationalize a baseline for "normal response" of the measured parameters to external occurrences while isolating those cases in which "deviations" from that base line is recorded. We apply several analysis techniques both in time and frequency domain with the measured signal as well as statistical analysis of several measured earthquake parameters, which indicate potential correlations between earthquakes occurrences and the measured signal. We show that at least in one seismic event (5.1 Md) a potential precursor may have been recorded. Reference: Anker, Y., N. Inbar, A. Y. Dror, Y. Reuveni, J. Guttman, A. Flexer, (2016). Groundwater response to ground movements, as a tool for earthquakes monitoring and a possible precursor. 8th International Conference on Urban Planning and Transportation. Guttman, J., Flexer, A. & Yellin-Dror, A. (2005). Water level changes in wells - a predictor for earthquakes? IAHS Publ. Vol. 303, pp. 1-5.

Search for compounds contributing to onion-like off-flavor in beer and investigation of the cause of the flavor.

PubMed

Noba, Shigekuni; Yako, Nana; Kobayashi, Minoru; Masuda, Susumu; Watanabe, Tetsuya

2017-10-01

Onion-like off-flavor is a highly undesirable property in beer. Although several compounds that impart onion-like odors have been identified, the individual contribution of these compounds to the onion-like off-flavor in beer is not clear. In the present study, we searched for compounds that impart an onion-like odor by gas chromatography (GC)-olfactometry. The analysis of several types of beer revealed that 2-mercapto-3-methyl-1-butanol (2M3MB) and 3-mercapto-3-methyl-1-butanol (3M3MB) were possible causative compounds. Based on the difference threshold values in beer (0.13 ng/mL for 2M3MB and 17.5 ng/mL for 3M3MB) and the quantification values of these compounds in beer samples, only 2M3MB was considered to contribute to the onion-like off-flavor in beer. A further formation factor analysis of 2M3MB revealed that 2M3MB was formed in hopped wort after fermentation, and that the concentration of 2M3MB increased following the hot aeration treatment of wort. These results suggest that preventing the hot aeration of wort is a key factor for reducing 2M3MB levels in beer. In a previous report, 3-methyl-2-buten-1-ol (3MBol) was speculated to be the precursor of 2M3MB and 3M3MB; however, the results of the present quantification analysis and wort addition tests indicate that 3MBol did not contribute to the formation of 2M3MB in the brewing process and that unknown precursors of 2M3MB originated in wort. Identifying the precursor of 2M3MB may facilitate elucidation of the mechanism of 2M3MB formation. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Annealing of aromatic polyimide precursors

NASA Technical Reports Server (NTRS)

Wakelyn, N. T.

1975-01-01

A study has been made of the thermal behavior of polyimide precursors: an isomeric pair of crystals of the complex formed by p-phenylenediamine with the separated isomers of the di-isopropyl ester of pyromellitic acid. Specimens of this material were isothermally annealed in the temperature range 120 C to 170 C for periods of time up to 1 week. Although this temperature range is well below that customarily used for imidizations, the working hypothesis was that it would be more likely that a polymer embodying at least part of the precursor structure could be formed if the molecular motion was minimized to that actually required for the formation of the imide linkage. The progress of the annealing was followed by: infrared spectroscopy, differential thermal analysis, powder X-ray diffraction, and thermal gravimetric analysis. Single crystal X-ray analysis of the meta monomer yields a structure of chains of alternating acid and base and suggests that this monomer is amenable to polymerization with a minimum of geometrical disruption.

Four residues of propeptide are essential for precursor folding of nattokinase.

PubMed

Jia, Yan; Cao, Xinhua; Deng, Yu; Bao, Wei; Tang, Changyan; Ding, Hanjing; Zheng, Zhongliang; Zou, Guolin

2014-11-01

Subtilisin propeptide functions as an intramolecular chaperone that guides precursor folding. Nattokinase, a member of subtilisin family, is synthesized as a precursor consisting of a signal peptide, a propeptide, and a subtilisin domain, and the mechanism of its folding remains to be understood. In this study, the essential residues of nattokinase propeptide which contribute to precursor folding were determined. Deletion analysis showed that the conserved regions in propeptide were important for precursor folding. Single-site and multi-site mutagenesis studies confirmed the role of Tyr10, Gly13, Gly34, and Gly35. During stage (i) and (ii) of precursor folding, Tyr10 and Gly13 would form the part of interface with subtilisin domain. While Gly34 and Gly35 connected with an α-helix that would stabilize the structure of propeptide. The quadruple Ala mutation, Y10A/G13A/G34A/G35A, resulted in a loss of the chaperone function for the propeptide. This work showed the essential residues of propeptide for precursor folding via secondary structure and kinetic parameter analyses. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Tropospheric ozone using an emission tagging technique in the CAM-Chem and WRF-Chem models

NASA Astrophysics Data System (ADS)

Lupascu, A.; Coates, J.; Zhu, S.; Butler, T. M.

2017-12-01

Tropospheric ozone is a short-lived climate forcing pollutant. High concentration of ozone can affect human health (cardiorespiratory and increased mortality due to long-term exposure), and also it damages crops. Attributing ozone concentrations to the contributions from different sources would indicate the effects of locally emitted or transported precursors on ozone levels in specific regions. This information could be used as an important component of the design of emissions reduction strategies by indicating which emission sources could be targeted for effective reductions, thus reducing the burden of ozone pollution. Using a "tagging" approach within the CAM-Chem (global) and WRF-Chem (regional) models, we can quantify the contribution of individual emission of NOx and VOC precursors on air quality. Hence, when precursor emissions of NOx are tagged, we have seen that the largest contributors on ozone levels are the anthropogenic sources, while in the case of precursor emissions of VOCs, the biogenic sources and methane account for more than 50% of ozone levels. Further, we have extended the NOx tagging method in order to investigate continental source region contributions to concentrations of ozone over various receptor regions over the globe, with a zoom over Europe. In general, summertime maximum ozone in most receptor regions is largely attributable to local emissions of anthropogenic NOx and biogenic VOC. During the rest of the year, especially during springtime, ozone in most receptor regions shows stronger influences from anthropogenic emissions of NOx and VOC in remote source regions.

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor.

PubMed

Fernández-Del-Río, Lucía; Nag, Anish; Gutiérrez Casado, Elena; Ariza, Julia; Awad, Agape M; Joseph, Akil I; Kwon, Ohyun; Verdin, Eric; de Cabo, Rafael; Schneider, Claus; Torres, Jorge Z; Burón, María I; Clarke, Catherine F; Villalba, José M

2017-09-01

Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q 10 , but due to its highly lipophilic nature, Q 10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13 C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4' of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in springtime tropospheric ozone at Mt. Happo from 1998 to 2016, linked to Asian emissions and North Pacific climate

NASA Astrophysics Data System (ADS)

Okamoto, S.; Tanimoto, H.; Hirota, N.; Ikeda, K.; Akimoto, H.

2017-12-01

During the past decades, springtime ozone concentrations in the downwind regions of East Asia have rapidly increased with the increase of anthropogenic emissions. However, recent several studies based on the analysis of satellite tropospheric nitrogen dioxides data inferred possible peaking out of nitrogen oxides emissions in China. In addition to the precursor emissions, climate plays an important role in controlling the variations and distributions of tropospheric ozone. Here we revisited and updated the long-term trend of tropospheric ozone at Mt. Happo, Japan, for the period from 1998 to 2016. Since 1998 the springtime ozone concentration has shown a large increase until 2007, very likely caused by the increase in the emissions of ozone precursors associated with economic growth in eastern China, as evidenced from satellite observations of nitrogen dioxides. After the monotonic increase until 2007, the ozone level has been flattened associated with substantial drop in 2008. Recent low ozone levels were largely influenced by the decrease of the anthropogenic emissions from eastern China. We also found that the efficiency of long-range transport from central eastern China, driven by North Pacific climate, play a role in modulating the year-to-year variations of ozone at Mt. Happo.

LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.

PubMed

Barker, Steven A; Borjigin, Jimo; Lomnicka, Izabela; Strassman, Rick

2013-12-01

We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat. Copyright © 2013 John Wiley & Sons, Ltd.

Absence of TERT promoter mutations in colorectal precursor lesions and cancer

PubMed Central

Cruvinel-Carloni, Adriana; Yamane, Letícia; Scapulatempo-Neto, Cristovam; Guimarães, Denise; Reis, Rui Manuel

2018-01-01

Abstract Hotspot mutations (c.-124bp G > A and c.-146bp G > A) in the promoter region of the TERT gene have been recently described in several types of solid tumors, including glioma, bladder, thyroid, liver and skin neoplasms. However, knowledge with respect to colorectal precursor lesions and cancer is scarce. In the present study we aimed to determine the frequency of hotspot TERT promoter mutations in 145 Brazilian patients, including 103 subjects with precursor lesions and 42 with colorectal carcinomas, and we associated the presence of such mutations with the patients clinical-pathological features. The mutation analysis was conclusive in 123 cases, and none of the precursor and colorectal carcinoma cases showed TERT promoter mutations. We conclude that TERT mutations are not a driving factor in colorectal carcinogenesis. PMID:29473934

2-Hydroxyethyl substituted NHC precursors: Synthesis, characterization, crystal structure and carbonic anhydrase, α-glycosidase, butyrylcholinesterase, and acetylcholinesterase inhibitory properties

NASA Astrophysics Data System (ADS)

Erdemir, Fatoş; Barut Celepci, Duygu; Aktaş, Aydın; Taslimi, Parham; Gök, Yetkin; Karabıyık, Hasan; Gülçin, İlhami

2018-03-01

This study contains novel a serie synthesis of N-heterocyclic carbene (NHC) precursors that 2-hydroxyethyl substituted. The NHC precursors have been prepared from 1-(2- hydroxyethyl)benzimidazole and alkyl halides. The novel NHC precursors have been characterized by using 1H NMR, 13C NMR, FTIR spectroscopy and elemental analysis techniques. Molecular and crystal structures of 2a, 2d, 2e, 2f and 2g were obtained with single-crystal X-ray diffraction studies. These novel NHC precursor's derivatives effectively inhibited the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Inhibition constant (Ki) were found in the range of 0.30-9.22 nM for α-glycosidase, 13.90-41.46 nM for hCA I, 12.82-49.95 nM for hCA II, 145.82-882.01 nM for BChE, and 280.92-1370.01 nM for AChE, respectively.

Thermal Studies of New Precursors to Indium-tin Oxides for Use as Sensor Materials in the Detection of NO(x)

NASA Technical Reports Server (NTRS)

Goldsby, J. C.; Kacik, T.; Hockensmith, C. M.

1999-01-01

Control of combustion product emissions in both sub and super-sonic jet engines can be facilitated by measurement of NO(x) levels with metal oxide sensors, In2O3, metal-doped SnO2, and SnO, (as well as other materials) show resistivity changes in the presence of NO(x), but often their sensitivity, stability, and selectivity are low. This study was designed to develop new synthetic pathways to precursors that produce high purity, two phase In2O3-SnO2. The precursors were formed by complexation of tin with any oxide ligands to give the ammonium salt (NH4). Thermal studies of these precursors were carried out by thermal gravimetry (TG) and differential scanning calorimetry (DSC). Further studies by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) were also conducted.

Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients.

PubMed

Yamamoto, N; Naraparaju, V R; Srinivasula, S M

1995-11-01

A serum glycoprotein, vitamin D3-binding protein (Gc protein), can be converted by beta-galactosidase of stimulated B lymphocytes and sialidase of T lymphocytes to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is a precursor for MAF. Treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high-titered MAF (GcMAF). When peripheral blood monocytes/macrophages of 46 HIV-infected patients were treated with GcMAF (100 pg/ml), the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of plasma Gc protein was low in 16 (35%) of of these patients. Loss of the MAF precursor activity appeared to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase found in the patient blood stream. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Thus, precursor activity of Gc protein and alpha-N-acetylgalactosaminidase activity in patient blood can serve as diagnostic and prognostic indices.

Characterization of Graphite Oxide and Reduced Graphene Oxide Obtained from Different Graphite Precursors and Oxidized by Different Methods Using Raman Spectroscopy.

PubMed

Muzyka, Roksana; Drewniak, Sabina; Pustelny, Tadeusz; Chrubasik, Maciej; Gryglewicz, Grażyna

2018-06-21

In this paper, the influences of the graphite precursor and the oxidation method on the resulting reduced graphene oxide (especially its composition and morphology) are shown. Three types of graphite were used to prepare samples for analysis, and each of the precursors was oxidized by two different methods (all samples were reduced by the same method of thermal reduction). Each obtained graphite oxide and reduced graphene oxide was analysed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy (RS).

Carbon reactivation kinetics in GaAs: Its dependence on dopant precursor, doping level, and layer thickness

NASA Astrophysics Data System (ADS)

Mimila-Arroyo, J.; Bland, S.; Barbé, M.

2002-05-01

The reactivation kinetics of the acceptor behavior of carbon, its dependence on dopant precursors, doping level, layer thickness, and annealing temperature, as well as the behavior of carbon-hydrogen complexes in GaAs grown by metalorganic chemical vapor deposition are studied. Independent of the carbon source, in the "as grown" material, systematically carbon hydrogen complexes are present and the hole concentration is lower than the corresponding carbon concentration. The carbon reactivation kinetics was achieved by ex situ rapid thermal annealing through a series of multistage annealing experiments and assessed at each annealing stage by infrared absorption, hydrogen secondary ion mass spectroscopy profiling, and hole concentration measurements. Carbon reactivation occurs solely by the debonding of hydrogen from the isolated carbon acceptor and its out-diffusion from the sample. The carbon reactivation kinetics can be treated as a first order one with an activation energy, Ea=1.42±0.01 eV, independent of doping precursors, doping level, and layer thickness. The reactivation constant results to decrease as doping level and layer thickness increase. An empirical formula has been obtained that allows one to calculate the reactivation constant as a function of the carbon doping, layer thickness, and annealing temperature, allowing one to determine the optimal carbon reactivation conditions for any C:GaAs layer.

A Synthesis of Solar Cycle Prediction Techniques

NASA Technical Reports Server (NTRS)

Hathaway, David H.; Wilson, Robert M.; Reichmann, Edwin J.

1999-01-01

A number of techniques currently in use for predicting solar activity on a solar cycle timescale are tested with historical data. Some techniques, e.g., regression and curve fitting, work well as solar activity approaches maximum and provide a month-by-month description of future activity, while others, e.g., geomagnetic precursors, work well near solar minimum but only provide an estimate of the amplitude of the cycle. A synthesis of different techniques is shown to provide a more accurate and useful forecast of solar cycle activity levels. A combination of two uncorrelated geomagnetic precursor techniques provides a more accurate prediction for the amplitude of a solar activity cycle at a time well before activity minimum. This combined precursor method gives a smoothed sunspot number maximum of 154 plus or minus 21 at the 95% level of confidence for the next cycle maximum. A mathematical function dependent on the time of cycle initiation and the cycle amplitude is used to describe the level of solar activity month by month for the next cycle. As the time of cycle maximum approaches a better estimate of the cycle activity is obtained by including the fit between previous activity levels and this function. This Combined Solar Cycle Activity Forecast gives, as of January 1999, a smoothed sunspot maximum of 146 plus or minus 20 at the 95% level of confidence for the next cycle maximum.

Analysis of sublethal arsenic toxicity to Ceratophyllum demersum: subcellular distribution of arsenic and inhibition of chlorophyll biosynthesis

PubMed Central

Mishra, Seema; Alfeld, Matthias; Sobotka, Roman; Andresen, Elisa; Falkenberg, Gerald; Küpper, Hendrik

2016-01-01

Arsenic (As) pollution is a serious concern worldwide. Recent studies under environmentally relevant conditions revealed that, in the aquatic plant Ceratophyllum demersum, pigments are the first observable target of toxicity, prior to any effect on photosynthetic parameters or to oxidative stress. Lethal toxicity was initiated by a change of As species and their distribution pattern in various tissues. Here, the localization of As was investigated at the subcellular level through X-ray fluorescence using a submicron beam and a Maia detector. Further, it was possible to obtain useful tissue structural information from the ratio of the tomogram of photon flux behind the sample to the tomogram of Compton scattering. The micro-X-ray fluorescence tomograms showed that As predominantly accumulated in the nucleus of the epidermal cells in young mature leaves exposed to sublethal 1 µM As. This suggests that As may exert toxic effects in the nucleus, for example, by interfering with nucleic acid synthesis by replacing phosphorous with As. At higher cellular concentrations, As was mainly stored in the vacuole, particularly in mature leaves. An analysis of precursors of chlorophyll and degradation metabolites revealed that the observed decrease in chlorophyll concentration was associated with hindered biosynthesis, and was not due to degradation. Coproporphyrinogen III could not be detected after exposure to only 0.5 µM As. Levels of subsequent precursors, for example, protoporphyrin IX, Mg-protoporphyrin, Mg-protoporphyrin methyl ester, and divinyl protochlorophyllide, were significantly decreased at this concentration as well, indicating that the pathway was blocked upstream of tetrapyrrole synthesis. PMID:27340233

Subcellular Distribution of Glutathione Precursors in Arabidopsis thaliana

PubMed Central

Koffler, Barbara Eva; Maier, Romana; Zechmann, Bernd

2011-01-01

Abstract Glutathione is an important antioxidant and has many important functions in plant development, growth and defense. Glutathione synthesis and degradation is highly compartment-specific and relies on the subcellular availability of its precursors, cysteine, glutamate, glycine and γ-glutamylcysteine especially in plastids and the cytosol which are considered as the main centers for glutathione synthesis. The availability of glutathione precursors within these cell compartments is therefore of great importance for successful plant development and defense. The aim of this study was to investigate the compartment-specific importance of glutathione precursors in Arabidopsis thaliana. The subcellular distribution was compared between wild type plants (Col-0), plants with impaired glutathione synthesis (glutathione deficient pad2-1 mutant, wild type plants treated with buthionine sulfoximine), and one complemented line (OE3) with restored glutathione synthesis. Immunocytohistochemistry revealed that the inhibition of glutathione synthesis induced the accumulation of the glutathione precursors cysteine, glutamate and glycine in most cell compartments including plastids and the cytosol. A strong decrease could be observed in γ-glutamylcysteine (γ-EC) contents in these cell compartments. These experiments demonstrated that the inhibition of γ-glutamylcysteine synthetase (GSH1) – the first enzyme of glutathione synthesis – causes a reduction of γ-EC levels and an accumulation of all other glutathione precursors within the cells. PMID:22050910

Size and Morphology Controlled Synthesis of Boehmite Nanoplates and Crystal Growth Mechanisms

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

Zhang, Xin; Cui, Wenwen; Page, Katharine L.

The aluminum oxyhydroxide boehmite is an important crystalline phase in nature and industry. We report development of a flexible additive-free hydrothermal synthesis method to prepare high quality boehmite nanoplates with sizes ranging from under 20 nm to 5 um via using hydrated alumina gels and amorphous powders as precursors. The size and morphology of the boehmite nanoplates was systematically varied between hexagonal and rhombic by adjusting precursor concentrations, pH, and the synthesis temperature, due to face-specific effects. The transformation mechanism is consistent with dissolution and reprecipitation, and involves transitory initial appearance of metastable gibbsite that is later consumed upon nucleationmore » of boehmite. Detailed X-ray pair distribution characterization of the solids over time showed similarities in short-range order that suggest linkages in local chemistry and bonding topology between the precursors and product boehmite, yet also that precursor-specific differences in long-range order appear to manifest subtle changes in resulting boehmite characteristics, suggesting that the rate and extent of water release or differences in the resulting solubilized aluminate speciation leads to slightly different polymerization and condensation pathways. The findings suggest that during dissolution of the precursor that precursor-specific dehydration or solution speciation could be important aspects of the transformation impacting the molecular level details of boehmite nucleation and growth.« less

Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production

PubMed Central

Belenky, Peter; Stebbins, Rebecca; Bogan, Katrina L.; Evans, Charles R.; Brenner, Charles

2011-01-01

NAD+ is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD+ consuming enzymes. NAD+ biosynthesis is required for two different regimens that extend lifespan in yeast. NAD+ is synthesized from tryptophan and the three vitamin precursors of NAD+: nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD+ precursors increases intracellular NAD+ levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD+ metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD+ metabolism by balancing import and export of NAD+ precursor vitamins. PMID:21589930

Reduced endothelin converting enzyme-1 and endothelin-3 mRNA in the developing bowel of male mice may increase expressivity and penetrance of Hirschsprung disease-like distal intestinal aganglionosis.

PubMed

Vohra, Bhupinder P S; Planer, William; Armon, Jennifer; Fu, Ming; Jain, Sanjay; Heuckeroth, Robert O

2007-01-01

Hirschsprung disease (distal intestinal aganglionosis, HSCR) is a multigenic disorder with incomplete penetrance, variable expressivity, and a strong male gender bias. Recent studies demonstrated that these genetic patterns arise because gene interactions determine whether enteric nervous system (ENS) precursors successfully proliferate and migrate into the distal bowel. We now demonstrate that male gender bias in the extent of distal intestinal aganglionosis occurs in mice with Ret dominant-negative mutations (RetDN) that mimic human HSCR. We hypothesized that male gender bias could result from reduced expression of a gene already known to be essential for ENS development. Using quantitative real-time polymerase chain reaction (PCR) we demonstrated reduced levels of endothelin converting enzyme-1 and endothelin-3 mRNA in the male mouse bowel at the time that ENS precursors migrate into the colon. Other HSCR-associated genes are expressed at comparable levels in male and female mice. Testosterone and Mullerian inhibiting substance had no deleterious effect on ENS precursor development, but adding EDN3 peptide to E11.5 male RetDN heterozygous mouse gut explants in organ culture significantly increased the rate of ENS precursor migration through the bowel.

Nrt1 and Tna1-independent export of NAD+ precursor vitamins promotes NAD+ homeostasis and allows engineering of vitamin production.

PubMed

Belenky, Peter; Stebbins, Rebecca; Bogan, Katrina L; Evans, Charles R; Brenner, Charles

2011-05-11

NAD(+) is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+) consuming enzymes. NAD(+) biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+) is synthesized from tryptophan and the three vitamin precursors of NAD(+): nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD(+) precursors increases intracellular NAD(+) levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD(+) metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD(+) metabolism by balancing import and export of NAD(+) precursor vitamins.

Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

PubMed Central

Lee, Joung Wook; Namkoong, Hong; Kim, Hyun Kee; Kim, Sanghee; Hwang, Dong Whi; Na, Hae Ri; Ha, Seon-Ah; Kim, Jae-Ryong; Kim, Jin Woo

2007-01-01

Background Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects. Methods We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia. Results We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group. Conclusion These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD. PMID:17565664

Next generation offline approaches to trace organic compound speciation: Approaching comprehensive speciation with soft ionization and very high resolution tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Khare, P.; Marcotte, A.; Sheu, R.; Ditto, J.; Gentner, D. R.

2017-12-01

Intermediate- and semi-volatile organic compounds (IVOCs and SVOCs) have high secondary organic aerosol (SOA) yields, as well as significant ozone formation potentials. Yet, their emission sources and oxidation pathways remain largely understudied due to limitations in current analytical capabilities. Online mass spectrometers are able to collect real time data but their limited mass resolving power renders molecular level characterization of IVOCs and SVOCs from the unresolved complex mixture unfeasible. With proper sampling techniques and powerful analytical instrumentation, our offline tandem mass spectrometry (i.e. MS×MS) techniques provide molecular-level and structural identification over wide polarity and volatility ranges. We have designed a novel analytical system for offline analysis of gas-phase SOA precursors collected on custom-made multi-bed adsorbent tubes. Samples are desorbed into helium via a gradual temperature ramp and sample flow is split equally for direct-MS×MS analysis and separation via gas chromatography (GC). The effluent from GC separation is split again for analysis via atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (APCI-Q×TOF) and traditional electron ionization mass spectrometry (EI-MS). The compounds for direct-MS×MS analysis are delivered via a transfer line maintained at 70ºC directly to APCI-Q×TOF, thus preserving the molecular integrity of thermally-labile, or other highly-reactive, organic compounds. Both our GC-MS×MS and direct-MS×MS analyses report high accuracy parent ion masses as well as information on molecular structure via MS×MS, which together increase the resolution of unidentified complex mixtures. We demonstrate instrument performance and present preliminary results from urban atmospheric samples collected from New York City with a wide range of compounds including highly-functionalized organic compounds previously understudied in outdoor air. Our work offers new insights into emerging emission sources in urban environments that can have a major impact on public health and also improves understanding of anthropogenic SOA precursor emissions.

New Ir Bis-Carbonyl Precursor for Water Oxidation Catalysis

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

Huang, Daria L.; Beltrán-Suito, Rodrigo; Thomsen, Julianne M.

2016-02-05

This paper introduces IrI(CO)2(pyalc) (pyalc = (2-pyridyl)-2-propanoate) as an atom-efficient precursor for Ir-based homogeneous oxidation catalysis. This compound was chosen to simplify analysis of the water oxidation catalyst species formed by the previously reported Cp*IrIII(pyalc)OH water oxidation precatalyst. Here, we present a comparative study on the chemical and catalytic properties of these two precursors. Previous studies show that oxidative activation of Cp*Ir-based precursors with NaIO4 results in formation of a blue IrIV species. This activation is concomitant with the loss of the placeholder Cp* ligand which oxidatively degrades to form acetic acid, iodate, and other obligatory byproducts. The activation processmore » requires substantial amounts of primary oxidant, and the degradation products complicate analysis of the resulting IrIV species. The species formed from oxidation of the Ir(CO)2(pyalc) precursor, on the other hand, lacks these degradation products (the CO ligands are easily lost upon oxidation) which allows for more detailed examination of the resulting Ir(pyalc) active species both catalytically and spectroscopically, although complete structural analysis is still elusive. Once Ir(CO)2(pyalc) is activated, the system requires acetic acid or acetate to prevent the formation of nanoparticles. Investigation of the activated bis-carbonyl complex also suggests several Ir(pyalc) isomers may exist in solution. By 1H NMR, activated Ir(CO)2(pyalc) has fewer isomers than activated Cp*Ir complexes, allowing for advanced characterization. Future research in this direction is expected to contribute to a better structural understanding of the active species. A diol crystallization agent was needed for the structure determination of 3.« less

The effect of precursor on the optical properties of carbon quantum dots synthesized by hydrothermal/solvothermal method

NASA Astrophysics Data System (ADS)

Mozdbar, Afsaneh; Nouralishahi, Amideddin; Fatemi, Shohreh; Mirakhori, Ghazaleh

2018-01-01

In the recent decade, Carbon Quantum Dots (CQDs) have attracted lots of attention due to their excellent properties such as tunable photoluminescence, high chemical stability, low toxicity, and biocompatibility. Among all synthesis methods, the hydrothermal/solvothermal rout has been considered as one of the most common and simplest method. The type of precursors can affect the size of CQDs and determine their surface functional groups, the essential properties that deeply influence the optical specifications. In this work, the effect of different precursors on the final properties of carbon quantum dots is investigated. The carbon quantum dots were synthesized by hydrothermal/solvothermal rout using citric acid, thiourea, ethylamine and monoethanolamine as precursors in almost the same conditions of time and temperature. Resultant CQDs were characterized by using FTIR, UV-Visible Spectroscopy and Photoluminescence (PL) analysis. The results of UV-Vis spectroscopy showed that quantum dots synthesized from monoethanolamine have wider absorption band rather than the CQDs from other precursors and the absorption edge shifted from about 270 nm for ethylamine to about 470 nm in monoethanolamine. Furthermore, the results demonstrate that using citric acid and monoethanolamine as precursor improved production efficiency and emission quantum yield of the carbon dots.

Perfluoroalkyl acids and their precursors in Swedish food: The relative importance of direct and indirect dietary exposure.

PubMed

Gebbink, Wouter A; Glynn, Anders; Darnerud, Per Ola; Berger, Urs

2015-03-01

We analyzed food market basket samples obtained in Sweden from 1999, 2005, and 2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds. Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2) were detected in the year pools with the highest ∑diPAP concentrations in 1999 and 2005. All precursors were predominantly found in meat, fish, and/or eggs based on analysis of individual food groups from 1999. Based on year pools, PFOS precursors contributed between 4 and 1% as an indirect source to total dietary PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total exposure. The lowest precursor contributions were generally seen in food samples from 2010. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Thermal decomposition kinetics of hydrazinium cerium 2,3-Pyrazinedicarboxylate hydrate: a new precursor for CeO2.

PubMed

Premkumar, Thathan; Govindarajan, Subbiah; Coles, Andrew E; Wight, Charles A

2005-04-07

The thermal decomposition kinetics of N(2)H(5)[Ce(pyrazine-2,3-dicarboxylate)(2)(H(2)O)] (Ce-P) have been studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), for the first time; TGA analysis reveals an oxidative decomposition process yielding CeO(2) as the final product with an activation energy of approximately 160 kJ mol(-1). This complex may be used as a precursor to fine particle cerium oxides due to its low temperature of decomposition.

Adaptive laboratory evolution resolves energy depletion to maintain high aromatic metabolite phenotypes in Escherichia coli strains lacking the Phosphotransferase System.

PubMed

McCloskey, Douglas; Xu, Sibei; Sandberg, Troy E; Brunk, Elizabeth; Hefner, Ying; Szubin, Richard; Feist, Adam M; Palsson, Bernhard O

2018-06-15

Aromatic metabolites provide the backbone for numerous industrial and pharmaceutical compounds of high value. The Phosphotransferase System (PTS) is common to many bacteria, and is the primary mechanism for glucose uptake by Escherichia coli. The PTS was removed to conserve phosphoenolpyruvate (pep), which is a precursor for aromatic metabolites and consumed by the PTS, for aromatic metabolite production. Replicate adaptive laboratory evolution (ALE) of PTS and detailed omics data sets collected revealed that the PTS bridged the gap between respiration and fermentation, leading to distinct high fermentative and high respiratory rate phenotypes. It was also found that while all strains retained high levels of aromatic amino acid (AAA) biosynthetic precursors, only one replicate from the high glycolytic clade retained high levels of intracellular AAAs. The fast growth and high AAA precursor phenotypes could provide a starting host for cell factories targeting the overproduction aromatic metabolites. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Effect of Climate Change on Surface Ozone over North America, Europe, and East Asia

NASA Technical Reports Server (NTRS)

Schnell, Jordan L.; Prather, Michael J.; Josse, Beatrice; Naik, Vaishali; Horowitz, Larry W.; Zeng, Guang; Shindell, Drew T.; Faluvegi, Greg

2016-01-01

The effect of future climate change on surface ozone over North America, Europe, and East Asia is evaluated using present-day (2000s) and future (2100s) hourly surface ozone simulated by four global models. Future climate follows RCP8.5, while methane and anthropogenic ozone precursors are fixed at year-2000 levels. Climate change shifts the seasonal surface ozone peak to earlier in the year and increases the amplitude of the annual cycle. Increases in mean summertime and high-percentile ozone are generally found in polluted environments, while decreases are found in clean environments. We propose climate change augments the efficiency of precursor emissions to generate surface ozone in polluted regions, thus reducing precursor export to neighboring downwind locations. Even with constant biogenic emissions, climate change causes the largest ozone increases at high percentiles. In most cases, air quality extreme episodes become larger and contain higher ozone levels relative to the rest of the distribution.

Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke.

PubMed

Niimi, Masachika; Hashimoto, Kenji; Kakuda, Wataru; Miyano, Satoshi; Momosaki, Ryo; Ishima, Tamaki; Abo, Masahiro

2016-01-01

Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis. Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels. Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (ρ = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism. The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery.

Detection, formation and occurrence of 13 new polar phenolic chlorinated and brominated disinfection byproducts in drinking water.

PubMed

Pan, Yang; Wang, Ying; Li, Aimin; Xu, Bin; Xian, Qiming; Shuang, Chendong; Shi, Peng; Zhou, Qing

2017-04-01

Recently, 13 new polar phenolic chlorinated and brominated disinfection byproducts (Cl- and Br-DBPs) were identified and quantified in simulated chlorinated drinking water by adopting product ion scan, precursor ion scan, and multiple reaction monitoring (MRM) analyses using ultra performance liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry (UPLC/ESI-tqMS). The 13 new DBPs have been drawing increasing concern not only because they possess significantly higher growth inhibition, developmental toxicity, and chronic cytotoxicity than commonly known aliphatic DBPs, but also because they act as intermediate DBPs that can decompose to form the U.S. EPA regulated DBPs. In this study, through MS parameter optimization of the UPLC/ESI-tqMS MRM analysis, the instrument detection and quantitation limits of the 13 new DBPs were substantially lowered to 0.42-6.44 and 1.35-16.51 μg/L, respectively. The total levels of the 13 new DBPs formed in chlorination were much higher than those formed in chloramination within a contact time of 3 d. In chlorination, the 13 new DBPs formed quickly and decomposed rapidly, and their total concentration kept on decreasing with contact time. In chloramination, the levels of the dominant species (i.e., trihalo-phenols) firstly increased and then decreased with contact time, whereas the levels of the other new DBPs were relatively low and kept on increasing with contact time. An increasing of pH from 6.0 to 9.0 decreased the formation of the 13 new DBPs by 57.8% and 62.3% in chlorination and chloramination, respectively. Gallic acid was found to be present in various simulated and real source water samples and was demonstrated to be a precursor of the 13 new DBPs with elucidated formation pathways. Furthermore, 12 of the 13 new DBPs were detected in 16 tap water samples obtained from major cities in East China, at total levels from 9.5 to 329.8 ng/L. The concentrations of the new DBPs were higher in samples with source waters containing higher bromide levels. Ozone-activated carbon treatment prior to disinfection might reduce the formation of the new DBPs since it was effective in precursor reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and optical properties of Co2+-doped ZnO Network prepared by new precursors

NASA Astrophysics Data System (ADS)

Akhtari, Fereshteh; Zorriasatein, Suzan; Farahmandjou, Majid; Elahi, Seyed Mohammad

2018-06-01

Pure ZnO nanoparticles (NPs) and Co/ZnO alloy NPs were synthesized with different percentages of cobalt impurity (1%, 3%, 5%, and 25%) with new precursors through the coprecipitation method. The structural results of the XRD analysis indicated that the pure and impure samples have a wurtzite hexagonal structure such that with an elevation of Co impurity up to 1%, the size of the nanocrystals declines by up to 30 nm. Furthermore, the FESEM analysis results suggest the homogeneity of the NPs such that with increased cobalt impurity, its level declines. The TEM analysis results revealed that the NPs with 5% impurity have a mean size of 32 nm in spherical form. The FTIR optical analysis results suggest a very sharp absorption peak within the wavelength ranges of 434–448 cm‑1, belonging to the Zn-O vibration bond. In addition, the absorption peak developed at the wavelength of 3428 cm‑1 is related to the activation of the OH radicals, whose absorption value grows with the addition of an impurity, thereby, causing enhanced photocatalytic activity. The UV-DRS optical analysis indicated that the absorption wavelength grows with increased impurity, causing the development of redshift and a reduction of the energy band gap. In this regard, for the pure sample, the band gap value was 3.18 eV, while for the sample with 5% impurity, the band gap was obtained as 2.68 eV. The VSM magnetic analysis suggests ferromagnetic development in the impure sample, with a saturation magnetism of 16 memu g‑1 and a coercivity field of 342 G.

Differential and directional estrogenic signaling pathways induced by enterolignans and their precursors

PubMed Central

Zhu, Yun; Kawaguchi, Kayoko; Kiyama, Ryoiti

2017-01-01

Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level. PMID:28152041

Biosynthesis of sesquiterpenes in grape berry exocarp of Vitis vinifera L.: evidence for a transport of farnesyl diphosphate precursors from plastids to the cytosol

PubMed Central

May, Bianca; Lange, B. Markus; Wüst, Matthias

2013-01-01

The participation of the mevalonic acid (MVA) and 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol-4-phosphate (DOXP/MEP) pathways in sesquiterpene biosynthesis of grape berries was investigated. There is an increasing interest in this class of terpenoids, since the oxygenated sesquiterpene rotundone was identified as the peppery aroma impact compound in Australian Shiraz wines. To investigate precursor supply pathway utilization, in vivo feeding experiments were performed with the deuterium labeled, pathway specific, precursors [5,5-2H2]-1-deoxy-D-xylulose and [5,5-2H2]-mevalonic acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites demonstrated that de novo sesquiterpene biosynthesis is mainly located in the grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh) of the Lemberger variety. Interestingly, precursors from both the (primarily) cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape sesquiterpenes in the varieties Lemberger, Gewürztraminer and Syrah. Our labeling data provide evidence for a homogenous, cytosolic pool of precursors for sesquiterpene biosynthesis, indicating that a transport of precursors occurs mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene germacrene D were in agreement with a cyclization mechanism analogous to that of a previously cloned enantioselective (R)-germacrene D synthase from Solidago canadensis. This observation was subsequently confirmed by enantioselective GC-MS analysis demonstrating the exclusive presence of (R)-germacrene D, and not the (S)-enantiomer, in grape berries. PMID:23954075

Biosynthesis of sesquiterpenes in grape berry exocarp of Vitis vinifera L.: evidence for a transport of farnesyl diphosphate precursors from plastids to the cytosol.

PubMed

May, Bianca; Lange, B Markus; Wüst, Matthias

2013-11-01

The participation of the mevalonic acid (MVA) and 1-deoxy-d-xylulose 5-phosphate/2-C-methyl-d-erythritol-4-phosphate (DOXP/MEP) pathways in sesquiterpene biosynthesis of grape berries was investigated. There is an increasing interest in this class of terpenoids, since the oxygenated sesquiterpene rotundone was identified as the peppery aroma impact compound in Australian Shiraz wines. To investigate precursor supply pathway utilization, in vivo feeding experiments were performed with the deuterium labeled, pathway specific, precursors [5,5-(2)H2]-1-deoxy-d-xylulose and [5,5-(2)H2]-mevalonic acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites demonstrated that de novo sesquiterpene biosynthesis is mainly located in the grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh) of the Lemberger variety. Interestingly, precursors from both the (primarily) cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape sesquiterpenes in the varieties Lemberger, Gewürztraminer and Syrah. Our labeling data provide evidence for a homogenous, cytosolic pool of precursors for sesquiterpene biosynthesis, indicating that a transport of precursors occurs mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene germacrene D were in agreement with a cyclization mechanism analogous to that of a previously cloned enantioselective (R)-germacrene D synthase from Solidago canadensis. This observation was subsequently confirmed by enantioselective GC-MS analysis demonstrating the exclusive presence of (R)-germacrene D, and not the (S)-enantiomer, in grape berries. Copyright © 2013 Elsevier Ltd. All rights reserved.

Highly efficient up-conversion and bright white light in RE co-doped KYF4 nanocrystals in sol-gel silica matrix

NASA Astrophysics Data System (ADS)

Méndez-Ramos, J.; Yanes, A. C.; Santana-Alonso, A.; del-Castillo, J.

2013-01-01

Transparent nano-glass-ceramics comprising Yb3+, Er3+ and Tm3+ co-doped KYF4 nanocrystals have been developed from sol-gel method. A structural analysis by means of X-ray diffraction confirmed the precipitation of cubic KYF4 nanocrystals into a silica matrix. Visible luminescence has been analyzed as function of treatment temperature of precursor sol-gel glasses. Highly efficient up-conversion emissions have been obtained under 980 nm excitation and studied by varying the doping level, processing temperature and pump power. Color tuneability has been quantified in terms of CIE diagram and in particular, a white-balanced overall emission has been achieved for a certain doping level and thermal treatment.

Functional Characterization of Preadipocytes Derived from Human Periaortic Adipose Tissue

PubMed Central

Camacho, Jaime; Duque, Juan; Carreño, Marisol; Acero, Edward; Pérez, Máximo; Ramirez, Sergio; Umaña, Juan; Obando, Carlos; Guerrero, Albert; Sandoval, Néstor; Rodríguez, Gina

2017-01-01

Adipose tissue can affect the metabolic control of the cardiovascular system, and its anatomic location can affect the vascular function differently. In this study, biochemical and phenotypical characteristics of adipose tissue from periaortic fat were evaluated. Periaortic and subcutaneous adipose tissues were obtained from areas surrounding the ascending aorta and sternotomy incision, respectively. Adipose tissues were collected from patients undergoing myocardial revascularization or mitral valve replacement surgery. Morphological studies with hematoxylin/eosin and immunohistochemical assay were performed in situ to quantify adipokine expression. To analyze adipogenic capacity, adipokine expression, and the levels of thermogenic proteins, adipocyte precursor cells were isolated from periaortic and subcutaneous adipose tissues and induced to differentiation. The precursors of adipocytes from the periaortic tissue accumulated less triglycerides than those from the subcutaneous tissue after differentiation and were smaller than those from subcutaneous adipose tissue. The levels of proteins involved in thermogenesis and energy expenditure increased significantly in periaortic adipose tissue. Additionally, the expression levels of adipokines that affect carbohydrate metabolism, such as FGF21, increased significantly in mature adipocytes induced from periaortic adipose tissue. These results demonstrate that precursors of periaortic adipose tissue in humans may affect cardiovascular events and might serve as a target for preventing vascular diseases. PMID:29209367

Metabolic Precursors to Amphetamine and Methamphetamine.

PubMed

Cody, J D

1993-12-01

Analysis and interpretation of amphetamine results is a challenging process made difficult by a number of factors. One of the complications comes from determination of the origin of amphetamine or methamphetamine in a sample. Given the relatively rare occasions that either of these two drugs are prescribed, legal prescription of one of these drugs is seldom a reason for positive findings. A number of other precursor compounds are metabolized by the body to amphetamine or methamphetamine, many of which could be used for legitimate reasons. Fourteen different metabolic precursors of amphetamine or methamphetamine are included in this review. They are amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Medical use, metabolism, analysis, and interpretation are described to afford sufficient information to evaluate the possible involvement of these drugs in positive amphetamine or methamphetamine results. Copyright © 1993 Central Police University.

Emission properties of Ce3+ centers in barium borate glasses prepared from different precursor materials

NASA Astrophysics Data System (ADS)

Torimoto, Aya; Masai, Hirokazu; Okada, Go; Kawaguchi, Noriaki; Yanagida, Takayuki; Ohkubo, Takahiro

2017-10-01

The photoluminescence (PL) and X-ray induced luminescence properties of Ce-doped barium borate glasses prepared from different precursor materials have been investigated. Oxidation of Ce3+ takes place during the melting process performed using a pre-vitrified non-doped glass. Residual groups originated from the precursor materials, such as fluorine atoms and OH groups, are found to affect the optical and emission properties of the glasses. Moreover, both the PL and the X-ray induced luminescence properties of the glasses depend on the precursor materials used for their synthesis. Based on a thorough analysis of the emission properties, we conclude that the best synthesis conditions involve melting a batch containing Ce(CH3COO)3·H2O, BaCO3, and B2O3 in Ar atmosphere.

Development of precursors recognition methods in vector signals

NASA Astrophysics Data System (ADS)

Kapralov, V. G.; Elagin, V. V.; Kaveeva, E. G.; Stankevich, L. A.; Dremin, M. M.; Krylov, S. V.; Borovov, A. E.; Harfush, H. A.; Sedov, K. S.

2017-10-01

Precursor recognition methods in vector signals of plasma diagnostics are presented. Their requirements and possible options for their development are considered. In particular, the variants of using symbolic regression for building a plasma disruption prediction system are discussed. The initial data preparation using correlation analysis and symbolic regression is discussed. Special attention is paid to the possibility of using algorithms in real time.

VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias.

PubMed

Bauer, S R; Kubagawa, H; Maclennan, I; Melchers, F

1991-09-15

We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage.

Reduction of precursor decay anomaly in single crystal lithium fluoride

NASA Astrophysics Data System (ADS)

Sano, Yukio

2000-08-01

The purpose of this study is to reveal that the precursor decay anomaly in single crystal lithium fluoride is reduced by Sano's decay curve [Y. Sano, J. Appl. Phys. 85, 7616 (1999)], which is much smaller in slope than Asay's decay curve [J. R. Asay, G. R. Fowles, G. E. Duvall, M. H. Miles, and R. F. Tinder, J. Appl. Phys. 43, 2132 (1972)]. To this end, strain, particle, velocity, and stress in a precursor and near the leading edge of the follower changing with time along Sano's decay curve are first analyzed quantitatively. The analysis verified the existence of degenerate contraction waves I and II and a subrarefaction wave R', and the decay process [Y. Sano, J. Appl. Phys. 77, 3746 (1995)] caused in sequence by evolving followers C, I, II, R', Rb. Next, inequalities relating decay rates qualitatively to plastic strain rates at the leading edge of the follower, which are derived using the properties of the followers, are incorporated into the analysis. Calculation results showed that the plastic strain rates were reduced by low decay rates. This indicates that the precursor decay anomaly might be greatly reduced by Sano's decay curve.

Impact of US and Canadian precursor regulation on methamphetamine purity in the United States.

PubMed

Cunningham, James K; Liu, Lon-Mu; Callaghan, Russell

2009-03-01

Reducing drug purity is a major, but largely unstudied, goal of drug suppression. This study examines whether US methamphetamine purity was impacted by the suppression policy of US and Canadian precursor chemical regulation. Autoregressive integrated moving average (ARIMA)-intervention time-series analysis. Continental United States and Hawaii (1985-May 2005). Interventions US federal regulations targeting precursors, ephedrine and pseudoephedrine, in forms used by large-scale producers were implemented in November 1989, August 1995 and October 1997. US regulations targeting precursors in forms used by small-scale producers (e.g. over-the-counter medications) were implemented in October 1996 and October 2001. Canada implemented federal precursor regulations in January 2003 and July 2003 and an essential chemical (e.g. acetone) regulation in January 2004. Monthly median methamphetamine purity series. US regulations targeting large-scale producers were associated with purity declines of 16-67 points; those targeting small-scale producers had little or no impact. Canada's precursor regulations were associated with purity increases of 13-15 points, while its essential chemical regulation was associated with a 13-point decrease. Hawaii's purity was consistently high, and appeared to vary little with the 1990s/2000s regulations. US precursor regulations targeting large-scale producers were associated with substantial decreases in continental US methamphetamine purity, while regulations targeting over-the-counter medications had little or no impact. Canada's essential chemical regulation was also associated with a decrease in continental US purity. However, Canada's precursor regulations were associated with purity increases: these regulations may have impacted primarily producers of lower-quality methamphetamine, leaving higher-purity methamphetamine on the market by default. Hawaii's well-known preference for 'ice' (high-purity methamphetamine) may have helped to constrain purity there to a high, attenuated range, possibly limiting its sensitivity to precursor regulation.

Requirement of zebrafish pcdh10a and pcdh10b in melanocyte precursor migration.

PubMed

Williams, Jason S; Hsu, Jessica Y; Rossi, Christy Cortez; Artinger, Kristin Bruk

2018-03-29

Melanocytes derive from neural crest cells, which are a highly migratory population of cells that play an important role in pigmentation of the skin and epidermal appendages. In most vertebrates, melanocyte precursor cells migrate solely along the dorsolateral pathway to populate the skin. However, zebrafish melanocyte precursors also migrate along the ventromedial pathway, in route to the yolk, where they interact with other neural crest derivative populations. Here, we demonstrate the requirement for zebrafish paralogs pcdh10a and pcdh10b in zebrafish melanocyte precursor migration. pcdh10a and pcdh10b are expressed in a subset of melanocyte precursor and somatic cells respectively, and knockdown and TALEN mediated gene disruption of pcdh10a results in aberrant migration of melanocyte precursors resulting in fully melanized melanocytes that differentiate precociously in the ventromedial pathway. Live cell imaging analysis demonstrates that loss of pchd10a results in a reduction of directed cell migration of melanocyte precursors, caused by both increased adhesion and a loss of cell-cell contact with other migratory neural crest cells. Also, we determined that the paralog pcdh10b is upregulated and can compensate for the genetic loss of pcdh10a. Disruption of pcdh10b alone by CRISPR mutagenesis results in somite defects, while the loss of both paralogs results in enhanced migratory melanocyte precursor phenotype and embryonic lethality. These results reveal a novel role for pcdh10a and pcdh10b in zebrafish melanocyte precursor migration and suggest that pcdh10 paralogs potentially interact for proper transient migration along the ventromedial pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

The Expression and Function of the Achaete-Scute Genes in Tribolium castaneum Reveals Conservation and Variation in Neural Pattern Formation and Cell Fate Specification

NASA Technical Reports Server (NTRS)

Wheeler, Scott R.; Carrico, Michelle L.; Wilson, Beth A.; Brown, Susan J.; Skeath, James B.

2003-01-01

SUMMARY The study of achaete-scute (ac/sc) genes has recently become a paradigm to understand the evolution and development of the arthropod nervous system. We describe the identification and characterization of the ache genes in the coleopteran insect species Tribolium castaneum. We have identified two Tribolium ache genes - achaete-scute homolog (Tc-ASH) a proneural gene and asense (Tc-ase) a neural precursor gene that reside in a gene complex. Focusing on the embryonic central nervous system we fmd that Tc-ASH is expressed in all neural precursors and the proneural clusters from which they segregate. Through RNAi and misexpression studies we show that Tc-ASH is necessary for neural precursor formation in Triboliurn and sufficient for neural precursor formation in Drosophila. Comparison of the function of the Drosophila and Triboliurn proneural ac/sc genes suggests that in the Drosophila lineage these genes have maintained their ancestral function in neural precursor formation and have acquired a new role in the fate specification of individual neural precursors. Furthermore, we find that Tc-use is expressed in all neural precursors suggesting an important and conserved role for asense genes in insect nervous system development. Our analysis of the Triboliurn ache genes indicates significant plasticity in gene number, expression and function, and implicates these modifications in the evolution of arthropod neural development.

The expression and function of the achaete-scute genes in Tribolium castaneum reveals conservation and variation in neural pattern formation and cell fate specification

NASA Technical Reports Server (NTRS)

Wheeler, Scott R.; Carrico, Michelle L.; Wilson, Beth A.; Brown, Susan J.; Skeath, James B.

2003-01-01

The study of achaete-scute (ac/sc) genes has recently become a paradigm to understand the evolution and development of the arthropod nervous system. We describe the identification and characterization of the ac/sc genes in the coleopteran insect species Tribolium castaneum. We have identified two Tribolium ac/sc genes - achaete-scute homolog (Tc-ASH) a proneural gene and asense (Tc-ase) a neural precursor gene that reside in a gene complex. Focusing on the embryonic central nervous system we find that Tc-ASH is expressed in all neural precursors and the proneural clusters from which they segregate. Through RNAi and misexpression studies we show that Tc-ASH is necessary for neural precursor formation in Tribolium and sufficient for neural precursor formation in Drosophila. Comparison of the function of the Drosophila and Tribolium proneural ac/sc genes suggests that in the Drosophila lineage these genes have maintained their ancestral function in neural precursor formation and have acquired a new role in the fate specification of individual neural precursors. Furthermore, we find that Tc-ase is expressed in all neural precursors suggesting an important and conserved role for asense genes in insect nervous system development. Our analysis of the Tribolium ac/sc genes indicates significant plasticity in gene number, expression and function, and implicates these modifications in the evolution of arthropod neural development.

Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

PubMed

Babona-Pilipos, Robart; Droujinine, Ilia A; Popovic, Milos R; Morshead, Cindi M

2011-01-01

The existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

PubMed Central

Dalgin, Gökhan; Prince, Victoria E.

2015-01-01

During development a network of transcription factors functions to differentiate foregut cells into pancreatic endocrine cells. Differentiation of appropriate numbers of each hormone-expressing endocrine cell type is essential for the normal development of the pancreas and ultimately for effective maintenance of blood glucose levels. A fuller understanding of the details of endocrine cell differentiation may contribute to development of cell replacement therapies to treat diabetes. In this study, by using morpholino and gRNA/Cas9 mediated knockdown we establish that differential levels of the basic-helix loop helix (bHLH) transcription factor Neurod are required for the differentiation of distinct endocrine cell types in developing zebrafish. While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-expressing beta cells is less sensitive to Neurod depletion. The endocrine cells that arise during embryonic stages to produce the primary islet, and those that arise subsequently during larval stages from the intra-pancreatic duct (IPD) to ultimately contribute to the secondary islets, show similar dependence on differential Neurod levels. Intriguingly, Neurod-deficiency triggers premature formation of endocrine precursors from the IPD during early larval stages. However, the Neurod-deficient endocrine precursors fail to differentiate appropriately, and the larvae are unable to maintain normal glucose levels. In summary, differential levels of Neurod are required to generate endocrine pancreas subtypes from precursors during both embryonic and larval stages, and Neurod function is in turn critical to endocrine function. PMID:25797153

Stable-carbon isotope ratios for sourcing the nerve-agent precursor methylphosphonic dichloride and its products

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

Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. It is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ13C analysis to be used as a fingerprinting toolmore » in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. We demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a measureable isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

Stable-Carbon Isotope Ratios for Sourcing the Nerve-Agent Precursor Methylphosphonic Dichloride and Its Products

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

Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13C analysis to be used as a fingerprintingmore » tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. Here, we demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

Stable-Carbon Isotope Ratios for Sourcing the Nerve-Agent Precursor Methylphosphonic Dichloride and Its Products

DOE PAGES

Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

2018-04-01

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13C analysis to be used as a fingerprintingmore » tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. Here, we demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

Stable-carbon isotope ratios for sourcing the nerve-agent precursor methylphosphonic dichloride and its products.

PubMed

Moran, James J; Fraga, Carlos G; Nims, Megan K

2018-08-15

The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13 C analysis to be used as a fingerprinting tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. We demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool. Copyright © 2018. Published by Elsevier B.V.

Lipidomics in research on yeast membrane lipid homeostasis.

PubMed

de Kroon, Anton I P M

2017-08-01

Mass spectrometry is increasingly used in research on membrane lipid homeostasis, both in analyses of the steady state lipidome at the level of molecular lipid species, and in pulse-chase approaches employing stable isotope-labeled lipid precursors addressing the dynamics of lipid metabolism. Here my experience with, and view on mass spectrometry-based lipid analysis is presented, with emphasis on aspects of quantification of membrane lipid composition of the yeast Saccharomyces cerevisiae. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone marrow cells.

PubMed

Kalyonova, L F; Novikova, M A; Kostolomova, E G

2015-01-01

The effects of a new microorganism species (Bacillus spp., strain M3) isolated from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone marrow hemopoiesis were studied on laboratory mice. Analysis of the count and immunophenotype of bone marrow cells indicated that even in low doses (1000-5000 microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-)) increased, intensity of lymphocyte precursor proliferation and differentiation (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria. These changes in activity of hemopoiesis were associated with changes in the level of regulatory T lymphocytes (reduced expression of TCRαβ) and were most likely compensatory. The possibility of modulating hemopoiesis activity in the bone marrow by low doses of one microorganism strain isolated from the permafrost could be useful for evaluating the effects of other low dose bacteria on the bone marrow hemopoiesis.

Down- and up-conversion emissions in Er-doped transparent fluorotellurite glass-ceramics

NASA Astrophysics Data System (ADS)

Miguel, A.; Morea, R.; Gonzalo, J.; Fernandez, J.; Balda, R.

2015-03-01

In this work, we report the near infrared and upconversion emissions of Er3+-doped transparent fluorotellurite glassceramics obtained by heat treatment of the precursor Er-doped TeO2-ZnO-ZnF2 glass. Structural analysis shows that ErF3 nanocrystals nucleated in the glass-ceramic sample are homogeneously distributed in the glass matrix with a typical size of 45±10 nm. The comparison of the fluorescence properties of Er3+-doped precursor glass and glass-ceramic confirms the successful incorporation of the rare-earth into the nanocrystals. An enhancement of the red upconversion emission due to 4F9/2→4I15/2 transition together with weak emission bands due to transitions from 2H9/2, 4F3/2,5/2, and 4F7/2 levels to the ground state are observed under excitation at 801 nm in the glass-ceramic sample. The temporal evolution of the red emission together with the excitation upconversion spectrum suggest that energy transfer processes are responsible for the enhancement of the red emission.

Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle.

PubMed Central

Zimmermann, K; Herget, T; Salbaum, J M; Schubert, W; Hilbich, C; Cramer, M; Masters, C L; Multhaup, G; Kang, J; Lemaire, H G

1988-01-01

Cloning and sequence analysis revealed the putative amyloid A4 precursor (pre-A4) of Alzheimer's disease to have characteristics of a membrane-spanning glycoprotein. In addition to brain, pre-A4 mRNA was found in adult human muscle and other tissues. We demonstrate by in situ hybridization that pre-A4 mRNA is present in adult human muscle, in cultured human myoblasts and myotubes. Immunofluorescence with antipeptide antibodies shows the putative pre-A4 protein to be expressed in adult human muscle and associated with some but not all nuclear envelopes. Despite high levels of a single 3.5-kb pre-A4 mRNA species in cultured myoblasts and myotubes, the presence of putative pre-A4 protein could not be detected by immunofluorescence. This suggests that putative pre-A4 protein is stabilized and therefore functioning in the innervated muscle tissue but not in developing, i.e. non-innervated cultured muscle cells. The selective localization of the protein on distinct nuclear envelopes could reflect an interaction with motor endplates. Images PMID:2896589

Low-Temperature Molecular Layer Deposition Using Monofunctional Aromatic Precursors and Ozone-Based Ring-Opening Reactions.

PubMed

Svärd, Laura; Putkonen, Matti; Kenttä, Eija; Sajavaara, Timo; Krahl, Fabian; Karppinen, Maarit; Van de Kerckhove, Kevin; Detavernier, Christophe; Simell, Pekka

2017-09-26

Molecular layer deposition (MLD) is an increasingly used deposition technique for producing thin coatings consisting of purely organic or hybrid inorganic-organic materials. When organic materials are prepared, low deposition temperatures are often required to avoid decomposition, thus causing problems with low vapor pressure precursors. Monofunctional compounds have higher vapor pressures than traditional bi- or trifunctional MLD precursors, but do not offer the required functional groups for continuing the MLD growth in subsequent deposition cycles. In this study, we have used high vapor pressure monofunctional aromatic precursors in combination with ozone-triggered ring-opening reactions to achieve sustained sequential growth. MLD depositions were carried out by using three different aromatic precursors in an ABC sequence, namely with TMA + phenol + O 3 , TMA + 3-(trifluoromethyl)phenol + O 3 , and TMA + 2-fluoro-4-(trifluoromethyl)benzaldehyde + O 3 . Furthermore, the effect of hydrogen peroxide as a fourth step was evaluated for all studied processes resulting in a four-precursor ABCD sequence. According to the characterization results by ellipsometry, infrared spectroscopy, and X-ray reflectivity, self-limiting MLD processes could be obtained between 75 and 150 °C with each of the three aromatic precursors. In all cases, the GPC (growth per cycle) decreased with increasing temperature. In situ infrared spectroscopy indicated that ring-opening reactions occurred in each ABC sequence. Compositional analysis using time-of-flight elastic recoil detection indicated that fluorine could be incorporated into the film when 3-(trifluoromethyl)phenol and 2-fluoro-4-(trifluoromethyl)benzaldehyde were used as precursors.

Ion Mobility Separation of Isomeric Carbohydrate Precursor Ions and Acquisition of their Independent Tandem Mass Spectra

PubMed Central

Zhu, Maolei; Bendiak, Brad; Clowers, Brian; Hill, Herbert H.

2010-01-01

The rapid separation of isomeric precursor ions of oligosaccharides prior to their analysis by MSn was demonstrated using an ambient pressure ion mobility spectrometer (IMS) interfaced with a quadrupole ion trap. Separations were not limited to specific types of isomers; representative isomers differing solely in the stereochemistry of sugars, in their anomeric configurations, and in their overall branching patterns and linkage positions could be resolved in the millisecond time frame. Physical separation of precursor ions permitted independent mass spectra of individual oligosaccharide isomers to be acquired to at least MS3, the number of stages of dissociation limited only practically by the abundance of specific product ions. IMS-MSn analysis was particularly valuable in the evaluation of isomeric oligosaccharides that yielded identical sets of product ions in MS/MS experiments, revealing pairs of isomers that would otherwise not be known to be present in a mixture if evaluated solely by MS dissociation methods alone. A practical example of IMS-MSn analysis of a set of isomers included within a single HPLC fraction of oligosaccharides released from bovine submaxillary mucin is described. PMID:19562326

Absence of Genomic Ikaros/IKZF1 Deletions in Pediatric B-Precursor Acute Lymphoblastic Leukemia

PubMed Central

Qazi, Sanjive; Ma, Hong; Uckun, Fatih M

2013-01-01

Here we report the results of gene expression analyses using multiple probesets aimed at determining the incidence of Ikaros/IKZF1 deletions in pediatric B-precursor acute lymphoblastic leukemia (BPL). Primary leukemia cells from 122 Philadelphia chromosome (Ph)+ BPL patients and 237 Ph− BPL patients as well as normal hematopoietic cells from 74 normal non-leukemic bone marrow specimens were organized according to expression levels of IKZF1 transcripts utilizing two-way hierarchical clustering technique to identify specimens with low IKZF1 expression for the 10 probesets interrogating Exons 1 through 4 and Exon 8. Our analysis demonstrated no changes in expression that would be expected from homozygous or heterozygous deletions of IKZF1 in primary leukemic cells. Similar results were obtained in gene expression analysis of primary leukemic cells from 20 Ph+ positive and 155 Ph− BPL patients in a validation dataset. Taken together, our gene expression analyses in 534 pediatric BPL cases, including 142 cases with Ph+ BPL, contradict previous reports that were based on SNP array data and suggested that Ph+ pediatric BPL is characterized by a high frequency of homozygous or heterozygous IKZF1 deletions. Further, exon-specific genomic PCR analysis of primary leukemia cells from 21 high-risk pediatric BPL patients and 11 standard-risk pediatric BPL patients, and 8 patients with infant BPL did not show any evidence for homozygous IKZF1 locus deletions. Nor was there any evidence for homozygous or heterozygous intragenic IKZF1 deletions. PMID:24478816

XANES Analysis of Organic Residues Produced from the UV Irradiation of Astrophysical Ice Analogs

DTIC Science & Technology

2011-01-01

indicate that they contain molecular precursors of prebiotic interest such as amino acids, nitrile-bearing compounds, and amphiphilic compounds. In...living organisms on Earth remains a mystery. Among the most studied scenarios are those encompassing an extraterres- trial origin of prebiotic ...products of these residues have been partly identified using chromatography techniques, which indicate that they contain molecular precursors of prebiotic

Coevolution of Domain Interactions in the Chloroplast TGD1, 2, 3 Lipid Transfer Complex Specific to Brassicaceae and Poaceae Plants.

PubMed

Yang, Yang; Zienkiewicz, Agnieszka; Lavell, Anastasiya; Benning, Christoph

2017-06-01

The import of lipids into the chloroplast is essential for photosynthetic membrane biogenesis. This process requires an ABC transporter in the inner envelope membrane with three subunits, TRIGALACTOSYLDIACYLGLYCEROL (TGD) 1, 2, and 3, named after the oligogalactolipids that accumulate in the respective Arabidopsis thaliana mutants. Unlike Arabidopsis, in the model grass Brachypodium distachyon , chloroplast lipid biosynthesis is largely dependent on imported precursors, resulting in a characteristic difference in chloroplast lipid acyl composition between the two plants. Accordingly, Arabidopsis is designated as a 16:3 (acyl carbons:double bounds) plant and Brachypodium as an 18:3 plant. Repression of TGD1 (Bd TGD1 ) in Brachypodium affected growth without triggering oligogalactolipid biosynthesis. Moreover, expressing Bd TGD1 in the Arabidopsis tgd1-1 mutant restored some phenotypes but did not reverse oligogalactolipid biosynthesis. A 27-amino acid loop (L45) is solely responsible for the incomplete functioning of BdTGD1 in Arabidopsis tgd1-1 Coevolutionary analysis and coimmunoprecipitation assays showed that the TGD1 L45 loop interacts with the mycobacterial cell entry domain of TGD2. To explain the observed differences in oligogalactolipid biosynthesis between the two species, we suggest that excess monogalactosyldiacylglycerol derived from chloroplast-derived precursors in Arabidopsis tgd1-1 is converted into oligogalactolipids, a process absent from Brachypodium with reduced TGD1 levels, which assembles monogalactosyldiacylglycerol exclusively from imported precursors. © 2017 American Society of Plant Biologists. All rights reserved.

Coevolution of Domain Interactions in the Chloroplast TGD1, 2, 3 Lipid Transfer Complex Specific to Brassicaceae and Poaceae Plants

PubMed Central

Yang, Yang; Lavell, Anastasiya

2017-01-01

The import of lipids into the chloroplast is essential for photosynthetic membrane biogenesis. This process requires an ABC transporter in the inner envelope membrane with three subunits, TRIGALACTOSYLDIACYLGLYCEROL (TGD) 1, 2, and 3, named after the oligogalactolipids that accumulate in the respective Arabidopsis thaliana mutants. Unlike Arabidopsis, in the model grass Brachypodium distachyon, chloroplast lipid biosynthesis is largely dependent on imported precursors, resulting in a characteristic difference in chloroplast lipid acyl composition between the two plants. Accordingly, Arabidopsis is designated as a 16:3 (acyl carbons:double bounds) plant and Brachypodium as an 18:3 plant. Repression of TGD1 (BdTGD1) in Brachypodium affected growth without triggering oligogalactolipid biosynthesis. Moreover, expressing BdTGD1 in the Arabidopsis tgd1-1 mutant restored some phenotypes but did not reverse oligogalactolipid biosynthesis. A 27-amino acid loop (L45) is solely responsible for the incomplete functioning of BdTGD1 in Arabidopsis tgd1-1. Coevolutionary analysis and coimmunoprecipitation assays showed that the TGD1 L45 loop interacts with the mycobacterial cell entry domain of TGD2. To explain the observed differences in oligogalactolipid biosynthesis between the two species, we suggest that excess monogalactosyldiacylglycerol derived from chloroplast-derived precursors in Arabidopsis tgd1-1 is converted into oligogalactolipids, a process absent from Brachypodium with reduced TGD1 levels, which assembles monogalactosyldiacylglycerol exclusively from imported precursors. PMID:28526713

Surface passivation of Fe{sub 3}O{sub 4} nanoparticles with Al{sub 2}O{sub 3} via atomic layer deposition in a rotating fluidized bed reactor

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

Duan, Chen-Long; Deng, Zhang; Cao, Kun

2016-07-15

Iron(II,III) oxide (Fe{sub 3}O{sub 4}) nanoparticles have shown great promise in many magnetic-related applications such as magnetic resonance imaging, hyperthermia treatment, and targeted drug delivery. Nevertheless, these nanoparticles are vulnerable to oxidation and magnetization loss under ambient conditions, and passivation is usually required for practical applications. In this work, a home-built rotating fluidized bed (RFB) atomic layer deposition (ALD) reactor was employed to form dense and uniform nanoscale Al{sub 2}O{sub 3} passivation layers on Fe{sub 3}O{sub 4} nanoparticles. The RFB reactor facilitated the precursor diffusion in the particle bed and intensified the dynamic dismantling of soft agglomerates, exposing every surfacemore » reactive site to precursor gases. With the aid of in situ mass spectroscopy, it was found that a thicker fluidization bed formed by larger amount of particles increased the residence time of precursors. The prolonged residence time allowed more thorough interactions between the particle surfaces and the precursor gas, resulting in an improvement of the precursor utilization from 78% to nearly 100%, even under a high precursor feeding rate. Uniform passivation layers around the magnetic cores were demonstrated by both transmission electron microscopy and the statistical analysis of Al mass concentrations. Individual particles were coated instead of the soft agglomerates, as was validated by the specific surface area analysis and particle size distribution. The results of thermogravimetric analysis suggested that 5 nm-thick ultrathin Al{sub 2}O{sub 3} coatings could effectively protect the Fe{sub 3}O{sub 4} nanoparticles from oxidation. The x-ray diffraction patterns also showed that the magnetic core crystallinity of such passivated nanoparticles could be well preserved under accelerated oxidation conditions. The precise thickness control via ALD maintained the saturation magnetization at 66.7 emu/g with a 5 nm-thick Al{sub 2}O{sub 3} passivation layer. This good preservation of the magnetic properties with superior oxidation resistance will be beneficial for practical magnetic-based applications.« less

Methyl 3-[3',4'-(methylenedioxy)phenyl]-2-methyl glycidate: an ecstasy precursor seized in Sydney, Australia.

PubMed

Collins, Michael; Heagney, Aaron; Cordaro, Frank; Odgers, David; Tarrant, Gregory; Stewart, Samantha

2007-07-01

Five 44 gallon drums labeled as glycidyl methacrylate were seized by the Australian Customs Service and the Australian Federal Police at Port Botany, Sydney, Australia, in December 2004. Each drum contained a white, semisolid substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine (MDMA). Gas chromatography-mass spectroscopy (GC/MS) analysis demonstrated that the material was neither glycidyl methacrylate nor MDMA. Because intelligence sources employed by federal agents indicated that this material was in some way connected to MDMA production, suspicion fell on the various MDMA precursor chemicals. Using a number of techniques including proton nuclear magnetic resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown substance was eventually identified as methyl 3-[3',4'(methylenedioxy)phenyl]-2-methyl glycidate. The substance was also subjected to a published hydrolysis and decarboxylation procedure and gave a high yield of the MDMA precursor chemical, 3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a "precursor to a precursor."

In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

PubMed Central

Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

2015-01-01

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. PMID:19463691

Enhanced production of L-DOPA in cell cultures of Mucuna pruriens L. and Mucuna prurita H.

PubMed

Raghavendra, S; Kumar, V; Ramesh, C K; Khan, M H Moinuddin

2012-01-01

A comparative study on the production of 3,4-dihydroxyphenylalanine (L-DOPA) was carried out in cell cultures of two Mucuna species by elicitor treatment and precursor feeding. The influence of elicitors and the precursor molecule on L-DOPA production, polyphenol oxidase (PPO) and tyrosinase activities was also studied. Callus cultures were initiated in Mucuna pruriens L. and Mucuna prurita H. on MS medium supplemented with BAP and IAA at different concentrations. Suspension cultures were established in MS liquid medium supplemented with BAP, IAA, the elicitors methyl jasmonate, chitin and pectin or the precursor L-tyrosine at different concentrations for L-DOPA production. Compared to the controls, several-fold increases in L-DOPA concentration were observed in elicitor-treated and precursor-fed suspension cultures of both plant species. L-DOPA concentrations were comparatively higher in precursor-fed cultures than those receiving elicitor treatments. A parallel increase in tyrosinase and PPO levels was also observed. Loss of cell viability was observed at high concentrations of elicitor-treated cultures, whereas L-tyrosine did not cause any cell death. Compared to elicitor treatments, precursor feeding resulted in higher concentrations of L-DOPA production and tyrosinase activity. The efficacy of L-DOPA production was found to be higher for suspension cultures of M. pruriens compared to M. prurita in all treatments.

Morphology and stability in a half-metallic ferromagnetic CrO 2 compound of nanoparticles synthesized via a polymer precursor

NASA Astrophysics Data System (ADS)

Biswas, S.; Ram, S.

2004-11-01

Nanoparticles of stable CrO2 of a half-metallic ferromagnet are synthesized with a novel chemical method involving a Cr4+-polymer composite precursor. A single phase CrO2 of D4h 14 : P42 / mnm tetragonal crystal structure (lattice parameters a = 0.4250 and c = 0.3190 nm) lies after firing the precursor at 350 °C for 1 h in air. Microstructure reveals single domain CrO2 particles of thin platelets (aspect ratio ∼1) of average 50 nm diameter and 35 nm thickness. In air, unless heating at temperatures above 500 °C, no due CrO2 → Cr2O3 phase transformation encounters. The results are presented in terms of X-ray diffraction and thermal or thermogravimetric analysis of precursor and derived CrO2 powder.

Discovery of a widely distributed toxin biosynthetic gene cluster

PubMed Central

Lee, Shaun W.; Mitchell, Douglas A.; Markley, Andrew L.; Hensler, Mary E.; Gonzalez, David; Wohlrab, Aaron; Dorrestein, Pieter C.; Nizet, Victor; Dixon, Jack E.

2008-01-01

Bacteriocins represent a large family of ribosomally produced peptide antibiotics. Here we describe the discovery of a widely conserved biosynthetic gene cluster for the synthesis of thiazole and oxazole heterocycles on ribosomally produced peptides. These clusters encode a toxin precursor and all necessary proteins for toxin maturation and export. Using the toxin precursor peptide and heterocycle-forming synthetase proteins from the human pathogen Streptococcus pyogenes, we demonstrate the in vitro reconstitution of streptolysin S activity. We provide evidence that the synthetase enzymes, as predicted from our bioinformatics analysis, introduce heterocycles onto precursor peptides, thereby providing molecular insight into the chemical structure of streptolysin S. Furthermore, our studies reveal that the synthetase exhibits relaxed substrate specificity and modifies toxin precursors from both related and distant species. Given our findings, it is likely that the discovery of similar peptidic toxins will rapidly expand to existing and emerging genomes. PMID:18375757

A Splash to Nano-Sized Inorganic Energy-Materials by the Low-Temperature Molecular Precursor Approach.

PubMed

Driess, Matthias; Panda, Chakadola; Menezes, Prashanth Wilfried

2018-05-07

The low-temperature synthesis of inorganic materials and their interfaces at the atomic and molecular level provides numerous opportunities for the design and improvement of inorganic materials in heterogeneous catalysis for sustainable chemical energy conversion or other energy-saving areas. Using suitable molecular precursors for functional inorganic nanomaterial synthesis allows for facile control over uniform particle size distribution, stoichiometry, and leads to desired chemical and physical properties. This minireview outlines some advantages of the molecular precursor approach in light of selected recent developments of molecule-to-nanomaterials synthesis for renewable energy applications, relevant for the oxygen evolution reaction (OER), hydrogen evolution reaction (HER) and overall water-splitting. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Weak-link capacitor

DOEpatents

Dirk, Shawn M [Albuquerque, NM; Johnson, Ross S [Albuquerque, NM; Wheeler, David R [Albuquerque, NM; Bogart, Gregory R [Corrales, NM

2011-06-07

A process for making a dielectric material where a precursor polymer selected from poly(phenylene vinylene) polyacetylene, poly(p-phenylene), poly(thienylene vinylene), poly(1,4-naphthylene vinylene), and poly(p-pyridine vinylene) is energized said by exposure by radiation or increase in temperature to a level sufficient to eliminate said leaving groups contained within the precursor polymer, thereby transforming the dielectric material into a conductive polymer. The leaving group in the precursor polymer can be a chloride, a bromide, an iodide, a fluoride, an ester, an xanthate, a nitrile, an amine, a nitro group, a carbonate, a dithiocarbamate, a sulfonium group, an oxonium group, an iodonium group, a pyridinium group, an ammonium group, a borate group, a borane group, a sulphinyl group, or a sulfonyl group.

Weak-link capacitor

DOEpatents

Dirk, Shawn M.; Johnson, Ross S.; Wheeler, David R.; Bogart, Gregory R.

2013-04-23

A process for making a dielectric material where a precursor polymer selected from poly(phenylene vinylene)polyacetylene, poly(p-phenylene), poly(thienylene vinylene), poly(1,4-naphthylene vinylene), and poly(p-pyridine vinylene) is energized said by exposure by radiation or increase in temperature to a level sufficient to eliminate said leaving groups contained within the precursor polymer, thereby transforming the dielectric material into a conductive polymer. The leaving group in the precursor polymer can be a chloride, a bromide, an iodide, a fluoride, an ester, an xanthate, a nitrile, an amine, a nitro group, a carbonate, a dithiocarbamate, a sulfonium group, an oxonium group, an iodonium group, a pyridinium group, an ammonium group, a borate group, a borane group, a sulphinyl group, or a sulfonyl group.

COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.

PubMed

Wang, Hongjie; Dey, Debleena; Carrera, Ivan; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

2013-09-13

Increased processing of amyloid precursor protein (APP) and accumulation of neurotoxic amyloid β peptide (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Therefore, the identification of molecules that regulate Aβ generation is crucial for future therapeutic approaches for AD. We demonstrated previously that RanBP9 regulates Aβ generation in a number of cell lines and primary neuronal cultures by forming tripartite protein complexes with APP, low-density lipoprotein-related protein, and BACE1, consequently leading to increased amyloid plaque burden in the brain. RanBP9 is a scaffold protein that exists and functions in multiprotein complexes. To identify other proteins that may bind RanBP9 and regulate Aβ levels, we used a two-hybrid analysis against a human brain cDNA library and identified COPS5 as a novel RanBP9-interacting protein. This interaction was confirmed by coimmunoprecipitation experiments in both neuronal and non-neuronal cells and mouse brain. Colocalization of COPS5 and RanBP9 in the same subcellular compartments further supported the interaction of both proteins. Furthermore, like RanBP9, COPS5 robustly increased Aβ generation, followed by increased soluble APP-β (sAPP-β) and decreased soluble-APP-α (sAPP-α) levels. Most importantly, down-regulation of COPS5 by siRNAs reduced Aβ generation, implying that endogenous COPS5 regulates Aβ generation. Finally, COPS5 levels were increased significantly in AD brains and APΔE9 transgenic mice, and overexpression of COPS5 strongly increased RanBP9 protein levels by increasing its half-life. Taken together, these results suggest that COPS5 increases Aβ generation by increasing RanBP9 levels. Thus, COPS5 is a novel RanBP9-binding protein that increases APP processing and Aβ generation by stabilizing RanBP9 protein levels.

Cu-Fe-S Nanocrystals Exhibiting Tunable Localized Surface Plasmon Resonance in the Visible to NIR Spectral Ranges.

PubMed

Gabka, Grzegorz; Bujak, Piotr; Ostrowski, Andrzej; Tomaszewski, Waldemar; Lisowski, Wojciech; Sobczak, Janusz W; Pron, Adam

2016-07-05

Cu-Fe-S nanocrystals exhibiting a strong localized surface plasmon resonance (LSPR) effect were synthesized for the first time. The elaborated reproducible preparation procedure involved copper(II) oleate, iron(III) stearate, and sulfur powder dissolved in oleylamine (OLA) as precursors. The wavelength of the plasmonic resonance maximum could be tuned by changing the Cu/Fe ratio in the resulting nanocrystals, being the most energetic for the 1:1 ratio (486 nm) and undergoing a bathochromic shift to ca. 1200 nm with an increase to 6:1. LSPR could also be observed in nanocrystals prepared from the same metal precursors and sulfur powder dissolved in 1-octadecene (ODE), provided that the sulfur precursor was taken in excess. Detailed analysis of the reaction mixture by chromatographic techniques, supplemented by mass spectrometry and (1)H NMR spectroscopy enabled the identification of the true chemical nature of the sulfur precursor in S/OLA, namely, (C18H35NH3(+))(C18H35NH-S8(-)), a reactive product of the reduction of elemental sulfur by the amine groups of OLA. In the case of the S/ODE precursor, the true precursors are much less reactive primary or secondary thioethers and dialkyl polysulfides.

Role of precursors and coating polymers in sol-gel chemistry toward enhanced selectivity and efficiency in solid phase microextraction.

PubMed

Bagheri, Habib; Piri-Moghadam, Hamed; Ahdi, Tayebeh

2012-09-12

To evaluate the selectivity and efficiency of solid phase microextraction (SPME) fiber coatings, synthesized by sol-gel technology, roles of precursors and coating polymers were extensively investigated. An on-line combination of capillary microextraction (CME) technique and high performance liquid chromatography (HPLC) was set up to perform the investigation. Ten different fiber coatings were synthesized in which five of them contained only the precursor and the rests were prepared using both the precursor and coating polymer. All the coatings were chemically bonded to the inner surface of copper tubes, intended to be used as the CME device and already functionalized by self-assembly monolayers of 3-(mercaptopropyl)trimethoxysilane (3MPTMOS). The selected precursors included tetramethoxysilane (TMOS), 3-(trimethoxysilyl)propylmethacrylate (TMSPMA), 3-(triethoxysilyl)-propylamine (TMSPA), 3MPTMOS, [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane (EPPTMOS) while poly(ethyleneglycol) (PEG) was chosen as the coating polymer. The effects of different precursors on the extraction efficiency and selectivity, was studied by selecting a list of compounds ranging from non-polar to polar ones, i.e. polycyclic aromatic hydrocarbon, herbicides, estrogens and triazines. The results from CME-HPLC analysis revealed that there is no significant difference between precursors, except TMOS, in which has the lowest extraction efficiency. Most of the selected precursors have rather similar interactions toward the selected analytes which include Van der Walls, dipole-dipole and hydrogen bond while TMOS has only dipole-dipole interaction and therefore the least efficiency. TMOS is silica but the other sorbents are organically modified silica (ORMOSIL). Our investigation revealed that it is rather impossible to prepare a selective coating using conventional sol-gel methodologies. The comparison study performed among the fiber coatings contained only a precursor and those synthesized by a precursor along with coating polymer proved that the extraction efficiency obtained for all coatings are the same. This is an indication that by selecting the appropriate precursor there is no need to use any coating polymer. In overall, a fiber coating in sol-gel process could be synthesize with no coating polymer which leads to faster, easier, cheaper and more controllable synthesis. Copyright © 2012 Elsevier B.V. All rights reserved.

Frontalin pheromone biosynthesis in the mountain pine beetle, Dendroctonus ponderosae, and the role of isoprenyl diphosphate synthases

PubMed Central

Keeling, Christopher I.; Chiu, Christine C.; Aw, Tidiane; Li, Maria; Henderson, Hannah; Tittiger, Claus; Weng, Hong-Biao; Blomquist, Gary J.; Bohlmann, Joerg

2013-01-01

The mountain pine beetle (Dendroctonus ponderosae Hopkins) is the most destructive pest of western North American pine forests. Adult males produce frontalin, an eight-carbon antiaggregation pheromone, via the mevalonate pathway, as part of several pheromones that initiate and modulate the mass attack of host trees. Frontalin acts as a pheromone, attractant, or kairomone in most Dendroctonus species, other insects, and even elephants. 6-Methylhept-6-en-2-one, a frontalin precursor, is hypothesized to originate from 10-carbon geranyl diphosphate (GPP), 15-carbon farnesyl diphosphate (FPP), or 20-carbon geranylgeranyl diphosphate (GGPP) via a dioxygenase- or cytochrome P450-mediated carbon–carbon bond cleavage. To investigate the role of isoprenyl diphosphate synthases in pheromone biosynthesis, we characterized a bifunctional GPP/FPP synthase and a GGPP synthase in the mountain pine beetle. The ratio of GPP to FPP produced by the GPP/FPP synthase was highly dependent on the ratio of the substrates isopentenyl diphosphate and dimethylallyl diphosphate used in the assay. Transcript levels in various tissues and life stages suggested that GGPP rather than GPP or FPP is used as a precursor to frontalin. Reduction of transcript levels by RNA interference of the isoprenyl diphosphate synthases identified GGPP synthase as having the largest effect on frontalin production, suggesting that frontalin is derived from a 20-carbon isoprenoid precursor rather than from the 10- or 15-carbon precursors. PMID:24167290

Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-β or Pathologic Phenotype

PubMed Central

Baybutt, Herbert; Diack, Abigail B.; Kellett, Katherine A. B.; Piccardo, Pedro; Manson, Jean C.

2016-01-01

The cellular prion protein (PrPC) has been proposed to play an important role in the pathogenesis of Alzheimer’s disease. In cellular models PrPC inhibited the action of the β-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-β (Aβ) peptides. Here we have assessed the effect of genetic ablation of PrPC in transgenic mice expressing human wild type amyloid precursor protein (line I5). Deletion of PrPC had no effect on the α- and β-secretase proteolysis of the amyloid precursor protein (APP) nor on the amount of Aβ38, Aβ40 or Aβ42 in the brains of the mice. In addition, ablation of PrPC did not alter Aβ deposition or histopathology phenotype in this transgenic model. Thus using this transgenic model we could not provide evidence to support the hypothesis that PrPC regulates Aβ production. PMID:27447728

Identification of Isopentenol Biosynthetic Genes from Bacillus subtilis by a Screening Method Based on Isoprenoid Precursor Toxicity▿

PubMed Central

Withers, Sydnor T.; Gottlieb, Shayin S.; Lieu, Bonny; Newman, Jack D.; Keasling, Jay D.

2007-01-01

We have developed a novel method to clone terpene synthase genes. This method relies on the inherent toxicity of the prenyl diphosphate precursors to terpenes, which resulted in a reduced-growth phenotype. When these precursors were consumed by a terpene synthase, normal growth was restored. We have demonstrated that this method is capable of enriching a population of engineered Escherichia coli for those clones that express the sesquiterpene-producing amorphadiene synthase. In addition, we enriched a library of genomic DNA from the isoprene-producing bacterium Bacillus subtilis strain 6051 in E. coli engineered to produce elevated levels of isopentenyl diphosphate and dimethylallyl diphosphate. The selection resulted in the discovery of two genes (yhfR and nudF) whose protein products acted directly on the prenyl diphosphate precursors and produced isopentenol. Expression of nudF in E. coli engineered with the mevalonate-based isopentenyl pyrophosphate biosynthetic pathway resulted in the production of isopentenol. PMID:17693564

Ozone pollution in China: A review of concentrations, meteorological influences, chemical precursors, and effects.

PubMed

Wang, Tao; Xue, Likun; Brimblecombe, Peter; Lam, Yun Fat; Li, Li; Zhang, Li

2017-01-01

High concentrations of ozone in urban and industrial regions worldwide have long been a major air quality issue. With the rapid increase in fossil fuel consumption in China over the past three decades, the emission of chemical precursors to ozone-nitrogen oxides and volatile organic compounds-has increased sharply, surpassing that of North America and Europe and raising concerns about worsening ozone pollution in China. Historically, research and control have prioritized acid rain, particulate matter, and more recently fine particulate matter (PM 2.5 ). In contrast, less is known about ozone pollution, partly due to a lack of monitoring of atmospheric ozone and its precursors until recently. This review summarizes the main findings from published papers on the characteristics and sources and processes of ozone and ozone precursors in the boundary layer of urban and rural areas of China, including concentration levels, seasonal variation, meteorology conducive to photochemistry and pollution transport, key production and loss processes, ozone dependence on nitrogen oxides and volatile organic compounds, and the effects of ozone on crops and human health. Ozone concentrations exceeding the ambient air quality standard by 100-200% have been observed in China's major urban centers such as Jing-Jin-Ji, the Yangtze River delta, and the Pearl River delta, and limited studies suggest harmful effect of ozone on human health and agricultural corps; key chemical precursors and meteorological conditions conductive to ozone pollution have been investigated, and inter-city/region transport of ozone is significant. Several recommendations are given for future research and policy development on ground-level ozone. Copyright © 2016 Elsevier B.V. All rights reserved.

NDMA formation in secondary wastewater effluent.

PubMed

Hatt, J W; Lamy, C; Germain, E; Tupper, M; Judd, S J

2013-03-01

Concern over prospective levels of N-nitrosodimethylamine (NDMA) in waters has increased in recent years due to its disinfection byproduct formation potential from chloramination. It has been mooted that this is promoted by organic precursors from municipal wastewaters, such that there is a more significant risk of excessive levels in water reuse applications. Experiments conducted on chloramination and chlorination of secondary wastewater have confirmed that that significant NDMA formation arises only from chloramination, with its concentration varying with test conditions used. A full factor analysis revealed all parameters studied (temperature, pH, monochloramine dose and contact time), both individually and synergistically, to have a statistically significant impact on NDMA formation with contact time being the most important. At raw water temperatures below 10 °C, the NDMA concentration can be minimised to below the 10 ng L(-1) threshold by not exceeding a monochloramine dose of 2 mg L(-1) as Cl(2). However, at higher water temperatures other measures are required to suppress NDMA formation, such as reducing the contact time (which could prove impractical in most applications) or maintaining a pH below 6. Further trials are required to fully develop the operating envelope to ensure NDMA concentrations do not exceed the 10 ng L(-1) threshold, or else to identify effective pretreatment methods for removing the NDMA precursors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Defective cholesterol metabolism in amyotrophic lateral sclerosis[S

PubMed Central

Abdel-Khalik, Jonas; Yutuc, Eylan; Crick, Peter J.; Gustafsson, Jan-Åke; Warner, Margaret; Roman, Gustavo; Talbot, Kevin; Gray, Elizabeth; Turner, Martin R.; Wang, Yuqin

2017-01-01

As neurons die, cholesterol is released in the central nervous system (CNS); hence, this sterol and its metabolites may represent a biomarker of neurodegeneration, including in amyotrophic lateral sclerosis (ALS), in which altered cholesterol levels have been linked to prognosis. More than 40 different sterols were quantified in serum and cerebrospinal fluid (CSF) from ALS patients and healthy controls. In CSF, the concentration of cholesterol was found to be elevated in ALS samples. When CSF metabolite levels were normalized to cholesterol, the cholesterol metabolite 3β,7α-dihydroxycholest-5-en-26-oic acid, along with its precursor 3β-hydroxycholest-5-en-26-oic acid and product 7α-hydroxy-3-oxocholest-4-en-26-oic acid, were reduced in concentration, whereas metabolites known to be imported from the circulation into the CNS were not found to differ in concentration between groups. Analysis of serum revealed that (25R)26-hydroxycholesterol, the immediate precursor of 3β-hydroxycholest-5-en-26-oic acid, was reduced in concentration in ALS patients compared with controls. We conclude that the acidic branch of bile acid biosynthesis, known to be operative in-part in the brain, is defective in ALS, leading to a failure of the CNS to remove excess cholesterol, which may be toxic to neuronal cells, compounded by a reduction in neuroprotective 3β,7α-dihydroxycholest-5-en-26-oic acid. PMID:27811233

Detailed investigation of Long-Period activity at Campi Flegrei by Convolutive Independent Component Analysis

NASA Astrophysics Data System (ADS)

Capuano, P.; De Lauro, E.; De Martino, S.; Falanga, M.

2016-04-01

This work is devoted to the analysis of seismic signals continuously recorded at Campi Flegrei Caldera (Italy) during the entire year 2006. The radiation pattern associated with the Long-Period energy release is investigated. We adopt an innovative Independent Component Analysis algorithm for convolutive seismic series adapted and improved to give automatic procedures for detecting seismic events often buried in the high-level ambient noise. The extracted waveforms characterized by an improved signal-to-noise ratio allows the recognition of Long-Period precursors, evidencing that the seismic activity accompanying the mini-uplift crisis (in 2006), which climaxed in the three days from 26-28 October, had already started at the beginning of the month of October and lasted until mid of November. Hence, a more complete seismic catalog is then provided which can be used to properly quantify the seismic energy release. To better ground our results, we first check the robustness of the method by comparing it with other blind source separation methods based on higher order statistics; secondly, we reconstruct the radiation patterns of the extracted Long-Period events in order to link the individuated signals directly to the sources. We take advantage from Convolutive Independent Component Analysis that provides basic signals along the three directions of motion so that a direct polarization analysis can be performed with no other filtering procedures. We show that the extracted signals are mainly composed of P waves with radial polarization pointing to the seismic source of the main LP swarm, i.e. a small area in the Solfatara, also in the case of the small-events, that both precede and follow the main activity. From a dynamical point of view, they can be described by two degrees of freedom, indicating a low-level of complexity associated with the vibrations from a superficial hydrothermal system. Our results allow us to move towards a full description of the complexity of the source, which can be used, by means of the small-intensity precursors, for hazard-model development and forecast-model testing, showing an illustrative example of the applicability of the CICA method to regions with low seismicity in high ambient noise.

Amyloid Precursor Protein Translation Is Regulated by a 3’UTR Guanine Quadruplex

PubMed Central

Sharoni, Michal; Olson, Kalee; Sebastian, Neeraj P.; Ansaloni, Sara; Schweitzer-Stenner, Reinhard; Akins, Michael R.; Bevilacqua, Philip C.; Saunders, Aleister J.

2015-01-01

A central event in Alzheimer’s disease is the accumulation of amyloid β (Aβ) peptides generated by the proteolytic cleavage of the amyloid precursor protein (APP). APP overexpression leads to increased Aβ generation and Alzheimer’s disease in humans and altered neuronal migration and increased long term depression in mice. Conversely, reduction of APP expression results in decreased Aβ levels in mice as well as impaired learning and memory and decreased numbers of dendritic spines. Together these findings indicate that therapeutic interventions that aim to restore APP and Aβ levels must do so within an ideal range. To better understand the effects of modulating APP levels, we explored the mechanisms regulating APP expression focusing on post-transcriptional regulation. Such regulation can be mediated by RNA regulatory elements such as guanine quadruplexes (G-quadruplexes), non-canonical structured RNA motifs that affect RNA stability and translation. Via a bioinformatics approach, we identified a candidate G-quadruplex within the APP mRNA in its 3’UTR (untranslated region) at residues 3008–3027 (NM_201414.2). This sequence exhibited characteristics of a parallel G-quadruplex structure as revealed by circular dichroism spectrophotometry. Further, as with other G-quadruplexes, the formation of this structure was dependent on the presence of potassium ions. This G-quadruplex has no apparent role in regulating transcription or mRNA stability as wild type and mutant constructs exhibited equivalent mRNA levels as determined by real time PCR. Instead, we demonstrate that this G-quadruplex negatively regulates APP protein expression using dual luciferase reporter and Western blot analysis. Taken together, our studies reveal post-transcriptional regulation by a 3’UTR G-quadruplex as a novel mechanism regulating APP expression. PMID:26618502

Silencing of Amyloid Precursor Protein Expression Using a New Engineered Delta Ribozyme

PubMed Central

Ben Aissa, Manel; April, Marie-Claude; Bergeron, Lucien-Junior; Perreault, Jean-Pierre; Levesque, Georges

2012-01-01

Alzheimer's disease (AD) etiological studies suggest that an elevation in amyloid-β peptides (Aβ) level contributes to aggregations of the peptide and subsequent development of the disease. The major constituent of these amyloid peptides is the 1 to 40–42 residue peptide (Aβ 40−42) derived from amyloid protein precursor (APP). Most likely, reducing Aβ levels in the brain may block both its aggregation and neurotoxicity and would be beneficial for patients with AD. Among the several possible ways to lower Aβ accumulation in the cells, we have selectively chosen to target the primary step in the Aβ cascade, namely, to reduce APP gene expression. Toward this end, we engineered specific SOFA-HDV ribozymes, a new generation of catalytic RNA tools, to decrease APP mRNA levels. Additionally, we demonstrated that APP-ribozymes are effective at decreasing APP mRNA and protein levels as well as Aβ levels in neuronal cells. Our results could lay the groundwork for a new protective treatment for AD. PMID:22482079

Impact of synoptic weather patterns on 24 h-average PM2.5 concentrations in the North China Plain during 2013-2017.

PubMed

Zhang, Hao; Yuan, Haiou; Liu, Xiaohui; Yu, Junyi; Jiao, Yongli

2018-06-15

North China Plain area (NCP) is one of the most densely populated and heavily polluted regions in the world. In the last five years, frequently happened fine particulate matter (PM 2.5 ) serious pollution events were one of the top environmental concerns in China. As PM 2.5 concentrations are highly influenced by synoptic flow patterns and local meteorological conditions, a two-stage hierarchical clustering method based on dynamic principal component analysis (DPCA) and standard k-means clustering algorithm was employed to classify synoptic wind fields into 6 patterns over the NCP area using the data of 5 PM 2.5 seasons (Sept. 15th-Apr. 15th) from 2013 to 2017. Among the six identified synoptic patterns, pattern of uniform pressure field (U) and that of zonal high pressure (Z H ) accounted for 78.21%, 65.55%, 63.56%, 57.11%, 59.13% and 58.27% studied heavy smog pollution events in Beijing, Tianjin, Tangshan, Baoding, Shijiazhuang and Xingtai city. The two particular patterns were associated with uniform pressure field and sparsely latitudinal isobar in 850 hPa level, respectively. They were also characterized by high relative humidity, low temperature, low-speed northerly wind in Tianjin and Tangshan, and southerly wind in the other cities. Under the continuous control of pattern Z H , the values of 24 h-average PM 2.5 were found to increase at a rate of 31.78 μg/m 3 per day. To evaluate the contribution of meteorological factors and precursors to PM 2.5 levels, linear mixed-effects models (LMMs) were applied to establish relations among 24 h-average PM 2.5 concentrations, concentrations of main precursors, local meteorological factors and synoptic patterns. Results show that the variations of precursors, local meteorological factors and synoptic flow patterns can explain 51.67%, 19.15% and 14.01% changes of the 24 h-average PM 2.5 concentrations, respectively. This study illustrates that dense precursor emissions are still the main cause for heavy haze pollution events, although meteorological conditions play almost equal roles sometimes. Copyright © 2018 Elsevier B.V. All rights reserved.

Predicting Solar Cycle 24 Using a Geomagnetic Precursor Pair

NASA Technical Reports Server (NTRS)

Pesnell, W. Dean

2014-01-01

We describe using Ap and F(10.7) as a geomagnetic-precursor pair to predict the amplitude of Solar Cycle 24. The precursor is created by using F(10.7) to remove the direct solar-activity component of Ap. Four peaks are seen in the precursor function during the decline of Solar Cycle 23. A recurrence index that is generated by a local correlation of Ap is then used to determine which peak is the correct precursor. The earliest peak is the most prominent but coincides with high levels of non-recurrent solar activity associated with the intense solar activity of October and November 2003. The second and third peaks coincide with some recurrent activity on the Sun and show that a weak cycle precursor closely following a period of strong solar activity may be difficult to resolve. A fourth peak, which appears in early 2008 and has recurrent activity similar to precursors of earlier solar cycles, appears to be the "true" precursor peak for Solar Cycle 24 and predicts the smallest amplitude for Solar Cycle 24. To determine the timing of peak activity it is noted that the average time between the precursor peak and the following maximum is approximately equal to 6.4 years. Hence, Solar Cycle 24 would peak during 2014. Several effects contribute to the smaller prediction when compared with other geomagnetic-precursor predictions. During Solar Cycle 23 the correlation between sunspot number and F(10.7) shows that F(10.7) is higher than the equivalent sunspot number over most of the cycle, implying that the sunspot number underestimates the solar-activity component described by F(10.7). During 2003 the correlation between aa and Ap shows that aa is 10 % higher than the value predicted from Ap, leading to an overestimate of the aa precursor for that year. However, the most important difference is the lack of recurrent activity in the first three peaks and the presence of significant recurrent activity in the fourth. While the prediction is for an amplitude of Solar Cycle 24 of 65 +/- 20 in smoothed sunspot number, a below-average amplitude for Solar Cycle 24, with maximum at 2014.5+/-0.5, we conclude that Solar Cycle 24 will be no stronger than average and could be much weaker than average.

Spatio-temporal patterns of high summer ozone events in the Madrid Basin, Central Spain

NASA Astrophysics Data System (ADS)

Reche, C.; Moreno, T.; Amato, F.; Pandolfi, M.; Pérez, J.; de la Paz, D.; Diaz, E.; Gómez-Moreno, F. J.; Pujadas, M.; Artíñano, B.; Reina, F.; Orio, A.; Pallarés, M.; Escudero, M.; Tapia, O.; Crespo, E.; Vargas, R.; Alastuey, A.; Querol, X.

2018-07-01

Complex spatial and temporal patterns of ground-level O3 and NO2 concentrations have been revealed across an important southern European O3 exceedance area (Madrid Basin, central Spain). Data were obtained from 102 diffusion tube sites and 49 monitoring stations (25 urban/suburban, 12 urban/suburban-traffic, 7 remote, 3 rural, 2 urban-industrial) located through a wide area inside and beyond the city. This new, high-density database confirms that current locations of monitoring stations in the Madrid networks are well positioned to record representative levels of O3 across the area. Two air quality monitoring stations were identified as reference measurement points, based on their lower O3 and NO2 concentrations, and used as a proxy for regional and hemispheric background levels. Although a main regional contribution was evidenced, emissions of local precursors within the Madrid urban plume play a key role in the generation of O3 exceedances, which are higher and occur earlier near the city than at rural sites, where the effect of NO titration is lower. Despite the fact that weekend emissions of O3 precursors in Madrid are typically lower than on weekdays, mainly due to fewer road traffic emissions, there is little difference in average values of weekday and weekend O3. However, more subtle "weekend effect" differences are revealed by probability density analysis, with high O3 and low NO2 at the highest temperature range (30-35° C) at weekends reflecting lower NO titration. This analysis highlights the importance of NO timing with respect to the photochemical activity timing. The complexity of these O3 pollution patterns in and around the city is dependent on an ever-changing interplay between weather conditions, emission sources, and the timescale required for pollutant transport, chemical processing and recirculation in an evolving contaminated airmass.

A deletion mutation in the 5' part of the pol gene of Moloney murine leukemia virus blocks proteolytic processing of the gag and pol polyproteins.

PubMed Central

Crawford, S; Goff, S P

1985-01-01

Deletion mutations in the 5' part of the pol gene of Moloney murine leukemia virus were generated by restriction enzyme site-directed mutagenesis of cloned proviral DNA. DNA sequence analysis indicated that one such deletion was localized entirely within the 5' part of the pol gene, did not affect the region encoding reverse transcriptase, and preserved the translational reading frame downstream of the mutation. The major viral precursor polyproteins (Pr65gag, Pr200gag-pol, and gPr80env) were synthesized at wild-type levels in cell lines carrying the mutant genome. These cell lines assembled and released wild-type levels of virion particles into the medium. Cleavage of both Pr65gag and Pr200gag-pol precursors to the mature proteins was completely blocked in the mutant virions. Surprisingly, these virions contained high levels of active reverse transcriptase; examination of the endogenous reverse transcription products synthesized by the mutant virions revealed normal amounts of minus-strand strong-stop DNA, indicating that the RNA genome was packaged and that reverse transcription in detergent-permeabilized virions was not significantly impaired. Processing of gPr80env to gP70env and P15E was not affected by the mutation, but cleavage of P15E to P12E was not observed. The mutant particles were poorly infectious; analysis indicated that infection was blocked at an early stage. The data are consistent with the idea that the 5' part of the pol gene encodes a protease directly responsible for processing Pr65gag, and possibly Pr200gag-pol, to the structural virion proteins. It appears that cleavage of the gag gene product is not required for budding and release of virions and that complete processing of the pol gene product to the mature form of reverse transcriptase is not required for its functional activation. Images PMID:3882995

Analysis of sublethal arsenic toxicity to Ceratophyllum demersum: subcellular distribution of arsenic and inhibition of chlorophyll biosynthesis.

PubMed

Mishra, Seema; Alfeld, Matthias; Sobotka, Roman; Andresen, Elisa; Falkenberg, Gerald; Küpper, Hendrik

2016-08-01

Arsenic (As) pollution is a serious concern worldwide. Recent studies under environmentally relevant conditions revealed that, in the aquatic plant Ceratophyllum demersum, pigments are the first observable target of toxicity, prior to any effect on photosynthetic parameters or to oxidative stress. Lethal toxicity was initiated by a change of As species and their distribution pattern in various tissues. Here, the localization of As was investigated at the subcellular level through X-ray fluorescence using a submicron beam and a Maia detector. Further, it was possible to obtain useful tissue structural information from the ratio of the tomogram of photon flux behind the sample to the tomogram of Compton scattering. The micro-X-ray fluorescence tomograms showed that As predominantly accumulated in the nucleus of the epidermal cells in young mature leaves exposed to sublethal 1 µM As. This suggests that As may exert toxic effects in the nucleus, for example, by interfering with nucleic acid synthesis by replacing phosphorous with As. At higher cellular concentrations, As was mainly stored in the vacuole, particularly in mature leaves. An analysis of precursors of chlorophyll and degradation metabolites revealed that the observed decrease in chlorophyll concentration was associated with hindered biosynthesis, and was not due to degradation. Coproporphyrinogen III could not be detected after exposure to only 0.5 µM As. Levels of subsequent precursors, for example, protoporphyrin IX, Mg-protoporphyrin, Mg-protoporphyrin methyl ester, and divinyl protochlorophyllide, were significantly decreased at this concentration as well, indicating that the pathway was blocked upstream of tetrapyrrole synthesis. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

An analysis of effects of San Diego wildfire on ambient air quality.

PubMed

Viswanathan, Shekar; Eria, Luis; Diunugala, Nimal; Johnson, Jeffrey; McClean, Christopher

2006-01-01

The impact of major gaseous and particulate pollutants emitted by the wildfire of October 2003 on ambient air quality and health of San Diego residents before, during, and after the fire are analyzed using data available from the San Diego County Air Pollution Control District and California Air Resources Board. It was found that fine particulate matter (PM) levels exceeded the federal daily 24-hr average standard during the fire. There was a slight increase in some of the gaseous pollutants, such as carbon monoxide, which exceeded federal standards. Ozone (O3) precursors, such as total hydrocarbons and methane gases, experienced elevated concentration during the fire. Fortunately, the absence of sunlight because of the cloud of thick smoke that covered most of the county during the fire appears to have prevented the photochemical conversion of the precursor gases to harmful concentrations of O3. Statistical analysis of the compiled medical surveillance data has been used to establish correlations between pollutant levels in the region and the resultant health problems experienced by the county citizens. The study shows that the increased PM concentration above the federal standard resulted in a significant increase in hospital emergency room visits for asthma, respiratory problems, eye irritation, and smoke inhalation. On the basis of the findings, it is recommended that hospitals and emergency medical facilities engage in pre-event planning that would ensure a rapid response to an impact on the healthcare system as a result of a large wildfire and appropriate agencies engage in the use of all available meteorological forecasting resources, including real-time satellite imaging assets, to accurately forecast air quality and assist firefighting efforts.

Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile.

PubMed

Peltier, Johann; Courtin, Pascal; El Meouche, Imane; Catel-Ferreira, Manuella; Chapot-Chartier, Marie-Pierre; Lemée, Ludovic; Pons, Jean-Louis

2013-07-01

Primary antibiotic treatment of Clostridium difficile intestinal diseases requires metronidazole or vancomycin therapy. A cluster of genes homologous to enterococcal glycopeptides resistance vanG genes was found in the genome of C. difficile 630, although this strain remains sensitive to vancomycin. This vanG-like gene cluster was found to consist of five ORFs: the regulatory region consisting of vanR and vanS and the effector region consisting of vanG, vanXY and vanT. We found that 57 out of 83 C. difficile strains, representative of the main lineages of the species, harbour this vanG-like cluster. The cluster is expressed as an operon and, when present, is found at the same genomic location in all strains. The vanG, vanXY and vanT homologues in C. difficile 630 are co-transcribed and expressed to a low level throughout the growth phases in the absence of vancomycin. Conversely, the expression of these genes is strongly induced in the presence of subinhibitory concentrations of vancomycin, indicating that the vanG-like operon is functional at the transcriptional level in C. difficile. Hydrophilic interaction liquid chromatography (HILIC-HPLC) and MS analysis of cytoplasmic peptidoglycan precursors of C. difficile 630 grown without vancomycin revealed the exclusive presence of a UDP-MurNAc-pentapeptide with an alanine at the C terminus. UDP-MurNAc-pentapeptide [d-Ala] was also the only peptidoglycan precursor detected in C. difficile grown in the presence of vancomycin, corroborating the lack of vancomycin resistance. Peptidoglycan structures of a vanG-like mutant strain and of a strain lacking the vanG-like cluster did not differ from the C. difficile 630 strain, indicating that the vanG-like cluster also has no impact on cell-wall composition.

Preparation of glass-forming materials from granulated blast furnace slag

NASA Astrophysics Data System (ADS)

Alonso, M.; Sáinz, E.; Lopez, F. A.

1996-10-01

Glass precursor materials, to be used for the vitrification of hazardous wastes, have been prepared from blast furnace slag powder through a sol-gel route. The slag is initially reacted with a mixture of alcohol (ethanol or methanol) and mineral acid (HNO3 or H2SO4) to give a sol principally consisting of Si, Ca, Al, and Mg alkoxides. Gelation is carried out with variable amounts of either ammonia or water. The gelation rate can be made as fast as desired by adding excess hydrolizing agent or else by distilling the excess alcohol out of the alkoxide solution. The resulting gel is first dried at low temperature and ground. The powder thus obtained is then heat treated at several temperatures. The intermediate and final materials are characterized by thermal analysis, infrared (IR) spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), and chemical analysis. From the results, the operating conditions yielding a variety of glass precursors differing in their composition are established. The method, in comparison with direct vitrification of slag, presents a number of advantages: (1) the glass precursor obtained devitrifies at higher temperatures; (2) it enables the adjustment, to a certain extent, of the chemical composition of the glass precursor; and (3) it permits recovering marketable materials at different stages of the process.

Differential gene expression in notochord and nerve cord fate segregation in the Ciona intestinalis embryo.

PubMed

Kobayashi, Kenji; Yamada, Lixy; Satou, Yutaka; Satoh, Nori

2013-09-01

During early embryogenesis, embryonic cells gradually restrict their developmental potential and are eventually destined to give rise to one type of cells. Molecular mechanisms underlying developmental fate restriction are one of the major research subjects within developmental biology. In this article, this subject was addressed by combining blastomere isolation with microarray analysis. During the 6th cleavage of the Ciona intestinalis embryo, from the 32-cell to the 64-cell stage, four mother cells divide into daughter cells with two distinct fates, one giving rise to notochord precursor cells and the other to nerve cord precursors. Approximately 2,200 each of notochord and nerve cord precursor cells were isolated, and their mRNA expression profiles were compared by microarray. This analysis identified 106 and 68 genes, respectively, that are differentially expressed in notochord and nerve cord precursor cells. These included not only genes for transcription factors and signaling molecules but also those with generalized functions observed in many types of cells. In addition, whole-mount in situ hybridization showed dynamic spatial expression profiles of these genes during segregation of the two fates: partitioning of transcripts present in the mother cells into either type of daughter cells, and initiation of preferential gene expression in either type of cells. Copyright © 2013 Wiley Periodicals, Inc.

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.

PubMed

Miyai, Kosuke; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.

Structural Evolution of Iron Antimonides from Amorphous Precursors to Crystalline Products Studied by Total Scattering Techniques.

PubMed

Bauers, Sage R; Wood, Suzannah R; Jensen, Kirsten M Ø; Blichfeld, Anders B; Iversen, Bo B; Billinge, Simon J L; Johnson, David C

2015-08-05

Homogeneous reaction precursors may be used to form several solid-state compounds inaccessible by traditional synthetic routes, but there has been little development of techniques that allow for a priori prediction of what may crystallize in a given material system. Here, the local structures of FeSbx designed precursors are determined and compared with the structural motifs of their crystalline products. X-ray total scattering and atomic pair distribution function (PDF) analysis are used to show that precursors that first nucleate a metastable FeSb3 compound share similar local structure to the product. Interestingly, precursors that directly crystallize to thermodynamically stable FeSb2 products also contain local structural motifs of the metastable phase, despite their compositional disagreement. While both crystalline phases consist of distorted FeSb6 octahedra with Sb shared between either two or three octahedra as required for stoichiometry, a corner-sharing arrangement indicative of AX3-type structures is the only motif apparent in the PDF of either precursor. Prior speculation was that local composition controlled which compounds nucleate from amorphous intermediates, with different compositions favoring different local arrangements and hence different products. This data suggests that local environments in these amorphous intermediates may not be very sensitive to overall composition. This can provide insight into potential metastable phases which may form in a material system, even with a precursor that does not crystallize to the kinetically stabilized product. Determination of local structure in homogeneous amorphous reaction intermediates from techniques such as PDF can be a valuable asset in the development of systematic methods to prepare targeted solid-state compounds from designed precursors.

Effects of SiO2 substitution on wettability of laser deposited Ca-P biocoating on Ti-6Al-4V.

PubMed

Yang, Yuling; Paital, Sameer R; Dahotre, Narendra B

2010-09-01

Silicon (Si) substitution in the crystal structure of calcium phosphate (CaP) ceramics has proved to generate materials with improved bioactivity than their stoichiometric counterpart. In light of this, in the current work, 100 wt% hydroxyapatite (HA) precursor and 25 wt% SiO(2)-HA precursors were used to prepare bioactive coatings on Ti-6Al-4V substrates by a laser cladding technique. The effects of SiO(2) on phase constituents, crystallite size, surface roughness, and surface energy of the CaP coatings were studied. Furthermore, on the basis of these results, the effects and roles of SiO(2) substitution in HA were systematically discussed. X-ray diffraction analysis of the coated samples indicated the presence of various phases such as CaTiO(3), Ca(2)SiO(4), Ca(3)(PO(4))(2), TiO(2) (Anatase), and TiO(2) (Rutile). The addition of SiO(2) in the HA precursor resulted in the refinement of grain size. Confocal laser microscopy characterization of the surface morphology demonstrated an improved surface roughness for samples with 25 wt% SiO(2)-HA precursor compared to the samples with 100 wt% HA precursor processed at 125 cm/min laser speed. The addition of SiO(2) in the HA precursor resulted in the highest surface energy, increased hydrophilicity, and improved biomineralization as compared to the control (untreated Ti-6Al-4V) and the sample with 100 wt% HA as precursor. The microstructural evolution observed using a scanning electron microscopy indicated that the addition of SiO(2) in the HA precursor resulted in the presence of reduced cracking across the cross-section of the bioceramic coating.

Childhood Precursors of Adult Borderline Personality Disorder Features: A Longitudinal Study.

PubMed

Cramer, Phebe

2016-07-01

This study identifies childhood personality traits that are precursors of adult Borderline Personality Disorder (BPD) features. In a longitudinal study, childhood personality traits were assessed at age 11 (N = 100) using the California Child Q-set (CCQ: Block and Block, 1980). A number of these Q-items were found to be significantly correlated (p < 0.001) with a prototype-based measure of BPD features at age 23. Factor analysis of these Q-items suggested that they could be characterized by two underlying personality dimensions: Impulsivity and Nonconformity/Aggression. The findings thus provide evidence that childhood personality traits predict adult BPD features. Identifying such childhood precursors provides an opportunity for early intervention.

Precursor routes to quaternary intermetallics: Synthesis, crystal structure, and physical properties of clathrate-II Cs8Na16Al24Si112

NASA Astrophysics Data System (ADS)

Wei, Kaya; Dong, Yongkwan; Nolas, George S.

2016-05-01

A new quaternary clathrate-II composition, Cs8Na16Al24Si112, was synthesized by kinetically controlled thermal decomposition (KCTD) employing both NaSi and NaAlSi as the precursors and CsCl as a reactive flux. The crystal structure and composition of Cs8Na16Al24Si112 were investigated using both Rietveld refinement and elemental analysis, and the temperature dependent transport properties were investigated. Our results indicate that KCTD with multiple precursors is an effective method for the synthesis of multinary inorganic phases that are not easily accessible by traditional solid-state synthesis or crystal growth techniques.

Solution properties and spectroscopic characterization of polymeric precursors to SiNCB and BN ceramic materials

NASA Astrophysics Data System (ADS)

Cortez, E.; Remsen, E.; Chlanda, V.; Wideman, T.; Zank, G.; Carrol, P.; Sneddon, L.

1998-06-01

Boron Nitride, BN, and composite SiNCB ceramic fibers are important structural materials because of their excellent thermal and oxidative stabilities. Consequently, polymeric materials as precursors to ceramic composites are receiving increasing attention. Characterization of these materials requires the ability to evaluate simultaneous molecular weight and compositional heterogeneity within the polymer. Size exclusion chromatography equipped with viscometric and refractive index detection as well as coupled to a LC-transform device for infrared absorption analysis has been employed to examine these heterogeneities. Using these combined approaches, the solution properties and the relative amounts of individual functional groups distributed through the molecular weight distribution of SiNCB and BN polymeric precursors were characterized.

Spectroscopic evidence of jet-cooled p-methyl-α-methylbenzyl radical

NASA Astrophysics Data System (ADS)

Chae, Sang Youl; Yoon, Young Wook; Lim, Manho; Lee, Sang Kuk

2015-08-01

We report spectroscopic evidence of the jet-cooled p-methyl-α-methylbenzyl radical in corona discharge. The visible vibronic emission spectra were recorded from the corona discharge of three precursors, p-xylene, p-ethyltoluene, and p-isopropyltoluene seeded in a large amount of carrier gas helium using a pinhole-type glass nozzle. From the analysis of the vibronic spectra observed from each precursor and the bond dissociation energies of precursor molecules, we are able to confirm the formation of the jet-cooled p-methyl-α-methylbenzyl radical in corona discharge, and determine the energy of the D1 → D0 transition and a few vibrational mode frequencies in the D0 state.

Mediterranean Diet Score: Associations with Metabolic Products of the Intestinal Microbiome, Carotid Plaque Burden, and Renal Function.

PubMed

Pignanelli, Michael; Just, Caroline; Bogiatzi, Chrysi; Dinculescu, Vincent; Gloor, Gregory B; Allen-Vercoe, Emma; Reid, Gregor; Urquhart, Bradley L; Ruetz, Kelsey N; Velenosi, Thomas J; Spence, J David

2018-06-16

Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO) that accumulate in renal failure (gut-derived uremic toxins, GDUTs) affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would have lower levels of GDUTs. Patients attending vascular prevention clinics completed a Harvard Food Frequency Questionnaire (FFQ) and had plasma levels of TMAO, p-cresylsulfate, hippuric acid, indoxyl sulfate, p-cresyl glucuronide, phenyl acetyl glutamine, and phenyl sulfate measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Carotid plaque burden was measured by ultrasound; CKD-Epi equations were used to estimate the glomerular filtration rate. In total, 276 patients completed the study. Even moderate renal function significantly increased plasma GDUTs, which were significantly associated with higher carotid plaque burden. There was no significant difference in plasma levels of any GDUT associated with a Mediterranean diet score or with intake of dietary precursors. In omnivorous patients with vascular disease, the intake of dietary precursors of intestinal metabolites or adherence to a Mediterranean diet did not change plasma GDUT. Approaches other than diet, such as probiotics and repopulation of the intestinal microbiome, may be required to mitigate the adverse effects of GDUTs.

Ozone process insights from field experiments - part I: overview

NASA Astrophysics Data System (ADS)

Hidy, G. M.

This paper gives an overview of selected approaches recently adopted to analyze observations from field experiments that characterize the tropospheric physics and chemistry of ozone and related oxidation products. Analysis of ambient oxidant and precursor concentration measurements, combined with meteorological observations, has provided important information about tropospheric processes. Projection of the response of tropospheric ozone concentrations to changes in precursor emissions is achieved through emissions based air quality models (AQMs). These models integrate several "process" elements from source emissions to meteorological and chemical phenomena. Through field campaigns, new knowledge has become available which has enabled workers to better understand the strengths and weaknesses of AQMs and their components. Examples of insightful results include: (a) reconciliation of ambient concentrations of speciated volatile organic compounds (VOCs) with estimates from emissions models, and inventories, (b) verification of chemical mechanisms for ozone formation from its precursors using approximations applicable in different chemical regimes, (c) inference of regimes of sensitivity in ozone concentration to changes in VOC and NO x precursors from ozone management practices, (d) conceptualization of important air mass transport and mixing processes on different spatial and temporal scales that affect ozone and precursor concentrations distributions, and (e) application of the analysis of spatial and temporal variance to infer the origins of chemical product transport, and precursor distributions. Studies from the first category have been used to improve emissions models substantially over previous forms. The remainder of the analyses has yielded valuable insight into the chemical and meteorological mechanisms at work on different spatial and temporal scales. The methods have provided an observationally based framework for effective choices to improve ozone management, notably in terms of NO x or VOC sensitive regimes. Investigation of meteorological processes relevant to ozone accumulation has illustrated the importance of accounting for both transport winds and the day-night vertical structure of the atmosphere in AQM analyses. Finally, variance analyses of O 3 concentrations with other aerometric parameters offer significant opportunities to use semi-empirically air monitoring data as a means determining space and time scales of O 3 variance, and detecting precursor emissions source-ozone receptor relationships.

Essential/precursor chemicals and drug consumption: impacts of US sodium permanganate and Mexico pseudoephedrine controls on the numbers of US cocaine and methamphetamine users.

PubMed

Cunningham, James K; Liu, Lon-Mu; Callaghan, Russell C

2016-11-01

In December 2006 the United States regulated sodium permanganate, a cocaine essential chemical. In March 2007 Mexico, the United States' primary source for methamphetamine, closed a chemical company accused of illicitly importing 60+ tons of pseudoephedrine, a methamphetamine precursor chemical. US cocaine availability and methamphetamine availability, respectively, decreased in association. This study tested whether the controls had impacts upon the numbers of US cocaine users and methamphetamine users. Auto-regressive integrated moving average (ARIMA) intervention time-series analysis. Comparison series-heroin and marijuana users-were used. United States, 2002-14. The National Survey on Drug Use and Health (n = 723 283), a complex sample survey of the US civilian, non-institutionalized population. Estimates of the numbers of (1) past-year users and (2) past-month users were constructed for each calendar quarter from 2002 to 2014, providing each series with 52 time-periods. Downward shifts in cocaine users started at the time of the cocaine regulation. Past-year and past-month cocaine users series levels decreased by approximately 1 946 271 (-32%) (P < 0.05) and 694 770 (-29%) (P < 0.01), respectively-no apparent recovery occurred through 2014. Downward shifts in methamphetamine users started at the time of the chemical company closure. Past-year and past-month methamphetamine series levels decreased by 494 440 (-35%) [P < 0.01; 95% confidence interval (CI) = -771 897, -216 982] and 277 380 (-45%) (P < 0.05; CI = -554 073, -686), respectively-partial recovery possibly occurred in 2013. The comparison series changed little at the intervention times. Essential/precursor chemical controls in the United States (2006) and Mexico (2007) were associated with large, extended (7+ years) reductions in cocaine users and methamphetamine users in the United States. © 2016 Society for the Study of Addiction.

Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells

PubMed Central

Kim, Yi Young; Roubal, Ivan; Lee, Youn Soo; Kim, Jin Seok; Hoang, Michael; Mathiyakom, Nathan; Kim, Yong

2016-01-01

Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol’s effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event associated with alcohol-related peripheral neuropathy of an enhanced nociceptive response. PMID:27682028

Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker Trimethylamine N-oxide from dietary precursors

PubMed Central

Petriello, Michael C; Hoffman, Jessie B; Sunkara, Manjula; Wahlang, Banrida; Perkins, Jordan T; Morris, Andrew J; Hennig, Bernhard

2016-01-01

The etiology of cardiovascular disease (CVD) is impacted by multiple modifiable and non-modifiable risk factors including dietary choices, genetic predisposition, and environmental exposures. However, mechanisms linking diet, exposure to pollutants, and CVD risk are largely unclear. Recent studies identified a strong link between plasma levels of nutrient-derived Trimethylamine N-oxide (TMAO) and coronary artery disease. Dietary precursors of TMAO include carnitine and phosphatidylcholine, which are abundant in animal-derived foods. Dioxin-like pollutants can upregulate a critical enzyme responsible for TMAO formation, hepatic flavin containing monooxygenase 3 (FMO3), but a link between dioxin-like PCBs, upregulation of FMO3, and increased TMAO has not been reported. Here, we show that mice exposed acutely to dioxin-like PCBs exhibit increased hepatic FMO3 mRNA, protein, as well as an increase in circulating levels of TMAO following oral administration of its metabolic precursors. C57BL/6 mice were exposed to 5 μmol PCB 126/kg mouse weight (1.63 mg/kg). At 48 h post-PCB exposure, mice were subsequently given a single gavage of phosphatidylcholine dissolved in corn oil. Exposure to 5 μmole/kg PCB 126 resulted in greater than 100-fold increase in FMO3 mRNA expression, robust induction of FMO3 protein, and a 5-fold increase in TMAO levels compared with vehicle treated mice. We made similar observations in mice exposed to PCB 77 (49.6 mg/kg twice); stable isotope tracer studies revealed increased formation of plasma TMAO from an orally administered precursor trimethylamine (TMA). Taken together, these observations suggest a novel diet-toxicant interaction that results in increased production of a circulating biomarker of cardiovascular disease risk. PMID:27155921

Poly- and perfluoroalkyl substances in wastewater: Significance of unknown precursors, manufacturing shifts, and likely AFFF impacts.

PubMed

Houtz, Erika F; Sutton, Rebecca; Park, June-Soo; Sedlak, Margaret

2016-05-15

In late 2014, wastewater effluent samples were collected from eight treatment plants that discharge to San Francisco (SF) Bay in order to assess poly- and perfluoroalkyl substances (PFASs) currently released from municipal and industrial sources. In addition to direct measurement of twenty specific PFAS analytes, the total concentration of perfluoroalkyl acid (PFAA) precursors was also indirectly measured by adapting a previously developed oxidation assay. Effluent from six municipal treatment plants contained similar amounts of total PFASs, with highest median concentrations of PFHxA (24 ng/L), followed by PFOA (23 ng/L), PFBA (19 ng/L), and PFOS (15 ng/L). Compared to SF Bay municipal wastewater samples collected in 2009, the short chain perfluorinated carboxylates PFBA and PFHxA rose significantly in concentration. Effluent samples from two treatment plants contained much higher levels of PFASs: over two samplings, wastewater from one municipal plant contained an average of 420 ng/L PFOS and wastewater from an airport industrial treatment plant contained 560 ng/L PFOS, 390 ng/L 6:2 FtS, 570 ng/L PFPeA, and 500 ng/L PFHxA. The elevated levels observed in effluent samples from these two plants are likely related to aqueous film forming foam (AFFF) sources impacting their influent; PFASs attributable to both current use and discontinued AFFF formulations were observed. Indirectly measured PFAA precursor compounds accounted for 33%-63% of the total molar concentration of PFASs across all effluent samples and the PFAA precursors indicated by the oxidation assay were predominately short-chained. PFAS levels in SF Bay effluent samples reflect the manufacturing shifts towards shorter chained PFASs while also demonstrating significant impacts from localized usage of AFFF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solid-State Kinetic Investigations of Nonisothermal Reduction of Iron Species Supported on SBA-15

PubMed Central

2017-01-01

Iron oxide catalysts supported on nanostructured silica SBA-15 were synthesized with various iron loadings using two different precursors. Structural characterization of the as-prepared FexOy/SBA-15 samples was performed by nitrogen physisorption, X-ray diffraction, DR-UV-Vis spectroscopy, and Mössbauer spectroscopy. An increasing size of the resulting iron species correlated with an increasing iron loading. Significantly smaller iron species were obtained from (Fe(III), NH4)-citrate precursors compared to Fe(III)-nitrate precursors. Moreover, smaller iron species resulted in a smoother surface of the support material. Temperature-programmed reduction (TPR) of the FexOy/SBA-15 samples with H2 revealed better reducibility of the samples originating from Fe(III)-nitrate precursors. Varying the iron loading led to a change in reduction mechanism. TPR traces were analyzed by model-independent Kissinger method, Ozawa, Flynn, and Wall (OFW) method, and model-dependent Coats-Redfern method. JMAK kinetic analysis afforded a one-dimensional reduction process for the FexOy/SBA-15 samples. The Kissinger method yielded the lowest apparent activation energy for the lowest loaded citrate sample (Ea ≈ 39 kJ/mol). Conversely, the lowest loaded nitrate sample possessed the highest apparent activation energy (Ea ≈ 88 kJ/mol). For samples obtained from Fe(III)-nitrate precursors, Ea decreased with increasing iron loading. Apparent activation energies from model-independent analysis methods agreed well with those from model-dependent methods. Nucleation as rate-determining step in the reduction of the iron oxide species was consistent with the Mampel solid-state reaction model. PMID:29230346

Prediction of the total cycle 24 of solar activity by several autoregressive methods and by the precursor method

NASA Astrophysics Data System (ADS)

Ozheredov, V. A.; Breus, T. K.; Obridko, V. N.

2012-12-01

As follows from the statement of the Third Official Solar Cycle 24 Prediction Panel created by the National Aeronautics and Space Administration (NASA), the National Oceanic and Atmospheric Administration (NOAA), and the International Space Environment Service (ISES) based on the results of an analysis of many solar cycle 24 predictions, there has been no consensus on the amplitude and time of the maximum. There are two different scenarios: 90 units and August 2012 or 140 units and October 2011. The aim of our study is to revise the solar cycle 24 predictions by a comparative analysis of data obtained by three different methods: the singular spectral method, the nonlinear neural-based method, and the precursor method. As a precursor for solar cycle 24, we used the dynamics of the solar magnetic fields forming solar spots with Wolf numbers Rz. According to the prediction on the basis of the neural-based approach, it was established that the maximum of solar cycle 24 is expected to be 70. The precursor method predicted 50 units for the amplitude and April of 2012 for the time of the maximum. In view of the fact that the data used in the precursor method were averaged over 4.4 years, the amplitude of the maximum can be 20-30% larger (i.e., around 60-70 units), which is close to the values predicted by the neural-based method. The protracted minimum of solar cycle 23 and predicted low values of the maximum of solar cycle 24 are reminiscent of the historical Dalton minimum.

New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia.

PubMed

van der Velden, Vincent H J; de Launaij, Daphne; de Vries, Jeltje F; de Haas, Valerie; Sonneveld, Edwin; Voerman, Jane S A; de Bie, Maaike; Revesz, Tamas; Avigad, Smadar; Yeoh, Allen E J; Swagemakers, Sigrid M A; Eckert, Cornelia; Pieters, Rob; van Dongen, Jacques J M

2016-03-01

In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray-analysis, we discovered multiple differentially expressed genes between B-cell precursor (BCP) ALL cells in bone marrow (BM) and BCP-ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real-time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP-ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP-ALL cells (>1%) with a 'CNS protein profile' (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP-ALL cells with a 'CNS protein profile' at diagnosis (particularly SCD-positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity. © 2015 John Wiley & Sons Ltd.

Ozone concentrations and damage for realistic future European climate and air quality scenarios

NASA Astrophysics Data System (ADS)

Hendriks, Carlijn; Forsell, Nicklas; Kiesewetter, Gregor; Schaap, Martijn; Schöpp, Wolfgang

2016-11-01

Ground level ozone poses a significant threat to human health from air pollution in the European Union. While anthropogenic emissions of precursor substances (NOx, NMVOC, CH4) are regulated by EU air quality legislation and will decrease further in the future, the emissions of biogenic NMVOC (mainly isoprene) may increase significantly in the coming decades if short-rotation coppice plantations are expanded strongly to meet the increased biofuel demand resulting from the EU decarbonisation targets. This study investigates the competing effects of anticipated trends in land use change, anthropogenic ozone precursor emissions and climate change on European ground level ozone concentrations and related health and environmental impacts until 2050. The work is based on a consistent set of energy consumption scenarios that underlie current EU climate and air quality policy proposals: a current legislation case, and an ambitious decarbonisation case. The Greenhouse Gas-Air Pollution Interactions and Synergies (GAINS) integrated assessment model was used to calculate air pollutant emissions for these scenarios, while land use change because of bioenergy demand was calculated by the Global Biosphere Model (GLOBIOM). These datasets were fed into the chemistry transport model LOTOS-EUROS to calculate the impact on ground level ozone concentrations. Health damage because of high ground level ozone concentrations is projected to decline significantly towards 2030 and 2050 under current climate conditions for both energy scenarios. Damage to plants is also expected to decrease but to a smaller extent. The projected change in anthropogenic ozone precursor emissions is found to have a larger impact on ozone damage than land use change. The increasing effect of a warming climate (+2-5 °C across Europe in summer) on ozone concentrations and associated health damage, however, might be higher than the reduction achieved by cutting back European ozone precursor emissions. Global action to reduce air pollutant emissions is needed to make sure that ozone damage in Europe decreases towards the middle of this century.

Synthesis and decomposition of a novel carboxylate precursor to indium oxide

NASA Technical Reports Server (NTRS)

Hepp, Aloysius F.; Andras, Maria T.; Duraj, Stan A.; Clark, Eric B.; Hehemann, David G.; Scheiman, Daniel A.; Fanwick, Phillip E.

1994-01-01

Reaction of metallic indium with benzoyl peroxide in 4-1 methylpyridine (4-Mepy) at 25 C produces an eight-coordinate mononuclear indium(III) benzoate, In(eta(sup 2)-O2CC6H5)3(4-Mepy)2 4H2O (I), in yields of up to 60 percent. The indium(III) benzoate was fully characterized by elemental analysis, spectroscopy, and X-ray crystallography; (I) exists in the crystalline state as discrete eight-coordinate molecules; the coordination sphere around the central indium atom is best described as pseudo-square pyramidal. Thermogravimetric analysis of (I) and X-ray diffraction powder studies on the resulting pyrolysate demonstrate that this new benzoate is an inorganic precursor to indium oxide. Decomposition of (I) occurs first by loss of 4-methylpyridine ligands (100 deg-200 deg C), then loss of benzoates with formation of In2O3 at 450 C. We discuss both use of carboxylates as precursors and our approach to their preparation.

A Real-Time Earthquake Precursor Detection Technique Using TEC from a GPS Network

NASA Astrophysics Data System (ADS)

Alp Akyol, Ali; Arikan, Feza; Arikan, Orhan

2016-07-01

Anomalies have been observed in the ionospheric electron density distribution prior to strong earthquakes. However, most of the reported results are obtained by earthquake analysis. Therefore, their implementation in practice is highly problematic. Recently, a novel earthquake precursor detection technique based on spatio-temporal analysis of Total Electron Content (TEC) data obtained from Turkish National Permanent GPS Network (TNPGN) is developed by IONOLAB group (www.ionolab.org). In the present study, the developed detection technique is implemented in a causal setup over the available data set in test phase that enables the real time implementation. The performance of the developed earthquake prediction technique is evaluated by using 10 fold cross validation over the data obtained in 2011. Among the 23 earthquakes that have magnitudes higher than 5, the developed technique can detect precursors of 14 earthquakes while producing 8 false alarms. This study is supported by TUBITAK 115E915 and Joint TUBITAK 114E092 and AS CR 14/001 projects.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

PubMed

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Isolation of dermatoxin from frog skin, an antibacterial peptide encoded by a novel member of the dermaseptin genes family.

PubMed

Amiche, M; Seon, A A; Wroblewski, H; Nicolas, P

2000-07-01

A 32-residue peptide, named dermatoxin, has been extracted from the skin of a single specimen of the tree frog Phyllomedusa bicolor, and purified to homogeneity using a four-step protocol. Mass spectral analysis and sequencing of the purified peptide, as well as chemical synthesis and cDNA analysis were consistent with the structure: SLGSFLKGVGTTLASVGKVVSDQF GKLLQAGQ. This peptide proved to be bactericidal towards mollicutes (wall-less eubacteria) and Gram-positive eubacteria, and also, though to a lesser extent, towards Gram-negative eubacteria. Measurement of the bacterial membrane potential revealed that the plasma membrane is the primary target of dermatoxin. Observation of bacterial cells using reflected light fluorescence microscopy after DNA-staining was consistent with a mechanism of cell killing based upon the alteration of membrane permeability rather than membrane solubilization, very likely by forming ion-conducting channels through the plasma membrane. CD spectroscopy and secondary structure predictions indicated that dermatoxin assumes an amphipathic alpha-helical conformation in low polarity media which mimic the lipophilicity of the membrane of target microorganisms. PCR analysis coupled with cDNA cloning and sequencing revealed that dermatoxin is expressed in the skin, the intestine and the brain. Preprodermatoxin from the brain and the intestine have the same sequence as the skin preproform except for two amino-acid substitutions in the preproregion of the brain precursor. The dermatoxin precursor displayed the characteristic features of preprodermaseptins, a family of peptide precursors found in the skin of Phyllomedusa ssp. Precursors of this family have a common N-terminal preproregion followed by markedly different C-terminal domains that give rise to 19-34-residue peptide antibiotics named dermaseptins B and phylloxin, and to the D-amino-acid-containing opioid heptapeptides dermorphins and deltorphins. Because the structures and cidal mechanisms of dermatoxin, dermaseptins B and phylloxin are very different, dermatoxin extends the repertoire of structurally and functionally diverse peptides derived from the rapidly evolving C-terminal domains of precursors of the dermaseptins family.

Bleogens: Cactus-Derived Anti-Candida Cysteine-Rich Peptides with Three Different Precursor Arrangements

PubMed Central

Loo, Shining; Kam, Antony; Xiao, Tianshu; Tam, James P.

2017-01-01

Cysteine-rich peptides (CRPs) play important host-defense roles in plants. However, information concerning CRPs in the Cactaceae (cactus) family is limited, with only a single cactus-derived CRP described to date. Here, we report the identification of 15 novel CRPs with three different precursor architectures, bleogens pB1-15 from Pereskia bleo of the Cactaceae family. By combining proteomic and transcriptomic methods, we showed that the prototype, bleogen pB1, contained 36 amino acid residues, a six-cysteine motif typical of the six-cysteine-hevein-like peptide (6C-HLP) family, and a type I two-domain precursor consisting of an endoplasmic reticulum (ER) and a mature domain. In contrast, the precursors of the other 14 bleogens contained a type II three-domain architecture with a propeptide domain inserted between the ER and the mature bleogen domain. Four of these 14 bleogens display a third type of architecture with a tandemly repeating bleogen domain. A search of the Onekp database revealed that <1% plant species possess three different precursor architectures for the biosynthesis of 6C-HLPs, including Lophophora williamsii, Pereskia aculeate, Portulaca cryptopetala, Portulaca oleracea, Portulaca suffruticosa, and Talinum sp. NMR analysis confirmed that bleogen pB1 has cystine-knot disulfide connectivity as well as a two-beta-sheet and a four-loop structural fold that is similar to other 6C-HLPs. Sequence analysis, structural studies, and in silico modeling revealed that bleogen pB1 has a cation-polar-cation motif, a signature heparin-binding motif that was confirmed by heparin affinity chromatography. Cell-based assays showed that bleogen pB1 is non-toxic to mammalian cells but functions as an anti-Candida peptide. Taken together, our findings provide insight into the occurrence, functions and precursor architectures of CRPs in the cactus family. PMID:29312404

Hydrothermal synthesis and characterization of Si and Sr co-substituted hydroxyapatite nanowires using strontium containing calcium silicate as precursors.

PubMed

Zhang, Na; Zhai, Dong; Chen, Lei; Zou, Zhaoyong; Lin, Kaili; Chang, Jiang

2014-04-01

In the absence of any organic surfactants and solvents, the silicon (Si) and strontium (Sr) co-substituted hydroxyapatite [Ca10(PO4)6(OH)2, Si/Sr-HAp] nanowires were synthesized via hydrothermal treatment of the Sr-containing calcium silicate (Sr-CS) powders as the precursors in trisodium phosphate (Na3PO4) aqueous solution. The morphology, phase, chemical compositions, lattice constants and the degradability of the products were characterized. The Si/Sr-HAp nanowires with diameter of about 60nm and up to 2μm in length were obtained after hydrothermal treatment of the Sr-CS precursors. The Sr and Si substitution amount of the HAp nanowires could be well regulated by facile tailoring the Sr substitution level of the precursors and the reaction ratio of the precursor/solution, respectively. The SiO4 tetrahedra and Sr(2+) ions occupied the crystal sites of the HAp, and the lattice constants increased apparently with the increase of the substitution amount. EDS mapping also suggested the uniform distribution of Si and Sr in the synthetic nanowires. Moreover, the Si/Sr-substitution apparently improved the degradability of the HAp materials. Our study suggested that the precursor transformation method provided a facile approach to synthesize the Si/Sr co-substituted HAp nanowires with controllable substitution amount, and the synthetic Si/Sr-HAp nanowires might be used as bioactive materials for hard tissue regeneration applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Occurrence of THM and NDMA precursors in a watershed: Effect of seasons and anthropogenic pollution.

PubMed

Aydin, Egemen; Yaman, Fatma Busra; Ates Genceli, Esra; Topuz, Emel; Erdim, Esra; Gurel, Melike; Ipek, Murat; Pehlivanoglu-Mantas, Elif

2012-06-30

In pristine watersheds, natural organic matter is the main source of disinfection by-product (DBP) precursors. However, the presence of point or non-point pollution sources in watersheds may lead to increased levels of DBP precursors which in turn form DBPs in the drinking water treatment plant upon chlorination or chloramination. In this study, water samples were collected from a lake used to obtain drinking water for Istanbul as well as its tributaries to investigate the presence of the precursors of two disinfection by-products, trihalomethanes (THM) and N-nitrosodimethylamine (NDMA). In addition, the effect of seasons and the possible relationships between these precursors and water quality parameters were evaluated. The concentrations of THM and NDMA precursors measured as total THM formation potential (TTHMFP) and NDMA formation potential (NDMAFP) ranged between 126 and 1523μg/L THM and <2 and 1648ng/L NDMA, respectively. Such wide ranges imply that some of the tributaries are affected by anthropogenic pollution sources, which is also supported by high DOC, Cl(-) and NH(3) concentrations. No significant correlation was found between the water quality parameters and DBP formation potential, except for a weak correlation between NDMAFP and DOC concentrations. The effect of the sampling location was more pronounced than the seasonal variation due to anthropogenic pollution in some tributaries and no significant correlation was obtained between the seasons and water quality parameters. Copyright © 2012 Elsevier B.V. All rights reserved.

Isolation of Oct4-Expressing Extraembryonic Endoderm Precursor Cell Lines

PubMed Central

Debeb, Bisrat G.; Galat, Vasiliy; Epple-Farmer, Jessica; Iannaccone, Steve; Woodward, Wendy A.; Bader, Michael; Iannaccone, Philip; Binas, Bert

2009-01-01

Background The extraembryonic endoderm (ExEn) defines the yolk sac, a set of membranes that provide essential support for mammalian embryos. Recent findings suggest that the committed ExEn precursor is present already in the embryonic Inner Cell Mass (ICM) as a group of cells that intermingles with the closely related epiblast precursor. All ICM cells contain Oct4, a key transcription factor that is first expressed at the morula stage. In vitro, the epiblast precursor is most closely represented by the well-characterized embryonic stem (ES) cell lines that maintain the expression of Oct4, but analogous ExEn precursor cell lines are not known and it is unclear if they would express Oct4. Methodology/Principal Findings Here we report the isolation and characterization of permanently proliferating Oct4-expressing rat cell lines (“XEN-P cell lines”), which closely resemble the ExEn precursor. We isolated the XEN-P cell lines from blastocysts and characterized them by plating and gene expression assays as well as by injection into embryos. Like ES cells, the XEN-P cells express Oct4 and SSEA1 at high levels and their growth is stimulated by leukemia inhibitory factor, but instead of the epiblast determinant Nanog, they express the ExEn determinants Gata6 and Gata4. Further, they lack markers characteristic of the more differentiated primitive/visceral and parietal ExEn stages, but exclusively differentiate into these stages in vitro and contribute to them in vivo. Conclusions/Significance Our findings (i) suggest strongly that the ExEn precursor is a self-renewable entity, (ii) indicate that active Oct4 gene expression (transcription plus translation) is part of its molecular identity, and (iii) provide an in vitro model of early ExEn differentiation. PMID:19784378

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

PubMed

Bond, Jonathan; Marchand, Tony; Touzart, Aurore; Cieslak, Agata; Trinquand, Amélie; Sutton, Laurent; Radford-Weiss, Isabelle; Lhermitte, Ludovic; Spicuglia, Salvatore; Dombret, Hervé; Macintyre, Elizabeth; Ifrah, Norbert; Hamel, Jean-François; Asnafi, Vahid

2016-06-01

Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% versus 14.5%, P=0.0004), chemoresistance (59.3% versus 40.8%, P=0.026) and positivity for minimal residual disease (48.5% versus 23.5%, P=0.01) than the HOXA-negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA-positive cases harboring fusion oncoproteins that transactivate HOXA Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA-positive group (5-year overall survival 31.2% in HOXA-positive early thymic precursor versus 66.7% in HOXA-positive non-early thymic precursor, P=0.03), but not in HOXA-negative cases (5-year overall survival 74.2% in HOXA-negative early thymic precursor versus 57.2% in HOXA-negative non-early thymic precursor, P=0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (P=0.053) and relapse risk (P=0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates the clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA-positive patients, suggesting that early treatment intensification is currently suboptimal for therapeutic rescue of HOXA-positive chemoresistant adult early thymic precursor acute lymphoblastic leukemia. The GRAALL-2003 and -2005 studies were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. Copyright© Ferrata Storti Foundation.

Hotspot ignition using a Z-pinch precursor plasma in a magneto-inertial ICF scheme

NASA Astrophysics Data System (ADS)

Chittenden, J. P.; Vincent, P.; Jennings, C. A.; Ciardi, A.

2006-01-01

Precursor plasma flow is a common feature of wire array Z-pinches. The precursor flow represents a fraction of the mass of the array which arrives on the axis early in time and remains confined at high density by the inertia of further material bombarding the axis. Later on, the main implosion of the Z-pinch then compresses this precursor to substantially higher density. We show that if the same system can be generated with a Deuterium-Tritium plasma then the precursor provides an ideal target for a cylindrical magneto-inertial ICF scheme. The implosion of the DT Z-pinch produces a dense, low temperature shell which compressively heats the precursor target to high temperatures and tamps its expansion. The azimuthal magnetic field in the hotspot is sufficient to reduce the Larmor radius for the alpha particles to much less than the hotspot size, which dramatically reduces the pR required for ignition. A computational analysis of this approach is presented, including a study of the thermonuclear burn wave propagation. The robustness of the scheme with respect to instabilities, confinement time and drive parameters is examined. The results indicate that a high energy gain can be achieved using Z-pinches with 50-100 MA currents and a few hundred nanosecond rise-times. This work was partially supported by the U.S. Department of Energy through cooperative agreement DE-FC03-02NA00057.

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

Rorsman, F.; Bywater, M.; Knott, T.J.

The human platelet-derived growth factor (PDGF) A-chain locus was characterized by restriction endonuclease analysis, and the nucleotide sequence of its exons was determined. Seven exons were identified, spanning approximately 22 kilobase pairs of genomic DNA. Alternative exon usage, identified by cDNA cloning, occurs in a human glioblastoma cell line and may give rise to two types of A-chain precursors with different C termini. The exon-intron arrangement was similar to that of the PDGF B-chain/sis locus and seemed to divide the precursor proteins into functional domains. Southern blot analysis of genomic DNA showed that a single PDGF A-chain gene was presentmore » in the human genome.« less

Thermodynamic analysis of vapor-phase epitaxy of CdTe using a metallic Cd source

NASA Astrophysics Data System (ADS)

Iso, Kenji; Murakami, Hisashi; Koukitu, Akinori

2017-07-01

Thermodynamic analysis of CdTe growth using cost-effective metallic Cd and dialkyl telluride was performed. The major vapor species at source zone in equilibrium were gaseous Cd for the group-II precursor, and Te2 and H2Te for the group-VI precursors. The driving force for the CdTe deposition was still positive even at 650 °C. This indicates that CdTe formation from gaseous Cd can proceed thermodynamically. Furthermore, the calculations showed that CdTe decomposes at higher temperature and increasing the II/VI ratio increases the limit of the growth temperature, which coincides with the experimental results.

Synthesis and characterization of Co3O4 prepared from atmospheric pressure acid leach liquors of nickel laterite ores

NASA Astrophysics Data System (ADS)

Meng, Long; Guo, Zhan-cheng; Qu, Jing-kui; Qi, Tao; Guo, Qiang; Hou, Gui-hua; Dong, Peng-yu; Xi, Xin-guo

2018-01-01

A chemical precipitation-thermal decomposition method was developed to synthesize Co3O4 nanoparticles using cobalt liquor obtained from the atmospheric pressure acid leaching process of nickel laterite ores. The effects of the precursor reaction temperature, the concentration of Co2+, and the calcination temperature on the specific surface area, morphology, and the electrochemical behavior of the obtained Co3O4 particles were investigated. The precursor basic cobaltous carbonate and cobaltosic oxide products were characterized and analyzed by Fourier transform infrared spectroscopy, thermogravimetric differential thermal analysis, X-ray diffraction, field-emission scanning electron microscopy, specific surface area analysis, and electrochemical analysis. The results indicate that the specific surface area of the Co3O4 particles with a diameter of 30 nm, which were obtained under the optimum conditions of a precursor reaction temperature of 30°C, 0.25 mol/L Co2+, and a calcination temperature of 350°C, was 48.89 m2/g. Electrodes fabricated using Co3O4 nanoparticles exhibited good electrochemical properties, with a specific capacitance of 216.3 F/g at a scan rate of 100 mV/s.

Global Profiling and Novel Structure Discovery Using Multiple Neutral Loss/Precursor Ion Scanning Combined with Substructure Recognition and Statistical Analysis (MNPSS): Characterization of Terpene-Conjugated Curcuminoids in Curcuma longa as a Case Study.

PubMed

Qiao, Xue; Lin, Xiong-hao; Ji, Shuai; Zhang, Zheng-xiang; Bo, Tao; Guo, De-an; Ye, Min

2016-01-05

To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.

A Review of Single Source Precursors for the Deposition of Ternary Chalcopyrite Materials

NASA Technical Reports Server (NTRS)

Banger, K. K.; Cowen, J.; Harris, J.; McClarnon, R.; Hehemann, D. G.; Duraj, S. A.; Scheiman, D.; Hepp, A. F.

2002-01-01

The development of thin-film solar cells on flexible, lightweight, space-qualified durable substrates (i.e. Kapton) provides an attractive solution to fabricating solar arrays with high specific power, (W/kg). The syntheses and thermal modulation of ternary single source precursors, based on the [{LR}2Cu(SR')2In(SR')2] architecture in good yields are described. Thermogravimetric analyses (TGA) and Low temperature Differential Scanning Caloriometry, (DSC) demonstrate that controlled manipulation of the steric and electronic properties of either the group five-donor and/or chalcogenide moiety permits directed adjustment of the thermal stability and physical properties of the precursors. TGA-Evolved Gas Analysis, confirms that single precursors decompose by the initial extrusion of the sulphide moiety, followed by the loss of the neutral donor group, (L) to release the ternary chalcopyrite matrix. X-ray diffraction studies, EDS and SEM on the non-volatile pyrolized material demonstrate that these derivatives afford single-phase CuInS2/CuInSe2 materials at low temperature. Thin-film fabrication studies demonstrate that these single source precursors can be used in a spray chemical vapor deposition process, for depositing CuInS2 onto flexible polymer substrates at temperatures less than 400 C.

Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein.

PubMed

Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Kubo, Shinichi; Hori, Hitoshi

2004-01-01

Serum vitamin D-binding protein (Gc protein or DBP) is a highly expressed polymorphic protein, which is a precursor of the inflammation-primed macrophage activating factor, GcMAF, by a cascade of carbohydrate processing reactions. In order to elucidate the relationship between Gc polymorphism and GcMAF precursor activity, we estimated the phagocytic ability of three homotypes of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their carbohydrate moiety. We performed Gc typing of human serum samples by isoelectric focusing (IEF). Gc protein from human serum was purified by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried out. The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc linkage by the analysis of GcMAF precursor activity using beta1-4 linkage-specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F-1F phenotype was highest among three Gc homotypes. The Gc polymorphism and carbohydrate diversity of Gc protein are significant for its pleiotropic effects.

Supramolecular structure formation of Langmuir-Blodgett films of comblike precursor and polyimide

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

Goloudina, S. I., E-mail: goloudina@mail.ru; Luchinin, V. V.; Rozanov, V. V.

2013-03-15

The surface structure of Langmuir-Blodgett films of a comblike polyimide precursor-a rigid-chain polyamic acid alkylamine salt bearing multichains of tertiary amine-and films of the corresponding polyimide were studied by atomic force microscopy (AFM). An analysis of the images of the surface of three-layer films revealed a domain structure. It was found that the Langmuir-Blodgett film formation of the precursor occurs as a result of the layer-by-layer deposition of two-dimensional domains (composed of polyamic acid salt molecules on the water surface) onto a substrate. The formation of domains in a monolayer is associated with the chemical structure of the precursor, tomore » be more precise, with the rigidity of the main chain and the presence of closely spaced aliphatic side chains in the polymer chain, whose total cross-section area is close to the surface area of the projection onto the plane of the repeating unit of the main chain. Polyimide films inherit the domain structure of the precursor films; the inhomogeneity of the film thickness substantially decreases, whereas the domain size and character of their distribution in the film remain unchanged.« less

Precursor effect on the property and catalytic behavior of Fe-TS-1 in butadiene epoxidation

NASA Astrophysics Data System (ADS)

Wu, Mei; Zhao, Huahua; Yang, Jian; Zhao, Jun; Song, Huanling; Chou, Lingjun

2017-11-01

The effect of iron precursor on the property and catalytic behavior of iron modified titanium silicalite molecular sieve (Fe-TS-1) catalysts in butadiene selective epoxidation has been studied. Three Fe-TS-1 catalysts were prepared, using iron nitrate, iron chloride and iron sulfate as precursors, which played an important role in adjusting the textural properties and chemical states of TS-1. Of the prepared Fe-TS-1 catalysts, those modified by iron nitrate (FN-TS-1) exhibited a significant enhanced performance in butadiene selective epoxidation compared to those derived from iron sulfate (FS-TS-1) or iron chloride (FC-TS-1) precursors. To obtain a deep understanding of their structure-performance relationship, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Temperature programmed desorption of NH3 (NH3-TPD), Diffuse reflectance UV-Vis spectra (DR UV-Vis), Fourier transformed infrared spectra (FT-IR) and thermal gravimetric analysis (TGA) were conducted to characterize Fe-TS-1 catalysts. Experimental results indicated that textural structures and acid sites of modified catalysts as well as the type of Fe species influenced by the precursors were all responsible for the activity and product distribution.

Identification and characterization of the reptilian GnRH-II gene in the leopard gecko, Eublepharis macularius, and its evolutionary considerations.

PubMed

Ikemoto, Tadahiro; Park, Min Kyun

2003-10-16

To elucidate the molecular phylogeny and evolution of a particular peptide, one must analyze not the limited primary amino acid sequences of the low molecular weight mature polypeptide, but rather the sequences of the corresponding precursors from various species. Of all the structural variants of gonadotropin-releasing hormone (GnRH), GnRH-II (chicken GnRH-II, or cGnRH-II) is remarkably conserved without any sequence substitutions among vertebrates, but its precursor sequences vary considerably. We have identified and characterized the full-length complementary DNA (cDNA) encoding the GnRH-II precursor and determined its genomic structure, consisting of four exons and three introns, in a reptilian species, the leopard gecko Eublepharis macularius. This is the first report about the GnRH-II precursor cDNA/gene from reptiles. The deduced leopard gecko prepro-GnRH-II polypeptide had the highest identities with the corresponding polypeptides of amphibians. The GnRH-II precursor mRNA was detected in more than half of the tissues and organs examined. This widespread expression is consistent with the previous findings in several species, though the roles of GnRH outside the hypothalamus-pituitary-gonadal axis remain largely unknown. Molecular phylogenetic analysis combined with sequence comparison showed that the leopard gecko is more similar to fishes and amphibians than to eutherian mammals with respect to the GnRH-II precursor sequence. These results strongly suggest that the divergence of the GnRH-II precursor sequences seen in eutherian mammals may have occurred along with amniote evolution.

Entry, Descent and Landing Systems Analysis: Exploration Feed Forward Internal Peer Review Slide Package

NASA Technical Reports Server (NTRS)

Dwyer Cianciolo, Alicia M. (Editor)

2011-01-01

NASA senior management commissioned the Entry, Descent and Landing Systems Analysis (EDL-SA) Study in 2008 to identify and roadmap the Entry, Descent and Landing (EDL) technology investments that the agency needed to successfully land large payloads at Mars for both robotic and human-scale missions. Year 1 of the study focused on technologies required for Exploration-class missions to land payloads of 10 to 50 mt. Inflatable decelerators, rigid aeroshell and supersonic retro-propulsion emerged as the top candidate technologies. In Year 2 of the study, low TRL technologies identified in Year 1, inflatables aeroshells and supersonic retropropulsion, were combined to create a demonstration precursor robotic mission. This part of the EDL-SA Year 2 effort, called Exploration Feed Forward (EFF), took much of the systems analysis simulation and component model development from Year 1 to the next level of detail.

Entry, Descent and Landing Systems Analysis Study: Phase 2 Report on Exploration Feed-Forward Systems

NASA Technical Reports Server (NTRS)

Dwyer Ciancolo, Alicia M.; Davis, Jody L.; Engelund, Walter C.; Komar, D. R.; Queen, Eric M.; Samareh, Jamshid A.; Way, David W.; Zang, Thomas A.; Murch, Jeff G.; Krizan, Shawn A.;

Senseless acts as a binary switch during sensory organ precursor selection

NASA Technical Reports Server (NTRS)

Jafar-Nejad, Hamed; Acar, Melih; Nolo, Riitta; Lacin, Haluk; Pan, Hongling; Parkhurst, Susan M.; Bellen, Hugo J.

2003-01-01

During sensory organ precursor (SOP) specification, a single cell is selected from a proneural cluster of cells. Here, we present evidence that Senseless (Sens), a zinc-finger transcription factor, plays an important role in this process. We show that Sens is directly activated by proneural proteins in the presumptive SOPs and a few cells surrounding the SOP in most tissues. In the cells that express low levels of Sens, it acts in a DNA-binding-dependent manner to repress transcription of proneural genes. In the presumptive SOPs that express high levels of Sens, it acts as a transcriptional activator and synergizes with proneural proteins. We therefore propose that Sens acts as a binary switch that is fundamental to SOP selection.

Cytometry of DNA Replication and RNA Synthesis: Historical Perspective and Recent Advances Based on “Click Chemistry”

PubMed Central

Darzynkiewicz, Zbigniew; Traganos, Frank; Zhao, Hong; Halicka, H. Dorota; Li, Jiangwei

2011-01-01

This review covers progress in the development of cytometric methodologies designed to assess DNA replication and RNA synthesis. The early approaches utilizing autoradiography to detect incorporation of 3H- or 14C-labeled thymidine were able to identify the four fundamental phases of the cell cycle G1, S, G2, and M, and by analysis of the fraction of labeled mitosis (FLM), to precisely define the kinetics of cell progression through these phases. Analysis of 3H-uridine incorporation and RNA content provided the means to distinguish quiescent G0 from cycling G1 cells. Subsequent progress in analysis of DNA replication was based on the use of BrdU as a DNA precursor and its detection by the quenching of the fluorescence intensity of DNA-bound fluorochromes such as Hoechst 33358 or acridine orange as measured by flow cytometry. Several variants of this methodology have been designed and used in studies to detect anticancer drug-induced perturbations of cell cycle kinetics. The next phase of method development, which was particularly useful in studies of the cell cycle in vivo, including clinical applications, relied on immunocytochemical detection of incorporated halogenated DNA or RNA precursors. This approach however was hampered by the need for DNA denaturation, which made it difficult to concurrently detect other cell constituents for multiparametric analysis. The recently introduced “click chemistry” approach has no such limitation and is the method of choice for analysis of DNA replication and RNA synthesis. This method is based on the use of 5-ethynyl-2′deoxyuridine (EdU) as a DNA precursor or 5-ethynyluridine (EU) as an RNA precursor and their detection with fluorochrome-tagged azides utilizing a copper (I) catalyzed [3+2] cycloaddition. Several examples are presented that illustrate incorporation of EdU or EU in cells subjected to DNA damage detected as histone H2AX phosphorylation that have been analyzed by flow or laser scanning cytometry. PMID:21425239

The role of amorphous precursors in the crystallization of La and Nd carbonates

NASA Astrophysics Data System (ADS)

Vallina, Beatriz; Rodriguez-Blanco, Juan Diego; Brown, Andrew P.; Blanco, Jesus A.; Benning, Liane G.

2015-07-01

Crystalline La and Nd carbonates can be formed from poorly-ordered nanoparticulate precursors, termed amorphous lanthanum carbonate (ALC) and amorphous neodymium carbonate (ANC). When reacted in air or in aqueous solutions these precursors show highly variable lifetimes and crystallization pathways. We have characterized these precursors and the crystallization pathways and products with solid-state, spectroscopic and microscopic techniques to explain the differences in crystallization mechanisms between the La and Nd systems. ALC and ANC consist of highly hydrated, 10-20 nm spherical nanoparticles with a general formula of REE2(CO3)3.5H2O (REE = La, Nd). The stabilities differ by ~2 orders of magnitude, with ANC being far more stable than ALC. This difference is due to the Nd3+ ion having a far higher hydration energy compared to the La3+ ion. This, together with temperature and reaction times, leads to clear differences not only in the kinetics and mechanisms of crystallization of the amorphous precursor La- and Nd-carbonate phases but also in the resulting crystallite sizes and morphologies of the end products. All crystalline La and Nd carbonates developed spherulitic morphologies when crystallization occurred from hydrous phases in solution at temperatures above 60 °C (La system) and 95 °C (Nd system). We suggest that spherulitic growth occurs due to a rapid breakdown of the amorphous precursors and a concurrent rapid increase in supersaturation levels in the aqueous solution. The kinetic data show that the crystallization pathway for both La and Nd carbonate systems is dependent on the reaction temperature and the ionic potential of the REE3+ ion.Crystalline La and Nd carbonates can be formed from poorly-ordered nanoparticulate precursors, termed amorphous lanthanum carbonate (ALC) and amorphous neodymium carbonate (ANC). When reacted in air or in aqueous solutions these precursors show highly variable lifetimes and crystallization pathways. We have characterized these precursors and the crystallization pathways and products with solid-state, spectroscopic and microscopic techniques to explain the differences in crystallization mechanisms between the La and Nd systems. ALC and ANC consist of highly hydrated, 10-20 nm spherical nanoparticles with a general formula of REE2(CO3)3.5H2O (REE = La, Nd). The stabilities differ by ~2 orders of magnitude, with ANC being far more stable than ALC. This difference is due to the Nd3+ ion having a far higher hydration energy compared to the La3+ ion. This, together with temperature and reaction times, leads to clear differences not only in the kinetics and mechanisms of crystallization of the amorphous precursor La- and Nd-carbonate phases but also in the resulting crystallite sizes and morphologies of the end products. All crystalline La and Nd carbonates developed spherulitic morphologies when crystallization occurred from hydrous phases in solution at temperatures above 60 °C (La system) and 95 °C (Nd system). We suggest that spherulitic growth occurs due to a rapid breakdown of the amorphous precursors and a concurrent rapid increase in supersaturation levels in the aqueous solution. The kinetic data show that the crystallization pathway for both La and Nd carbonate systems is dependent on the reaction temperature and the ionic potential of the REE3+ ion. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01497b

Integrated Analysis of the Effects of Cold and Dehydration on Rice Metabolites, Phytohormones, and Gene Transcripts1[W][OPEN

PubMed Central

Maruyama, Kyonoshin; Urano, Kaoru; Yoshiwara, Kyouko; Morishita, Yoshihiko; Sakurai, Nozomu; Suzuki, Hideyuki; Kojima, Mikiko; Sakakibara, Hitoshi; Shibata, Daisuke; Saito, Kazuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2014-01-01

Correlations between gene expression and metabolite/phytohormone levels under abiotic stress conditions have been reported for Arabidopsis (Arabidopsis thaliana). However, little is known about these correlations in rice (Oryza sativa ‘Nipponbare’), despite its importance as a model monocot. We performed an integrated analysis to clarify the relationships among cold- and dehydration-responsive metabolites, phytohormones, and gene transcription in rice. An integrated analysis of metabolites and gene expression indicated that several genes encoding enzymes involved in starch degradation, sucrose metabolism, and the glyoxylate cycle are up-regulated in rice plants exposed to cold or dehydration and that these changes are correlated with the accumulation of glucose (Glc), fructose, and sucrose. In particular, high expression levels of genes encoding isocitrate lyase and malate synthase in the glyoxylate cycle correlate with increased Glc levels in rice, but not in Arabidopsis, under dehydration conditions, indicating that the regulation of the glyoxylate cycle may be involved in Glc accumulation under dehydration conditions in rice but not Arabidopsis. An integrated analysis of phytohormones and gene transcripts revealed an inverse relationship between abscisic acid (ABA) signaling and cytokinin (CK) signaling under cold and dehydration stresses; these stresses increase ABA signaling and decrease CK signaling. High levels of Oryza sativa 9-cis-epoxycarotenoid dioxygenase transcripts correlate with ABA accumulation, and low levels of Cytochrome P450 (CYP) 735A transcripts correlate with decreased levels of a CK precursor in rice. This reduced expression of CYP735As occurs in rice but not Arabidopsis. Therefore, transcriptional regulation of CYP735As might be involved in regulating CK levels under cold and dehydration conditions in rice but not Arabidopsis. PMID:24515831

Chemical composition of volatile aroma metabolites and their glycosylated precursors that can uniquely differentiate individual grape cultivars.

PubMed

Ghaste, Manoj; Narduzzi, Luca; Carlin, Silvia; Vrhovsek, Urska; Shulaev, Vladimir; Mattivi, Fulvio

2015-12-01

Every grape cultivar has its own unique genetic characteristics, leading to the production of a different secondary metabolite profile. Aroma is one of the most important aspects in terms of the quality of grapes and previous studies have assigned specific aromas to particular grape cultivars. In this study we present the molecular profiling of volatile aroma metabolites and their precursors in ten selected genotypes, including six Vitis vinifera cultivars, two American species (Arizonica Texas, Vitis cinerea) and two interspecific crosses. Chemical profiling was achieved through combined use of two orthogonal techniques, GC-MS and LC-HRMS, before and after enzymatic hydrolysis. The results show that both free and glycosidically bound aroma precursors behave differently in each different grape cultivar and species. As many as 66 free aroma volatile molecules (originally existing and released after hydrolysis) were profiled through GC-MS analysis, while 15 glycosylated precursors of volatiles were identified through LC-HRMS and correlation with GC-MS data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of precursor supply on structural and morphological characteristics of fe nanomaterials synthesized via chemical vapor condensation method.

PubMed

Ha, Jong-Keun; Ahn, Hyo-Jun; Kim, Ki-Won; Nam, Tae-Hyun; Cho, Kwon-Koo

2012-01-01

Various physical, chemical and mechanical methods, such as inert gas condensation, chemical vapor condensation, sol-gel, pulsed wire evaporation, evaporation technique, and mechanical alloying, have been used to synthesize nanoparticles. Among them, chemical vapor condensation (CVC) has the benefit of its applicability to almost all materials because a wide range of precursors are available for large-scale production with a non-agglomerated state. In this work, Fe nanoparticles and nanowires were synthesized by chemical vapor condensation method using iron pentacarbonyl (Fe(CO)5) as the precursor. The effect of processing parameters on the microstructure, size and morphology of Fe nanoparticles and nanowires were studied. In particular, we investigated close correlation of size and morphology of Fe nanoparticles and nanowires with atomic quantity of inflow precursor into the electric furnace as the quantitative analysis. The atomic quantity was calculated by Boyle's ideal gas law. The Fe nanoparticles and nanowires with various diameter and morphology have successfully been synthesized by the chemical vapor condensation method.

Dedifferentiated Schwann Cell Precursors Secreting Paracrine Factors Are Required for Regeneration of the Mammalian Digit Tip.

PubMed

Johnston, Adam P W; Yuzwa, Scott A; Carr, Matthew J; Mahmud, Neemat; Storer, Mekayla A; Krause, Matthew P; Jones, Karen; Paul, Smitha; Kaplan, David R; Miller, Freda D

2016-10-06

Adult mammals have lost multi-tissue regenerative capacity, except for the distal digit, which is able to regenerate via mechanisms that remain largely unknown. Here, we show that, after adult mouse distal digit removal, nerve-associated Schwann cell precursors (SCPs) dedifferentiate and secrete growth factors that promote expansion of the blastema and digit regeneration. When SCPs were dysregulated or ablated, mesenchymal precursor proliferation in the blastema was decreased and nail and bone regeneration were impaired. Transplantation of exogenous SCPs rescued these regeneration defects. We found that SCPs secrete factors that promote self-renewal of mesenchymal precursors, and we used transcriptomic and proteomic analysis to define candidate factors. Two of these, oncostatin M (OSM) and platelet-derived growth factor AA (PDGF-AA), are made by SCPs in the regenerating digit and rescued the deficits in regeneration caused by loss of SCPs. As all peripheral tissues contain nerves, these results could have broad implications for mammalian tissue repair and regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of local meteorology and NO2 conditions on ground-level ozone concentrations in the eastern part of Texas, USA.

PubMed

Gorai, A K; Tuluri, F; Tchounwou, P B; Ambinakudige, S

2015-02-01

The influence of local climatic factors on ground-level ozone concentrations is an area of increasing interest to air quality management in regards to future climate change. This study presents an analysis on the role of temperature, wind speed, wind direction, and NO 2 level on ground-level ozone concentrations over the region of Eastern Texas, USA. Ozone concentrations at the ground level depend on the formation and dispersion processes. Formation process mainly depends on the precursor sources, whereas, the dispersion of ozone depends on meteorological factors. Study results showed that the spatial mean of ground-level ozone concentrations was highly dependent on the spatial mean of NO 2 concentrations. However, spatial distributions of NO 2 and ozone concentrations were not uniformed throughout the study period due to uneven wind speeds and wind directions. Wind speed and wind direction also played a significant role in the dispersion of ozone. Temperature profile in the area rarely had any effects on the ozone concentrations due to low spatial variations.

Influence of local meteorology and NO2 conditions on ground-level ozone concentrations in the eastern part of Texas, USA

PubMed Central

Gorai, A. K.; Tuluri, F.; Tchounwou, P. B.; Ambinakudige, S.

2014-01-01

The influence of local climatic factors on ground-level ozone concentrations is an area of increasing interest to air quality management in regards to future climate change. This study presents an analysis on the role of temperature, wind speed, wind direction, and NO2 level on ground-level ozone concentrations over the region of Eastern Texas, USA. Ozone concentrations at the ground level depend on the formation and dispersion processes. Formation process mainly depends on the precursor sources, whereas, the dispersion of ozone depends on meteorological factors. Study results showed that the spatial mean of ground-level ozone concentrations was highly dependent on the spatial mean of NO2 concentrations. However, spatial distributions of NO2 and ozone concentrations were not uniformed throughout the study period due to uneven wind speeds and wind directions. Wind speed and wind direction also played a significant role in the dispersion of ozone. Temperature profile in the area rarely had any effects on the ozone concentrations due to low spatial variations. PMID:25755687

Hydroxyurea-Mediated Cytotoxicity Without Inhibition of Ribonucleotide Reductase.

PubMed

Liew, Li Phing; Lim, Zun Yi; Cohen, Matan; Kong, Ziqing; Marjavaara, Lisette; Chabes, Andrei; Bell, Stephen D

2016-11-01

In many organisms, hydroxyurea (HU) inhibits class I ribonucleotide reductase, leading to lowered cellular pools of deoxyribonucleoside triphosphates. The reduced levels for DNA precursors is believed to cause replication fork stalling. Upon treatment of the hyperthermophilic archaeon Sulfolobus solfataricus with HU, we observe dose-dependent cell cycle arrest, accumulation of DNA double-strand breaks, stalled replication forks, and elevated levels of recombination structures. However, Sulfolobus has a HU-insensitive class II ribonucleotide reductase, and we reveal that HU treatment does not significantly impact cellular DNA precursor pools. Profiling of protein and transcript levels reveals modulation of a specific subset of replication initiation and cell division genes. Notably, the selective loss of the regulatory subunit of the primase correlates with cessation of replication initiation and stalling of replication forks. Furthermore, we find evidence for a detoxification response induced by HU treatment. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection.

PubMed

Theunissen, Prisca M J; Sedek, Lukasz; De Haas, Valerie; Szczepanski, Tomasz; Van Der Sluijs, Alita; Mejstrikova, Ester; Nováková, Michaela; Kalina, Tomas; Lecrevisse, Quentin; Orfao, Alberto; Lankester, Arjan C; van Dongen, Jacques J M; Van Der Velden, Vincent H J

2017-07-01

Flow cytometric detection of minimal residual disease (MRD) in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic discrimination between residual leukaemic cells and B-cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages. This pathway was subsequently used as a reference to characterize the immunophenotypic maturation of regenerating BCPs in BM from children treated for BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in contrast to the classical CD34 high pre-B-I cell immunophenotype. These CD34 -dim pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I subset), while hardly present in healthy control BM (9-13% within pre-B-I subset; P = 0·0037). Furthermore, we showed that some of the BCP-ALL diagnosis immunophenotypes (23%) overlapped with CD34 -dim pre-B-I cells. Our results indicate that newly identified CD34 -dim pre-B-I cells can be mistaken for residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes. Therefore, regenerating BM, in which CD34 -dim pre-B-I cells are relatively abundant, should be used as reference frame in flow cytometric MRD measurements. © 2017 John Wiley & Sons Ltd.

Deposition of a-C/B films from o-carborane and trimethyl boron precursors

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

Geddes, J.B.; Getty, W.D.

1996-12-31

Vacuum wall deposition of a-B/C films has had tremendous positive impact on the performance of tokamak fusion reactors. In this work, precursor vapor and helium carrier gas have been used to create a plasma using a novel plasma source. Either trimethyl boron (TMB) or sublimed vapor from o-carborane solid can be used as deposition precursors. The plasma operates in a pressure range of 5 to 15 mTorr and typical flow rates are 5 sccm He plus 0.5-1 sccm o-carborane or TMB vapor. The film deposition rate ranges from less than 100 {angstrom}/minute to over 1,000 {angstrom}/minute. Microwave power levels rangemore » from 300--400 W at 2.45 GHz. The temperature and bias of the substrate can be varied, and the temperature of the substrate is recorded during deposition. The films have been analyzed using XPS. The atomic composition of the films has been measured. The o-carborane films have a much higher boron concentration than those deposited from TMB. The chemical bond characteristics of the different species have also been examined for each type of film. The thickness of the films is measured by profilometry, and this is combined with measurements of the film area and weight to calculate the film density. X-ray diffraction analysis has been performed; no evidence of any crystalline structure was found. Films with a thickness of a few thousand {angstrom} are routinely obtained. Deposition rates were 350 {angstrom}/minute on average.« less

Rrp5p, Noc1p and Noc2p form a protein module which is part of early large ribosomal subunit precursors in S. cerevisiae

PubMed Central

Hierlmeier, Thomas; Merl, Juliane; Sauert, Martina; Perez-Fernandez, Jorge; Schultz, Patrick; Bruckmann, Astrid; Hamperl, Stephan; Ohmayer, Uli; Rachel, Reinhard; Jacob, Anja; Hergert, Kristin; Deutzmann, Rainer; Griesenbeck, Joachim; Hurt, Ed; Milkereit, Philipp; Baßler, Jochen; Tschochner, Herbert

2013-01-01

Eukaryotic ribosome biogenesis requires more than 150 auxiliary proteins, which transiently interact with pre-ribosomal particles. Previous studies suggest that several of these biogenesis factors function together as modules. Using a heterologous expression system, we show that the large ribosomal subunit (LSU) biogenesis factor Noc1p of Saccharomyces cerevisiae can simultaneously interact with the LSU biogenesis factor Noc2p and Rrp5p, a factor required for biogenesis of the large and the small ribosomal subunit. Proteome analysis of RNA polymerase-I-associated chromatin and chromatin immunopurification experiments indicated that all members of this protein module and a specific set of LSU biogenesis factors are co-transcriptionally recruited to nascent ribosomal RNA (rRNA) precursors in yeast cells. Further ex vivo analyses showed that all module members predominantly interact with early pre-LSU particles after the initial pre-rRNA processing events have occurred. In yeast strains depleted of Noc1p, Noc2p or Rrp5p, levels of the major LSU pre-rRNAs decreased and the respective other module members were associated with accumulating aberrant rRNA fragments. Therefore, we conclude that the module exhibits several binding interfaces with pre-ribosomes. Taken together, our results suggest a co- and post-transcriptional role of the yeast Rrp5p–Noc1p–Noc2p module in the structural organization of early LSU precursors protecting them from non-productive RNase activity. PMID:23209026

Volatiles and water- and fat-soluble precursors of Saanen goat and cross Suffolk lamb flavour.

PubMed

Madruga, Marta; Dantas, Ingrid; Queiroz, Angela; Brasil, Luciana; Ishihara, Yuri

2013-02-07

This paper evaluates the concentrations of water- and fat-soluble precursors of meat flavour, with the aim of characterising the effect of species on the volatile profile of grilled goat and lamb meat. Compared to goat, lamb meat had higher levels of saturated fatty acids--SFA, monounsaturated fatty acids--MUFA and polyunsaturated fatty acids--PUFA and similar levels of sugars and free amino acids, except for lysine and glycine, which were higher in goat. Major differences were detected in lipid-derived volatiles; only pyrazine, thiazole, and some Strecker aldehydes were at different concentrations in these species. Volatile compounds derived from the oxidation of linoleic acid were at higher levels in meat from lamb due to the higher concentration of the latter, while compounds formed from α-linolenic acid were at higher levels in goat. It can be concluded that lamb meat has a stronger flavour profile compared to goat meat because it has the highest concentrations of lipid-derived volatile compounds, primarily straight saturated alkanals, pyrazines and thiazole.

Copeptin as a biomarker and a diagnostic tool in the evaluation of patients with polyuria-polydipsia and hyponatremia.

PubMed

Christ-Crain, M; Morgenthaler, N G; Fenske, W

2016-03-01

Copeptin is part of the 164 amino acid precursor protein preprovasopressin together with vasopressin and neurophysin II. During precursor processing, copeptin is released together with vasopressin. Copeptin concentrations respond as rapidly as vasopressin to changes in osmolality, a decrease in blood pressure or stress and there is a close correlation of vasopressin and copeptin concentrations. For these reasons, copeptin is propagated as a surrogate marker for vasopressin in the differential diagnosis of the polyuria-polydipsia syndromes and hyponatremia. Results of prospective studies show that a baseline copeptin level without prior fluid deprivation >20 pmol/L is able to identify patients with nephrogenic diabetes insipidus, whereas osmotically stimulated copeptin levels differentiate between patients with partial central diabetes insipidus and primary polydipsia with a high sensitivity and specificity >94%. In hyponatremia, low copeptin levels point to primary polydipsia and high levels to hypovolemic hyponatremia. The copeptin to urinary sodium ratio differentiates accurately between volume-depleted and normovolemic disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Resolution P'P' Precursor Imaging of Nazca-South America Plate Boundary Zones and Inferences for Transition Zone Temperature and Composition

NASA Astrophysics Data System (ADS)

Gu, Y. J.; Schultz, R.

2013-12-01

Knowledge of upper mantle transition zone stratification and composition is highly dependent on our ability to efficiently extract and properly interpret small seismic arrivals. A promising high-frequency seismic phase group particularly suitable for a global analysis is P'P' precursors, which are capable of resolving mantle structures at vertical and lateral resolution of approximately 5 and 200 km, respectively, owing to their shallow incidence angle and small, quasi-symmetric Fresnel zones. This study presents a simultaneous analysis of SS and P'P' precursors based on deconvolution, Radon transform and depth migration. Our multi-resolution survey of the mantle near Nazca-South America subduction zone reveals both olivine and garnet related transitions at depth below 400 km. We attribute a depressed 660 to thermal variations, whereas compositional variations atop the upper-mantle transition zone are needed to explain the diminished or highly complex reflected/scattered signals from the 410 km discontinuity. We also observe prominent P'P' reflections within the transition zone, especially near the plate boundary zone where anomalously high reflection amplitudes result from a sharp (~10 km thick) mineral phase change resonant with the dominant frequency of the P'P' precursors. Near the base of the upper mantle, the migration of SS precursors shows no evidence of split reflections near the 660-km discontinuity, but potential majorite-ilmenite (590-640 km) and ilmenite-perovskite transitions (740-750 km) are identified based on similarly processed high-frequency P'P' precursors. At nominal mantle temperatures these two phase changes may be seismically indistinguishable, but colder mantle conditions from the descending Nazca plate, the presence of water and variable Fe contents may cause sufficient separation for a reliable analysis. In addition, our preliminary results provide compelling evidence for multiple shallow lower-mantle reflections (at ~800 km) along the elongated plate boundary zones of South America. Slab stagnation at the base of the transition zone could play a key role, though a proper interpretation of this finding would likely entail compositional (rather than strictly thermal) variations in the vicinity of the descending oceanic crust and lithosphere. Overall, the resolution and sensitivity differences between low/intermediate- S and high-frequency P wave reflections are key considerations toward reconciling seismic and mineralogical models of transition zone structure, both at the study location and worldwide.

A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine.

PubMed

Neri, Monica; Frustaci, Alessandra; Milic, Mirta; Valdiglesias, Vanessa; Fini, Massimo; Bonassi, Stefano; Barbanti, Piero

2015-09-01

Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels. © International Headache Society 2015.

Cross influences of ozone and sulfate precursor emissions changes on air quality and climate

PubMed Central

Unger, Nadine; Shindell, Drew T.; Koch, Dorothy M.; Streets, David G.

2006-01-01

Tropospheric O3 and sulfate both contribute to air pollution and climate forcing. There is a growing realization that air quality and climate change issues are strongly connected. To date, the importance of the coupling between O3 and sulfate has not been fully appreciated, and thus regulations treat each pollutant separately. We show that emissions of O3 precursors can dramatically affect regional sulfate air quality and climate forcing. At 2030 in an A1B future, increased O3 precursor emissions enhance surface sulfate over India and China by up to 20% because of increased levels of OH and gas-phase SO2 oxidation rates and add up to 20% to the direct sulfate forcing for that region relative to the present day. Hence, O3 precursors impose an indirect forcing via sulfate, which is more than twice the direct O3 forcing itself (compare −0.61 vs. +0.35 W/m2). Regulatory policy should consider both air quality and climate and should address O3 and sulfate simultaneously because of the strong interaction between these species. PMID:16537360

A mobile precursor determines protein resistance on nanostructured surfaces.

PubMed

Wang, Kang; Chen, Ye; Gong, Xiangjun; Xia, Jianlong; Zhao, Junpeng; Shen, Lei

2018-05-09

Biomaterials are often engineered with nanostructured surfaces to control interactions with proteins and thus regulate their biofunctions. However, the mechanism of how nanostructured surfaces resist or attract proteins together with the underlying design rules remains poorly understood at a molecular level, greatly limiting attempts to develop high-performance biomaterials and devices through the rational design of nanostructures. Here, we study the dynamics of nonspecific protein adsorption on block copolymer nanostructures of varying adhesive domain areas in a resistant matrix. Using surface plasmon resonance and single molecule tracking techniques, we show that weakly adsorbed proteins with two-dimensional diffusivity are critical precursors to protein resistance on nanostructured surfaces. The adhesive domain areas must be more than tens or hundreds of times those of the protein footprints to slow down the 2D-mobility of the precursor proteins for their irreversible adsorption. This precursor model can be used to quantitatively analyze the kinetics of nonspecific protein adsorption on nanostructured surfaces. Our method is applicable to precisely manipulate protein adsorption and resistance on various nanostructured surfaces, e.g., amphiphilic, low-surface-energy, and charged nanostructures, for the design of protein-compatible materials.

Formulating Precursors for Coating Metals and Ceramics

NASA Technical Reports Server (NTRS)

Morales, Wilfredo; Gatica, Jorge E.; Reye, John T.

2005-01-01

A protocol has been devised for formulating low-vapor-pressure precursors for protective and conversion coatings on metallic and ceramic substrates. The ingredients of a precursor to which the protocol applies include additives with phosphate esters, or aryl phosphate esters in solution. Additives can include iron, chromium, and/or other transition metals. Alternative or additional additives can include magnesium compounds to facilitate growth of films on substrates that do not contain magnesium. Formulation of a precursor begins with mixing of the ingredients into a high-vapor-pressure solvent to form a homogeneous solution. Then the solvent is extracted from the solution by evaporation - aided, if necessary, by vacuum and/or slight heating. The solvent is deemed to be completely extracted when the viscosity of the remaining solution closely resembles the viscosity of the phosphate ester or aryl phosphate ester. In addition, satisfactory removal of the solvent can be verified by means of a differential scanning calorimetry essay: the absence of endothermic processes for temperatures below 150 C would indicate that the residual solvent has been eliminated from the solution beyond a detectable dilution level.

Copper stabilization via spinel formation during the sintering of simulated copper-laden sludge with aluminum-rich ceramic precursors.

PubMed

Tang, Yuanyuan; Chui, Stephen Sin-Yin; Shih, Kaimin; Zhang, Lingru

2011-04-15

The feasibility of incorporating copper-laden sludge into low-cost ceramic products, such as construction ceramics, was investigated by sintering simulated copper-laden sludge with four aluminum-rich ceramic precursors. The results indicated that all of these precursors (γ-Al(2)O(3), corundum, kaolinite, mullite) could crystallochemically stabilize the hazardous copper in the more durable copper aluminate spinel (CuAl(2)O(4)) structure. To simulate the process of copper transformation into a spinel structure, CuO was mixed with the four aluminum-rich precursors, and fired at 650-1150 °C for 3 h. The products were examined using powder X-ray diffraction (XRD) and scanning electron microscopic techniques. The efficiency of copper transformation among crystalline phases was quantitatively determined through Rietveld refinement analysis of the XRD data. The sintering experiment revealed that the optimal sintering temperature for CuAl(2)O(4) formation was around 1000 °C and that the efficiency of copper incorporation into the crystalline CuAl(2)O(4) structure after 3 h of sintering ranged from 40 to 95%, depending on the type of aluminum precursor used. Prolonged leaching tests were carried out by using acetic acid with an initial pH value of 2.9 to leach CuO and CuAl(2)O(4) samples for 22 d. The sample leachability analysis revealed that the CuAl(2)O(4) spinel structure was more superior to stabilize copper, and suggested a promising and reliable technique for incorporating copper-laden sludge or its incineration ash into usable ceramic products. Such results also demonstrated the potential of a waste-to-resource strategy by using waste materials as part of the raw materials with the attainable temperature range used in the production of ceramics.

Investigation of the origin of ephedrine and methamphetamine by stable isotope ratio mass spectrometry: a Japanese experience.

PubMed

Makino, Y; Urano, Y; Nagano, T

2005-01-01

Illicit drug abuse is a serious global problem that can only be solved through international cooperation. In Asian countries, the abuse of methamphetamine is one of the most pressing problems. To assist in the control of methamphetamine, the authors investigated in detail the character of ephedrine, which is a key precursor for the illicit manufacture of methamphetamine. Commercial ephedrine is produced by one of three methods: (a) extraction from Ephedra plants, (b) full chemical synthesis or (c) via a semi-synthetic process involving the fermentation of sugar, followed by amination. Although chemically there is no difference between ephedrine samples from different origins (natural, synthetic or semi-synthetic), scientific and analytical tools such as drug-characterization and impurity-profiling programmes may provide valuable information for law enforcement and regulatory activities as part of precursor control strategies. During the research under discussion in the present article, in addition to classical impurity profiling of manufacturing by-products, the use of stable isotope ratio mass spectrometry was investigated for determining the origin of the ephedrine that had been used as a precursor in seized methamphetamine samples. The results of carbon and nitrogen stable isotope ratio (delta13C and delta15N) analysis of samples of crystalline methamphetamine seized in Japan suggested that the drug had been synthesized from either natural or semi-synthetic ephedrine and not from synthetic ephedrine. Stable isotope ratio analysis is expected to be a useful tool for tracing the origins of seized methamphetamine. It has attracted much interest from precursor control authorities in Japan and the East Asian region and may prove useful in the international control of precursors.

Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons.

PubMed

Iwakura, Yuriko; Wang, Ran; Inamura, Naoko; Araki, Kazuaki; Higashiyama, Shigeki; Takei, Nobuyuki; Nawa, Hiroyuki

2017-01-01

The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells. Using a two-site enzyme immunoassay to detect soluble NRG1, we show that, of various neurotransmitters, glutamate was the most potent inducer of NRG1 release in neuron-enriched cultures. NRG1 release in glia-enriched cultures was relatively limited. Furthermore, among glutamate receptor agonists, N-Methyl-D-Aspartate (NMDA) and kainate (KA), but not AMPA or tACPD, mimicked the effects of glutamate. Similar findings were acquired from analysis of the hippocampus of rats with KA-induced seizures. To evaluate the contribution of members of a disintegrin and metalloproteinase (ADAM) families to NRG1 release, we transfected primary cultures of neurons with cDNA vectors encoding NRG1 types I, II, or III precursors, each tagged with the alkaline phosphatase reporter. Analysis of alkaline phosphatase activity revealed that the NRG1 type II precursor was subjected to tumor necrosis factor-α-converting enzyme (TACE) / a Disintegrin And Metalloproteinase 17 (ADAM17) -dependent ectodomain shedding in a protein kinase C-dependent manner. These results suggest that glutamatergic neurotransmission positively regulates the ectodomain shedding of NRG1 type II precursors and liberates the active NRG1 domain in an activity-dependent manner.

Influence of thermal treatment on the formation of zirconia nanostructured powder by thermal decomposition of different precursors

NASA Astrophysics Data System (ADS)

Stoia, Marcela; Barvinschi, Paul; Barbu-Tudoran, Lucian; Negrea, Adina; Barvinschi, Floricica

2013-10-01

The paper presents some results concerning the preparation of zirconia powders starting from ZrOCl2·8H2O by using two synthesis methods: (a) precipitation with NH3, at 90 °C, and (b) thermal decomposition of carboxylate precursors, obtained in the reaction of zirconium nitrate and two different alcohols, 1,3-propanediol (PD) and poly(vinyl alcohol) (PVA), at 150 °C. The precursors obtained at different temperatures have been characterized by thermal analysis (TG, DTA) and FT-IR spectroscopy. DTA analysis evidenced very clearly the transition temperatures between zirconia crystalline phases. The precursors have been annealed at different temperatures in order to obtain zirconia powders and the as obtained powders have been characterized by means of X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM). In case of precipitation method the presence of the tetragonal phase was observed at 400 °C, while the monoclinic phase appears at temperatures higher than 400 °C, becoming major crystalline phase starting with 700 °C. In case of the powders prepared by thermal decomposition of carboxylate precursors, the tetragonal phase was formed at temperatures below 700 °C, when the monoclinic phase begin to crystallize as secondary phase, in a higher proportion for the samples synthesized with 1,3-propanediol. All powders annealed at 1200 °C are pure monoclinic zirconia. SEM images have evidenced for the zirconia powders annealed at 1000 °C particles with diameters up to 150 nm, agglomerated in micrometer-sized aggregates, more individualized and homogenous than that obtained in the case of zirconia powder synthesized with poly(vinyl alcohol).

Quantitative estimation of time-variable earthquake hazard by using fuzzy set theory

NASA Astrophysics Data System (ADS)

Deyi, Feng; Ichikawa, M.

1989-11-01

In this paper, the various methods of fuzzy set theory, called fuzzy mathematics, have been applied to the quantitative estimation of the time-variable earthquake hazard. The results obtained consist of the following. (1) Quantitative estimation of the earthquake hazard on the basis of seismicity data. By using some methods of fuzzy mathematics, seismicity patterns before large earthquakes can be studied more clearly and more quantitatively, highly active periods in a given region and quiet periods of seismic activity before large earthquakes can be recognized, similarities in temporal variation of seismic activity and seismic gaps can be examined and, on the other hand, the time-variable earthquake hazard can be assessed directly on the basis of a series of statistical indices of seismicity. Two methods of fuzzy clustering analysis, the method of fuzzy similarity, and the direct method of fuzzy pattern recognition, have been studied is particular. One method of fuzzy clustering analysis is based on fuzzy netting, and another is based on the fuzzy equivalent relation. (2) Quantitative estimation of the earthquake hazard on the basis of observational data for different precursors. The direct method of fuzzy pattern recognition has been applied to research on earthquake precursors of different kinds. On the basis of the temporal and spatial characteristics of recognized precursors, earthquake hazards in different terms can be estimated. This paper mainly deals with medium-short-term precursors observed in Japan and China.

Poly(ADP-Ribose) Polymerase 1 (PARP-1) Regulates Ribosomal Biogenesis in Drosophila Nucleoli

PubMed Central

Boamah, Ernest K.; Kotova, Elena; Garabedian, Mikael; Jarnik, Michael; Tulin, Alexei V.

2012-01-01

Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis. PMID:22242017

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

PubMed

Wu, Junjun; Zhang, Xia; Zhu, Yingjie; Tan, Qinyu; He, Jiacheng; Dong, Mingsheng

2017-05-03

Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.

CMAQ modeling of near-ground ozone pollution during the CAREBeijing-2006 campaign in Beijing, China

NASA Astrophysics Data System (ADS)

Wang, Xuesong; Song, Yu; Zhang, Yuanhang; Hu, Min; Zeng, Limin; Zhu, Tong

2010-05-01

The Community Multiscale Air Quality (CMAQ) modeling system, a 3-D regional chemical transport model, was used to simulate the O3 episodes during the Campaign of Air Quality Research in Beijing and surrounding areas in 2006 (CAREBeijing-2006). The model reproduced the temporal and spatial variations of the observed ozone and precursors well during the campaign. The modeling results showed the evolution of near ground O3 and the feature of vertical O3 profile on pollution days with different meteorological conditions. Process analysis was applied to investigate the contributions of local production and regional transport, and found different relative importance at different locations of Beijing. O3-NOx-VOCs sensitivity was also addressed with different precursor emission scenarios. The Beijing downtown area and downwind urban plume were usually in VOC-limited regime, whereas the upwind regions and northern mountain areas were generally characterized by NOx-sensitive chemistry. Ozone production efficiency of NOx was also calculated based on simulation results and compared with that derived from observations. For reducing O3 levels in Beijing, the above results suggest a regional emission control strategy with more emphasis on VOCs reduction in Beijing urban areas.

Supplementing glycosylation: A review of applying nucleotide-sugar precursors to growth medium to affect therapeutic recombinant protein glycoform distributions.

PubMed

Blondeel, Eric J M; Aucoin, Marc G

2018-06-15

Glycosylation is a critical quality attribute (CQA) of many therapeutic proteins, particularly monoclonal antibodies (mAbs), and is a major consideration in the approval of biosimilar biologics due to its effects to therapeutic efficacy. Glycosylation generates a distribution of glycoforms, resulting in glycoproteins with inherent molecule-to-molecule heterogeneity, capable of activating (or failing to activate) different effector functions of the immune system. Glycoforms can be affected by the supplementation of nucleotide-sugar precursors, and related components, to culture growth medium, affecting the metabolism of glycosylation. These supplementations has been demonstrated to increase nucleotide-sugar intracellular pools, and impact glycoform distributions, but with varied results. These variations can be attributed to five key factors: Differences between cell platforms (enzyme/transporter expression levels); differences between recombinant proteins produced (glycan-site accessibility); the fermentation and sampling timeline (glucose availability and exoglycosidase accumulation); glutamine levels (affecting ammonia levels, which impact Golgi pH, as well as UDP-GlcNAc pools); and finally, a lack of standardized metrics for observing shifts in glycoform distributions (glycosylation indices) across different experiments. The purpose of this review is to provide detail and clarity on the state of the art of supplementation strategies for nucleotide-sugar precursors for affecting glycosylation in cell culture processes, and to apply glycosylation indices for standardized comparisons across the field. Copyright © 2018. Published by Elsevier Inc.

In situ monitoring of cytoplasmic precursor and mature microRNA using gold nanoparticle and graphene oxide composite probes.

PubMed

Hong, Min; Sun, Hongxiao; Xu, Lidan; Yue, Qiaoli; Shen, Guodong; Li, Meifang; Tang, Bo; Li, Chen-Zhong

2018-08-27

This study strategically fabricates a nucleic acid functionalized gold nanoparticle and graphene oxide composite probe (AuNP/GO probe) to achieve both the recognition and in situ monitoring of cytoplasmic target precursor microRNAs (pre-miRNAs) and mature microRNAs (miRNAs) in living cells. The pre-miRNA-21 detection with AuNP probes has a good linear range of 0-300 nM and a limit of detection (LOD) of 4.5 nM, whereas the GO probe has a linear relationship with mature miRNA-21 from 0.1 to 10 nM with a LOD of 1.74 nM. This assay was utilized to directly visualize the relative expression levels of pre- and mature forms of miRNA-21 and let-7a. The results suggested that the expression levels of precursor miRNAs remain constant in cancer cells and normal cells. However, the expression levels of mature miRNAs vary widely, demonstrating the "up-regulation" of miRNA-21 and "down-regulation" of let-7a in cancer cells in contrast to that in normal cells. The practicality of this strategy was verified by in situ monitoring changes in cytoplasmic pre-miRNA-21 and mature miRNA-21 in response to small-molecule inhibitors of miRNA-21. Copyright © 2018 Elsevier B.V. All rights reserved.

Inflammatory responses to secondary organic aerosols (SOA) generated from biogenic and anthropogenic precursors

NASA Astrophysics Data System (ADS)

Tuet, Wing Y.; Chen, Yunle; Fok, Shierly; Champion, Julie A.; Ng, Nga L.

2017-09-01

Cardiopulmonary health implications resulting from exposure to secondary organic aerosols (SOA), which comprise a significant fraction of ambient particulate matter (PM), have received increasing interest in recent years. In this study, alveolar macrophages were exposed to SOA generated from the photooxidation of biogenic and anthropogenic precursors (isoprene, α-pinene, β-caryophyllene, pentadecane, m-xylene, and naphthalene) under different formation conditions (RO2 + HO2 vs. RO2 + NO dominant, dry vs. humid). Various cellular responses were measured, including reactive oxygen and nitrogen species (ROS/RNS) production and secreted levels of cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). SOA precursor identity and formation condition affected all measured responses in a hydrocarbon-specific manner. With the exception of naphthalene SOA, cellular responses followed a trend where TNF-α levels reached a plateau with increasing IL-6 levels. ROS/RNS levels were consistent with relative levels of TNF-α and IL-6, due to their respective inflammatory and anti-inflammatory effects. Exposure to naphthalene SOA, whose aromatic-ring-containing products may trigger different cellular pathways, induced higher levels of TNF-α and ROS/RNS than suggested by the trend. Distinct cellular response patterns were identified for hydrocarbons whose photooxidation products shared similar chemical functionalities and structures, which suggests that the chemical structure (carbon chain length and functionalities) of photooxidation products may be important for determining cellular effects. A positive nonlinear correlation was also detected between ROS/RNS levels and previously measured DTT (dithiothreitol) activities for SOA samples. In the context of ambient samples collected during summer and winter in the greater Atlanta area, all laboratory-generated SOA produced similar or higher levels of ROS/RNS and DTT activities. These results suggest that the health effects of SOA are important considerations for understanding the health implications of ambient aerosols.

The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer’s disease

PubMed Central

Kalinin, Sergey; Polak, Paul E.; Lin, Shao Xia; Sakharkar, Amul J.; Pandey, Subhash C.; Feinstein, Douglas L.

2013-01-01

Damage to noradrenergic neurons in the locus coeruleus (LC) is a hallmark of Alzheimer’s disease (AD) and may contribute to disease progression. In 5xFAD transgenic mice, which accumulate amyloid burden at early ages, the LC undergoes stress as evidenced by increased astrocyte activation, neuronal hypertrophy, reduced levels of LC-enriched messenger RNAs (mRNAs), and increased inflammatory gene expression. Central nervous system (CNS) noradrenaline (NA) levels in 5-month-old male 5xFAD mice were increased using the NA precursor L-threo-3,4-dihydroxyphenylserine (L-DOPS). After 1 month, L-DOPS treatment improved learning in the Morris water maze test compared with vehicle-treated mice. L-DOPS increased CNS NA levels, and average latency times in the water maze test were inversely correlated to NA levels. L-DOPS reduced astrocyte activation and Thioflavin-S staining; increased mRNA levels of neprilysin and insulin degrading enzyme, and of several neurotrophins; and increased brain-derived neurotrophic factor protein levels. These data demonstrate the presence of LC stress in a robust mouse model of AD, and suggest that raising CNS NA levels could provide benefit in AD. PMID:21705113

The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer's disease.

PubMed

Kalinin, Sergey; Polak, Paul E; Lin, Shao Xia; Sakharkar, Amul J; Pandey, Subhash C; Feinstein, Douglas L

2012-08-01

Damage to noradrenergic neurons in the locus coeruleus (LC) is a hallmark of Alzheimer's disease (AD) and may contribute to disease progression. In 5xFAD transgenic mice, which accumulate amyloid burden at early ages, the LC undergoes stress as evidenced by increased astrocyte activation, neuronal hypertrophy, reduced levels of LC-enriched messenger RNAs (mRNAs), and increased inflammatory gene expression. Central nervous system (CNS) noradrenaline (NA) levels in 5-month-old male 5xFAD mice were increased using the NA precursor L-threo-3,4-dihydroxyphenylserine (L-DOPS). After 1 month, L-DOPS treatment improved learning in the Morris water maze test compared with vehicle-treated mice. L-DOPS increased CNS NA levels, and average latency times in the water maze test were inversely correlated to NA levels. L-DOPS reduced astrocyte activation and Thioflavin-S staining; increased mRNA levels of neprilysin and insulin degrading enzyme, and of several neurotrophins; and increased brain-derived neurotrophic factor protein levels. These data demonstrate the presence of LC stress in a robust mouse model of AD, and suggest that raising CNS NA levels could provide benefit in AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of PFASs contamination in the freshwater and terrestrial environments by analysis of eggs from osprey (Pandion haliaetus), tawny owl (Strix aluco), and common kestrel (Falco tinnunculus).

PubMed

Eriksson, Ulrika; Roos, Anna; Lind, Ylva; Hope, Kjell; Ekblad, Alf; Kärrman, Anna

2016-08-01

The level of PFAS (per- and polyfluorinated alkyl substances) contamination in freshwater and terrestrial Swedish environments in 2013/2014 was assessed by analyzing a range of perfluorinated alkyl acids, fluorotelomer acids, sulfonamides, sulfonamidoethanols and polyfluoralkyl phosphate diesters (diPAPs) in predator bird eggs. Stable isotopes ((13)C and (15)N) were analyzed to elucidate the dietary source. The tawny owl (Strix aluco, n=10) and common kestrel (Falco tinnunculus, n=40), two terrestrial species, and the osprey (Pandion haliaetus, n=30), a freshwater specie were included. In addition, a temporal trend (1997-2001, 2008-2009, 2013) in osprey was studied as well. The PFAS profile was dominated by perfluorooctane sulfonic acid (PFOS) in eggs from osprey and tawny owl, while for common kestrel perfluorinated carboxylic acids (∑PFCA) exceeded the level of PFOS. PFOS concentration in osprey eggs remained at the same level between 1997 and 2001 and 2013. For the long-chained PFCAs, there were a significant increase in concentrations in osprey eggs between 1997 and 2001 and 2008-2009. The levels of PFOS and PFCAs were about 10 and five times higher, respectively, in osprey compared to tawny owl and common kestrel. Evidence of direct exposure from PFCA precursor compounds to birds in both freshwater and terrestrial environment was observed. Low levels of diPAPs were detected in a few samples of osprey (<0.02-2.4ng/g) and common kestrel (<0.02-0.16ng/g) eggs, and 6:2 FTSA was detected in a majority of the osprey eggs (<6.3-52ng/g). One saturated telomer acid (7:3 FTCA), which is a transformation marker from precursor exposure, was detected in all species (<0.24-2.7ng/g). The (15)N data showed higher levels in osprey eggs compared to tawny owl and common kestrel, indicating that they feed on a 2-3 times higher trophic level. We conclude that ospreys are continuously exposed to PFAS at levels where adverse toxic effects have been observed in birds. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeted Lipidomic Analysis of Oxysterols in the Embryonic Central Nervous System

PubMed Central

Wang, Yuqin; Sousa, Kyle M.; Bodin, Karl; Theofilopoulos, Spyridon; Sacchetti, Paola; Hornshaw, Martin; Woffendin, Gary; Karu, Kersti; Sjövall, Jan; Arenas, Ernest; Griffiths, William J.

2009-01-01

Summary In this study two regions of embryonic (E11) mouse central nervous system (CNS) have been profiled for their unesterified sterol content. Using high-performance liquid chromatography (HPLC) – mass spectrometry (MS) and tandem mass spectrometry (MSn) low levels of oxysterols (estimated 2 – 165 ng/g wet weight) were identified in cortex (Ctx) and spinal cord (Sc). The identified oxysterols include 7α-, 7β-, 22R-, 24S-, 25- and 27-hydroxycholesterol; 24,25- and 24,27-dihydroxycholesterol; and 24S,25-epoxycholesterol. Of these, 24S-hydroxycholesterol is biosynthesised exclusively in brain. In comparison to adult mouse where the 24S-hydroxycholesterol level is about 40 μg/g in brain the level of 24S-hydroxycholesterol reported here (estimated 26 ng/g in Ctx and 13 ng/g in Sc) is extremely low. Interestingly, the level of 24S,25-epoxycholesterol in both CNS regions (estimated 165 ng/g in Ctx and 91 ng/g in Sc) is somewhat higher than the levels of the hydroxycholesterols. This oxysterol is formed in parallel to cholesterol via a shunt of the mevalonate pathway and its comparatively high abundance may be a reflection of a high rate of cholesterol synthesis at this stage of development. Levels of cholesterol (estimated 1.25 mg/g in Ctx and 1.15 mg/g in Sc) and its precursors were determined by gas chromatography – mass spectrometry (GC-MS). In both CNS regions cholesterol levels were found to be lower than those reported in the adult, but in relation to cholesterol the levels of cholesterol precursors were higher than found in adult indicating a high rate of cholesterol synthesis. In summary, our data provide evidence for the presence of endogenous oxysterols in two brain regions of the developing CNS. Moreover, while most of the enzymes involved in hydroxysterol synthesis are minimally active at E11, our results suggest that the mevalonate pathway is significantly active, opening up the possibility for a function of 24S,25-epoxycholesterol during brain development. PMID:19381367

Structural, electrical and optical properties of indium tin oxide thin film grown by metal organic chemical vapor deposition with tetramethyltin-precursor

NASA Astrophysics Data System (ADS)

Zhuo, Yi; Chen, Zimin; Tu, Wenbin; Ma, Xuejin; Wang, Gang

2018-01-01

Tin-doped indium oxide (ITO) is grown by metal organic chemical vapor deposition (MOCVD) using tetramethyltin (TDMASn) as tin precursor. The as-grown ITO films are polycrystalline with (111) and (100) textures. A gradual transition of crystallographic orientation from (111) preferred to (100) preferred is observed as the composition of tin changes. By precisely controlling the Sn doping, the ITO thin films present promising optical and electrical performances at either near-infrared-visible or visible-near-ultraviolet ranges. At low Sn doping level, the as-grown ITO possesses high electron mobility of 48.8 cm2 V-1 s-1, which results in high near-infrared transmittance and low resistivity. At higher Sn doping level, high carrier concentration (8.9 × 1020 cm-3) and low resistivity (3 × 10-4 Ω cm) are achieved. The transmittance is 97.8, 99.1, and 82.3% at the wavelength of 550, 365, and 320 nm, respectively. The results strongly suggest that MOCVD with TDMASn as tin precursor is an effective method to fabricate high quality ITO thin film for near-infrared, visible light, and near-ultraviolet application.

N-Nitrosodimethylamine (NDMA) and its precursors in water and wastewater: A review on formation and removal.

PubMed

Sgroi, Massimiliano; Vagliasindi, Federico G A; Snyder, Shane A; Roccaro, Paolo

2018-01-01

This review summarizes major findings over the last decade related to N-Nitrosodimethylamine (NDMA) in water and wastewater. In particular, the review is focused on the removal of NDMA and of its precursors by conventional and advanced water and wastewater treatment processes. New information regarding formation mechanisms and precursors are discussed as well. NDMA precursors are generally of anthropogenic origin and their main source in water have been recognized to be wastewater discharges. Chloramination is the most common process that results in formation of NDMA during water and wastewater treatment. However, ozonation of wastewater or highly contaminated surface water can also generate significant levels of NDMA. Thus, NDMA formation control and remediation has become of increasing interest, particularly during treatment of wastewater-impacted water and during potable reuse application. NDMA formation has also been associated with the use of quaternary amine-based coagulants and anion exchange resins. UV photolysis with UV fluence far higher than typical disinfection doses is generally considered the most efficient technology for NDMA mitigation. However, recent studies on the optimization of biological processes offer a potentially lower-energy solution. Options for NDMA control include attenuation of precursor materials through physical removal, biological treatment, and/or deactivation by application of oxidants. Nevertheless, NDMA precursor identification and removal can be challenging and additional research and optimization is needed. As municipal wastewater becomes increasingly used as a source water for drinking, NDMA formation and mitigation strategies will become increasingly more important. The following review provides a summary of the most recent information available. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing

PubMed Central

Le Thomas, Adrien; Stuwe, Evelyn; Li, Sisi; Marinov, Georgi; Rozhkov, Nikolay; Chen, Yung-Chia Ariel; Luo, Yicheng; Sachidanandam, Ravi; Toth, Katalin Fejes; Patel, Dinshaw; Aravin, Alexei A.

2014-01-01

Small noncoding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that transgenerationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the histone 3 Lys9 trimethylation (H3K9me3) mark on genomic piRNA cluster sequences. The heterochromatin protein 1 (HP1) homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that transgenerationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels: by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors. PMID:25085419

De Novo Synthesis of Benzenoid Compounds by the Yeast Hanseniaspora vineae Increases the Flavor Diversity of Wines.

PubMed

Martin, Valentina; Giorello, Facundo; Fariña, Laura; Minteguiaga, Manuel; Salzman, Valentina; Boido, Eduardo; Aguilar, Pablo S; Gaggero, Carina; Dellacassa, Eduardo; Mas, Albert; Carrau, Francisco

2016-06-08

Benzyl alcohol and other benzenoid-derived metabolites of particular importance in plants confer floral and fruity flavors to wines. Among the volatile aroma components in Vitis vinifera grape varieties, benzyl alcohol is present in its free and glycosylated forms. These compounds are considered to originate from grapes only and not from fermentative processes. We have found increased levels of benzyl alcohol in red Tannat wine compared to that in grape juice, suggesting de novo formation of this metabolite during vinification. In this work, we show that benzyl alcohol, benzaldehyde, p-hydroxybenzaldehyde, and p-hydroxybenzyl alcohol are synthesized de novo in the absence of grape-derived precursors by Hanseniaspora vineae. Levels of benzyl alcohol produced by 11 different H. vineae strains were 20-200 times higher than those measured in fermentations with Saccharomyces cerevisiae strains. These results show that H. vineae contributes to flavor diversity by increasing grape variety aroma concentration in a chemically defined medium. Feeding experiments with phenylalanine, tryptophan, tyrosine, p-aminobenzoic acid, and ammonium in an artificial medium were tested to evaluate the effect of these compounds either as precursors or as potential pathway regulators for the formation of benzenoid-derived aromas. Genomic analysis shows that the phenylalanine ammonia-lyase (PAL) and tyrosine ammonia lyase (TAL) pathways, used by plants to generate benzyl alcohols from aromatic amino acids, are absent in the H. vineae genome. Consequently, alternative pathways derived from chorismate with mandelate as an intermediate are discussed.

Linking a sea level pressure anomaly dipole over North America to the central Pacific El Niño

NASA Astrophysics Data System (ADS)

Ding, Ruiqiang; Li, Jianping; Tseng, Yu-heng; Sun, Cheng; Zheng, Fei

2017-08-01

This study demonstrates the close connection between the north-south dipole pattern of sea level pressure anomalies over northeastern North America to the western tropical North Atlantic, referred to as the North American dipole (NAD), and the central Pacific (CP)-type El Niño a year later. In contrast to other ENSO precursors, such as the North Pacific Oscillation (NPO) and Pacific-North America (PNA) pattern, the NAD appears more closely related to the CP-type El Niño than to the eastern Pacific (EP)-type El Niño, indicating that the NAD may serve as a unique precursor for the CP El Niño. The wintertime NAD induces sea surface temperature anomalies in the northern tropical Atlantic (NTA), which subsequently play an important role in developing the CP El Niño-like pattern in the tropical Pacific over the course of the following year. It appears that the NAD influence on CP El Niño involves air-sea interaction over several major basins, including the subtropical/tropical Pacific and the NTA. Additional analysis indicates that the correlation of either the NAD index or the NPO index with the CP El Niño state a year later depends on the status of the other index. When the wintertime NAD index is of the opposite sign to the simultaneous NPO index, the correlation of the NAD or NPO index with the Niño4 index becomes much weaker.

Pro-neurotensin/neuromedin N expression and processing in human colon cancer cell lines.

PubMed

Rovère, C; Barbero, P; Maoret, J J; Laburthe, M; Kitabgi, P

1998-05-08

The regulatory peptide neurotensin NT has been proposed to exert an autocrine trophic effect on human colon cancers. In the present study, pro-neurotensin/neuromedin N (proNT/NN) expression and processing were investigated in 13 human colon cancer cell lines using a combination of radioimmunoassay and HPLC techniques. All 13 cell lines displayed low to moderate levels of proNT/NN ranging from 10 to 250 fmol/mg protein. However, only 6 (HCT8, LoVo, HT29, C119A, LS174T, and coloDM320) processed the precursor. Three of the latter (HCT8, LS174T, and coloDM320) were analysed in detail with regard to proNT/NN processing pattern and were found to produce NT and large precursor fragments ending with the NT or NN sequence. They had no detectable level of NN. Such a processing pattern resembles that generated by the prohormone convertase PC5. Northern and Western blot analysis of prohormone convertase expression in the 3 cell lines revealed that they were devoid of PC1 and PC2, whereas they all expressed PC5. These data indicate that proNT/NN is a good marker of human colon cancer cell lines while NT is found in only about half of the cell lines. They also suggest that, in addition to NT, several proNT/NN-derived products, possibly generated by PC5, might exert an autocrine positive effect on human colon cancer growth.

Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression

PubMed Central

Phoenix, Inaia; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

2016-01-01

The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm’-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed efficient secretion of Gn/gLuc protein from the precursor made from the 2nd AUG, while the removal of the untranslated region upstream of the 2nd AUG (AUG2-M) increased the secretion of the Gn/gLuc protein. Subsequently, recombinant MP-12 strains encoding mutations in the pre-Gn region were rescued, and virological phenotypes were characterized. Recombinant MP-12 encoding the AUG2-M mutation replicated slightly less efficiently than the control, indicating that viral replication is further influenced by the biological processes occurring after Gn expression, rather than the Gn abundance. This study showed that, not only the abolishment of AUG, but also the truncation of viral UTR, affects the expression of Gn protein by the RVFV M-segment. PMID:27231931

Analysis of PKP scattering using mantle mixing simulations and axisymmetric 3D waveforms

NASA Astrophysics Data System (ADS)

Haugland, Samuel M.; Ritsema, Jeroen; van Keken, Peter E.; Nissen-Meyer, Tarje

2018-03-01

The scattering of PKP waves in the lower mantle produces isolated signals before the PKIKP phase. We explore whether these so-called PKIKP precursors can be related to wave scattering off mid ocean ridge basalt (MORB) fragments that have been advected in the deep mantle throughout geologic time. We construct seismic models of small-scale (>20 km) heterogeneity in the lower mantle informed by mantle mixing simulations from Brandenburg et al. (2008) and generate PKIKP precursors using 3D, axisymmetric waveform simulations up to 0.75 Hz. We consider two end-member geodynamic models with fundamentally different distributions of MORB in the lower mantle. Our results suggest that the accumulation of MORB at the base of the mantle is a viable hypothesis for the origin of PKP scattering. We find that the strength of the PKIKP precursor amplitudes is consistent with P wave speed heterogeneity of 0.1-0.2%, as reported previously. The radial distribution of MORB has a profound effect on the strength of PKIKP precursors. Simulation of PKIKP precursors for models with an increasing MORB concentration in the lowermost 500 km of the mantle appears to reproduce most accurately the strength of PKIKP precursors in Global Seismic Network waveforms. These models assume that MORB has an excess density of at least 7%. Additional simulations of more complex geodynamic models will better constrain the geodynamic conditions to explain the significant variability of PKP scattering strength.

Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression.

PubMed

Phoenix, Inaia; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

2016-05-24

The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm'-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed efficient secretion of Gn/gLuc protein from the precursor made from the 2nd AUG, while the removal of the untranslated region upstream of the 2nd AUG (AUG2-M) increased the secretion of the Gn/gLuc protein. Subsequently, recombinant MP-12 strains encoding mutations in the pre-Gn region were rescued, and virological phenotypes were characterized. Recombinant MP-12 encoding the AUG2-M mutation replicated slightly less efficiently than the control, indicating that viral replication is further influenced by the biological processes occurring after Gn expression, rather than the Gn abundance. This study showed that, not only the abolishment of AUG, but also the truncation of viral UTR, affects the expression of Gn protein by the RVFV M-segment.

Oligodendrogenesis and neurogenesis in remyelination in the cuprizone model of multiple sclerosis: correlation with the degree of lesion

NASA Astrophysics Data System (ADS)

Pishchelko, A.; Khodanovich, M.; Pan, E.; Glazacheva, V.; Akulov, A.; Yarnykh, V.

2017-08-01

In this research, a cuprizone model of multiple sclerosis (MS) was used to study oligodendrogenesis and neurogenesis in remyelination. It has been shown that, with the administration of cuprizone, the amount of myelin in a number of structures of white and gray matter and the level of neurogenesis decrease, while the level of oligodendrogenesis increases. The withdrawal of cuprizone leads to the restoration of myelin content, the reduction of the excessive production of oligodendrocytes and to the restoration of the number of neurons to control values. The negative correlation between the number of oligodendrocyte precursors (OPCs) and the degree of demyelination of the corpus callosum indicates migration of OLG precursors from the subventricular zone (SVZ) to the structure during demyelination.

Mars MetNet Mission - Martian Atmospheric Observational Post Network

NASA Astrophysics Data System (ADS)

Haukka, Harri; Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

2016-10-01

A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL).The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior.The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.Full Qualification Model (QM) of the MetNet landing unit with the Precursor Mission payload is currently under functional tests. In the near future the QM unit will be exposed to environmental tests with qualification levels including vibrations, thermal balance, thermal cycling and mechanical impact shock. One complete flight unit of the entry, descent and landing systems (EDLS) has been manufactured and tested with acceptance levels. Another flight-like EDLS has been exposed to most of the qualification tests, and hence it may be used for flight after refurbishments. Accordingly two flight-capable EDLS systems exist. The eventual goal is to create a network of atmospheric observational posts around the Martian surface. The next step in the MetNet Precursor Mission is the demonstration of the technical robustness and scientific capabilities of the MetNet type of landing vehicle. Definition of the Precursor Mission and discussions on launch opportunities are currently under way. The baseline program development funding exists for the next five years. Flight unit manufacture of the payload bay takes about 18 months, and it will be commenced after the Precursor Mission has been defined.

Surface defects on the Gd{sub 2}Zr{sub 2}O{sub 7} oxide films grown on textured NiW technical substrates by chemical solution method

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

Zhao, Y., E-mail: yuezhao@sjtu.edu.cn

2017-02-15

Epitaxial growth of oxide thin films has attracted much interest because of their broad applications in various fields. In this study, we investigated the microstructure of textured Gd{sub 2}Zr{sub 2}O{sub 7} films grown on (001)〈100〉 orientated NiW alloy substrates by a chemical solution deposition (CSD) method. The aging effect of precursor solution on defect formation was thoroughly investigated. A slight difference was observed between the as-obtained and aged precursor solutions with respect to the phase purity and global texture of films prepared using these solutions. However, the surface morphologies are different, i.e., some regular-shaped regions (mainly hexagonal or dodecagonal) weremore » observed on the film prepared using the as-obtained precursor, whereas the film prepared using the aged precursor exhibits a homogeneous structure. Electron backscatter diffraction and scanning electron microscopy analyses showed that the Gd{sub 2}Zr{sub 2}O{sub 7} grains present within the regular-shaped regions are polycrystalline, whereas those present in the surrounding are epitaxial. Some polycrystalline regions ranging from several micrometers to several tens of micrometers grew across the NiW grain boundaries underneath. To understand this phenomenon, the properties of the precursors and corresponding xerogel were studied by Fourier transform infrared spectroscopy and coupled thermogravimetry/differential thermal analysis. The results showed that both the solutions mainly contain small Gd−Zr−O clusters obtained by the reaction of zirconium acetylacetonate with propionic acid during the precursor synthesis. The regular-shaped regions were probably formed by large Gd−Zr−O frameworks with a metastable structure in the solution with limited aging time. This study demonstrates the importance of the precise control of chemical reaction path to enhance the stability and homogeneity of the precursors of the CSD route. - Highlights: •We investigate microstructure of Gd{sub 2}Zr{sub 2}O{sub 7} films grown by a chemical solution route. •The aging effect of precursor solution on formation of surface defect was thoroughly studied. •Gd−Zr−O clusters are present in the precursor solutions.« less

An Accident Precursor Analysis Process Tailored for NASA Space Systems

NASA Technical Reports Server (NTRS)

Groen, Frank; Stamatelatos, Michael; Dezfuli, Homayoon; Maggio, Gaspare

2010-01-01

Accident Precursor Analysis (APA) serves as the bridge between existing risk modeling activities, which are often based on historical or generic failure statistics, and system anomalies, which provide crucial information about the failure mechanisms that are actually operative in the system and which may differ in frequency or type from those in the various models. These discrepancies between the models (perceived risk) and the system (actual risk) provide the leading indication of an underappreciated risk. This paper presents an APA process developed specifically for NASA Earth-to-Orbit space systems. The purpose of the process is to identify and characterize potential sources of system risk as evidenced by anomalous events which, although not necessarily presenting an immediate safety impact, may indicate that an unknown or insufficiently understood risk-significant condition exists in the system. Such anomalous events are considered accident precursors because they signal the potential for severe consequences that may occur in the future, due to causes that are discernible from their occurrence today. Their early identification allows them to be integrated into the overall system risk model used to intbrm decisions relating to safety.

Deglycosylation of serum vitamin D3-binding protein by alpha-N-acetylgalactosaminidase detected in the plasma of patients with systemic lupus erythematosus.

PubMed

Yamamoto, N; Naraparaju, V R; Moore, M; Brent, L H

1997-03-01

A serum glycoprotein, Gc protein (vitamin D3-binding protein), can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor for MAF. Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates a remarkably high titered macrophage-activating factor (GcMAF). When peripheral blood monocytes/ macrophages (designated macrophages) of 33 systemic lupus erythematosus patients were incubated with GcMAF (100 pg/ml), the macrophages of all patients were activated as determined by superoxide generation. However, the precursor activity of patient plasma Gc protein was lost or reduced in these patients. Loss of the precursor activity was the result of deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase activity found in the patient plasma. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Deglycosylated Gc protein cannot be converted to macro-phage-activating factor. The resulting defect in macro-phage activation may lead to an inability to clear pathogenic immune complexes. Thus, elevated plasma alpha-N-acetylgalactosaminidase activity resulting in the loss of MAF precursor activity and reduced macro-phage activity may play a role in the pathogenesis of systemic lupus erythematosus.

Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus.

PubMed

van Dop, Willemijn A; Rosekrans, Sanne L; Uhmann, Anja; Jaks, Viljar; Offerhaus, G Johan A; van den Bergh Weerman, Marius A; Kasper, Maria; Heijmans, Jarom; Hardwick, James C H; Verspaget, Hein W; Hommes, Daan W; Toftgård, Rune; Hahn, Heidi; van den Brink, Gijs R

2013-03-01

In the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus. The authors used transgenic mice in which the Hh receptor Patched1 (Ptch1) could be conditionally inactivated in a body-wide manner and mice in which Gli1 could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR. Sonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets GLI1, HHIP and PTCH1 were increased in SCC compared with normal tissue from the same patients. Here the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation.

Formation, precursors, control, and occurrence of nitrosamines in drinking water: a review.

PubMed

Krasner, Stuart W; Mitch, William A; McCurry, Daniel L; Hanigan, David; Westerhoff, Paul

2013-09-01

This review summarizes major findings over the last decade related to nitrosamines in drinking water, with a particular focus on N-nitrosodimethylamine (NDMA), because it is among the most widely detected nitrosamines in drinking waters. The reaction of inorganic dichloramine with amine precursors is likely the dominant mechanism responsible for NDMA formation in drinking waters. Even when occurrence surveys found NDMA formation in chlorinated drinking waters, it is unclear whether chloramination resulted from ammonia in the source waters. NDMA formation has been associated with the use of quaternary amine-based coagulants and anion exchange resins, and wastewater-impaired source waters. Specific NDMA precursors in wastewater-impacted source waters may include tertiary amine-containing pharmaceuticals or other quaternary amine-containing constituents of personal care products. Options for nitrosamine control include physical removal of precursors by activated carbon or precursor deactivation by application of oxidants, particularly ozone or chlorine, upstream of chloramination. Although NDMA has been the most prevalent nitrosamine detected in worldwide occurrence surveys, it may account for only ≈ 5% of all nitrosamines in chloraminated drinking waters. Other significant contributors to total nitrosamines are poorly characterized. However, high levels of certain low molecular weight nitrosamines have been detected in certain Chinese waters suspected to be impaired by industrial effluents. The review concludes by identifying research needs that should be addressed over the next decade. Copyright © 2013 Elsevier Ltd. All rights reserved.

ACBC to Balcite: Bioinspired Synthesis of a Highly Substituted High-Temperature Phase from an Amorphous Precursor

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

Whittaker, Michael L.; Joester, Derk

2017-04-28

Energy-efficient synthesis of materials locked in compositional and structural states far from equilibrium remains a challenging goal, yet biomineralizing organisms routinely assemble such materials with sophisticated designs and advanced functional properties, often using amorphous precursors. However, incorporation of organics limits the useful temperature range of these materials. Herein, the bioinspired synthesis of a highly supersaturated calcite (Ca0.5Ba0.5CO3) called balcite is reported, at mild conditions and using an amorphous calcium–barium carbonate (ACBC) (Ca1- x Ba x CO3·1.2H2O) precursor. Balcite not only contains 50 times more barium than the solubility limit in calcite but also displays the rotational disorder on carbonate sitesmore » that is typical for high-temperature calcite. It is significantly harder (30%) and less stiff than calcite, and retains these properties after heating to elevated temperatures. Analysis of balcite local order suggests that it may require the formation of the ACBC precursor and could therefore be an example of nonclassical nucleation. These findings demonstrate that amorphous precursor pathways are powerfully enabling and provide unprecedented access to materials far from equilibrium, including high-temperature modifications by room-temperature synthesis.« less

Using a Z-pinch precursor plasma to produce a cylindrical, hotspot ignition, ICF

NASA Astrophysics Data System (ADS)

Chittenden, Jeremy

2005-10-01

We show that if the same precursor plasma that exists in metal wire arrays can be generated with a Deuterium-Tritium plasma then this precursor provides an ideal target for a cylindrical magneto-inertial ICF scheme. The precursor is generated from a fraction of the mass of the array which arrives on the axis early in time and remains confined at high density by the inertia of further material bombarding the axis. Later on, the main implosion of the DT Z-pinch produces a dense, low temperature shell which compressively heats the precursor target to high temperatures and tamps its expansion. The azimuthal magnetic field in the hotspot is sufficient to reduce the Larmor radius for the alpha particles to much less than the hotspot size, which dramatically reduces the ρR required for ignition. A computational analysis of this approach is presented, including a study of the thermonuclear burn wave propagation. The robustness of the scheme with respect to instabilities, confinement time and drive parameters is examined. The results indicate that a high energy gain can be achieved using Z-pinches with 50-100 MA currents and a few hundred nanosecond rise-times. This work was partially supported by the U.S. Department of Energy through cooperative agreement DE-FC03-02NA00057.

Identification of the chemical constituents of Chinese medicine Yi-Xin-Shu capsule by molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation.

PubMed

Wang, Hong-ping; Chen, Chang; Liu, Yan; Yang, Hong-Jun; Wu, Hong-Wei; Xiao, Hong-Bin

2015-11-01

The incomplete identification of the chemical components of traditional Chinese medicinal formula has been one of the bottlenecks in the modernization of traditional Chinese medicine. Tandem mass spectrometry has been widely used for the identification of chemical substances. Current automatic tandem mass spectrometry acquisition, where precursor ions were selected according to their signal intensity, encounters a drawback in chemical substances identification when samples contain many overlapping signals. Compounds in minor or trace amounts could not be identified because most tandem mass spectrometry information was lost. Herein, a molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation method for complex Chinese medicine chemical constituent analysis was developed. The precursor ions were selected according to their two-dimensional characteristics of retention times and mass-to-charge ratio ranges from herbal compounds, so that all precursor ions from herbal compounds were included and more minor chemical constituents in Chinese medicine were identified. Compared to the conventional automatic tandem mass spectrometry setups, the approach is novel and can overcome the drawback for chemical substances identification. As an example, 276 compounds from the Chinese Medicine of Yi-Xin-Shu capsule were identified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

PubMed Central

Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

2016-01-01

Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. PMID:26497474

Ultrasmall Zeolite L Crystals Prepared from Highly-Interdispersed Alkali-Silicate Precursors.

PubMed

Li, Rui; Linares, Noemi; Sutjianto, James G; Chawla, Aseem; Garcia Martinez, Javier; Rimer, Jeffrey D

2018-06-19

The preparation of nanosized zeolites is critical for applications where mass transport limitations within microporous networks hinder their performance. Oftentimes the ability to generate ultrasmall zeolite crystals is dependent upon the use of expensive organics with limited commercial relevance. Here, we report the generation of zeolite L crystals with uniform sizes less than 30 nm using a facile, organic-free method. Time-resolved analysis of precursor assembly and evolution during nonclassical crystallization highlights key differences among silicon sources. Our findings reveal that a homogenous dispersion of potassium ions throughout silicate precursors is critical to enhancing the rate of nucleation and facilitating the formation of ultrasmall crystals. Intimate contact between the inorganic structure-directing agent and silica leads to the formation of a metastable nonporous phase, identified as KAlSi2O6, which undergoes an intercrystalline transformation to zeolite L. The presence of highly-interdispersed alkali-silicate precursors is seemingly integral to a reduced zeolite induction time and may facilitate the development of ultrasmall crystals. Given the general difficulty of achieving nanosized crystals in zeolite synthesis, it is likely that using well-dispersed precursors does not have the same effect on all framework types; however, in select cases it may provide an alternative strategy for optimizing zeolite synthesis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Ying, Minju, E-mail: mjying@bnu.edu.cn, E-mail: g.gehring@sheffield.ac.uk; Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875; Blythe, Harry J.

We investigate the magnetic properties of ZnCoO thin films grown by pulsed laser deposition (PLD) from targets made containing metallic Co or CoO precursors instead of the usual Co{sub 3}O{sub 4}. We find that the films grown from metallic Co precursors in an oxygen rich environment contain negligible amounts of Co metal and have a large magnetization at room temperature. Structural analysis by X-ray diffraction and magneto-optical measurements indicate that the enhanced magnetism is due, in part, from Zn vacancies that partially compensate the naturally occurring n-type defects. We conclude that strongly magnetic films of Zn{sub 0.95}Co{sub 0.05}O that domore » not contain metallic cobalt can be grown by PLD from Co-metal-precursor targets if the films are grown in an oxygen atmosphere.« less

Differentiating between precursor and control variables when analyzing reasoned action theories.

PubMed

Hennessy, Michael; Bleakley, Amy; Fishbein, Martin; Brown, Larry; Diclemente, Ralph; Romer, Daniel; Valois, Robert; Vanable, Peter A; Carey, Michael P; Salazar, Laura

2010-02-01

This paper highlights the distinction between precursor and control variables in the context of reasoned action theory. Here the theory is combined with structural equation modeling to demonstrate how age and past sexual behavior should be situated in a reasoned action analysis. A two wave longitudinal survey sample of African-American adolescents is analyzed where the target behavior is having vaginal sex. Results differ when age and past behavior are used as control variables and when they are correctly used as precursors. Because control variables do not appear in any form of reasoned action theory, this approach to including background variables is not correct when analyzing data sets based on the theoretical axioms of the Theory of Reasoned Action, the Theory of Planned Behavior, or the Integrative Model.

Differentiating Between Precursor and Control Variables When Analyzing Reasoned Action Theories

PubMed Central

Hennessy, Michael; Bleakley, Amy; Fishbein, Martin; Brown, Larry; DiClemente, Ralph; Romer, Daniel; Valois, Robert; Vanable, Peter A.; Carey, Michael P.; Salazar, Laura

2010-01-01

This paper highlights the distinction between precursor and control variables in the context of reasoned action theory. Here the theory is combined with structural equation modeling to demonstrate how age and past sexual behavior should be situated in a reasoned action analysis. A two wave longitudinal survey sample of African-American adolescents is analyzed where the target behavior is having vaginal sex. Results differ when age and past behavior are used as control variables and when they are correctly used as precursors. Because control variables do not appear in any form of reasoned action theory, this approach to including background variables is not correct when analyzing data sets based on the theoretical axioms of the Theory of Reasoned Action, the Theory of Planned Behavior, or the Integrative Model PMID:19370408

Synthesis of liquid crystalline epoxy monomers

NASA Astrophysics Data System (ADS)

Fabia, J.; Galina, H.; Mossety-Leszczak, B.; Ulanski, J.; Wojciechowski, Piotr; Wlochowicz, Andrzej

2002-06-01

A two-stage method of synthesis of liquid-crystalline diepoxy monomers has been developed. In the first stage, esterification of 4-hydroxyphenyl-4-hydroxybenzoate or 4,4'- biphenol or 4,4'-dihydroxyazobenzene was carried out using 4-penetenoic acid. The resulting olefinic precursors were oxidized with m-chloroperoxybenzoic acid to introduce the epoxy groups. The structure of products was confirmed by FT- IR and 1H NMR. Examinations on a polarization microscope with a hot plate confirmed the presence of mesomorphic phases in both the precursors and monomers. The phase transition temperatures were in the range of 73.5 (at cooling) to 128.0 degree(s)C for olefinic precursors and in the range 57.1 (at cooling) to 143 degree(s)C for epoxy compounds, as determined by DSC and thermo-optical analysis (TOA).

Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis.

PubMed

Conter, Valentino; Valsecchi, Maria Grazia; Buldini, Barbara; Parasole, Rosanna; Locatelli, Franco; Colombini, Antonella; Rizzari, Carmelo; Putti, Maria Caterina; Barisone, Elena; Lo Nigro, Luca; Santoro, Nicola; Ziino, Ottavio; Pession, Andrea; Testi, Anna Maria; Micalizzi, Concetta; Casale, Fiorina; Pierani, Paolo; Cesaro, Simone; Cellini, Monica; Silvestri, Daniela; Cazzaniga, Giovanni; Biondi, Andrea; Basso, Giuseppe

2016-02-01

Early T-cell precursor acute lymphoblastic leukaemia was recently recognised as a distinct leukaemia and reported as associated with poor outcomes. We aimed to assess the outcome of early T-cell precursor acute lymphoblastic leukaemia in patients from the Italian Association of Pediatric Hematology Oncology (AIEOP) centres treated with AIEOP-Berlin-Frankfurt-Münster (AIEOP-BFM) protocols. In this retrospective analysis, we included all children aged from 1 to less than 18 years with early T-cell precursor acute lymphoblastic leukaemia immunophenotype diagnosed between Jan 1, 2008, and Oct 31, 2014, from AIEOP centres. Early T-cell precursors were defined as being CD1a and CD8 negative, CD5 weak positive or negative, and positive for at least one of the following antigens: CD34, CD117, HLADR, CD13, CD33, CD11b, or CD65. Treatment was based on AIEOP-BFM acute lymphoblastic leukaemia 2000 (NCT00613457) or AIEOP-BFM acute lymphoblastic leukaemia 2009 protocols (European Clinical Trials Database 2007-004270-43). The main differences in treatment and stratification of T-cell acute lymphoblastic leukaemia between the two protocols were that in the 2009 protocol only, pegylated L-asparaginase was substituted for Escherichia coli L-asparaginase, patients with prednisone poor response received an additional dose of cyclophosphamide at day 10 of phase IA, and high minimal residual disease at day 15 assessed by flow cytometry was used as a high-risk criterion. Outcomes were assessed in terms of event-free survival, disease-free survival, and overall survival. Early T-cell precursor acute lymphoblastic leukaemia was diagnosed in 49 patients. Compared with overall T-cell acute lymphoblastic leukaemia, it was associated with absence of molecular markers for PCR detection of minimal residual disease in 25 (56%) of 45 patients; prednisone poor response in 27 (55%) of 49 patients; high minimal residual disease at day 15 after starting therapy in 25 (64%) of 39 patients (bone marrow blasts ≥ 10%, by flow cytometry); no complete remission after phase IA in 7 (15%) of 46 patients (bone marrow blasts ≥ 5%, morphologically); and high PCR minimal residual disease (≥ 5 × 10(-4)) at day 33 after starting therapy in 17 (85%) of 20 patients with markers available. Overall, 38 (78%) of 49 patients are in continuous complete remission, including 13 of 18 after haemopoietic stem cell transplantation, with three deaths in induction, five deaths after haemopoietic stem cell transplantation, and three relapses. Severe adverse events in the 2009 study were reported in 10 (30%) of 33 patients with early T-cell precursor acute lymphoblastic leukaemia versus 24 (15%) of 164 patients without early T-cell precursor acute lymphoblastic leukaemia and life-threatening events in induction phase IA occurred in 4 (12%) of 33 patients with early T-cell precursor acute lymphoblastic leukaemia versus 7 (4%) of 164 patients without early T-cell precursor acute lymphoblastic leukaemia. No difference was seen in the subsequent consolidation phase IB of protocol I. Early T-cell precursor acute lymphoblastic leukaemia is characterised by poor early response to conventional induction treatment. Consolidation phase IB, based on cyclophosphamide, 6-mercaptopurine, and ara-C at conventional (non-high) doses is effective in reducing minimal residual disease. Although the number of patients and observational time are limited, patients with early T-cell precursor acute lymphoblastic leukaemia treated with current BFM stratification and treatment strategy have a favourable outcome compared with earlier reports. The role of innovative therapies and haemopoietic stem cell therapy in early T-cell precursor acute lymphoblastic leukaemia needs to be assessed. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transcriptome Analysis of Human Immune Responses Following Live Vaccine Strain (LVS) Francisella Tularensis Vaccination

DTIC Science & Technology

2007-03-08

with CD3D 50848 PAR1/UBE3A Prader–Willi syndrome chromosome region 1, GMCSFRalpha precursor, IL3Ralpha precursor (CD123) Brain development...intervention programs justifiable? Emerg. Infect. Dis. 3, 83–94. iebel, U., Kindler , B., Pepperkok, R., 2004. ‘Harvester’: a fast meta search engine of human...protein resources. Bioinformatics 20, 1962–1963. iebel, U., Kindler , B., Pepperkok, R., 2005. Bioinformatic “Harvester”: a search engine for genome

Chaotic Time Series Analysis Method Developed for Stall Precursor Identification in High-Speed Compressors

NASA Technical Reports Server (NTRS)

1997-01-01

A new technique for rotating stall precursor identification in high-speed compressors has been developed at the NASA Lewis Research Center. This pseudo correlation integral method uses a mathematical algorithm based on chaos theory to identify nonlinear dynamic changes in the compressor. Through a study of four various configurations of a high-speed compressor stage, a multistage compressor rig, and an axi-centrifugal engine test, this algorithm, using only a single pressure sensor, has consistently predicted the onset of rotating stall.

Dietary Precursors of Serotonin and Newborn State Behavior.

ERIC Educational Resources Information Center

Yogman, Michael W.; Zeisel, Steven

Although previous research with adult humans and nonhumans has suggested a relationship between sleep behavior and brain serotonin levels, no studies have been made of the relationship of normal children's or infants' sleep patterns to serotonin levels, tryptophan metabolism, or diet. This study investigates the relationship between dietary…

Time series of GNSS-derived ionospheric maps to detect anomalies as possible precursors of high magnitude earthquakes

NASA Astrophysics Data System (ADS)

Barbarella, M.; De Giglio, M.; Galeandro, A.; Mancini, F.

2012-04-01

The modification of some atmospheric physical properties prior to a high magnitude earthquake has been recently debated within the Lithosphere-Atmosphere-Ionosphere (LAI) Coupling model. Among this variety of phenomena the ionization of air at the higher level of the atmosphere, called ionosphere, is investigated in this work. Such a ionization occurrences could be caused by possible leaking of gases from earth crust and their presence was detected around the time of high magnitude earthquakes by several authors. However, the spatial scale and temporal domain over which such a disturbances come into evidence is still a controversial item. Even thought the ionospheric activity could be investigated by different methodologies (satellite or terrestrial measurements), we selected the production of ionospheric maps by the analysis of GNSS (Global Navigation Satellite Data) data as possible way to detect anomalies prior of a seismic event over a wide area around the epicentre. It is well known that, in the GNSS sciences, the ionospheric activity could be probed by the analysis of refraction phenomena occurred on the dual frequency signals along the satellite to receiver path. The analysis of refraction phenomena affecting data acquired by the GNSS permanent trackers is able to produce daily to hourly maps representing the spatial distribution of the ionospheric Total Electron Content (TEC) as an index of the ionization degree in the upper atmosphere. The presence of large ionospheric anomalies could be therefore interpreted in the LAI Coupling model like a precursor signal of a strong earthquake, especially when the appearance of other different precursors (thermal anomalies and/or gas fluxes) could be detected. In this work, a six-month long series of ionospheric maps produced from GNSS data collected by a network of 49 GPS permanent stations distributed within an area around the city of L'Aquila (Abruzzi, Italy), where an earthquake (M = 6.3) occurred on April 6, 2009, were investigated. Basically, the proposed methodology is able to perform a time series analysis of the TEC maps and, eventually, define the spatial and temporal domains of ionospheric disturbances. This goal was achieved by a time series analysis of the spatial dataset able to compare a local pattern of ionospheric activity with its historical mean value and detect areas where the TEC content exhibits anomalous values. This data processing shows some 1 to 2 days long anomalies about 20 days before of the seismic event (confirming also results provided in recent studies by means of ionospheric soundings).

Reduction of Brain β-Amyloid (Aβ) by Fluvastatin, a Hydroxymethylglutaryl-CoA Reductase Inhibitor, through Increase in Degradation of Amyloid Precursor Protein C-terminal Fragments (APP-CTFs) and Aβ Clearance*

PubMed Central

Shinohara, Mitsuru; Sato, Naoyuki; Kurinami, Hitomi; Takeuchi, Daisuke; Takeda, Shuko; Shimamura, Munehisa; Yamashita, Toshihide; Uchiyama, Yasuo; Rakugi, Hiromi; Morishita, Ryuichi

2010-01-01

Epidemiological studies suggest that statins (hydroxymethylglutaryl-CoA reductase inhibitors) could reduce the risk of Alzheimer disease. Although one possible explanation is through an effect on β-amyloid (Aβ) metabolism, its effect remains to be elucidated. Here, we explored the molecular mechanisms of how statins influence Aβ metabolism. Fluvastatin at clinical doses significantly reduced Aβ and amyloid precursor protein C-terminal fragment (APP-CTF) levels among APP metabolites in the brain of C57BL/6 mice. Chronic intracerebroventricular infusion of lysosomal inhibitors blocked these effects, indicating that up-regulation of the lysosomal degradation of endogenous APP-CTFs is involved in reduced Aβ production. Biochemical analysis suggested that this was mediated by enhanced trafficking of APP-CTFs from endosomes to lysosomes, associated with marked changes of Rab proteins, which regulate endosomal function. In primary neurons, fluvastatin enhanced the degradation of APP-CTFs through an isoprenoid-dependent mechanism. Because our previous study suggests additive effects of fluvastatin on Aβ metabolism, we examined Aβ clearance rates by using the brain efflux index method and found its increased rates at high Aβ levels from brain. As LRP1 in brain microvessels was increased, up-regulation of LRP1-mediated Aβ clearance at the blood-brain barrier might be involved. In cultured brain microvessel endothelial cells, fluvastatin increased LRP1 and the uptake of Aβ, which was blocked by LRP1 antagonists, through an isoprenoid-dependent mechanism. Overall, the present study demonstrated that fluvastatin reduced Aβ level by an isoprenoid-dependent mechanism. These results have important implications for the development of disease-modifying therapy for Alzheimer disease as well as understanding of Aβ metabolism. PMID:20472556

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

Munsat, Tobin

Overview of University of Colorado Efforts: The University of Colorado group has focused on two primary fronts during the grant period: development of a variety of multi-point diagnostic and/or imaging analysis techniques, and momentum-transport related experiments on a variety of devices (NSTX at PPPL, CSDX at UCSD, LAPD at UCLA, DIII-D at GA). Experimental work has taken advantage of several diagnostic instruments, including fast-framing cameras for imaging of electron density fluctuations (either directly or using injected gas puffs), ECEI for imaging of electron temperature fluctuations, and multi-tipped Langmuir and magnetic probes for corroborating measurements of Reynolds and Maxwell stresses. Modemore » Characterization in CSDX: We have performed a series of experiments at the CSDX linear device at UCSD, in collaboration with Center PI G. Tynan's group. The experiments included a detailed study of velocity estimation techniques, including direct comparisons between Langmuir probes and image-based velocimetry from fast-framing camera data. We used the camera data in a second set of studies to identify the spatial and spectral structure of coherent modes, which illuminates wave behavior to a level of detail previously unavailable, and enables direct comparison of dispersion curves to theoretical estimates. In another CSDX study, similar techniques were used to demonstrate a controlled transition from nonlinearly coupled discrete eigenmodes to fully developed broadband turbulence. The axial magnetic field was varied from 40-240 mT, which drove the transition. At low magnetic fields, the plasma is dominated by drift waves. As the magnetic field is increased, a strong potential gradient at the edge introduces an ExB shear-driven instability. At the transition, another mode with signatures of a rotation-induced Rayleigh–Taylor instability appears at the central plasma region. Concurrently, large axial velocities were found in the plasma core. For larger magnetic fields, all of the instabilities co-exist, leading to rich plasma dynamics and fully developed broadband turbulence. Edge-Turbulence and Flow Experiments in NSTX: A series of Gas Puff Imaging (GPI) observations on NSTX revealed a quasi-periodic oscillation in the plasma edge preceding the L-H transition in a limited set of neutral beam heated plasmas. These ~3 kHz flow oscillations exhibit both long wavelength and long correlation lengths, suggesting they are zonal-flow-like. The flow oscillations are strongly correlated with modulations of the level of edge turbulence, thus the system appears to undergo a predator--prey-type limit-cycle preceding the L-H transition. However, a clear trigger for the L-H transition was not observed. Reynolds stress profiles were obtained directly from image velocimetry for L-mode periods ELM-Precursor Studies in NSTX: A separate study based on NSTX-GPI data captured the two-dimensional evolution of edge-localized mode (ELM) precursors. Precursor events were observed preceding ELMs and ELM-induced H–L back-transitions in radio-frequency heated H-mode plasmas, and the growth of the precursor mode through the ELM filamentation was imaged in the plane perpendicular to the local B-field. Strong edge intensity modulations appeared to propagate in the electron diamagnetic direction while steadily drifting radially outwards. Intensity fluctuations were observed at frequencies around 20 kHz and wavenumbers of 0.05-0.2 cm -1. Upon growing to a trigger point, precursor fluctuations were seen to form filamentary structures and move into the scrape-off layer (SOL) explosively with radial velocities peaking at 8 km/s. Once in the SOL, filaments reverse their propagation direction and travel in the ion diamagnetic direction. Edge intensity fluctuations were strongly correlated with magnetic signals from Mirnov coils, and toroidally distributed coils estimated toroidal mode numbers of n=5-10. Quantitatively similar precursors have been observed in ohmic H-mode plasmas as well, though significantly fewer events are seen in the ohmic cases and none were observed in the near-threshold NBI H-modes studied. Development of Velocimetry and Image Analysis Techniques: Along with the experiments listed above, the Colorado group has continued to explore various velocimetry techniques and their range of validity. We have developed a “linear optical flow” code, which calculates smooth velocity maps while accurately assessing local regions of high curl. This is critical for separating spatial scales of velocity behavior, and thus transport. This code has recently come on-line, and we are currently using it to revisit a number of older datasets. Additionally, we have worked on developing pattern-recognition techniques for imaging diagnostics, based on established digital image compression algorithms. This has the potential to open the analysis of turbulent plasma behavior beyond the well-trodden Fourier and wavelet approaches. Finally, we have extended several of these image-analysis routines to multiple other diagnostic sets, including GPI datasets in NSTX and ECEI imaging on DIII-D. In one study, correlation maps were used to measure the full 2-D mode structure of drift-wave level structures using ECEI for the first time. This enabled direct comparison to gyrokinetic simulations using the GEM code, from which is was determined that TEM modes were being measured in DIII-D.« less

Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast

PubMed Central

Misra, Ashish; Conway, Matthew F.; Johnnie, Joseph; Qureshi, Tabish M.; Lige, Bao; Derrick, Anne M.; Agbo, Eddy C.; Sriram, Ganesh

2013-01-01

Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound. The potent antimalarial therapeutic artemisinin and its precursors are promising candidate molecules for production in microbial hosts. Recent advances have demonstrated the production of artemisinin precursors in engineered yeast strains as an alternative to extraction from plants. We report the application of in silico and in vivo metabolic pathway analyses to identify metabolic engineering targets to improve the yield of the direct artemisinin precursor dihydroartemisinic acid (DHA) in yeast. First, in silico extreme pathway (ExPa) analysis identified NADPH-malic enzyme and the oxidative pentose phosphate pathway (PPP) as mechanisms to meet NADPH demand for DHA synthesis. Next, we compared key DHA-synthesizing ExPas to the metabolic flux distributions obtained from in vivo 13C metabolic flux analysis of a DHA-synthesizing strain. This comparison revealed that knocking out ethanol synthesis and overexpressing glucose-6-phosphate dehydrogenase in the oxidative PPP (gene YNL241C) or the NADPH-malic enzyme ME2 (YKL029C) are vital steps toward overproducing DHA. Finally, we employed in silico flux balance analysis and minimization of metabolic adjustment on a yeast genome-scale model to identify gene knockouts for improving DHA yields. The best strategy involved knockout of an oxaloacetate transporter (YKL120W) and an aspartate aminotransferase (YKL106W), and was predicted to improve DHA yields by 70-fold. Collectively, our work elucidates multiple non-trivial metabolic engineering strategies for improving DHA yield in yeast. PMID:23898325

Methylamphetamine synthesized from cold medication as precursor source via two different routes show significantly different stable isotope signatures

NASA Astrophysics Data System (ADS)

Jayaram, S.; Daeid, N. Nic; Kerr, W. J.; Kemp, H. F.; Meier-Augenstein, W.

2012-04-01

This work exposes the variation in light element stable isotopic abundance values of 13C, 2H and 15N) derived from the analysis of methylamphetamine synthesized via 2 different synthetic routes popular with clandestine laboraties, the Hypophosphorous and the Moscow route. We repeatedly prepared the final product using known clandestine synthetic methods where the precursors, catalysts and reducing agents have themselves been derived from house hold products and commonly available cold medications. Methylamphetamine was prepared from both lab grade pseudoephedrine and pseudoephedrine extracted (using three different solvent systems) from Sudafed®, an over-the-counter cold medication widely available in the United Kingdom. Six repetitive batches of the final product were produced in each case to provide within and between batch variations thus yielding a total of 48 samples (24 for each route). We have demonstrated that stable isotope analysis by Isotope Ratio Mass Spectrometry (IRMS) is potentially useful in the comparison and discrimination of batches of methylamphetamine produced for each route and for each precursor depending on the solvent used for extracting the pseudoephedrine starting material. To our knowledge this is the first time multivariate stable isotope analysis has been applied to methylamphetamine samples synthesized from pseudoephedrine extracted from over-the-counter cold medications.

Analysis of ibuprofen and its main metabolites in roots, shoots, and seeds of cowpea (Vigna unguiculata L. Walp) using liquid chromatography-quadrupole time-of-flight mass spectrometry: uptake, metabolism, and translocation.

PubMed

Picó, Yolanda; Alvarez-Ruiz, Rodrigo; Wijaya, Leonard; Alfarhan, Ahmed; Alyemeni, Mohammed; Barceló, Damià

2018-01-01

A liquid chromatography quadruple time-of-flight mass spectrometry (LC-QqTOF-MS/MS) method was developed for simultaneous quantitative analysis of ibuprofen (IBU), 1- and 2-hydroxyibuprofen (1-OH IBU and 2-OH IBU), and carboxyibuprofen (CBX IBU) while preserving the ability of the instrument to get precursor and product ion mass spectra of non-target compounds. The trigger was the precursor ions reaching 100 cps intensity. Sample preparation was carried out by ultrasound solid-liquid extraction with methanol as extraction solvent at pH < 2 followed by solid-phase extraction (SPE) clean-up using STRATA-X cartridges and methanol as an eluent. Linearity was obtained in the range 50-10,000 ng mL -1 for IBU, each OH IBU and CBX IBU (r ≥ 0.99). The proposed method was satisfactorily validated showing absolute recoveries of > 70% for all target analytes at low and high concentration levels. The lowest limit of quantification was < 50 ng g -1 in plant. This method was applied to investigate IBP behavior in cowpea (Vigna unguiculata (L.) Walp) treated at high IBU concentrations and its presence in vegetables irrigated with treated water. Up to 46 metabolites, mostly hydroxylated metabolites and conjugates with hexosides and amino acids, were identified. The most abundant metabolites were also identified in an eggplant sample. Graphical Abstract ᅟ Ibuprofen metabolite identification.

Transcriptome-wide identification of Rauvolfia serpentina microRNAs and prediction of their potential targets.

PubMed

Prakash, Pravin; Rajakani, Raja; Gupta, Vikrant

2016-04-01

MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 19-24 nucleotides (nt) in length and considered as potent regulators of gene expression at transcriptional and post-transcriptional levels. Here we report the identification and characterization of 15 conserved miRNAs belonging to 13 families from Rauvolfia serpentina through in silico analysis of available nucleotide dataset. The identified mature R. serpentina miRNAs (rse-miRNAs) ranged between 20 and 22nt in length, and the average minimal folding free energy index (MFEI) value of rse-miRNA precursor sequences was found to be -0.815 kcal/mol. Using the identified rse-miRNAs as query, their potential targets were predicted in R. serpentina and other plant species. Gene Ontology (GO) annotation showed that predicted targets of rse-miRNAs include transcription factors as well as genes involved in diverse biological processes such as primary and secondary metabolism, stress response, disease resistance, growth, and development. Few rse-miRNAs were predicted to target genes of pharmaceutically important secondary metabolic pathways such as alkaloids and anthocyanin biosynthesis. Phylogenetic analysis showed the evolutionary relationship of rse-miRNAs and their precursor sequences to homologous pre-miRNA sequences from other plant species. The findings under present study besides giving first hand information about R. serpentina miRNAs and their targets, also contributes towards the better understanding of miRNA-mediated gene regulatory processes in plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex.

PubMed

García-Díaz, Beatriz; Riquelme, Raquel; Varela-Nieto, Isabel; Jiménez, Antonio Jesús; de Diego, Isabel; Gómez-Conde, Ana Isabel; Matas-Rico, Elisa; Aguirre, José Ángel; Chun, Jerold; Pedraza, Carmen; Santín, Luis Javier; Fernández, Oscar; Rodríguez de Fonseca, Fernando; Estivill-Torrús, Guillermo

2015-11-01

Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA(1-6)). Our previous studies using viable Malaga variant maLPA1-null mice demonstrated the requirement of the LPA1 receptor for normal proliferation, differentiation, and survival of the neuronal precursors. In the cerebral cortex LPA1 is expressed extensively in differentiating oligodendrocytes, in parallel with myelination. Although exogenous LPA-induced effects have been investigated in myelinating cells, the in vivo contribution of LPA1 to normal myelination remains to be demonstrated. This study identified a relevant in vivo role for LPA1 as a regulator of cortical myelination. Immunochemical analysis in adult maLPA1-null mice demonstrated a reduction in the steady-state levels of the myelin proteins MBP, PLP/DM20, and CNPase in the cerebral cortex. The myelin defects were confirmed using magnetic resonance spectroscopy and electron microscopy. Stereological analysis limited the defects to adult differentiating oligodendrocytes, without variation in the NG2+ precursor cells. Finally, a possible mechanism involving oligodendrocyte survival was demonstrated by the impaired intracellular transport of the PLP/DM20 myelin protein which was accompanied by cellular loss, suggesting stress-induced apoptosis. These findings describe a previously uncharacterized in vivo functional role for LPA1 in the regulation of oligodendrocyte differentiation and myelination in the CNS, underlining the importance of the maLPA1-null mouse as a model for the study of demyelinating diseases.

Biomimetic synthesis of calcite films by a polymer-induced liquid-precursor (PILP) process. 1. Influence and incorporation of magnesium

NASA Astrophysics Data System (ADS)

Cheng, Xingguo; Varona, Philip L.; Olszta, Matthew J.; Gower, Laurie B.

2007-09-01

Magnesium-bearing calcium carbonate films have been synthesized via a polymer-induced liquid-precursor (PILP) mineralization process. A variety of morphological features of biominerals can be mimicked with this PILP process; therefore, our group has proposed that this crystallization system can be used as an effective in vitro model system for examining mechanistic issues related to biomineralization. Here, the effect of the Mg 2+/Ca 2+ ratio on the rate of transformation of the amorphous precursor films was investigated using polarized optical microscopy (POM), and the final crystalline structure and composition were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), inductively coupled plasma spectroscopy (ICP) and energy dispersive spectroscopy (EDS). The entrapment of high levels of magnesium in the deposited precursor films had a pronounced inhibitory effect on the amorphous to crystalline transformation, and furthermore, influenced the polycrystalline nature of the film. The magnesium content incorporated within the calcite lattice (8-26%) resembles the range found in biologically formed high magnesium-bearing calcite, while much lower levels were formed via the conventional solution crystallization process. The formation of non-equilibrium morphologies and similar compositions of magnesium-bearing calcite via the PILP process further supports our hypothesis that the PILP process may play a fundamental role in the formation of calcitic biominerals in nature. In the realm of biomimetic engineering, the PILP process may also establish itself as a new method to produce thin ceramic films with variable compositions under ambient conditions.

Development of pollution reduction strategies for Mexico City: Estimating cost and ozone reduction effectiveness

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

Thayer, G.R.; Hardie, R.W.; Barrera-Roldan, A.

1993-12-31

This reports on the collection and preparation of data (costs and air quality improvement) for the strategic evaluation portion of the Mexico City Air Quality Research Initiative (MARI). Reports written for the Mexico City government by various international organizations were used to identify proposed options along with estimates of cost and emission reductions. Information from appropriate options identified by SCAQMD for Southem California were also used in the analysis. A linear optimization method was used to select a group of options or a strategy to be evaluated by decision analysis. However, the reduction of ozone levels is not a linearmore » function of the reduction of hydrocarbon and NO{sub x} emissions. Therefore, a more detailed analysis was required for ozone. An equation for a plane on an isopleth calculated with a trajectory model was obtained using two endpoints that bracket the expected total ozone precursor reductions plus the starting concentrations for hydrocarbons and NO{sub x}. The relationship between ozone levels and the hydrocarbon and NO{sub x} concentrations was assumed to lie on this plane. This relationship was used in the linear optimization program to select the options comprising a strategy.« less

Multidisciplinary Analysis of the NEXUS Precursor Space Telescope

NASA Astrophysics Data System (ADS)

de Weck, Olivier L.; Miller, David W.; Mosier, Gary E.

2002-12-01

A multidisciplinary analysis is demonstrated for the NEXUS space telescope precursor mission. This mission was originally designed as an in-space technology testbed for the Next Generation Space Telescope (NGST). One of the main challenges is to achieve a very tight pointing accuracy with a sub-pixel line-of-sight (LOS) jitter budget and a root-mean-square (RMS) wavefront error smaller than λ/50 despite the presence of electronic and mechanical disturbances sources. The analysis starts with the assessment of the performance for an initial design, which turns out not to meet the requirements. Twentyfive design parameters from structures, optics, dynamics and controls are then computed in a sensitivity and isoperformance analysis, in search of better designs. Isoperformance allows finding an acceptable design that is well "balanced" and does not place undue burden on a single subsystem. An error budget analysis shows the contributions of individual disturbance sources. This paper might be helpful in analyzing similar, innovative space telescope systems in the future.

Statistical study of single and multiple pulse laser-induced damage in glasses.

PubMed

Gallais, L; Natoli, J; Amra, C

2002-12-16

Single and multiple pulse laser damage studies are performed in Suprasil silica and BK-7 borosilicate glasses. Experiments are made in the bulk of materials at 1.064microm with nanosecond pulses, using an accurate and reliable measurement system. By means of a statistical study on laser damage probabilities, we demonstrate that the same nano-precursors could be involved in the multiple shot and single shot damage process. A damage mechanism with two stages is then proposed to explain the results. Firstly, a pre-damage process, corresponding to material changes at a microscopic level, leads the precursor to a state that can induce a one-pulse damage. And secondly a final damage occurs, with a mechanism identical to the single shot case. For each material, a law is found to predict the precursor life-time. We can then deduce the long term life of optical elements in high-power laser systems submitted to multipulse irradiation.

Do we really need to differentiate mesenchymal stem cells into insulin-producing cells for attenuation of the autoimmune responses in type 1 diabetes: immunoprophylactic effects of precursors to insulin-producing cells.

PubMed

Sharma, Anshu; Rani, Rajni

2017-07-12

Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines. MSCs cultured in high-glucose media for 11 to 13 passages were characterized for the expression of pancreatic lineage genes using real-time polymerase chain reaction. Expression of the PDX1 gene in pIPCs was assessed using Western blot and fluorescence-activated cell sorting (FACS). Triple-positive MSCs were differentiated into IPCs using a three-step protocol after sorting them for cell surface markers, i.e. CD29, CD44, and SCA-1. Nonobese diabetic mice were administered pIPCs, IPCs, or phosphate-buffered saline (PBS) into the tail vein at weeks 9 or 10 and followed-up for 29-30 weeks for fasting blood glucose levels. Two consecutive blood sugar levels of more than 250 mg/dl were considered diabetic. MSCs grown in high-glucose media for 11 to 13 passages expressed genes of the pancreatic lineage such as PDX1, beta2, neurogenin, PAX4, Insulin, and glucagon. Furthermore, Western blot and FACS analysis for PDX-1, a transcription factor necessary for beta cell maturation, confirmed that these cells were precursors of insulin-producing cells (pIPCs). NOD mice administered with pIPCs were better protected from developing diabetes with a protective efficacy of 78.4% (p < 0.009); however, administration of IPCs gave protective efficacy of 55% at the end of 28-30 weeks. Precursors to insulin-producing cells seem to have better potential to arrest autoimmune response in type 1 diabetes when administered before the onset of the disease in NOD mice. When translated to humans, autologous mesenchymal stem cells grown in high-glucose media for 10 to 13 passages may have beneficial effects in individuals at high risk of developing type 1 diabetes.

Sea level variations during rapid changing Arctic Ocean from tide gauge and satellite altimetry

NASA Astrophysics Data System (ADS)

Du, Ling; Xu, Daohuan

2016-04-01

Sea level variations can introduce the useful information under the circumstance of the rapid changing Arctic. Based on tide gauge records and the satellite altimetry data in the Arctic Ocean, the sea level variations in the 20th century are analyzed with the stochastic dynamic method. The average secular trend of the sea level record is about 1 mm/yr, which is smaller than the global mean cited by the IPCC climate assessment report. The secular trend in the coastal region differs from that in the deep water. After the mid-1970s, a weak acceleration of sea level rise is found along the coasts of the Siberian and Aleutian Islands. Analysis of synchronous TOPEX/Poseidon altimetry data indicates that the amplitude of the seasonal variation is less than that of the inter-annual variation, whose periods vary from 4.7 to 6 years. This relationship is different from that in the mid-latitudes. The climate indices are the pre-cursors of the sea level variations on multi-temporal scales. The model results show that while steric effects contribute significantly to the seasonal variation, the influence of atmospheric wind forcing is an important factor of sea level during ice free region.

Isolation and characterisation of mRNA encoding the salmon- and chicken-II type gonadotrophin-releasing hormones in the teleost fish Rutilus rutilus (Cyprinidae).

PubMed

Penlington, M C; Williams, M A; Sumpter, J P; Rand-Weaver, M; Hoole, D; Arme, C

1997-12-01

The complementary DNAs (cDNA) encoding the [Trp7,Leu8]-gonadotrophin-releasing hormone (salmon-type GnRH; sGnRH:GeneBank accession no. u60667) and the [His5,Trp7,Tyr8]-GnRH (chicken-II-type GnRH; cGnRH-II: GeneBank accession no. u60668) precursor in the roach (Rutilus rutilus) were isolated and sequenced following reverse transcription and rapid amplification of cDNA ends (RACE). The sGnRH and cGnRH-II precursor cDNAs consisted of 439 and 628 bp, and included open reading frames of 282 and 255 bp respectively. The structures of the encoded peptides were the same as GnRHs previously identified in other vertebrates. The sGnRH and cGnRH-II precursor cDNAs, including the non-coding regions, had 88.6 and 79.9% identity respectively, to those identified in goldfish (Carassius auratus). However, significant similarity was not observed between the non-coding regions of the GnRH cDNAs of Cyprinidae and other fish. The presumed third exon, encoding partial sGnRH associated peptide (GAP) of roach, demonstrated significant nucleotide and amino acid similarity with the appropriate regions in the goldfish, but not with other species, and this may indicate functional differences of GAP between different families of fish. cGnRH-II precursor cDNAs from roach had relatively high nucleotide similarity across this GnRH variant. Cladistic analysis classified the sGnRH and cGnRH-II precursor cDNAs into three and two groups respectively. However, the divergence between nucleotide sequences within the sGnRH variant was greater than those encoding the cGnRH-II precursors. Consistent with the consensus developed from previous studies, Northern blot analysis demonstrated that expression of sGnRH and cGnRH-II was restricted to the olfactory bulbs and midbrain of roach respectively. This work forms the basis for further study on the mechanisms by which the tapeworm, Ligula intestinalis, interacts with the pituitary-gonadal axis of its fish host.

Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors.

PubMed

Petriello, Michael C; Hoffman, Jessie B; Sunkara, Manjula; Wahlang, Banrida; Perkins, Jordan T; Morris, Andrew J; Hennig, Bernhard

2016-07-01

The etiology of cardiovascular disease (CVD) is impacted by multiple modifiable and non-modifiable risk factors including dietary choices, genetic predisposition, and environmental exposures. However, mechanisms linking diet, exposure to pollutants, and CVD risk are largely unclear. Recent studies identified a strong link between plasma levels of nutrient-derived Trimethylamine N-oxide (TMAO) and coronary artery disease. Dietary precursors of TMAO include carnitine and phosphatidylcholine, which are abundant in animal-derived foods. Dioxin-like pollutants can upregulate a critical enzyme responsible for TMAO formation, hepatic flavin containing monooxygenase 3 (FMO3), but a link between dioxin-like PCBs, upregulation of FMO3, and increased TMAO has not been reported. Here, we show that mice exposed acutely to dioxin-like PCBs exhibit increased hepatic FMO3 mRNA, protein, as well as an increase in circulating levels of TMAO following oral administration of its metabolic precursors. C57BL/6 mice were exposed to 5μmol PCB 126/kg mouse weight (1.63mg/kg). At 48h post-PCB exposure, mice were subsequently given a single gavage of phosphatidylcholine dissolved in corn oil. Exposure to 5 μmole/kg PCB 126 resulted in greater than 100-fold increase in FMO3 mRNA expression, robust induction of FMO3 protein, and a 5-fold increase in TMAO levels compared with vehicle treated mice. We made similar observations in mice exposed to PCB 77 (49.6mg/kg twice); stable isotope tracer studies revealed increased formation of plasma TMAO from an orally administered precursor trimethylamine (TMA). Taken together, these observations suggest a novel diet-toxicant interaction that results in increased production of a circulating biomarker of cardiovascular disease risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Sox2: A multitasking networker

PubMed Central

Reiprich, Simone; Wegner, Michael

2014-01-01

The transcription factor Sox2 is best known as a pluripotency factor in stem and precursor cells and its expression generally correlates with an undifferentiated state. Proposed modes of action include those as classical transcription factor and pre-patterning factor with influence on histone modifications and chromatin structure. Recently, we provided the first detailed analysis of Sox2 expression and function during development of oligodendrocytes, the myelin-forming cells of the CNS. Surprisingly, we found evidence for a role of Sox2 as differentiation factor and found it to act through modulation of microRNA levels. Thus, we add new facets to the functional repertoire of Sox2 and throw light on the networking activity of this multitasking developmental regulator. PMID:27502481

Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

NASA Technical Reports Server (NTRS)

Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

1992-01-01

Possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion were investigated in rats flown on Cosmos 1887 and 2044 biosatellites. Immunohistochemical (IHC)staining for the growth hormone-releasing factor (GRF), somatostatin (SS), and other hypothalamic hormones was performed on hypothalami obtained from rats. IHC analysis was complemented by quantitative in situ assessments of mRNAs encoding the precursors for these hormones. Data obtained suggest that exposure to microgravity causes a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impared GH secretion in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

PubMed

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells.

Preliminary assessment of DOC and THM precursor loads from a freshwater restored wetland, an agricultural field, and a tidal wetland in the Sacramento-San Joaquin River Delta

USGS Publications Warehouse

Fujii, R.; Bergamaschi, B.A.; Ganju, N.K.; Fleck, J.A.; Burow-Fogg, K.R.; Schoellhamer, D.; Deverel, S.J.

2003-01-01

Water exported from the Sacramento-San Joaquin River Delta supplies drinking water to more than 22 million people in California. At certain times of the year, Delta waters contain relatively high concentrations of dissolved organic carbon (DOC) and bromide. During these times, chlorination of Delta water for drinking water disinfection will form disinfection byproducts, such as trihalomethanes (THMs), that can exceed the U.S. Environmental Protection Agency's maximum contaminant level for THMs of 80 mg/L. Important sources of DOC and THM precursors (types of DOC that form THMs when chlorinated) to the Delta include rivers, drainage water from peat islands, water from wetlands and areas with extensive riparian vegetation, and in-channel growth of algae and macrophytes. Due to proposed ecosystem restoration and creation of wetlands in the Delta, there is an urgent need for information on the relative loads of DOC and THM precursors produced from three different land uses: restored wetlands constructed for subsidence mitigation, tidal wetlands, and agricultural operations. We have been conducting research in the Delta to provide this information. A restored wetland and agricultural field located on Twitchell Island, and a tidal wetland on Browns Island have been monitored for flow, DOC, and THM precursors. Initial results indicate that the loads of DOC and THM precursors are similar for the restored wetland (surface water only) and the agricultural field. These land uses produce DOC loads of about 14 and 11 g C/m2/yr, respectively, and THM precursor loads of about 1.7 and 1.0 g THM/m2/yr, respectively. Estimates of DOC and THM precursor loads for the tidal wetland site on Browns Island and seepage associated with the restored wetland are being developed.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

PubMed Central

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Purpose Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Methods Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Results Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Conclusions Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells. PMID:26815842

Synthesis of Er-doped Lu2O3 nanoparticles and transparent ceramics

NASA Astrophysics Data System (ADS)

Serivalsatit, K.; Wasanapiarnpong, T.; Kucera, C.; Ballato, J.

2013-05-01

Transparent rare earth-doped Lu2O3 ceramics have received much attention for use in solid-state scintillator and laser applications. The fabrication of these ceramics, however, requires ultrafine and uniform powders as precursors. Presented here is the synthesis of Er-doped Lu2O3 nanopowders by a solution precipitation method using Er-doped lutetium sulfate solution and hexamethylenetetramine as a precipitant and the fabrication of Er-doped Lu2O3 transparent ceramics from these nanopowders. The precipitated precursors were calcined at 1100 °C for 4 h in order to convert the precursors into Lu2O3 nanoparticles with an average particle size of 60 nm. Thermal decomposition and phase evolution of the precursors were studied by simultaneous thermal analysis (STA), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Er-doped Lu2O3 transparent ceramics were fabricated from these nanopowders using vacuum sintering followed by hot isostatic pressing at 1700 °C for 8 h. The transparent ceramics exhibit an optical transmittance of 78% at a wavelength of 1.55 μm.

Structural features of microRNA (miRNA) precursors and their relevance to miRNA biogenesis and small interfering RNA/short hairpin RNA design.

PubMed

Krol, Jacek; Sobczak, Krzysztof; Wilczynska, Urszula; Drath, Maria; Jasinska, Anna; Kaczynska, Danuta; Krzyzosiak, Wlodzimierz J

2004-10-01

We have established the structures of 10 human microRNA (miRNA) precursors using biochemical methods. Eight of these structures turned out to be different from those that were computer-predicted. The differences localized in the terminal loop region and at the opposite side of the precursor hairpin stem. We have analyzed the features of these structures from the perspectives of miRNA biogenesis and active strand selection. We demonstrated the different thermodynamic stability profiles for pre-miRNA hairpins harboring miRNAs at their 5'- and 3'-sides and discussed their functional implications. Our results showed that miRNA prediction based on predicted precursor structures may give ambiguous results, and the success rate is significantly higher for the experimentally determined structures. On the other hand, the differences between the predicted and experimentally determined structures did not affect the stability of termini produced through "conceptual dicing." This result confirms the value of thermodynamic analysis based on mfold as a predictor of strand section by RNAi-induced silencing complex (RISC).

Spectroscopy Identification of Benzyl-Type Radicals Generated by Corona Discharge of Precursors of Mixed Substituents

NASA Astrophysics Data System (ADS)

Yoon, Young Wook; Huh, Chang Soon; Lee, Sang Kuk

2012-06-01

We generated vibronically excited but jet-cooled benzyl-type radicals from corona discharge of precursor of mixed substituents using a technique of corona excited supersonic expansion coupled with a pinhole-type glass nozzle, from which the visible vibronic emission spectra were recorded with a long-path monochromator. The spectra exhibit the intensity variation of each species with discharging voltage, indicating the radical species generated in corona discharge is highly sensitive to excitation. From the analysis of the spectra, we found the Cl substituent is replaced in preference to the F substituent by the hydrogen atoms liberated from the dissociation of the C-H bond of the methyl group of the precursor, from which we proposed the possible mechanism for the elimination reaction of substituent in terms of the bond dissociation energy. Additionally, we obtained an accurate electronic energy in the D_1 → D_0 transition and the vibrational mode frequencies of newly detected benzyl-type radicals in the ground electronic state by comparison with those of ab initio calculations and the known spectroscopic data of precursors for the first time.

Synthesis of a Possible Precursor of α-Amylase in Wheat Aleurone Cells 1

PubMed Central

Okita, Thomas W.; Decaleya, Roberto; Rappaport, Lawrence

1979-01-01

α-Amylase from wheat aleurone (Triticum aestivum) was synthesized in a S-150 wheat germ readout system using polysomes, and a messenger RNA-dependent reticulocyte lysate system using polyadenylic acid [poly(A)]-enriched RNA. The product was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, precipitation by specific λ-globulin for α-amylase, and proteolysis. Two immunoprecipitated products were synthesized from the readout system, the predominant species migrating coincidentally with authentic α-amylase on sodium dodecyl sulfate-polyacrylamide gels. A putative precursor, 1,500 daltons larger, was evident but was less abundant. The relationship between the two polypeptides was established by proteolytic analysis using Staphylococcus aureus V8 protease. At least nine fragments were generated and were identical in both species. The poly(A)-enriched RNA synthesized only the putative precursor in the reticulocyte lysate system. Attempts to process the precursor to the mature size of α-amylase failed. These findings are discussed in connection with the signal hypothesis (proposed for the transport of proteins across membranes) and the mode of secretion of α-amylase in aleurone cells. Images PMID:16660677

Acrylamide in Caribbean foods - residual levels and their relation to reducing sugar and asparagine content.

PubMed

Bent, Grace-Anne; Maragh, Paul; Dasgupta, Tara

2012-07-15

The acrylamide levels in commercial and homemade Caribbean foods were determined by pre-derivatisation of acrylamide to 2-bromopropenamide and analysed by gas chromatography with mass spectrometric (GC/MS) detection. Over 100 Caribbean food samples were analysed for the presence of acrylamide. These samples include: biscuits, breakfast cereals, banana chips and home-prepared foods: breadfruit; Artocarpus altilis, banana fritters, and dumplings. The limit of detection (LOD) for the GC/MS method was found to be dependent on the type of column used for the GC/MS analysis. The DB-1701 and the DB-VRX columns gave LODs of 20 and 4 μg/kg, respectively. Acrylamide has not been found in raw foods or foods which have been cooked by boiling. Its content in all other foods had concentrations in the range, 65-3,640 μg/kg. The relationship between acrylamide levels and precursor concentration as well as the health implications of our findings are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

PubMed

Sagara, M; Satoh, J; Wada, R; Yagihashi, S; Takahashi, K; Fukuzawa, M; Muto, G; Muto, Y; Toyota, T

1996-03-01

N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NAC-treated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.

Foundations of reading comprehension in children with intellectual disabilities.

PubMed

van Wingerden, Evelien; Segers, Eliane; van Balkom, Hans; Verhoeven, Ludo

2017-01-01

Knowledge about predictors for reading comprehension in children with intellectual disabilities (ID) is still fragmented. This study compared reading comprehension, word decoding, listening comprehension, and reading related linguistic and cognitive precursor measures in children with mild ID and typically developing controls. Moreover, it was explored how the precursors related to reading achievement. Children with mild ID and typical controls were assessed on reading comprehension, decoding, language comprehension, and linguistic (early literacy skills, vocabulary, grammar) and cognitive (rapid naming, phonological short-term memory, working memory, temporal processing, nonverbal reasoning) precursor measures. It was tested to what extent variations in reading comprehension could be explained from word decoding, listening comprehension and precursor measures. The ID group scored significantly below typical controls on all measures. Word decoding was at or above first grade level in half the ID group. Reading comprehension in the ID group was related to word decoding, listening comprehension, early literacy skills, and temporal processing. The reading comprehension profile of children with mild ID strongly resembles typical early readers. The simple view of reading pertains to children with mild ID, with additional influence of early literacy skills and temporal processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectrum-based method to generate good decoy libraries for spectral library searching in peptide identifications.

PubMed

Cheng, Chia-Ying; Tsai, Chia-Feng; Chen, Yu-Ju; Sung, Ting-Yi; Hsu, Wen-Lian

2013-05-03

As spectral library searching has received increasing attention for peptide identification, constructing good decoy spectra from the target spectra is the key to correctly estimating the false discovery rate in searching against the concatenated target-decoy spectral library. Several methods have been proposed to construct decoy spectral libraries. Most of them construct decoy peptide sequences and then generate theoretical spectra accordingly. In this paper, we propose a method, called precursor-swap, which directly constructs decoy spectral libraries directly at the "spectrum level" without generating decoy peptide sequences by swapping the precursors of two spectra selected according to a very simple rule. Our spectrum-based method does not require additional efforts to deal with ion types (e.g., a, b or c ions), fragment mechanism (e.g., CID, or ETD), or unannotated peaks, but preserves many spectral properties. The precursor-swap method is evaluated on different spectral libraries and the results of obtained decoy ratios show that it is comparable to other methods. Notably, it is efficient in time and memory usage for constructing decoy libraries. A software tool called Precursor-Swap-Decoy-Generation (PSDG) is publicly available for download at http://ms.iis.sinica.edu.tw/PSDG/.

An integrated scheme for the simultaneous determination of biogenic amines, precursor amino acids, and related metabolites by liquid chromatography with electrochemical detection.

PubMed

Oka, K; Kojima, K; Togari, A; Nagatsu, T; Kiss, B

1984-06-08

A new method using high-performance liquid chromatography with electrochemical detection (HPLC-ED) for the simultaneous determination of monoamines, their precursor amino acids, and related major metabolites in small samples of brain tissue weighing from 0.5 to 50 mg is described. The method is based on the preliminary isolation of monoamines (dopamine, norepinephrine, epinephrine, and serotonin), their precursor amino acids (tyrosine, 3,4-dihydroxyphenylalanine, tryptophan and 5-hydroxytryptophan), and their major metabolites (3-methoxytyramine, normetanephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid) by chromatography on small columns of Amberlite CG-50 and Dowex 50W, and by ethyl acetate extraction. All the compounds in the four isolated fractions were measured by HPLC-ED on a reversed-phase column under four different conditions. The sensitivity was from 0.1 to 40 pmol, depending on the substances analysed. This newly established method was applied to the study of the effects of an aromatic L-amino acid decarboxylase inhibitor (NSD-1015) and a monoamine oxidase inhibitor (pargyline) on the levels of monoamines, their precursor amino acids and their major metabolites in brain regions of mice.

Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification.

PubMed

Williams, B A; Ordahl, C P

1994-04-01

Specification of the myogenic lineage begins prior to gastrulation and culminates in the emergence of determined myogenic precursor cells from the somites. The myoD family (MDF) of transcriptional activators controls late step(s) in myogenic specification that are closely followed by terminal muscle differentiation. Genes expressed in myogenic specification at stages earlier than MDFs are unknown. The Pax-3 gene is expressed in all the cells of the caudal segmental plate, the early mesoderm compartment that contains the precursors of skeletal muscle. As somites form from the segmental plate and mature, Pax-3 expression is progressively modulated. Beginning at the time of segmentation, Pax-3 becomes repressed in the ventral half of the somite, leaving Pax-3 expression only in the dermomyotome. Subsequently, differential modulation of Pax-3 expression levels delineates the medial and lateral halves of the dermomyotome, which contain precursors of axial (back) muscle and limb muscle, respectively. Pax-3 expression is then repressed as dermomyotome-derived cells activate MDFs. Quail-chick chimera and ablation experiments confirmed that the migratory precursors of limb muscle continue to express Pax-3 during migration. Since limb muscle precursors do not activate MDFs until 2 days after they leave the somite, Pax-3 represents the first molecular marker for this migratory cell population. A null mutation of the mouse Pax-3 gene, Splotch, produces major disruptions in early limb muscle development (Franz, T., Kothary, R., Surani, M. A. H., Halata, Z. and Grim, M. (1993) Anat. Embryol. 187, 153-160; Goulding, M., Lumsden, A. and Paquette, A. (1994) Development 120, 957-971). We conclude, therefore, that Pax-3 gene expression in the paraxial mesoderm marks earlier stages in myogenic specification than MDFs and plays a crucial role in the specification and/or migration of limb myogenic precursors.

Conversion of blood androgens to estrogens in normal adult men and women

PubMed Central

Longcope, Christopher; Kato, Tatsuo; Horton, Richard

1969-01-01

Continuous infusions of Δ4-androstenedione-7-3H and testosterone-7-3H have been used to demonstrate that these androgens are converted to estrone and 17β-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [χ-PRO] and free precursor steroid [χ-PRE], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [ρ]BBAE1, for androstenedione conversion to estrone ([ρ]BBAE1 = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [ρ]BBTE2, for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [ρ]BB value are greater in males than females. For the androgen interconversions, [ρ]BBAT is 4.5% in males and 2.2% in females; [ρ]BBTA is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03. PMID:5355335

Contribution of precursor compounds to the release of per- and polyfluoroalkyl substances (PFASs) from waste water treatment plants (WWTPs).

PubMed

Eriksson, Ulrika; Haglund, Peter; Kärrman, Anna

2017-11-01

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in sludge and water from waste water treatment plants, as a result of their incorporation in everyday products and industrial processes. In this study, we measured several classes of persistent PFASs, precursors, transformation intermediates, and newly identified PFASs in influent and effluent sewage water and sludge from three municipal waste water treatment plants in Sweden, sampled in 2015. For sludge, samples from 2012 and 2014 were analyzed as well. Levels of precursors in sludge exceeded those of perfluoroalkyl acids and sulfonic acids (PFCAs and PFSAs), in 2015 the sum of polyfluoroalkyl phosphoric acid esters (PAPs) were 15-20ng/g dry weight, the sum of fluorotelomer sulfonic acids (FTSAs) was 0.8-1.3ng/g, and the sum of perfluorooctane sulfonamides and ethanols ranged from non-detected to 3.2ng/g. Persistent PFSAs and PFCAs were detected at 1.9-3.9ng/g and 2.4-7.3ng/g dry weight, respectively. The influence of precursor compounds was further demonstrated by an observed substantial increase for a majority of the persistent PFCAs and PFSAs in water after waste water treatment. Perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) had a net mass increase in all WWTPs, with mean values of 83%, 28%, 37% and 58%, respectively. The load of precursors and intermediates in influent water and sludge combined with net mass increase support the hypothesis that degradation of precursor compounds is a significant contributor to PFAS contamination in the environment. Copyright © 2017. Published by Elsevier B.V.

Terpenoid Metabolism in Wild-Type and Transgenic Arabidopsis PlantsW⃞

PubMed Central

Aharoni, Asaph; Giri, Ashok P.; Deuerlein, Stephan; Griepink, Frans; de Kogel, Willem-Jan; Verstappen, Francel W. A.; Verhoeven, Harrie A.; Jongsma, Maarten A.; Schwab, Wilfried; Bouwmeester, Harro J.

2003-01-01

Volatile components, such as terpenoids, are emitted from aerial parts of plants and play a major role in the interaction between plants and their environment. Analysis of the composition and emission pattern of volatiles in the model plant Arabidopsis showed that a range of volatile components are released, primarily from flowers. Most of the volatiles detected were monoterpenes and sesquiterpenes, which in contrast to other volatiles showed a diurnal emission pattern. The active terpenoid metabolism in wild-type Arabidopsis provoked us to conduct an additional set of experiments in which transgenic Arabidopsis overexpressing two different terpene synthases were generated. Leaves of transgenic plants constitutively expressing a dual linalool/nerolidol synthase in the plastids (FaNES1) produced linalool and its glycosylated and hydroxylated derivatives. The sum of glycosylated components was in some of the transgenic lines up to 40- to 60-fold higher than the sum of the corresponding free alcohols. Surprisingly, we also detected the production and emission of nerolidol, albeit at a low level, suggesting that a small pool of its precursor farnesyl diphosphate is present in the plastids. Transgenic lines with strong transgene expression showed growth retardation, possibly as a result of the depletion of isoprenoid precursors in the plastids. In dual-choice assays with Myzus persicae, the FaNES1-expressing lines significantly repelled the aphids. Overexpression of a typical cytosolic sesquiterpene synthase resulted in the production of only trace amounts of the expected sesquiterpene, suggesting tight control of the cytosolic pool of farnesyl diphosphate, the precursor for sesquiterpenoid biosynthesis. This study further demonstrates the value of Arabidopsis for studies of the biosynthesis and ecological role of terpenoids and provides new insights into their metabolism in wild-type and transgenic plants. PMID:14630967

Engineering low phorbol ester Jatropha curcas seed by intercepting casbene biosynthesis.

PubMed

Li, Chunhong; Ng, Ailing; Xie, Lifen; Mao, Huizhu; Qiu, Chengxiang; Srinivasan, Ramachandran; Yin, Zhongchao; Hong, Yan

2016-01-01

Casbene is a precursor to phorbol esters and down-regulating casbene synthase effectively reduces phorbol ester biosynthesis. Seed-specific reduction of phorbol ester (PE) helps develop Jatropha seed cake for animal nutrition. Phorbol esters (PEs) are diterpenoids present in some Euphorbiaceae family members like Jatropha curcas L. (Jatropha), a tropical shrub yielding high-quality oil suitable as feedstock for biodiesel and bio jet fuel. Jatropha seed contains up to 40 % of oil and can produce oil together with cake containing high-quality proteins. However, skin-irritating and cancer-promoting PEs make Jatropha cake meal unsuitable for animal nutrition and also raise some safety and environmental concerns on its planting and processing. Two casbene synthase gene (JcCASA163 and JcCASD168) homologues were cloned from Jatropha genome and both genes were highly expressed during seed development. In vitro functional analysis proved casbene synthase activity of JcCASA163 in converting geranylgeranyl diphosphate into casbene which has been speculated to be the precursor to PEs. A seed-specific promoter driving inverted repeats for RNAi interference targeting at either JcCASA163 or both genes could effectively down-regulate casbene synthase gene expression with concurrent marked reduction of PE level (by as much as 85 %) in seeds with no pleiotropic effects observed. Such engineered low PE in seed was heritable and co-segregated with the transgene. Our work implicated casbene synthase in Jatropha PE biosynthesis and provided evidence for casbene being the precursor for PEs. The success in reducing seed PE content through down-regulation of casbene synthase demonstrates the feasibility of intercepting PE biosynthesis in Jatropha seed to help address safety concerns on Jatropha plantation and seed processing and facilitate use of its seed protein for animal nutrition.

Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF.

PubMed

Yamamoto, Nobuto; Suyama, Hirofumi; Nakazato, Hiroaki; Yamamoto, Nobuyuki; Koga, Yoshihiko

2008-07-01

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 microg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/ human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32-50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.

Metal Oxide Assisted Preparation of Core-Shell Beads with Dense Metal-Organic Framework Coatings for the Enhanced Extraction of Organic Pollutants.

PubMed

Del Rio, Mateo; Palomino Cabello, Carlos; Gonzalez, Veronica; Maya, Fernando; Parra, Jose B; Cerdà, Victor; Turnes Palomino, Gemma

2016-08-08

Dense and homogeneous metal-organic framework (MOF) coatings on functional bead surfaces are easily prepared by using intermediate sacrificial metal oxide coatings containing the metal precursor of the MOF. Polystyrene (PS) beads are coated with a ZnO layer to give ZnO@PS core-shell beads. The ZnO@PS beads are reactive in the presence of 2-methylimidazole to transform part of the ZnO coating into a porous zeolitic imidazolate framework-8 (ZIF-8) external shell positioned above the internal ZnO precursor shell. The obtained ZIF-8@ZnO@PS beads can be easily packed in column format for flow-through applications, such as the solid-phase extraction of trace priority-listed environmental pollutants. The prepared material shows an excellent permeance to flow when packed as a column to give high enrichment factors, facile regeneration, and excellent reusability for the extraction of the pollutant bisphenol A. It also shows an outstanding performance for the simultaneous enrichment of mixtures of endocrine disrupting chemicals (bisphenol A, 4-tert-octylphenol and 4-n-nonylphenol), facilitating their analysis when present at very low levels (<1 μg L(-1) ) in drinking waters. For the extraction of the pollutant bisphenol A, the prepared ZIF-8@ZnO@PS beads also show a superior extraction and preconcentration capacity to that of the PS beads used as precursors and the composite materials obtained by the direct growth of ZIF-8 on the surface of the PS beads in the absence of metal oxide intermediate coatings. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HPC simulations of shock front evolution for a study of the shock precursor decay in a submicron thick nanocrystalline aluminum

NASA Astrophysics Data System (ADS)

Valisetty, R.; Rajendran, A.; Agarwal, G.; Dongare, A.; Ianni, J.; Namburu, R.

2018-07-01

The Hugoniot elastic limit (HEL, or the shock precursor) decay phenomenon was investigated under an uniaxial strain condition, in a plate-on-plate impact configuration, using large-scale molecular dynamics (MD) high performance computing (HPC) simulations on a multi-billion 5000 Å thick nanocrystalline aluminum (nc-Al) system with an average grain size of 1000 Å and at five impact velocities ranging from 0.7 to 1.5 km s‑1. The averaged stress and strain distributions were obtained in the shock fronts’ travel direction using a material conserving atom slicing method. The loading paths in terms of the Rayleigh lines experienced by the atom system in the evolving shock fronts exhibited a strong dependency on the shock stress levels. This dependency decreased as the impact velocity increased from 0.7 to 1.5 km s‑1. By combining the HELs from MD results with plate impact experimental data, the precursor decay for the nc-Al was predicted from nano-to-macro scale thickness range. The evolving shock fronts were characterized in terms of parameters such as the shock front thickness, shock rise time and strain rate. The MD results were further analyzed using a crystal analysis algorithm and a twin dislocation identification method to obtain the densities of the atomistic defects evolving behind the evolving shock fronts. High-fidelity large-scale HPC simulation results showed that certain dislocation partials strongly influenced the elastic–plastic transition response across the HELs. The twinning dislocations increased by more than a factor of 10 during the transition and remained constant under further shock compression.

Goat red blood cells as precursor for iron oxide nanocrystal synthesis to develop nuclear targeted lung cancer therapy

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

Sreevani, Vellingiri; Shanthi, Krishnamurthy; Kannan, Soundarapandian, E-mail: sk_protein@buc.edu.in

Graphical abstract: - Highlights: • Molecular approach of synthesis of Fe{sub 2}O{sub 3}-NC using goat blood as a bio-precursor. • The method is simple, efficient and environment friendly. • Synthesized nanocrystals were characterized by UV–vis spectroscopy, XRD, SEM, TEM, DLS and EDS. • Nanocrystals exhibited potent cytotoxicity against A549 cancer cell. • Nuclear targeting with expression of caspase-3, caspase-7 and Bcl-2 in A549 cancer cells. - Abstract: In this study, we synthesised iron oxide nanocrystals (Fe{sub 2}O{sub 3}-NC) from goat blood (bio-precursor) using red blood cells (RBC) lysis method (a molecular level approach) for the first time. The formation ofmore » Fe{sub 2}O{sub 3}-NC was achieved through a single-phase chemical reduction method. The size distribution of Fe{sub 2}O{sub 3}-NC falls between 20–30 nm for pellet and 100–200 nm for lysate and were found to be crystalline. Fe{sub 2}O{sub 3}-NC demonstrated significant cytotoxicity on A549. We report the direct visualization of interactions between Fe{sub 2}O{sub 3}-NC and the cancer cell nucleus. The active transport of Fe{sub 2}O{sub 3}-NC to the nucleus induces major changes to nuclear phenotype via nuclear envelope invaginations. We further examined the root cause for the involvement of Fe{sub 2}O{sub 3}-NC on the expression of caspase-3, caspase-7 and Bcl-2 in A549 cancer cells. This functional proteomic analysis clearly implies that the lung cancer cell proliferation is perfectly targeted by the biosynthesised Fe{sub 2}O{sub 3}-NC which could provide new insight for nuclear-targeted cancer therapy.« less

Changing over-the-counter ephedrine and pseudoephedrine products to prescription only: impacts on methamphetamine clandestine laboratory seizures.

PubMed

Cunningham, James K; Callaghan, Russell C; Tong, Daoqin; Liu, Lon-Mu; Li, Hsiao-Yun; Lattyak, William J

2012-11-01

Clandestine laboratory operators commonly extract ephedrine and pseudoephedrine-precursor chemicals used to synthesize methamphetamine-from over-the-counter cold/allergy/sinus products. To prevent this activity, two states, Oregon in 07/2006 and Mississippi in 07/2010, implemented regulations classifying ephedrine and pseudoephedrine as Schedule III substances, making products containing them available by prescription only. Using simple pre-regulation versus post-regulation comparisons, reports claim that the regulations have substantially reduced clandestine laboratory seizures (an indicator of laboratory prevalence) in both states, motivating efforts to implement similar regulation nationally. This study uses ARIMA-intervention time-series analysis to more rigorously evaluate the regulations' impacts on laboratory seizures. Monthly counts of methamphetamine clandestine laboratory seizures were extracted from the Clandestine Laboratory Seizure System (2000-early 2011) for Oregon, Mississippi and selected nearby states (for quasi-control). Seizures in Oregon and nearby western states largely bottomed out months before Oregon's regulation, and changed little thereafter. No significant impact for Oregon's regulation was found. Mississippi and nearby states generally had elevated seizures before Mississippi's regulation. Mississippi experienced a regulation-associated drop of 28.9 seizures (50.2%) in the series level (p<0.01), while nearby states exhibited no comparable decline. Oregon's regulation encountered a floor effect, making any sizable impact infeasible. Mississippi, however, realized a substantial impact, suggesting that laboratories, if sufficiently extant, can be meaningfully impacted by prescription precursor regulation. It follows that national prescription precursor regulation would have little impact in western states with low indicated laboratory prevalence, but may be of significant use in regions facing higher indicated prevalence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Identification and characterization of microRNAs in Phaseolus vulgaris by high-throughput sequencing

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) are endogenously encoded small RNAs that post-transcriptionally regulate gene expression. MiRNAs play essential roles in almost all plant biological processes. Currently, few miRNAs have been identified in the model food legume Phaseolus vulgaris (common bean). Recent advances in next generation sequencing technologies have allowed the identification of conserved and novel miRNAs in many plant species. Here, we used Illumina's sequencing by synthesis (SBS) technology to identify and characterize the miRNA population of Phaseolus vulgaris. Results Small RNA libraries were generated from roots, flowers, leaves, and seedlings of P. vulgaris. Based on similarity to previously reported plant miRNAs,114 miRNAs belonging to 33 conserved miRNA families were identified. Stem-loop precursors and target gene sequences for several conserved common bean miRNAs were determined from publicly available databases. Less conserved miRNA families and species-specific common bean miRNA isoforms were also characterized. Moreover, novel miRNAs based on the small RNAs were found and their potential precursors were predicted. In addition, new target candidates for novel and conserved miRNAs were proposed. Finally, we studied organ-specific miRNA family expression levels through miRNA read frequencies. Conclusions This work represents the first massive-scale RNA sequencing study performed in Phaseolus vulgaris to identify and characterize its miRNA population. It significantly increases the number of miRNAs, precursors, and targets identified in this agronomically important species. The miRNA expression analysis provides a foundation for understanding common bean miRNA organ-specific expression patterns. The present study offers an expanded picture of P. vulgaris miRNAs in relation to those of other legumes. PMID:22394504

Red Bell Pepper Chromoplasts Exhibit in Vitro Import Competency and Membrane Targeting of Passenger Proteins from the Thylakoidal Sec and ΔpH Pathways but Not the Chloroplast Signal Recognition Particle Pathway1

PubMed Central

Summer, Elizabeth J.; Cline, Kenneth

1999-01-01

Chloroplast to chromoplast development involves new synthesis and plastid localization of nuclear-encoded proteins, as well as changes in the organization of internal plastid membrane compartments. We have demonstrated that isolated red bell pepper (Capsicum annuum) chromoplasts contain the 75-kD component of the chloroplast outer envelope translocon (Toc75) and are capable of importing chloroplast precursors in an ATP-dependent fashion, indicating a functional general import apparatus. The isolated chromoplasts were able to further localize the 33- and 17-kD subunits of the photosystem II O2-evolution complex (OE33 and OE17, respectively), lumen-targeted precursors that utilize the thylakoidal Sec and ΔpH pathways, respectively, to the lumen of an internal membrane compartment. Chromoplasts contained the thylakoid Sec component protein, cpSecA, at levels comparable to chloroplasts. Routing of OE17 to the lumen was abolished by ionophores, suggesting that routing is dependent on a transmembrane ΔpH. The chloroplast signal recognition particle pathway precursor major photosystem II light-harvesting chlorophyll a/b protein failed to associate with chromoplast membranes and instead accumulated in the stroma following import. The Pftf (plastid fusion/translocation factor), a chromoplast protein, integrated into the internal membranes of chromoplasts during in vitro assays, and immunoblot analysis indicated that endogenous plastid fusion/translocation factor was also an integral membrane protein of chromoplasts. These data demonstrate that the internal membranes of chromoplasts are functional with respect to protein translocation on the thylakoid Sec and ΔpH pathways. PMID:9952453

Viral Infection Induces Expression of Novel Phased MicroRNAs from Conserved Cellular MicroRNA Precursors

PubMed Central

Zhang, Jiayao; Zhao, Shuqi; Zheng, Hong; Gao, Ge; Wei, Liping; Li, Yi

2011-01-01

RNA silencing, mediated by small RNAs including microRNAs (miRNAs) and small interfering RNAs (siRNAs), is a potent antiviral or antibacterial mechanism, besides regulating normal cellular gene expression critical for development and physiology. To gain insights into host small RNA metabolism under infections by different viruses, we used Solexa/Illumina deep sequencing to characterize the small RNA profiles of rice plants infected by two distinct viruses, Rice dwarf virus (RDV, dsRNA virus) and Rice stripe virus (RSV, a negative sense and ambisense RNA virus), respectively, as compared with those from non-infected plants. Our analyses showed that RSV infection enhanced the accumulation of some rice miRNA*s, but not their corresponding miRNAs, as well as accumulation of phased siRNAs from a particular precursor. Furthermore, RSV infection also induced the expression of novel miRNAs in a phased pattern from several conserved miRNA precursors. In comparison, no such changes in host small RNA expression was observed in RDV-infected rice plants. Significantly RSV infection elevated the expression levels of selective OsDCLs and OsAGOs, whereas RDV infection only affected the expression of certain OsRDRs. Our results provide a comparative analysis, via deep sequencing, of changes in the small RNA profiles and in the genes of RNA silencing machinery induced by different viruses in a natural and economically important crop host plant. They uncover new mechanisms and complexity of virus-host interactions that may have important implications for further studies on the evolution of cellular small RNA biogenesis that impact pathogen infection, pathogenesis, as well as organismal development. PMID:21901091

A galvanotaxis assay for analysis of neural precursor cell migration kinetics in an externally applied direct current electric field.

PubMed

Babona-Pilipos, Robart; Popovic, Milos R; Morshead, Cindi M

2012-10-13

The discovery of neural stem and progenitor cells (collectively termed neural precursor cells) (NPCs) in the adult mammalian brain has led to a body of research aimed at utilizing the multipotent and proliferative properties of these cells for the development of neuroregenerative strategies. A critical step for the success of such strategies is the mobilization of NPCs toward a lesion site following exogenous transplantation or to enhance the response of the endogenous precursors that are found in the periventricular region of the CNS. Accordingly, it is essential to understand the mechanisms that promote, guide, and enhance NPC migration. Our work focuses on the utilization of direct current electric fields (dcEFs) to promote and direct NPC migration - a phenomenon known as galvanotaxis. Endogenous physiological electric fields function as critical cues for cell migration during normal development and wound repair. Pharmacological disruption of the trans-neural tube potential in axolotl embryos causes severe developmental malformations(1). In the context of wound healing, the rate of repair of wounded cornea is directly correlated with the magnitude of the epithelial wound potential that arises after injury, as shown by pharmacological enhancement or disruption of this dcEF(2-3). We have demonstrated that adult subependymal NPCs undergo rapid and directed cathodal migration in vitro when exposed to an externally applied dcEF. In this protocol we describe our lab's techniques for creating a simple and effective galvanotaxis assay for high-resolution, long-term observation of directed cell body translocation (migration) on a single-cell level. This assay would be suitable for investigating the mechanisms that regulate dcEF transduction into cellular motility through the use of transgenic or knockout mice, short interfering RNA, or specific receptor agonists/antagonists.

Long-term surveillance of H7 influenza viruses in American wild aquatic birds: are the H7N3 influenza viruses in wild birds the precursors of highly pathogenic strains in domestic poultry?

PubMed Central

Krauss, Scott; Stucker, Karla M; Schobel, Seth A; Danner, Angela; Friedman, Kimberly; Knowles, James P; Kayali, Ghazi; Niles, Lawrence J; Dey, Amanda D; Raven, Garnet; Pryor, Paul; Lin, Xudong; Das, Suman R; Stockwell, Timothy B; Wentworth, David E; Webster, Robert G

2015-01-01

The emergence of influenza A virus (IAV) in domestic avian species and associated transmissions to mammals is unpredictable. In the Americas, the H7 IAVs are of particular concern, and there have been four separate outbreaks of highly pathogenic (HP) H7N3 in domestic poultry in North and South America between 2002 and 2012, with occasional spillover into humans. Here, we use long-term IAV surveillance in North American shorebirds at Delaware Bay, USA, from 1985 to 2012 and in ducks in Alberta, Canada, from 1976 to 2012 to determine which hemagglutinin (HA)–neuraminidase (NA) combinations predominated in Anseriformes (ducks) and Charadriiformes (shorebirds) and whether there is concordance between peaks of H7 prevalence and transmission in wild aquatic birds and the emergence of H7 IAVs in poultry and humans. Whole-genome sequencing supported phylogenetic and genomic constellation analyses to determine whether HP IAVs emerge in the context of specific internal gene segment sequences. Phylogenetic analysis of whole-genome sequences of the H7N3 influenza viruses from wild birds and HP H7N3 outbreaks in the Americas indicate that each HP outbreak was an independent emergence event and that the low pathogenic (LP) avian influenza precursors were most likely from dabbling ducks. The different polybasic cleavage sites in the four HP outbreaks support independent origins. At the 95% nucleotide percent identity-level phylogenetic analysis showed that the wild duck HA, PB1, and M sequences clustered with the poultry and human outbreak sequences. The genomic constellation analysis strongly suggests that gene segments/virus flow from wild birds to domestic poultry. PMID:26954883

A facile thermal decomposition route to synthesise CoFe2O4 nanostructures

NASA Astrophysics Data System (ADS)

Kalpanadevi, K.; Sinduja, C. R.; Manimekalai, R.

2014-01-01

The synthesis of CoFe2O4 nanoparticles has been achieved by a simple thermal decomposition method from an inorganic precursor, cobalt ferrous cinnamate hydrazinate (CoFe2(cin)3(N2H4)3) which was obtained by a novel precipitation method from the corresponding metal salts, cinnamic acid and hydrazine hydrate. The precursor was characterized by hydrazine and metal analyses, infrared spectral analysis and thermo gravimetric analysis. Under appropriate annealing, CoFe2(cin)3(N2H4)3 yielded CoFe2O4 nanoparticles, which were characterized for their size and structure using X-Ray diffraction (XRD), high resolution transmission electron microscopic (HRTEM), selected area electron diffraction (SAED) and scanning electron microscopic (SEM) techniques.

Group 12 dithiocarbamate complexes: Synthesis, spectral studies and their use as precursors for metal sulfides nanoparticles and nanocomposites

NASA Astrophysics Data System (ADS)

Ajibade, Peter A.; Ejelonu, Benjamin C.

2013-09-01

Zn(II), Cd(II) and Hg(II) dithiocarbamate complexes have been synthesized and characterized by elemental analysis, thermogravimetric analysis, UV-Vis, FTIR, 1H- and 13C NMR spectroscopy. The complexes were thermolysed at 180 °C and used as single molecule precursors for the synthesis of HDA capped ZnS, CdS and HgS nanoparticles and polymethylmethacrylate (PMMA) nanocomposites. The optical and structural properties of the nanoparticles and nanocomposites were studied by UV-Vis, PL, XRD and SEM. The crystallites sizes of the nanoparticles varied between 3.03 and 23.45 nm. SEM and EDX analyses of the nanocomposites confirmed the presence of the nanoparticles in the polymer matrix.

Nutritional modifiers of aging brain function: Increasing the formation of brain synapses by administering uridine and other phosphatide precursors

PubMed Central

Wurtman, R.J.; Cansev, M; Sakamoto, T; Ulus, I.H.

2010-01-01

Brain phosphatide synthesis requires three circulating compounds: docosahexaenoic acid (DHA), uridine and choline. Oral administration of these phosphatide precursors to experimental animals increases the levels of phosphatides and synaptic proteins in the brain and per brain cell, as well as the numbers of dendritic spines on hippocampal neurons. Arachidonic acid (AA) fails to reproduce these effects of DHA. If similar increases occur in human brain, giving these compounds to patients with diseases – like Alzheimer’s disease – which cause the loss of brain synapses – could be beneficial. PMID:21091953

Multiscale analysis: a way to investigate laser damage precursors in materials for high power applications at nanosecond pulse duration

NASA Astrophysics Data System (ADS)

Natoli, J. Y.; Wagner, F.; Ciapponi, A.; Capoulade, J.; Gallais, L.; Commandré, M.

2010-11-01

The mechanism of laser induced damage in optical materials under high power nanosecond laser irradiation is commonly attributed to the presence of precursor centers. Depending on material and laser source, the precursors could have different origins. Some of them are clearly extrinsic, such as impurities or structural defects linked to the fabrication conditions. In most cases the center size ranging from sub-micrometer to nanometer scale does not permit an easy detection by optical techniques before irradiation. Most often, only a post mortem observation of optics permits to proof the local origin of breakdown. Multi-scale analyzes by changing irradiation beam size have been performed to investigate the density, size and nature of laser damage precursors. Destructive methods such as raster scan, laser damage probability plot and morphology studies permit to deduce the precursor densities. Another experimental way to get information on nature of precursors is to use non destructive methods such as photoluminescence and absorption measurements. The destructive and non destructive multiscale studies are also motivated for practical reasons. Indeed LIDT studies of large optics as those used in LMJ or NIF projects are commonly performed on small samples and with table top lasers whose characteristics change from one to another. In these conditions, it is necessary to know exactly the influence of the different experimental parameters and overall the spot size effect on the final data. In this paper, we present recent developments in multiscale characterization and results obtained on optical coatings (surface case) and KDP crystal (bulk case).

Origin of particulate matter and gaseous precursors in the Paris Megacity: Results from intensive campaigns, long term measurements and modelling

NASA Astrophysics Data System (ADS)

Beekmann, Matthias; Petetin, Hervé; Zhang, Qijie; Prevot, André S. H.; Sciare, Jean; Gros, Valérie; Ghersi, Véronique; Rosso, Amandine; Crippa, Monica; Zotter, Peter; Freutel, Fredericke; Poulain, Laurent; Freney, Evelyne; Sellegri, Karine; Drewnick, Frank; Borbon, Agnès; Wiedensohler, Aflred; Pandis, Spyros N.; Baltensperger, Urs

2016-04-01

Uncertainties on the origin of primary and secondary particulate matter and its gaseous precursors in megacities is still large and needs to be reduced. A detailed characterization of air quality in Paris (France), a megacity of more than 10 million inhabitants, during two one month intensive campaigns (MEGAPOLI) and from additional one year observations (PARTICULATE and FRANCIPOL), revealed that about 70% of the fine particulate matter (PM) at urban background is transported on average into the megacity from upwind regions. While advection of sulfate is well documented for other megacities, there was a surprisingly high contribution from long-range transport for both nitrate and organic aerosol. The data set of urban local and advected PM concentrations in the Paris area were used for a thorough evaluation of the CHIMERE model and revealed error compensation for the local and advected components of organic matter and nitrate. During spring time, CHIMERE simulations overestimate the sensitivity of ammonium nitrate peaks to NH3, because (i) they underestimate the urban background NH3 levels, probably due to neglecting enhanced NH3 emissions for larger temperatures, and because they overestimate HNO3. However, from an ensemble of mobile Max-DOAS NO2 column and airborne NOy measurements around Paris, no clear sign on a NOx emission bias in the TNO-Airparif data set was made evident. The origin of organic PM was investigated by a comprehensive analysis of aerosol mass spectrometer (AMS), radiocarbon and tracer measurements during two intensive campaigns. Primary fossil fuel combustion emissions contributed less than 20% in winter and 40% in summer to carbonaceous fine PM, unexpectedly little for a megacity. Cooking activities and, during winter, residential wood burning are the major primary organic PM sources. This analysis suggests that the major part of secondary organic aerosol is of modern origin, i.e. from biogenic precursors and from wood burning. Implementation of different configurations of the volatility basis set into the CHIMERE model allowed correctly representing summertime organic aerosol (OA) peaks within the agglomeration and attributing them to biogenic secondary OA as a major source. OA build-up from anthropogenic precursors within the plume was also correctly simulated, but it was not possible to attribute it specifically to oxidation of aromatic or of semi/ intermediate volatile organic compounds. Plume build-up of PM significantly contributes to regional air quality around the Paris region.

Interaction of Light and Ethylene on Stem Gravitropism

NASA Technical Reports Server (NTRS)

Harrison, Marcia A.

1996-01-01

The major objective of this study was to evaluate light-regulated ethylene production during gravitropic bending in etiolated pea stems. Previous investigations indicated that ethylene production increases after gravistimulation and is associated with the later (counter-reactive) phase of bending. Additionally, changes in the counter-reaction and locus of curvature during gravitropism are greatly influenced by red light and ethylene production. Ethylene production may be regulated by the levels of available precursor (1-aminocyclopropane-l-carboxylic acid, ACC) via its synthesis, conjugation to malonyl-ACC or glutamyl-ACC, or oxidation to ethylene. The regulation of ethylene production by quantifying ACC and conjugated ACC levels in gravistimulated pea stemswas examined. Also measured was the changes in protein and enzyme activity associated with gravitropic curvature by electrophoretic and spectrophotometric techniques. An image analysis system was used to visualize and quantify enzymatic activity and transcriptional products in gravistimulated and red-light treated etiolated pea stem tissues.

Engineering of GlcNAc-1-Phosphotransferase for Production of Highly Phosphorylated Lysosomal Enzymes for Enzyme Replacement Therapy.

PubMed

Liu, Lin; Lee, Wang-Sik; Doray, Balraj; Kornfeld, Stuart

2017-06-16

Several lysosomal enzymes currently used for enzyme replacement therapy in patients with lysosomal storage diseases contain very low levels of mannose 6-phosphate, limiting their uptake via mannose 6-phosphate receptors on the surface of the deficient cells. These enzymes are produced at high levels by mammalian cells and depend on endogenous GlcNAc-1-phosphotransferase α/β precursor to phosphorylate the mannose residues on their glycan chains. We show that co-expression of an engineered truncated GlcNAc-1-phosphotransferase α/β precursor and the lysosomal enzyme of interest in the producing cells resulted in markedly increased phosphorylation and cellular uptake of the secreted lysosomal enzyme. This method also results in the production of highly phosphorylated acid β-glucocerebrosidase, a lysosomal enzyme that normally has just trace amounts of this modification.

Proteinaceous Pheromone Homologs Identified from the Cloacal Gland Transcriptome of a Male Axolotl, Ambystoma mexicanum.

PubMed

Hall, Kevin W; Eisthen, Heather L; Williams, Barry L

2016-01-01

Pheromones play an important role in modifying vertebrate behavior, especially during courtship and mating. Courtship behavior in urodele amphibians often includes female exposure to secretions from the cloacal gland, as well as other scent glands. The first vertebrate proteinaceous pheromone discovered, the decapeptide sodefrin, is a female attracting pheromone secreted by the cloacal gland of male Cynops pyrrhogaster. Other proteinaceous pheromones in salamanders have been shown to elicit responses from females towards conspecific males. The presence and levels of expression of proteinaceous pheromones have not been identified in the family Ambystomatidae, which includes several important research models. The objective of this research was therefore to identify putative proteinaceous pheromones from male axolotls, Ambystoma mexicanum, as well as their relative expression levels. The results indicate that axolotls possess two different forms of sodefrin precursor-like factor (alpha and beta), as well as a putative ortholog of plethodontid modulating factor. The beta form of sodefrin precursor-like factor was amongst the most highly expressed transcripts within the cloacal gland. The ortholog of plethodontid modulating factor was expressed at a level equivalent to the beta sodefrin precursor-like factor. The results are from a single male axolotl; therefore, we are unable to assess how representative our results may be. Nevertheless, the presence of these highly expressed proteinaceous pheromones suggests that male axolotls use multiple chemical cues to attract female conspecifics. Behavioral assays would indicate whether the putative protein pheromones elicit courtship activity from female axolotls.

Proteinaceous Pheromone Homologs Identified from the Cloacal Gland Transcriptome of a Male Axolotl, Ambystoma mexicanum

PubMed Central

Hall, Kevin W.; Eisthen, Heather L.; Williams, Barry L.

2016-01-01

Pheromones play an important role in modifying vertebrate behavior, especially during courtship and mating. Courtship behavior in urodele amphibians often includes female exposure to secretions from the cloacal gland, as well as other scent glands. The first vertebrate proteinaceous pheromone discovered, the decapeptide sodefrin, is a female attracting pheromone secreted by the cloacal gland of male Cynops pyrrhogaster. Other proteinaceous pheromones in salamanders have been shown to elicit responses from females towards conspecific males. The presence and levels of expression of proteinaceous pheromones have not been identified in the family Ambystomatidae, which includes several important research models. The objective of this research was therefore to identify putative proteinaceous pheromones from male axolotls, Ambystoma mexicanum, as well as their relative expression levels. The results indicate that axolotls possess two different forms of sodefrin precursor-like factor (alpha and beta), as well as a putative ortholog of plethodontid modulating factor. The beta form of sodefrin precursor-like factor was amongst the most highly expressed transcripts within the cloacal gland. The ortholog of plethodontid modulating factor was expressed at a level equivalent to the beta sodefrin precursor-like factor. The results are from a single male axolotl; therefore, we are unable to assess how representative our results may be. Nevertheless, the presence of these highly expressed proteinaceous pheromones suggests that male axolotls use multiple chemical cues to attract female conspecifics. Behavioral assays would indicate whether the putative protein pheromones elicit courtship activity from female axolotls. PMID:26885665

SIRT3 activator Honokiol attenuates β-Amyloid by modulating amyloidogenic pathway

PubMed Central

Lynd, Tyler; Briggs, Gwyneth; Adamek, Danielle; Jones, Ellery; Heiner, Jake; Majrashi, Mohammed; Moore, Timothy; Amin, Rajesh; Suppiramaniam, Vishnu

2018-01-01

Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer’s disease (AD) and is related to the development of cognitive impairment and neuronal cell death. Aβ is generated from amyloid-β precursor protein (APP) through sequential cleavages, first by β-secretase and then by γ-secretase. Drugs modulating this pathway are believed to be one of the most promising strategies for AD treatment. In the present study, we found that Honokiol significantly enhanced SIRT3 expression, reduced reactive oxygen species generation and lipid peroxidation, enhanced antioxidant activities, and mitochondrial function thereby reducing Aβ and sAPPβ levels in Chinese Hamster Ovarian (CHO) cells (carrying the amyloid precursor protein-APP and Presenilin PS1 mutation). Mechanistic studies revealed that Honokiol affects neither protein levels of APP nor α-secretase activity. In contrast, Honokiol increased the expression of AMPK, CREB, and PGC-1α, thereby inhibiting β-secretase activity leading to reduced Aβ levels. These results suggest that Honokiol is an activator of SIRT3 capable of improving antioxidant activity, mitochondrial energy regulation, while decreasing Aβ, thereby indicating it to be a lead compound for AD drug development. PMID:29324783

Inhibition of Wnt signaling induces amyloidogenic processing of amyloid precursor protein and the production and aggregation of Amyloid-β (Aβ)42 peptides.

PubMed

Tapia-Rojas, Cheril; Burgos, Patricia V; Inestrosa, Nibaldo C

2016-12-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the most frequent cause of dementia in the aged population. According to the amyloid hypothesis, the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of AD. Aβ is generated from the amyloidogenic processing of amyloid precursor protein and can aggregate to form oligomers, which have been described as a major synaptotoxic agent in neurons. Dysfunction of Wnt signaling has been linked to increased Aβ formation; however, several other studies have argued against this possibility. Herein, we use multiple experimental approaches to confirm that the inhibition of Wnt signaling promoted the amyloidogenic proteolytic processing of amyloid precursor protein. We also demonstrate that inhibiting Wnt signaling increases the production of the Aβ 42 peptide, the Aβ 42 /Aβ 40 ratio, and the levels of Aβ oligomers such as trimers and tetramers. Moreover, we show that activating Wnt signaling reduces the levels of Aβ 42 and its aggregates, increases Aβ 40 levels, and reduces the Aβ 42 /Aβ 40 ratio. Finally, we show that the protective effects observed in response to activation of the Wnt pathway rely on β-catenin-dependent transcription, which is demonstrated experimentally via the expression of various 'mutant forms of β-catenin'. Together, our findings indicate that loss of the Wnt signaling pathway may contribute to the pathogenesis of AD. © 2016 International Society for Neurochemistry.

Nerve Growth Factor Increases mRNA Levels for the Prion Protein and the β -amyloid Protein Precursor in Developing Hamster Brain

NASA Astrophysics Data System (ADS)

Mobley, William C.; Neve, Rachael L.; Prusiner, Stanley B.; McKinley, Michael P.

1988-12-01

Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the β protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the β -protein precursor (β -PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and β -PP mRNAs. The increases in PrP and β -PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and β -PP mRNA levels. Increased PrP and β -PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and β -PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.

Metabolic Characterization of Intact Cells Reveals Intracellular Amyloid Beta but Not Its Precursor Protein to Reduce Mitochondrial Respiration

PubMed Central

Schaefer, Patrick M.; von Einem, Bjoern; Walther, Paul; Calzia, Enrico; von Arnim, Christine A. F.

2016-01-01

One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization. We performed an overexpression of APP or beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), increasing APP and Aβ levels or Aβ alone, respectively. Conducting a comprehensive metabolic characterization we demonstrate that only APP overexpression reduced mitochondrial respiration, despite lower extracellular Aβ levels compared to BACE overexpression. Surprisingly, this could be rescued by a gamma secretase inhibitor, oppositionally indicating an Aβ-mediated mitochondrial toxicity. Analyzing Aβ localization revealed that intracellular levels of Aβ and an increased spatial association of APP/Aβ with mitochondria are associated with reduced mitochondrial respiration. Thus, our data provide marked evidence for a prominent role of intracellular Aβ accumulation in Alzheimer´s disease associated mitochondrial dysfunction. Thereby it highlights the importance of the localization of APP processing and intracellular transport as a decisive factor for mitochondrial function, linking two prominent hallmarks of neurodegenerative diseases. PMID:28005987

Comparative Proteome Analysis in Schizosaccharomyces pombe Identifies Metabolic Targets to Improve Protein Production and Secretion*

PubMed Central

Hung, Chien-Wen; Klein, Tobias; Cassidy, Liam; Linke, Dennis; Lange, Sabrina; Anders, Uwe; Bureik, Matthias; Heinzle, Elmar; Schneider, Konstantin; Tholey, Andreas

2016-01-01

Protein secretion in yeast is a complex process and its efficiency depends on a variety of parameters. We performed a comparative proteome analysis of a set of Schizosaccharomyces pombe strains producing the α-glucosidase maltase in increasing amounts to investigate the overall proteomic response of the cell to the burden of protein production along the various steps of protein production and secretion. Proteome analysis of these strains, utilizing an isobaric labeling/two dimensional LC-MALDI MS approach, revealed complex changes, from chaperones and secretory transport machinery to proteins controlling transcription and translation. We also found an unexpectedly high amount of changes in enzyme levels of the central carbon metabolism and a significant up-regulation of several amino acid biosyntheses. These amino acids were partially underrepresented in the cellular protein compared with the composition of the model protein. Additional feeding of these amino acids resulted in a 1.5-fold increase in protein secretion. Membrane fluidity was identified as a second bottleneck for high-level protein secretion and addition of fluconazole to the culture caused a significant decrease in ergosterol levels, whereas protein secretion could be further increased by a factor of 2.1. In summary, we show that high level protein secretion causes global changes of protein expression levels in the cell and that precursor availability and membrane composition limit protein secretion in this yeast. In this respect, comparative proteome analysis is a powerful tool to identify targets for an efficient increase of protein production and secretion in S. pombe. Data are available via ProteomeXchange with identifiers PXD002693 and PXD003016. PMID:27477394

Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

PubMed

Swift, Wendy; Wong, Alex; Li, Kong M; Arnold, Jonathon C; McGregor, Iain S

2013-01-01

Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9)-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales "Cannabis Cautioning" scheme. A further 26 "Known Provenance" samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The "Cannabis Cautioning" samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (<0.1%). "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein.

PubMed

Zhang, Can; Browne, Andrew; Child, Daniel; Tanzi, Rudolph E

2010-09-10

Alzheimer disease (AD) is a devastating neurodegenerative disease with no cure. The pathogenesis of AD is believed to be driven primarily by amyloid-beta (Abeta), the principal component of senile plaques. Abeta is an approximately 4-kDa peptide generated via cleavage of the amyloid-beta precursor protein (APP). Curcumin is a compound in the widely used culinary spice, turmeric, which possesses potent and broad biological activities, including anti-inflammatory and antioxidant activities, chemopreventative effects, and effects on protein trafficking. Recent in vivo studies indicate that curcumin is able to reduce Abeta-related pathology in transgenic AD mouse models via unknown molecular mechanisms. Here, we investigated the effects of curcumin on Abeta levels and APP processing in various cell lines and mouse primary cortical neurons. We show for the first time that curcumin potently lowers Abeta levels by attenuating the maturation of APP in the secretory pathway. These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-beta pathology.

Curcumin Decreases Amyloid-β Peptide Levels by Attenuating the Maturation of Amyloid-β Precursor Protein*

PubMed Central

Zhang, Can; Browne, Andrew; Child, Daniel; Tanzi, Rudolph E.

2010-01-01

Alzheimer disease (AD) is a devastating neurodegenerative disease with no cure. The pathogenesis of AD is believed to be driven primarily by amyloid-β (Aβ), the principal component of senile plaques. Aβ is an ∼4-kDa peptide generated via cleavage of the amyloid-β precursor protein (APP). Curcumin is a compound in the widely used culinary spice, turmeric, which possesses potent and broad biological activities, including anti-inflammatory and antioxidant activities, chemopreventative effects, and effects on protein trafficking. Recent in vivo studies indicate that curcumin is able to reduce Aβ-related pathology in transgenic AD mouse models via unknown molecular mechanisms. Here, we investigated the effects of curcumin on Aβ levels and APP processing in various cell lines and mouse primary cortical neurons. We show for the first time that curcumin potently lowers Aβ levels by attenuating the maturation of APP in the secretory pathway. These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-β pathology. PMID:20622013

The effect of grape seed extract on estrogen levels of postmenopausal women: a pilot study.

PubMed

Wahner-Roedler, Dietlind L; Bauer, Brent A; Loehrer, Laura L; Cha, Stephen S; Hoskin, Tanya L; Olson, Janet E

2014-06-01

The role of estrogens in breast cancer (BC) development is widely accepted, leading to the development of selective estrogen receptor modulators and aromatase inhibitors for BC treatment and prevention. However, because of potential adverse effects, healthy women with high risk of BC are hesitant to take them. Preliminary evidence from animal studies shows that grapes may have an aromatase-inhibiting effect, decreasing estrogen synthesis and increasing androgen precursors. We conducted a randomized, double-blind, dose-finding early-phase trial on the effect of grape seed extract (GSE) on estrogen levels. Postmenopausal women who met study inclusion criteria (N = 46) were randomly assigned to daily GSE at a dose of 200, 400, 600, or 800 mg for 12 weeks. Primary outcome was change in plasma levels of estrogen conjugates from baseline to 12 weeks posttreatment. Thirty-nine participants (84.8%) completed the study. GSE in the 4 daily doses did not significantly decrease estrogen or increase androgen precursors.

40 CFR 141.135 - Treatment technique for control of disinfection byproduct (DBP) precursors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or enhanced softening to achieve the TOC percent removal levels specified in paragraph (b) of this... requirements in § 141.132(d). (i) The system's source water TOC level, measured according to § 141.131(d)(3... water TOC level, measured according to § 141.131(d)(3), is less than 2.0 mg/L, calculated quarterly as a...

The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

PubMed

Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

2017-02-01

Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central nervous system positivity in T-cell acute lymphoblastic leukemia (odds ratio=11.00, 95% confidence interval, 2.00-60.62). We propose zeta-chain-associated protein kinase 70, CCR7 and CXCR4 as markers of central nervous system infiltration in acute lymphoblastic leukemia warranting prospective investigation. Copyright© Ferrata Storti Foundation.

Mapping axillary microbiota responsible for body odours using a culture-independent approach.

PubMed

Troccaz, Myriam; Gaïa, Nadia; Beccucci, Sabine; Schrenzel, Jacques; Cayeux, Isabelle; Starkenmann, Christian; Lazarevic, Vladimir

2015-01-01

Human axillary odour is commonly attributed to the bacterial degradation of precursors in sweat secretions. To assess the role of bacterial communities in the formation of body odours, we used a culture-independent approach to study axillary skin microbiota and correlated these data with olfactory analysis. Twenty-four Caucasian male and female volunteers and four assessors showed that the underarms of non-antiperspirant (non-AP) users have significantly higher global sweat odour intensities and harboured on average about 50 times more bacteria than those of AP users. Global sweat odour and odour descriptors sulfury-cat urine and acid-spicy generally increased from the morning to the afternoon sessions. Among non-AP users, male underarm odours were judged higher in intensity with higher fatty and acid-spicy odours and higher bacterial loads. Although the content of odour precursors in underarm secretions varied widely among individuals, males had a higher acid: sulfur precursor ratio than females did. No direct correlations were found between measured precursor concentration and sweat odours. High-throughput sequencing targeting the 16S rRNA genes of underarm bacteria collected from 11 non-AP users (six females and five males) confirmed the strong dominance of the phyla Firmicutes and Actinobacteria, with 96% of sequences assigned to the genera Staphylococcus, Corynebacterium and Propionibacterium. The proportion of several bacterial taxa showed significant variation between males and females. The genera Anaerococcus and Peptoniphilus and the operational taxonomic units (OTUs) from Staphylococcus haemolyticus and the genus Corynebacterium were more represented in males than in females. The genera Corynebacterium and Propionibacterium were correlated and anti-correlated, respectively, with body odours. Within the genus Staphylococcus, different OTUs were either positively or negatively correlated with axillary odour. The relative abundance of five OTUs (three assigned to S. hominis and one each to Corynebacterium tuberculostearicum and Anaerococcus) were positively correlated with at least one underarm olfactory descriptor. Positive and negative correlations between bacterial taxa found at the phylum, genus and OTU levels suggest the existence of mutualism and competition among skin bacteria. Such interactions, and the types and quantities of underarm bacteria, affect the formation of body odours. These findings open the possibility of developing new solutions for odour control.

Functional integrins from normal and glycosylation-deficient baby hamster kidney cells. Terminal processing of asparagine-linked oligosaccharides is not correlated with fibronectin-binding activity.

PubMed

Koyama, T; Hughes, R C

1992-12-25

We have examined the properties of the alpha 5 beta 1 integrin of baby hamster kidney (BHK) cells, a ricin-resistant variant Ric14 lacking N-acetylglucosaminyl transferase I, and hence unable to complete assembly of hybrid- or complex-type N-glycans, and BHK cells treated with 1-deoxymannojirimycin (dMM), an inhibitor of Golgi mannosidases involved in the initial processing of N-glycan precursors. Comparable amounts of alpha 5 beta 1 integrin were isolated from these cells by chromatography of detergent extracts on a fibronectin cell-binding fragment affinity column and elution with EDTA. The alpha 5 beta 1 integrin obtained from normal BHK cells by fibronectin affinity chromatography contained mainly endoglycosidase H-resistant oligosaccharides, whereas in RicR14 cells or dMM-treated BHK cells these were entirely endoglycosidase H-sensitive. Analysis of lactoperoxidase labeled or long term biosynthetically 35S-labeled proteins from cultures of normal or glycosylation deficient cells showed similar steady state levels of alpha 5 beta 1 integrin and expression at the cell surface. Pulse-chase experiments in normal BHK cells showed rapid conversion of the alpha 5 subunit into a mature form containing oligosaccharides resistant to endoglycosidase H and slower maturation of a precursor beta 1 subunit, as in other cell types. In Ric14 cells the precursor beta 1 subunit was found to carry glycans larger than the fully processed Man5GlcNAc2 glycan of the mature subunit, indicating that the bulk precursor pool had not been translocated into the cis-Golgi compartment containing mannosidase I. We conclude that in BHK cells terminal oligosaccharide processing of alpha 5 beta 1 integrin subunits is not required for dimer formation, surface expression, and fibronectin binding, and that expression of the glycosylation defect of Ric14 cells on the alpha 5 beta 1 integrin does not account for the reduced adhesiveness of these cells on fibronectin compared with normal and dMM-treated BHK cells.

Investigating the variability in brown carbon light-absorption properties

NASA Astrophysics Data System (ADS)

Saleh, R.; Cheng, Z.; Atwi, K.

2017-12-01

Combustion of biomass fuels contributes a significant portion of brown carbon (BrC), the light-absorbing fraction of organic aerosols. BrC exhibits highly variable light-absorption properties, with imaginary part of the refractive indices (k) reported in the literature varying over two orders of magnitude. This high variability in k is attributed to the chaotic nature of combustion; however, there is a major gap in the fundamental understanding of this variability. To address this gap, we hypothesize that BrC is comprised of black carbon (BC) precursors whose transformation to BC has not seen fruition. Depending on the combustion conditions, these BC precursors exhibit different maturity levels which dictate their light-absorption properties (k). The more mature are the precursors, the more absorptive (or BC-like) they are. Therefore, k of BrC obtained from a certain measurement depends on the specific combustion conditions associated with the measurement, leading to the aforementioned variability in the literature. To test this hypothesis, we performed controlled combustion experiments in which the combustion conditions (temperature and air/fuel ratio) were varied and k was retrieved from real-time multi-wavelength light-absorption measurements at each condition. We used benzene, the inception of which during combustion is the initial critical step leading to BC formation, as a model fuel. By varying the combustion conditions from relatively inefficient (low temperature and/or air/fuel ratio) to relatively efficient (high temperature and/or air/fuel ratio), we isolated BrC components with progressively increasing k, spanning the wide range reported in the literature. We also performed thermodenuder measurements to constrain the volatility of the BrC, as well as laser desorption ionization mass spectrometry analysis to constrain its molecular mass. We found that as the combustion conditions approached the BC-formation threshold, the increase in k was associated with an increase in molecular mass and decrease in volatility. This confirms our hypothesis, since the BC precursors are expected to grow in size and become less volatile as they mature. These results provide the first correlation between the BrC physical, chemical, and consequent light-absorption properties.

Normalization for Relative Quantification of mRNA and microRNA in Soybean Exposed to Various Abiotic Stresses

PubMed Central

Zhou, Yonggang; Chen, Huan; Dong, Yuanyuan; Wang, Nan; Li, Xiaowei; Jameel, Aysha; Yang, He; Zhang, Min; Chen, Kai; Wang, Fawei; Li, Haiyan

2016-01-01

Plant microRNAs are small non-coding, endogenic RNA molecule (containing 20–24 nucleotides) produced from miRNA precursors (pri-miRNA and pre-miRNA). Evidence suggests that up and down regulation of the miRNA targets the mRNA genes involved in resistance against biotic and abiotic stresses. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a powerful technique to analyze variations in mRNA levels. Normalizing the data using reference genes is essential for the analysis of reliable RT-qPCR data. In this study, two groups of candidate reference mRNAs and miRNAs in soybean leaves and roots treated with various abiotic stresses (PEG-simulated drought, salinity, alkalinity, salinity+alkalinity, and abscisic acid) were analyzed by RT-qPCR. We analyzed the most appropriate reference mRNA/miRNAs using the geNorm, NormFinder, and BestKeeper algorithms. According to the results, Act and EF1b were the most suitable reference mRNAs in leaf and root samples, for mRNA and miRNA precursor data normalization. The most suitable reference miRNAs found in leaf and root samples were 166a and 167a for mature miRNA data normalization. Hence the best combinations of reference mRNAs for mRNA and miRNA precursor data normalization were EF1a + Act or EF1b + Act in leaf samples, and EF1a + EF1b or 60s + EF1b in root samples. For mature miRNA data normalization, the most suitable combinations of reference miRNAs were 166a + 167d in leaf samples, and 171a + 156a or 167a + 171a in root samples. We identified potential reference mRNA/miRNAs for accurate RT-qPCR data normalization for mature miRNA, miRNA precursors, and their targeted mRNAs. Our results promote miRNA-based studies on soybean plants exposed to abiotic stress conditions. PMID:27176476

Detection of 6-demethoxyubiquinone in CoQ10 deficiency disorders: Insights into enzyme interactions and identification of potential therapeutics.

PubMed

Herebian, Diran; Seibt, Annette; Smits, Sander H J; Bünning, Gisela; Freyer, Christoph; Prokisch, Holger; Karall, Daniela; Wredenberg, Anna; Wedell, Anna; López, Luis C; Mayatepek, Ertan; Distelmaier, Felix

2017-07-01

Coenzyme Q 10 (CoQ 10 ) is an essential cofactor of the mitochondrial oxidative phosphorylation (OXPHOS) system and its deficiency has important implications for several inherited metabolic disorders of childhood. The biosynthesis of CoQ 10 is a complicated process, which involves at least 12 different enzymes. One of the metabolic intermediates that are formed during CoQ 10 biosynthesis is the molecule 6-demethoxyubiquinone (6-DMQ). This CoQ precursor is processed at the level of COQ7 and COQ9. We selected this metabolite as a marker substance for metabolic analysis of cell lines with inherited genetic defects (COQ2, COQ4, COQ7 and COQ9) or siRNA knockdown in CoQ biosynthesis enzymes using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). In COQ4, COQ7 and COQ9 deficient cell lines, we detected significantly elevated levels of 6-DMQ. This suggests a functional interplay of these proteins. However, additional siRNA studies demonstrated that elevated 6-DMQ levels are not an exclusive marker of the COQ7/COQ9 enzymatic step of CoQ 10 biosynthesis but constitute a more general phenomenon that occurs in disorders impairing the function or stability of the CoQ-synthome. To further investigate the interdependence of CoQ 10 biosynthesis enzyme expression, we performed immunoblotting in various cell lines with CoQ 10 deficiency, indicating that COQ4, COQ7 and COQ9 protein expression levels are highly regulated depending on the underlying defect. Supplementation of cell lines with synthetic CoQ precursor compounds demonstrated beneficial effects of 2,4-dihydroxybenzoic acid in COQ7 and COQ9 deficiency. Moreover, vanillic acid selectively stimulated CoQ 10 biosynthesis and improved cell viability in COQ9 deficiency. However, compounds tested in this study failed to rescue COQ4 deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.