Topology of black hole binary-single interactions

NASA Astrophysics Data System (ADS)

Samsing, Johan; Ilan, Teva

2018-05-01

We present a study on how the outcomes of binary-single interactions involving three black holes (BHs) distribute as a function of the initial conditions; a distribution we refer to as the topology. Using a N-body code that includes BH finite sizes and gravitational wave (GW) emission in the equation of motion (EOM), we perform more than a million binary-single interactions to explore the topology of both the Newtonian limit and the limit at which general relativistic (GR) effects start to become important. From these interactions, we are able to describe exactly under which conditions BH collisions and eccentric GW capture mergers form, as well as how GR in general modifies the Newtonian topology. This study is performed on both large- and microtopological scales. We further describe how the inclusion of GW emission in the EOM naturally leads to scenarios where the binary-single system undergoes two successive GW mergers.

Remarks on non-maximal integral elements of the Cartan plane in jet spaces

NASA Astrophysics Data System (ADS)

Bächtold, M.; Moreno, G.

2014-11-01

There is a natural filtration on the space of degree-k homogeneous polynomials in n independent variables with coefficients in the algebra of smooth functions on the Grassmannian Gr (n,s), determined by the tautological bundle. In this paper we show that the space of s-dimensional integral elements of a Cartan plane on J(E,n), with dimE=n+m, has an affine bundle structure modeled by the so-obtained bundles over Gr (n,s), and we study a natural distribution associated with it. As an example, we show that a third-order nonlinear PDE of Monge-Ampère type is not contact-equivalent to a quasi-linear one.

Single Nucleotide Variations of the Human GR Gene Manifested as Pathologic Mutations or Polymorphisms.

PubMed

Kino, Tomoshige

2018-05-11

The human genome contains numerous single nucleotide variations (SNVs), and the human GR gene harbors ∼450 of these genetic changes. Among them, extremely rare non-synonymous variants known as pathologic GR gene mutations develop a characteristic pathologic condition, familial/sporadic generalized glucocorticoid resistance syndrome, by replacing the amino acids critical for GR protein structure and functions, whereas others known as pathologic polymorphisms develop mild manifestations recognized mainly at population bases by changing the GR activities slightly. Recent progress on the structural analysis to the GR protein and subsequent computer-based structural simulation revealed details of the molecular defects caused by such pathologic GR gene mutations, including their impact on the receptor interaction to ligands, nuclear receptor coactivators (NCoAs) or DNA glucocorticoid response elements (GREs). Indeed, those found in the GR ligand-binding domain significantly damage protein structure of the ligand-binding pocket and/or the activation function-2 transactivation domain and change their molecular interaction to glucocorticoids or the LxxLL signature motif of NCoAs. Two mutations found in GR DBD also affect interaction of the mutant receptors to GRE DNA by affecting the critical amino acid for the interaction or changing local hydrophobic circumstance. In this review, we discuss recent findings on the structural simulation of the pathologic GR mutants in connection to their functional and clinical impacts along with brief explanation to recent research achievement on the GR polymorphisms.

Electronic states of aryl radical functionalized graphenes: Density functional theory study

NASA Astrophysics Data System (ADS)

Tachikawa, Hiroto; Kawabata, Hiroshi

2016-06-01

Functionalized graphenes are known as a high-performance molecular device. In the present study, the structures and electronic states of the aryl radical functionalized graphene have been investigated by the density functional theory (DFT) method to elucidate the effects of functionalization on the electronic states of graphene (GR). Also, the mechanism of aryl radical reaction with GR was investigated. The benzene, biphenyl, p-terphenyl, and p-quaterphenyl radicals [denoted by (Bz) n (n = 1-4), where n means numbers of benzene rings in aryl radical] were examined as aryl radicals. The DFT calculation of GR-(Bz) n (n = 1-4) showed that the aryl radical binds to the carbon atom of GR, and a C-C single bond was formed. The binding energies of aryl radicals to GR were calculated to be ca. 6.0 kcal mol-1 at the CAM-B3LYP/6-311G(d,p) level. It was found that the activation barrier exists in the aryl radical addition: the barrier heights were calculated to be 10.0 kcal mol-1. The electronic states of GR-(Bz) n were examined on the basis of theoretical results.

Hierarchical clustering in chameleon f(R) gravity

NASA Astrophysics Data System (ADS)

Hellwing, Wojciech A.; Li, Baojiu; Frenk, Carlos S.; Cole, Shaun

2013-11-01

We use a suite of high-resolution state-of-the-art N-body dark matter simulations of chameleon f(R) gravity to study the higher order volume-averaged correlation functions overline{ξ _n} together with the hierarchical nth-order correlation amplitudes S_n=overline{ξ }_n/overline{ξ }_2^{n-1} and density distribution functions (PDF). We show that under the non-linear modifications of gravity the hierarchical scaling of the reduced cumulants is preserved. This is however characterized by significant changes in the values of both overline{ξ _n} and Sn and their scale dependence with respect to General Relativity gravity (GR). In addition, we measure a significant increase of the non-linear σ8 parameter reaching 14, 5 and 0.5 per cent in excess of the GR value for the three flavours of our f(R) models. We further note that the values of the reduced cumulants up to order n = 9 are significantly increased in f(R) gravity for all our models at small scales R ≲ 30 h-1 Mpc. In contrast, the values of the hierarchical amplitudes, Sn, are smaller in f(R) indicating that the modified gravity density distribution functions are deviating from the GR case. Furthermore, we find that the redshift evolution of relative deviations of the f(R) hierarchical correlation amplitudes is fastest at high and moderate redshifts 1 ≤ z ≤ 4. The growth of these deviations significantly slows down in the low-redshift universe. We also compute the PDFs and show that for scales below ˜20 h-1 Mpc, they are significantly shifted in f(R) gravity towards the low densities. Finally, we discuss the implications of our theoretical predictions for measurements of the hierarchical clustering in galaxy redshift surveys, including the important problems of the galaxy biasing and redshift space distortions.

Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

PubMed

Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

2018-03-01

This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathophysiology of Glucocorticoid Signaling.

PubMed

Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

2018-06-01

Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Brain-Derived Neurotrophic Factor Signaling Rewrites the Glucocorticoid Transcriptome via Glucocorticoid Receptor Phosphorylation

PubMed Central

Lambert, W. Marcus; Xu, Chong-Feng; Neubert, Thomas A.; Chao, Moses V.

2013-01-01

Abnormal glucocorticoid and neurotrophin signaling has been implicated in numerous psychiatric disorders. However, the impact of neurotrophic signaling on glucocorticoid receptor (GR)-dependent gene expression is not understood. We therefore examined the impact of brain-derived neurotrophic factor (BDNF) signaling on GR transcriptional regulatory function by gene expression profiling in primary rat cortical neurons stimulated with the selective GR agonist dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment with BDNF and Dex elicited a unique set of GR-responsive genes associated with neuronal growth and differentiation and also enhanced the induction of a large number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the transcriptional activity of a synthetic GR reporter, suggesting a direct effect of BDNF signaling on GR function. Indeed, BDNF treatment induces the phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation increased GR occupancy and cofactor recruitment at the promoter of a BDNF-enhanced gene. GR phosphorylation in vivo is sensitive to changes in the levels of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies and amplifies the GR transcriptome through a coordinated GR phosphorylation-dependent detection mechanism. PMID:23878391

Negative Correlation between the Diffusion Coefficient and Transcriptional Activity of the Glucocorticoid Receptor.

PubMed

Mikuni, Shintaro; Yamamoto, Johtaro; Horio, Takashi; Kinjo, Masataka

2017-08-25

The glucocorticoid receptor (GR) is a transcription factor, which interacts with DNA and other cofactors to regulate gene transcription. Binding to other partners in the cell nucleus alters the diffusion properties of GR. Raster image correlation spectroscopy (RICS) was applied to quantitatively characterize the diffusion properties of EGFP labeled human GR (EGFP-hGR) and its mutants in the cell nucleus. RICS is an image correlation technique that evaluates the spatial distribution of the diffusion coefficient as a diffusion map. Interestingly, we observed that the averaged diffusion coefficient of EGFP-hGR strongly and negatively correlated with its transcriptional activities in comparison to that of EGFP-hGR wild type and mutants with various transcriptional activities. This result suggests that the decreasing of the diffusion coefficient of hGR was reflected in the high-affinity binding to DNA. Moreover, the hyper-phosphorylation of hGR can enhance the transcriptional activity by reduction of the interaction between the hGR and the nuclear corepressors.

Versatile application of indirect Fourier transformation to structure factor analysis: from X-ray diffraction of molecular liquids to small angle scattering of protein solutions.

PubMed

Fukasawa, Toshiko; Sato, Takaaki

2011-02-28

We highlight versatile applicability of a structure-factor indirect Fourier transformation (IFT) technique, hereafter called SQ-IFT. The original IFT aims at the pair distance distribution function, p(r), of colloidal particles from small angle scattering of X-rays (SAXS) and neutrons (SANS), allowing the conversion of the experimental form factor, P(q), into a more intuitive real-space spatial autocorrelation function. Instead, SQ-IFT is an interaction potential model-free approach to the 'effective' or 'experimental' structure factor to yield the pair correlation functions (PCFs), g(r), of colloidal dispersions like globular protein solutions for small-angle scattering data as well as the radial distribution functions (RDFs) of molecular liquids in liquid diffraction (LD) experiments. We show that SQ-IFT yields accurate RDFs of liquid H(2)O and monohydric alcohol reflecting their local intermolecular structures, in which q-weighted structure function, qH(q), conventionally utilized in many LD studies out of necessity of performing direct Fourier transformation, is no longer required. We also show that SQ-IFT applied to theoretically calculated structure factors for uncharged and charged colloidal dispersions almost perfectly reproduces g(r) obtained as a solution of the Ornstein-Zernike (OZ) equation. We further demonstrate the relevance of SQ-IFT in its practical applications, using SANS effective structure factors of lysozyme solutions reported in recent literatures which revealed the equilibrium cluster formation due to coexisting long range electrostatic repulsion and short range attraction between the proteins. Finally, we present SAXS experiments on human serum albumin (HSA) at different ionic strength and protein concentration, in which we discuss the real space picture of spatial distributions of the proteins via the interaction potential model-free route.

Alternative splicing: a novel mechanism of regulation identified in the chorismate mutase gene of the potato cyst nematode Globodera rostochiensis.

PubMed

Lu, Shun-Wen; Tian, Duanhua; Borchardt-Wier, Harmony B; Wang, Xiaohong

2008-11-01

Chorismate mutase (CM) secreted from the stylet of plant-parasitic nematodes plays an important role in plant parasitism. We isolated and characterized a new nematode CM gene (Gr-cm-1) from the potato cyst nematode, Globodera rostochiensis. The Gr-cm-1 gene was found to exist in the nematode genome as a single-copy gene that has two different alleles, Gr-cm-1A and Gr-cm-1B, both of which could give rise to two different mRNA transcripts of Gr-cm-1 and Gr-cm-1-IRII. In situ mRNA hybridization showed that the Gr-cm-1 gene was exclusively expressed within the subventral oesophageal gland cells of the nematode. Gr-cm-1 was demonstrated to encode a functional CM (GR-CM-1) potentially having a dimeric structure as the secreted bacterial *AroQ CMs. Gr-cm-1-IRII, generated by retention of intron 2 of the Gr-cm-1 pre-mRNA through alternative splicing (AS), would encode a truncated protein (GR-CM-1t) lacking the CM domain with no CM activity. The quantitative real-time reverse transcription-PCR assay revealed that splicing of the Gr-cm-1 gene was developmentally regulated; Gr-cm-1 was up-regulated whereas Gr-cm-1-IRII was down-regulated in early nematode parasitic stages compared to the preparasitic juvenile stage. Low-temperature SDS-PAGE analysis revealed that GR-CM-1 could form homodimers when expressed in Escherichia coli and the dimerization domain was retained in the truncated GR-CM-1t protein. The specific interaction between the two proteins was demonstrated in yeast. Our data suggested that the novel splice variant might function as a dominant negative isoform through heterodimerization with the full-length GR-CM-1 protein and that AS may represent an important mechanism for regulating CM activity during nematode parasitism.

Checking the statistical theory of liquids by ultraacoustic measurements

NASA Technical Reports Server (NTRS)

Dima, V. N.

1974-01-01

The manner of theoretically obtaining radial distribution functions 9(r) for n-hexane as a function of temperature is described. With the aid of function g(r) the coefficient of dynamic viscosity and the coefficient of volumetric viscosity for temperatures ranging from 213 K to 273 K were calculated. With the aid of the two coefficients of viscosity the coefficient of absorption of ultrasounds in n-hexane referred to the square of the frequency was determined. The same values were measured experimentally. Comparison of theory with experiments resulted in satisfactory agreement.

Shear viscosity coefficient of liquid lanthanides

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

Patel, H. P., E-mail: patel.harshal2@gmail.com; Thakor, P. B., E-mail: pbthakore@rediffmail.com; Prajapati, A. V., E-mail: anand0prajapati@gmail.com

2015-05-15

Present paper deals with the computation of shear viscosity coefficient (η) of liquid lanthanides. The effective pair potential v(r) is calculated through our newly constructed model potential. The Pair distribution function g(r) is calculated from PYHS reference system. To see the influence of local field correction function, Hartree (H), Tailor (T) and Sarkar et al (S) local field correction function are used. Present results are compared with available experimental as well as theoretical data. Lastly, we found that our newly constructed model potential successfully explains the shear viscosity coefficient (η) of liquid lanthanides.

Shear viscosity coefficient of liquid lanthanides

NASA Astrophysics Data System (ADS)

Patel, H. P.; Sonvane, Y. A.; Thakor, P. B.; Prajapati, A. V.

2015-05-01

Present paper deals with the computation of shear viscosity coefficient (η) of liquid lanthanides. The effective pair potential v(r) is calculated through our newly constructed model potential. The Pair distribution function g(r) is calculated from PYHS reference system. To see the influence of local field correction function, Hartree (H), Tailor (T) and Sarkar et al (S) local field correction function are used. Present results are compared with available experimental as well as theoretical data. Lastly, we found that our newly constructed model potential successfully explains the shear viscosity coefficient (η) of liquid lanthanides.

A fructose receptor functions as a nutrient sensor in the Drosophila brain

PubMed Central

Miyamoto, Tetsuya; Slone, Jesse; Song, Xiangyu; Amrein, Hubert

2012-01-01

SUMMARY Internal nutrient sensors play important roles in feeding behavior, yet their molecular structure and mechanism of action are poorly understood. Using Ca2+ imaging and behavioral assays, we show that the Gustatory Receptor 43a functions as a narrowly tuned fructose receptor in taste neurons. Remarkably, GR43a also functions as a fructose receptor in the brain. Interestingly, hemolymph fructose levels are tightly linked to feeding status: after nutritious carbohydrate consumption, fructose levels rise several fold and reach a concentration sufficient to activate GR43a in the brain. By using different feeding paradigms and artificial activation of Gr43a-expressing brain neurons, we show that GR43a is both necessary and sufficient to sense hemolymph fructose and promote feeding in hungry flies, but suppress feeding in satiated flies. Thus, our studies indicate that the Gr43a-expressing brain neurons function as a nutrient sensor for hemolymph fructose and assign opposing valence to feeding experiences in a satiation-dependent manner. PMID:23178127

Tool use in left brain damage and Alzheimer's disease: What about function and manipulation knowledge?

PubMed

Jarry, Christophe; Osiurak, François; Besnard, Jérémy; Baumard, Josselin; Lesourd, Mathieu; Croisile, Bernard; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Le Gall, Didier

2016-03-01

Tool use disorders are usually associated with difficulties in retrieving function and manipulation knowledge. Here, we investigate tool use (Real Tool Use, RTU), function (Functional Association, FA) and manipulation knowledge (Gesture Recognition, GR) in 17 left-brain-damaged (LBD) patients and 14 AD patients (Alzheimer disease). LBD group exhibited predicted deficit on RTU but not on FA and GR while AD patients showed deficits on GR and FA with preserved tool use skills. These findings question the role played by function and manipulation knowledge in actual tool use. © 2016 The British Psychological Society.

Structural Analysis on the Pathologic Mutant Glucocorticoid Receptor Ligand-Binding Domains.

PubMed

Hurt, Darrell E; Suzuki, Shigeru; Mayama, Takafumi; Charmandari, Evangelia; Kino, Tomoshige

2016-02-01

Glucocorticoid receptor (GR) gene mutations may cause familial or sporadic generalized glucocorticoid resistance syndrome. Most of the missense forms distribute in the ligand-binding domain and impair its ligand-binding activity and formation of the activation function (AF)-2 that binds LXXLL motif-containing coactivators. We performed molecular dynamics simulations to ligand-binding domain of pathologic GR mutants to reveal their structural defects. Several calculated parameters including interaction energy for dexamethasone or the LXXLL peptide indicate that destruction of ligand-binding pocket (LBP) is a primary character. Their LBP defects are driven primarily by loss/reduction of the electrostatic interaction formed by R611 and T739 of the receptor to dexamethasone and a subsequent conformational mismatch, which deacylcortivazol resolves with its large phenylpyrazole moiety and efficiently stimulates transcriptional activity of the mutant receptors with LBP defect. Reduced affinity of the LXXLL peptide to AF-2 is caused mainly by disruption of the electrostatic bonds to the noncore leucine residues of this peptide that determine the peptide's specificity to GR, as well as by reduced noncovalent interaction against core leucines and subsequent exposure of the AF-2 surface to solvent. The results reveal molecular defects of pathologic mutant receptors and provide important insights to the actions of wild-type GR.

Thermal expansion behavior of LDEF metal matrix composites

NASA Technical Reports Server (NTRS)

Le, Tuyen D.; Steckel, Gary L.

1993-01-01

The thermal expansion behavior of Long Duration Exposure Facility (LDEF) metal matrix composite materials was studied by (1) analyzing the flight data that was recorded on orbit to determine the effects of orbital time and heating/cooling rates on the performance of the composite materials, and (2) characterizing and comparing the thermal expansion behavior of post-flight LDEF and lab-control samples. The flight data revealed that structures in space are subjected to nonuniform temperature distributions, and thermal conductivity of a material is an important factor in establishing a uniform temperature distribution and avoiding thermal distortion. The flight and laboratory data showed that both Gr/Al and Gr/Mg composites were stabilized after prolonged thermal cycling on orbit. However, Gr/Al composites showed more stable thermal expansion behavior than Gr/Mg composites and offer advantages for space structures particularly where very tight thermal stability requirements in addition to high material performance must be met.

The diversity of ice algal communities on the Greenland Ice Sheet as revealed by oligotyping

PubMed Central

Lutz, Stefanie; McCutcheon, Jenine; McQuaid, James B.; Benning, Liane G.

2018-01-01

The Arctic is being disproportionally affected by climate change compared with other geographic locations, and is currently experiencing unprecedented melt rates. The Greenland Ice Sheet (GrIS) can be regarded as the largest supraglacial ecosystem on Earth, and ice algae are the dominant primary producers on bare ice surfaces throughout the course of a melt season. Ice-algal-derived pigments cause a darkening of the ice surface, which in turn decreases albedo and increases melt rates. The important role of ice algae in changing melt rates has only recently been recognized, and we currently know little about their community compositions and functions. Here, we present the first analysis of ice algal communities across a 100 km transect on the GrIS by high-throughput sequencing and subsequent oligotyping of the most abundant taxa. Our data reveal an extremely low algal diversity with Ancylonema nordenskiöldii and a Mesotaenium species being by far the dominant taxa at all sites. We employed an oligotyping approach and revealed a hidden diversity not detectable by conventional clustering of operational taxonomic units and taxonomic classification. Oligotypes of the dominant taxa exhibit a site-specific distribution, which may be linked to differences in temperatures and subsequently the extent of the melting. Our results help to better understand the distribution patterns of ice algal communities that play a crucial role in the GrIS ecosystem. PMID:29547098

Expression Profiling Identifies Klf15 as a Glucocorticoid Target That Regulates Airway Hyperresponsiveness

PubMed Central

Masuno, Kiriko; Haldar, Saptarsi M.; Jeyaraj, Darwin; Mailloux, Christina M.; Huang, Xiaozhu; Panettieri, Rey A.; Jain, Mukesh K.

2011-01-01

Glucocorticoids (GCs), which activate GC receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. GCs exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM (HASM) gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7,500 genes had statistically distinguishable changes in expression; quantitative PCR validation of a 40-gene subset of putative GR-regulated genes in 6 HASM cell lines suggested that the early transcriptional targets of GR signaling are similar in independent HASM lines. Gene ontology analysis implicated GR targets in controlling multiple aspects of ASM function. One GR-regulated gene, the transcription factor, Kruppel-like factor 15 (Klf15), was already known to modulate vascular smooth and cardiac muscle function, but had no known role in the lung. We therefore analyzed the pulmonary phenotype of Klf15−/− mice after ovalbumin sensitization and challenge. We found diminished airway responses to acetylcholine in ovalbumin-challenged Klf15−/− mice without a significant change in the induction of asthmatic inflammation. In cultured cells, overexpression of Klf15 reduced proliferation of HASM cells, whereas apoptosis in Klf15−/− murine ASM cells was increased. Together, these results further characterize the GR-regulated gene network in ASM and establish a novel role for the GR target, Klf15, in modulating airway function. PMID:21257922

Convergence of glycogen synthase kinase 3β and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats.

PubMed

Mitic, Milos; Brkic, Zeljka; Lukic, Iva; Adzic, Miroslav

2017-08-30

Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3β, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3β-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3β targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress. Stress induced sex-specific GSK3β-targeted phosphorylation of pGR171 in the nucleus of the hippocampus of stressed animals. Namely, while in females stress triggered coupled action of GSK3β-pGR171 signaling, in males changes in pGR171 levels did not correspond to GSK3β activity. On the other hand, fluoxetine managed to up-regulate this pathway in sex-unbiased manner. Furthermore, fluoxetine reverted stress-induced changes in most of the analyzed genes in males, CRH, 5-HT1a and p11, while in females its effect was limited to CRH. These data further suggest that pGR171 signaling affects cellular localization of GR in response to chronic stress and fluoxetine in both sexes. Collectively, our results describe a novel convergence point between GR signaling and GSK3β pathway in rat hippocampus in response to stress and fluoxetine in both sexes and its involvement in fluoxetine-regulated brain function in males. Copyright © 2017 Elsevier B.V. All rights reserved.

A spectral measurement method for determining white OLED average junction temperatures

NASA Astrophysics Data System (ADS)

Zhu, Yiting; Narendran, Nadarajah

2016-09-01

The objective of this study was to investigate an indirect method of measuring the average junction temperature of a white organic light-emitting diode (OLED) based on temperature sensitivity differences in the radiant power emitted by individual emitter materials (i.e., "blue," "green," and "red"). The measured spectral power distributions (SPDs) of the white OLED as a function of temperature showed amplitude decrease as a function of temperature in the different spectral bands, red, green, and blue. Analyzed data showed a good linear correlation between the integrated radiance for each spectral band and the OLED panel temperature, measured at a reference point on the back surface of the panel. The integrated radiance ratio of the spectral band green compared to red, (G/R), correlates linearly with panel temperature. Assuming that the panel reference point temperature is proportional to the average junction temperature of the OLED panel, the G/R ratio can be used for estimating the average junction temperature of an OLED panel.

Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

PubMed Central

Andrews, Jonathan C.; Fernández, María Paz; Yu, Qin; Leary, Greg P.; Leung, Adelaine K. W.; Kavanaugh, Michael P.; Kravitz, Edward A.; Certel, Sarah J.

2014-01-01

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-FruM neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway. PMID:24852170

Analysis of the Glucocorticoid Receptor in Spontaneous and Drug-induced Steroid Resistant Mutants Isolated from the Human Leukemic Cell Line CEM-C7

DTIC Science & Technology

1991-01-04

be due to defects in GR function. However, the loss of GR function in x" S49 cells is paralleled by the loss of GR mRNA which is not seen in x’ OEM ...in the protein transcription factor IIIA from Xepopus oocytes. EMBO J. 4: 1609-1614. Milgrom. E.; Atger, M.; Baulieu, E.-E. 1973 Acidophilic

Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression

PubMed Central

Zhang, Kuo; Pan, Xing; Wang, Fang; Ma, Jie; Su, Guangyue; Dong, Yingxu; Yang, Jingyu; Wu, Chunfu

2016-01-01

Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation. PMID:27502757

The Santiago-Harvard-Edinburgh-Durham void comparison - I. SHEDding light on chameleon gravity tests

NASA Astrophysics Data System (ADS)

Cautun, Marius; Paillas, Enrique; Cai, Yan-Chuan; Bose, Sownak; Armijo, Joaquin; Li, Baojiu; Padilla, Nelson

2018-05-01

We present a systematic comparison of several existing and new void-finding algorithms, focusing on their potential power to test a particular class of modified gravity models - chameleon f(R) gravity. These models deviate from standard general relativity (GR) more strongly in low-density regions and thus voids are a promising venue to test them. We use halo occupation distribution (HOD) prescriptions to populate haloes with galaxies, and tune the HOD parameters such that the galaxy two-point correlation functions are the same in both f(R) and GR models. We identify both three-dimensional (3D) voids and two-dimensional (2D) underdensities in the plane of the sky to find the same void abundance and void galaxy number density profiles across all models, which suggests that they do not contain much information beyond galaxy clustering. However, the underlying void dark matter density profiles are significantly different, with f(R) voids being more underdense than GR ones, which leads to f(R) voids having a larger tangential shear signal than their GR analogues. We investigate the potential of each void finder to test f(R) models with near-future lensing surveys such as EUCLID and LSST. The 2D voids have the largest power to probe f(R) gravity, with an LSST analysis of tunnel (which is a new type of 2D underdensity introduced here) lensing distinguishing at 80 and 11σ (statistical error) f(R) models with parameters, |fR0| = 10-5 and 10-6, from GR.

HPA axis dysregulation and behavioral analysis of mouse mutants with altered GR or MR function

PubMed Central

Kolber, Benedict J.; Wieczorek, Lindsay; Muglia, Louis J.

2009-01-01

Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To properly understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that limbic MRs also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors. PMID:18609295

GrDHP: a general utility function representation for dual heuristic dynamic programming.

PubMed

Ni, Zhen; He, Haibo; Zhao, Dongbin; Xu, Xin; Prokhorov, Danil V

2015-03-01

A general utility function representation is proposed to provide the required derivable and adjustable utility function for the dual heuristic dynamic programming (DHP) design. Goal representation DHP (GrDHP) is presented with a goal network being on top of the traditional DHP design. This goal network provides a general mapping between the system states and the derivatives of the utility function. With this proposed architecture, we can obtain the required derivatives of the utility function directly from the goal network. In addition, instead of a fixed predefined utility function in literature, we conduct an online learning process for the goal network so that the derivatives of the utility function can be adaptively tuned over time. We provide the control performance of both the proposed GrDHP and the traditional DHP approaches under the same environment and parameter settings. The statistical simulation results and the snapshot of the system variables are presented to demonstrate the improved learning and controlling performance. We also apply both approaches to a power system example to further demonstrate the control capabilities of the GrDHP approach.

Shear Viscosity Coefficient of 5d Liquid Transition Metals

NASA Astrophysics Data System (ADS)

Thakor, P. B.; Sonvane, Y. A.; Gajjar, P. N.; Jani, A. R.

2011-07-01

In the present paper we have calculated shear viscosity coefficient (η) of 5 d liquid transition metals. To calculate effective pair potential ν(r) and pair distribution function g(r) we have used our own newly constructed model potential and Percus- Yevick hard sphere (PYHS) structure factor S(q) respectively. We have also investigated the effect of different correction function like Hartree (H), Taylor (T) and Sarkar et al. (S) on shear viscosity coefficient (η). Our newly constructed model potential successfully explains the shear viscosity coefficient (η) of 5 d liquid transition metals.

Longitudinal changes in glucocorticoid receptor exon 1F methylation and psychopathology after military deployment

PubMed Central

Schür, R R; Boks, M P; Rutten, B P F; Daskalakis, N P; de Nijs, L; van Zuiden, M; Kavelaars, A; Heijnen, C J; Joëls, M; Kahn, R S; Geuze, E; Vermetten, E; Vinkers, C H

2017-01-01

Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology. PMID:28742078

Structural and functional diversity of CLAVATA3/ESR (CLE)-like genes from the potato cyst nematode Globodera rostochiensis.

PubMed

Lu, Shun-Wen; Chen, Shiyan; Wang, Jianying; Yu, Hang; Chronis, Demosthenis; Mitchum, Melissa G; Wang, Xiaohong

2009-09-01

Plant CLAVATA3/ESR-related (CLE) peptides have diverse roles in plant growth and development. Here, we report the isolation and functional characterization of five new CLE genes from the potato cyst nematode Globodera rostochiensis. Unlike typical plant CLE peptides that contain a single CLE motif, four of the five Gr-CLE genes encode CLE proteins with multiple CLE motifs. These Gr-CLE genes were found to be specifically expressed within the dorsal esophageal gland cell of nematode parasitic stages, suggesting a role for their encoded proteins in plant parasitism. Overexpression phenotypes of Gr-CLE genes in Arabidopsis mimicked those of plant CLE genes, and Gr-CLE proteins could rescue the Arabidopsis clv3-2 mutant phenotype when expressed within meristems. A short root phenotype was observed when synthetic GrCLE peptides were exogenously applied to roots of Arabidopsis or potato similar to the overexpression of Gr-CLE genes in Arabidopsis and potato hairy roots. These results reveal that G. rostochiensis CLE proteins with either single or multiple CLE motifs function similarly to plant CLE proteins and that CLE signaling components are conserved in both Arabidopsis and potato roots. Furthermore, our results provide evidence to suggest that the evolution of multiple CLE motifs may be an important mechanism for generating functional diversity in nematode CLE proteins to facilitate parasitism.

The enhanced efficiency of graphene-silicon solar cells by electric field doping.

PubMed

Yu, Xuegong; Yang, Lifei; Lv, Qingmin; Xu, Mingsheng; Chen, Hongzheng; Yang, Deren

2015-04-28

The graphene-silicon (Gr-Si) Schottky junction solar cell has been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the low Gr-Si Schottky barrier height largely limits the power conversion efficiency of Gr-Si solar cells. Here, we demonstrate that electric field doping can be used to tune the work function of a Gr film and therefore improve the photovoltaic performance of the Gr-Si solar cell effectively. The electric field doping effects can be achieved either by connecting the Gr-Si solar cell to an external power supply or by polarizing a ferroelectric polymer layer integrated in the Gr-Si solar cell. Exploration of both of the device architecture designs showed that the power conversion efficiency of Gr-Si solar cells is more than twice of the control Gr-Si solar cells. Our study opens a new avenue for improving the performance of Gr-Si solar cells.

Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for Optimal Bactericidal Activity.

PubMed

Xavier, Gabriel R S; Carmona-Ribeiro, Ana M

2017-12-02

Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus . The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.

Analytical pair correlations in ideal quantum gases: temperature-dependent bunching and antibunching.

PubMed

Bosse, J; Pathak, K N; Singh, G S

2011-10-01

The fluctuation-dissipation theorem together with the exact density response spectrum for ideal quantum gases has been utilized to yield a new expression for the static structure factor, which we use to derive exact analytical expressions for the temperature-dependent pair distribution function g(r) of the ideal gases. The plots of bosonic and fermionic g(r) display "Bose pile" and "Fermi hole" typically akin to bunching and antibunching as observed experimentally for ultracold atomic gases. The behavior of spin-scaled pair correlation for fermions is almost featureless, but bosons show a rich structure including long-range correlations near T(c). The coherent state at T=0 shows no correlation at all, just like single-mode lasers. The depicted decreasing trend in correlation with decrease in temperature for T

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

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

Carroll, Sean Michael; Ortlund, Eric A; Thornton, Joseph W.

2012-03-16

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functionsmore » of GRs - reduced sensitivity to all hormones and increased selectivity for glucocorticoids - are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR-MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and function and reinforce the importance of permissive mutations in protein evolution.« less

Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.

PubMed

von Geldern, Thomas W; Tu, Noah; Kym, Philip R; Link, James T; Jae, Hwan-Soo; Lai, Chunqiu; Apelqvist, Theresa; Rhonnstad, Patrik; Hagberg, Lars; Koehler, Konrad; Grynfarb, Marlena; Goos-Nilsson, Annika; Sandberg, Johnny; Osterlund, Marie; Barkhem, Tomas; Höglund, Marie; Wang, Jiahong; Fung, Steven; Wilcox, Denise; Nguyen, Phong; Jakob, Clarissa; Hutchins, Charles; Färnegårdh, Mathias; Kauppi, Björn; Ohman, Lars; Jacobson, Peer B

2004-08-12

Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes. Copyright 2004 American Chemical Society

Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development

PubMed Central

Mueller, Kristina M.; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P.; Moriggl, Richard

2012-01-01

Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5–GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development. PMID:22564914

Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis.

PubMed

Müllers, Erik; Uhlig, Tobias; Stirnnagel, Kristin; Fiebig, Uwe; Zentgraf, Hanswalter; Lindemann, Dirk

2011-02-01

Prototype foamy virus (PFV) Gag lacks the characteristic orthoretroviral Cys-His motifs that are essential for various steps of the orthoretroviral replication cycle, such as RNA packaging, reverse transcription, infectivity, integration, and viral assembly. Instead, it contains three glycine-arginine-rich boxes (GR boxes) in its C terminus that putatively represent a functional equivalent. We used a four-plasmid replication-deficient PFV vector system, with uncoupled RNA genome packaging and structural protein translation, to analyze the effects of deletion and various substitution mutations within each GR box on particle release, particle-associated protein composition, RNA packaging, DNA content, infectivity, particle morphology, and intracellular localization. The degree of viral particle release by all mutants was similar to that of the wild type. Only minimal effects on Pol encapsidation, exogenous reverse transcriptase (RT) activity, and genomic viral RNA packaging were observed. In contrast, particle-associated DNA content and infectivity were drastically reduced for all deletion mutants and were undetectable for all alanine substitution mutants. Furthermore, GR box I mutants had significant changes in particle morphology, and GR box II mutants lacked the typical nuclear localization pattern of PFV Gag. Finally, it could be shown that GR boxes I and III, but not GR box II, can functionally complement each other. It therefore appears that, similar to the orthoretroviral Cys-His motifs, the PFV Gag GR boxes are important for RNA encapsidation, genome reverse transcription, and virion infectivity as well as for particle morphogenesis.

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome.

PubMed

Macut, Djuro; Božić Antić, Ivana; Nestorov, Jelena; Topalović, Vladanka; Bjekić Macut, Jelica; Panidis, Dimitrios; Kastratović Kotlica, Biljana; Papadakis, Efstathios; Matić, Gordana; Vojnović Milutinović, Danijela

2015-01-01

Most women with PCOS have increased adrenal androgen production, enhanced peripheral metabolism of cortisol and elevation in urinary excretion of its metabolites. Increased cortisol clearance in PCOS is followed by a compensatory overdrive of the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that oral contraceptives containing ethinylestradiol and drospirenone (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and function and thus affect HPA axis activity in PCOS patients. We analyzed 12 women with PCOS (age 24.17±4.88 years; body mass index 22.05±3.97 kg/m²) treated for 12 months with EE-DRSP and 20 BMI matched controls. In all subjects testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal and after dexamethasone), concentrations of GR protein, phospo-GR211 protein, number of GR per cell (B(max) and its equilibrium dissociation constant (K(D)) were measured. Before treatment, increased concentrations of testosterone and DHEAS (p<0.001, respectively), unaltered basal cortisol and an increased sensitivity (p<0.05) of the HPA axis to dexamethasone were observed in PCOS women in comparison to controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS women. There were no changes in GR protein concentration, GR phosphorylation nor in the receptor functional parameters B(max) and K(D) in women with PCOS before and after the therapy, and in comparison to controls. Prolonged treatment with EE-DRSP in PCOS women decreased serum androgens and increased cortisol in the presence of decreased sensitivity of the HPA axis and did not exert changes in GR expression and function.

Energy distributions of Bianchi type-VI h Universe in general relativity and teleparallel gravity

NASA Astrophysics Data System (ADS)

Özkurt, Ş.; eref; Aygün, Sezg&idot; n.

2017-04-01

In this paper, we have investigated the energy and momentum density distributions for the inhomogeneous generalizations of homogeneous Bianchi type-VI h metric with Einstein, Bergmann-Thomson, Landau-Lifshitz, Papapetrou, Tolman and Møller prescriptions in general relativity (GR) and teleparallel gravity (TG). We have found exactly the same results for Einstein, Bergmann-Thomson and Landau-Lifshitz energy-momentum distributions in Bianchi type-VI h metric for different gravitation theories. The energy-momentum distributions of the Bianchi type- VI h metric are found to be zero for h = -1 in GR and TG. However, our results agree with Tripathy et al, Tryon, Rosen and Aygün et al.

Maltose-Binding Protein Enhances Secretion of Recombinant Human Granzyme B Accompanied by In Vivo Processing of a Precursor MBP Fusion Protein

PubMed Central

Dälken, Benjamin; Jabulowsky, Robert A.; Oberoi, Pranav; Benhar, Itai; Wels, Winfried S.

2010-01-01

Background The apoptosis-inducing serine protease granzyme B (GrB) is an important factor contributing to lysis of target cells by cytotoxic lymphocytes. Expression of enzymatically active GrB in recombinant form is a prerequisite for functional analysis and application of GrB for therapeutic purposes. Methods and Findings We investigated the influence of bacterial maltose-binding protein (MBP) fused to GrB via a synthetic furin recognition motif on the expression of the MBP fusion protein also containing an N-terminal α-factor signal peptide in the yeast Pichia pastoris. MBP markedly enhanced the amount of GrB secreted into culture supernatant, which was not the case when GrB was fused to GST. MBP-GrB fusion protein was cleaved during secretion by an endogenous furin-like proteolytic activity in vivo, liberating enzymatically active GrB without the need of subsequent in vitro processing. Similar results were obtained upon expression of a recombinant fragment of the ErbB2/HER2 receptor protein or GST as MBP fusions. Conclusions Our results demonstrate that combination of MBP as a solubility enhancer with specific in vivo cleavage augments secretion of processed and functionally active proteins from yeast. This strategy may be generally applicable to improve folding and increase yields of recombinant proteins. PMID:21203542

Preparation and Characterization of Nanoparticle β-Cyclodextrin:Geraniol Inclusion Complexes.

PubMed

Hadian, Zahra; Maleki, Majedeh; Abdi, Khosro; Atyabi, Fatemeh; Mohammadi, Abdoreza; Khaksar, Ramin

2018-01-01

The aim of the present study was to formulate β-cyclodextrin (β-CD) nanoparticles loaded with geraniol (GR) essential oil (EO) with appropriate physicochemical properties. Complexation of GR with β-CD was optimized by evaluation of four formulations, using the co-precipitation method, and the encapsulation efficiency (EE), loading, size, particle size distribution (PDI) and zeta potential were investigated. Further characterization was performed with nuclear magnetic resonance spectroscopy ( 1 H NMR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and infra-red (IR) spectroscopy analysis. Results showed that the physicochemical properties of the nanoparticles were affected by GR content in formulations that yielded nanoscale-size particles ranging from 111 to 258 nm. The highest encapsulation efficiency (79.4 ± 5.4%) was obtained when the molar ratio of EO to β-CD was 0.44: 0.13 with negative zeta potential (-21.1 ± 0.5 mV). The 1 H-NMR spectrum confirmed the formation structure of the EO and β-CD nanoparticle complex. Complexation with geraniol resulted in changes of IR profile, NMR chemical shifts, DSC properties, and SEM of β-cyclodextrin. Inclusion complex of essential oil with β-cyclodextrin was considered as promising bioactive materials for designing functional food.

Preparation and Characterization of Nanoparticle β-Cyclodextrin:Geraniol Inclusion Complexes

PubMed Central

Hadian, Zahra; Maleki, Majedeh; Abdi, Khosro; Atyabi, Fatemeh; Mohammadi, Abdoreza; Khaksar, Ramin

2018-01-01

The aim of the present study was to formulate β-cyclodextrin (β-CD) nanoparticles loaded with geraniol (GR) essential oil (EO) with appropriate physicochemical properties. Complexation of GR with β-CD was optimized by evaluation of four formulations, using the co-precipitation method, and the encapsulation efficiency (EE), loading, size, particle size distribution (PDI) and zeta potential were investigated. Further characterization was performed with nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and infra-red (IR) spectroscopy analysis. Results showed that the physicochemical properties of the nanoparticles were affected by GR content in formulations that yielded nanoscale-size particles ranging from 111 to 258 nm. The highest encapsulation efficiency (79.4 ± 5.4%) was obtained when the molar ratio of EO to β-CD was 0.44: 0.13 with negative zeta potential (-21.1 ± 0.5 mV). The 1H-NMR spectrum confirmed the formation structure of the EO and β-CD nanoparticle complex. Complexation with geraniol resulted in changes of IR profile, NMR chemical shifts, DSC properties, and SEM of β-cyclodextrin. Inclusion complex of essential oil with β-cyclodextrin was considered as promising bioactive materials for designing functional food.

Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

Constraints on deviations from ΛCDM within Horndeski gravity

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

Bellini, Emilio; Cuesta, Antonio J.; Jimenez, Raul

2016-02-01

Recent anomalies found in cosmological datasets such as the low multipoles of the Cosmic Microwave Background or the low redshift amplitude and growth of clustering measured by e.g., abundance of galaxy clusters and redshift space distortions in galaxy surveys, have motivated explorations of models beyond standard ΛCDM. Of particular interest are models where general relativity (GR) is modified on large cosmological scales. Here we consider deviations from ΛCDM+GR within the context of Horndeski gravity, which is the most general theory of gravity with second derivatives in the equations of motion. We adopt a parametrization in which the four additional Horndeskimore » functions of time α{sub i}(t) are proportional to the cosmological density of dark energy Ω{sub DE}(t). Constraints on this extended parameter space using a suite of state-of-the art cosmological observations are presented for the first time. Although the theory is able to accommodate the low multipoles of the Cosmic Microwave Background and the low amplitude of fluctuations from redshift space distortions, we find no significant tension with ΛCDM+GR when performing a global fit to recent cosmological data and thus there is no evidence against ΛCDM+GR from an analysis of the value of the Bayesian evidence ratio of the modified gravity models with respect to ΛCDM, despite introducing extra parameters. The posterior distribution of these extra parameters that we derive return strong constraints on any possible deviations from ΛCDM+GR in the context of Horndeski gravity. We illustrate how our results can be applied to a more general frameworks of modified gravity models.« less

Step-by-step integration for fractional operators

NASA Astrophysics Data System (ADS)

Colinas-Armijo, Natalia; Di Paola, Mario

2018-06-01

In this paper, an approach based on the definition of the Riemann-Liouville fractional operators is proposed in order to provide a different discretisation technique as alternative to the Grünwald-Letnikov operators. The proposed Riemann-Liouville discretisation consists of performing step-by-step integration based upon the discretisation of the function f(t). It has been shown that, as f(t) is discretised as stepwise or piecewise function, the Riemann-Liouville fractional integral and derivative are governing by operators very similar to the Grünwald-Letnikov operators. In order to show the accuracy and capabilities of the proposed Riemann-Liouville discretisation technique and the Grünwald-Letnikov discrete operators, both techniques have been applied to: unit step functions, exponential functions and sample functions of white noise.

The Microtubule-Associated Protein Doublecortin-Like Regulates the Transport of the Glucocorticoid Receptor in Neuronal Progenitor Cells

PubMed Central

Fitzsimons, Carlos P.; Ahmed, Suaad; Wittevrongel, Christiaan F. W.; Schouten, Theo G.; Dijkmans, Thomas F.; Scheenen, Wim J. J. M.; Schaaf, Marcel J. M.; Ronald de Kloet, E.; Vreugdenhil, Erno

2008-01-01

In neuronal cells, activated glucocorticoid receptor (GR) translocates to the nucleus guided by the cytoskeleton. However, the detailed mechanisms underlying GR translocation remain unclear. Using gain and loss of function studies, we report here for the first time that the microtubule-associated protein doublecortin-like (DCL) controls GR translocation to the nucleus. DCL overexpression in COS-1 cells, neuroblastoma cells, and rat hippocampus organotypic slice cultures impaired GR translocation and decreased GR-dependent transcriptional activity, measured by a specific reporter gene assay, in COS-1 cells. Moreover, DCL and GR directly interact on microtubule bundles formed by DCL overexpression. A C-terminal truncated DCL with conserved microtubule-bundling activity did not influence GR translocation. In N1E-115 mouse neuroblastoma cells and neuronal progenitor cells in rat hippocampus organotypic slice cultures, laser-scanning confocal microscopy showed colabeling of endogenously expressed DCL and GR. In these systems, RNA-interference-mediated DCL knockdown hampered GR translocation. Thus, we conclude that DCL expression is tightly regulated to adequately control GR transport. Because DCL is primarily expressed in neuronal progenitor cells, our results introduce this microtubule-associated protein as a new modulator of GR signaling in this cell type and suggest the existence of cell-specific mechanisms regulating GR translocation to the nucleus. PMID:17975023

Is Electromagnetic Gravity Control Possible?

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

Vargas, Jose G.; Torr, Douglas G.

2004-02-04

We study the interplay of Einstein's Gravitation (GR) and Maxwell's Electromagnetism, where the distribution of energy-momentum is not presently known (The Feynman Lectures, Vol 2, Chapter 27, section 4). As Feynman himself stated, one might in principle use Einstein's equations of GR to find such a distribution. GR (born in 1915) presently uses the Levi-Civita connection, LCC (the LCC was born two years after GR as a new concept, and not just as the pre-existing Christoffel symbols that represent it). Around 1927, Einstein proposed for physics an alternative to the LCC that constitutes a far more sensible and powerful affinemore » enrichment of metric Riemannian geometry. It is called teleparallelism (TP). Its Finslerian version (i.e. in the space-time-velocity arena) permits an unequivocal identification of the EM field as a geometric quantity. This in turn permits one to identify a completely geometric set of Einstein equations from curvature equations. From their right hand side, one may obtain the actual distribution of EM energy-momentum. It is consistent with Maxwell's equations, since these also are implied by the equations of structure of TP. We find that the so-far-unknown terms in this distribution amount to a total differential and do not, therefore, alter the value of the total EM energy-momentum. And yet these extra terms are at macroscopic distances enormously larger than the standard quadratic terms. This allows for the generation of measurable gravitational fields by EM fields. We thus answer affirmatively the question of the title.« less

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

PubMed Central

Whirledge, Shannon D.; Oakley, Robert H.; Myers, Page H.; Lydon, John P.; DeMayo, Francesco; Cidlowski, John A.

2015-01-01

In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic–pituitary–adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PRcre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions. PMID:26598666

Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.

PubMed

Lopez-Gonzalez, Rodrigo; Lu, Yubing; Gendron, Tania F; Karydas, Anna; Tran, Helene; Yang, Dejun; Petrucelli, Leonard; Miller, Bruce L; Almeida, Sandra; Gao, Fen-Biao

2016-10-19

GGGGCC repeat expansions in C9ORF72 are the most common genetic cause of both ALS and FTD. To uncover underlying pathogenic mechanisms, we found that DNA damage was greater, in an age-dependent manner, in motor neurons differentiated from iPSCs of multiple C9ORF72 patients than control neurons. Ectopic expression of the dipeptide repeat (DPR) protein (GR) 80 in iPSC-derived control neurons increased DNA damage, suggesting poly(GR) contributes to DNA damage in aged C9ORF72 neurons. Oxidative stress was also increased in C9ORF72 neurons in an age-dependent manner. Pharmacological or genetic reduction of oxidative stress partially rescued DNA damage in C9ORF72 neurons and control neurons expressing (GR) 80 or (GR) 80 -induced cellular toxicity in flies. Moreover, interactome analysis revealed that (GR) 80 preferentially bound to mitochondrial ribosomal proteins and caused mitochondrial dysfunction. Thus, poly(GR) in C9ORF72 neurons compromises mitochondrial function and causes DNA damage in part by increasing oxidative stress, revealing another pathogenic mechanism in C9ORF72-related ALS and FTD. Copyright © 2016 Elsevier Inc. All rights reserved.

The Progestin-Only Contraceptive Medroxyprogesterone Acetate, but Not Norethisterone Acetate, Enhances HIV-1 Vpr-Mediated Apoptosis in Human CD4+ T Cells through the Glucocorticoid Receptor

PubMed Central

Tomasicchio, Michele; Avenant, Chanel; Du Toit, Andrea; Ray, Roslyn M.; Hapgood, Janet P.

2013-01-01

The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. The HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of the GR. Glucocorticoids (GCs) and Vpr have been reported to induce apoptosis in various cells, including T-cells. We have previously shown that the injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial to full agonist for the GR, unlike norethisterone acetate (NET-A). We investigated the functional cross talk between the GR and Vpr in inducing apoptosis in CD4+ T-cells, in the absence and presence of GCs and these progestins, as well as progesterone. By using flow cytometry, we show that, in contrast to NET-A and progesterone, the synthetic GR ligand dexamethasone (Dex), cortisol and MPA induce apoptosis in primary CD4+ T-cells. Furthermore, the C-terminal part of the Vpr peptide, or HIV-1 pseudovirus, together with Dex or MPA further increased the apoptotic phenotype, unlike NET-A and progesterone. By a combination of Western blotting, PCR and the use of receptor- selective agonists, we provide evidence that the GR and the estrogen receptor are the only steroid receptors expressed in peripheral blood mononuclear cells. These results, together with the findings that RU486, a GR antagonist, prevents Dex-, MPA- and Vpr-mediated apoptosis, provide evidence for the first time that GR agonists or partial agonists increase apoptosis in primary CD4+ T-cells via the GR. We show that apoptotic induction involves differential expression of key apoptotic genes by both Vpr and GCs/MPA. This work suggests that contraceptive doses of MPA but not NET-A or physiological doses of progesterone could potentially accelerate depletion of CD4+ T-cells in a GR-dependent fashion in HIV-1 positive women, thereby contributing to immunodeficiency. The results imply that choice of progestin used in contraception may be critical to susceptibility and progression of diseases such as HIV-1. PMID:23658782

Glucocorticoid receptor represses brain-derived neurotrophic factor expression in neuron-like cells.

PubMed

Chen, Hui; Lombès, Marc; Le Menuet, Damien

2017-04-12

Brain-derived neurotrophic factor (BDNF) is involved in many functions such as neuronal growth, survival, synaptic plasticity and memorization. Altered expression levels are associated with many pathological situations such as depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has been proposed that GR could be a regulator of BDNF expression, however the molecular mechanisms involved have not been clearly defined yet. Herein, we analyzed the effect of a GC agonist dexamethasone (DEX) on BDNF expression in mouse neuronal primary cultures and in the newly characterized, mouse hippocampal BZ cell line established by targeted oncogenesis. Mouse Bdnf gene exhibits a complex genomic structure with 8 untranslated exons (I to VIII) splicing onto one common and unique coding exon IX. We found that DEX significantly downregulated total BDNF mRNA expression by around 30%. Expression of the highly expressed exon IV and VI containing transcripts was also reduced by DEX. The GR antagonist RU486 abolished this effect, which is consistent with specific GR-mediated action. Transient transfection assays allowed us to define a short 275 bp region within exon IV promoter responsible for GR-mediated Bdnf repression. Chromatin immunoprecipitation experiments demonstrated GR recruitment onto this fragment, through unidentified transcription factor tethering. Altogether, GR downregulates Bdnf expression through direct binding to Bdnf regulatory sequences. These findings bring new insights into the crosstalk between GR and BDNF signaling pathways both playing a major role in physiology and pathology of the central nervous system.

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

PubMed

Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

2013-11-01

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise

PubMed Central

Charbonneau, Alexandre; Unson, Cecilia G; Lavoie, Jean-Marc

2007-01-01

Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (sd) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-α, suggesting a role of PKC-α in GR desensitization. EX increased significantly PKC-α protein content in both diets, suggesting a role of PKC-α in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-α. PMID:17053032

Mechanisms for the Evolution of a Derived Function in the Ancestral Glucocorticoid Receptor

PubMed Central

Carroll, Sean Michael; Ortlund, Eric A.; Thornton, Joseph W.

2011-01-01

Understanding the genetic, structural, and biophysical mechanisms that caused protein functions to evolve is a central goal of molecular evolutionary studies. Ancestral sequence reconstruction (ASR) offers an experimental approach to these questions. Here we use ASR to shed light on the earliest functions and evolution of the glucocorticoid receptor (GR), a steroid-activated transcription factor that plays a key role in the regulation of vertebrate physiology. Prior work showed that GR and its paralog, the mineralocorticoid receptor (MR), duplicated from a common ancestor roughly 450 million years ago; the ancestral functions were largely conserved in the MR lineage, but the functions of GRs—reduced sensitivity to all hormones and increased selectivity for glucocorticoids—are derived. Although the mechanisms for the evolution of glucocorticoid specificity have been identified, how reduced sensitivity evolved has not yet been studied. Here we report on the reconstruction of the deepest ancestor in the GR lineage (AncGR1) and demonstrate that GR's reduced sensitivity evolved before the acquisition of restricted hormone specificity, shortly after the GR–MR split. Using site-directed mutagenesis, X-ray crystallography, and computational analyses of protein stability to recapitulate and determine the effects of historical mutations, we show that AncGR1's reduced ligand sensitivity evolved primarily due to three key substitutions. Two large-effect mutations weakened hydrogen bonds and van der Waals interactions within the ancestral protein, reducing its stability. The degenerative effect of these two mutations is extremely strong, but a third permissive substitution, which has no apparent effect on function in the ancestral background and is likely to have occurred first, buffered the effects of the destabilizing mutations. Taken together, our results highlight the potentially creative role of substitutions that partially degrade protein structure and function and reinforce the importance of permissive mutations in protein evolution. PMID:21698144

Reverse Monte Carlo simulation of Se{sub 80}Te{sub 20} and Se{sub 80}Te{sub 15}Sb{sub 5} glasses

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

Abdel-Baset, A. M.; Rashad, M.; Moharram, A. H.

2013-12-16

Two-dimensional Monte Carlo of the total pair distribution functions g(r) is determined for Se{sub 80}Te{sub 20} and Se{sub 80}Te{sub 15}Sb{sub 5} alloys, and then it used to assemble the three-dimensional atomic configurations using the reverse Monte Carlo simulation. The partial pair distribution functions g{sub ij}(r) indicate that the basic structure unit in the Se{sub 80}Te{sub 15}Sb{sub 5} glass is di-antimony tri-selenide units connected together through Se-Se and Se-Te chain. The structure of Se{sub 80}Te{sub 20} alloys is a chain of Se-Te and Se-Se in addition to some rings of Se atoms.

Some Applications of Gröbner Bases in Robotics and Engineering

NASA Astrophysics Data System (ADS)

Abłamowicz, Rafał

Gröbner bases in polynomial rings have numerous applications in geometry, applied mathematics, and engineering. We show a few applications of Gröbner bases in robotics, formulated in the language of Clifford algebras, and in engineering to the theory of curves, including Fermat and Bézier cubics, and interpolation functions used in finite element theory.

Molecular characterization and functional analysis of ubiquitin extension genes from the potato cyst nematode Globodera rostochiensis

USDA-ARS?s Scientific Manuscript database

Ubiquitin is a highly conserved 76-amino acid protein found in every eukaryotic cell. It has been proposed that ubiquitin has many cellular functions including DNA repair, transcription regulation, regulation of cell cycle and apoptosis. We identified two ubiquitin extension genes (Gr-Ubi1 and Gr-Ub...

Formation of Supported Graphene Oxide: Evidence for Enolate Species

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

Novotny, Zbynek; Nguyen, Manh-Thuong; Netzer, Falko P.

Graphene oxides are promising materials for novel electronic devices or anchoring of the active sites for catalytic applications. Here we focus on understanding the oxygen binding on different regions of graphene (Gr) on Ru(0001). Differences in the Gr/Ru lattices result in the superstructure, which offers an array of distinct adsorption sites. We employ scanning tunneling microscopy and density functional theory to map out the chemical identity and stability of prepared oxygen functionalities in different Gr regions. We demonstrate that in the regions that are close to the metal substrate, the terminally-bonded enolate groups are strongly preferred over bridge-bonded epoxy configurations.more » No oxygen species are observed on the graphene regions that are far from the underlying Ru, indicating their low relative stability. This study provides a clear fundamental basis for understanding the structural and electronic factors that affect the stability of enolate and epoxy species as a function of Gr/Ru interactions.« less

The FKBP51-Glucocorticoid Receptor Balance in Stress-Related Mental Disorders.

PubMed

Fries, Gabriel R; Gassen, Nils C; Schmidt, Ulrike; Rein, Theo

2015-01-01

The immunophilin FK506 binding protein 51 (FKBP51) has emerged as one of the most intensely investigated proteins in stress-related mental disorders. It was originally characterized as Hsp90 cochaperone and part of the receptor-chaperone heterocomplex that governs the activity of steroid receptors. It turned out that the presence of FKBP51 in this heterocomplex leads to diminished activity of the corticosteroid receptors. In particular, based on its inhibitory action on the glucocorticoid receptor (GR), FKBP51 was included in a candidate gene approach to discover gene polymorphisms that might be relevant for the development and treatment of major depression. The discovery that polymorphisms in the gene coding for FKBP51 were linked to the treatment response of depressed patients intensified the research on the role of FKBP51 in stress-related diseases worldwide. It has become evident that FKBP51 is not only a regulator of GR action, but also a GR target. The function of this ultrashort intracellular feedback loop is critically important for cellular and physiological stress regulation as it does not only calibrate the function of GR, but also the levels of FKBP51. Given the pleiotropic functions of FKBP51, its levels might be equally important for mental disorders as GR function and hence for the development of potential FKBP51 drug targets.

Impact of the maze operation combined with left-sided valve surgery on the change in tricuspid regurgitation over time.

PubMed

Kim, Hyung-Kwan; Kim, Yong-Jin; Kim, Kwang-Il; Jo, Sang-Ho; Kim, Ki-Bong; Ahn, Hyuk; Sohn, Dae-Won; Oh, Byung-Hee; Lee, Myoung-Mook; Park, Young-Bae; Choi, Yun-Shik

2005-08-30

Atrial fibrillation (AF) has been reported to be a predisposing factor for the progression of TR in patients with previous mitral or combined mitral/aortic valve surgery. We hypothesized that the maze operation (MAZE) can prevent the progression of tricuspid regurgitation (TR) in these patients. We analyzed 170 patients (age, 45.5+/-10.9 years) who had undergone mitral or combined mitral/aortic valve surgery. On the basis of preoperative rhythm, patients were divided into 3 groups; GrI was composed of 44 patients with sinus rhythm, GrII of 48 who had undergone MAZE, and GrIII of 78 with AF who had not undergone MAZE. Echocardiographic examinations were performed before, immediately after, and 92.2+/-17.2 (range, 50 to 131) months after surgery. Preoperative and immediate postoperative clinical and echocardiographic parameters were similar among the groups. Insignificant TR at the immediate postoperative examination worsened with time in 7.3% of GrI (3 of 41), 12.8% of GrII (6 of 47), and 38.8% of GrIII (26 of 67) patients at the final examination (P=0.63 for GrI versus GrII, P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII). The incidence of significant TR at the final echocardiographic examination was higher in GrIII (39.7%) compared with GrI (9.1%) and GrII (14.6%) (P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII), whereas GrI and GrII did not show any difference (P=0.63). By multivariate analysis, the only factor identified to prevent TR progression was the group factor (GrI and GrII versus GrIII, P=0.002 and P=0.005, respectively). In a subgroup analysis of GrII according to the presence or absence of atrial mechanical activity, the absence of atrial mechanical activity was identified as an independent parameter for the progression of TR (P=0.001). AF predisposes patients undergoing mitral valve surgery to the progression of TR, which can be prevented by MAZE. This additional benefit of MAZE is largely dependent on the restoration and maintenance of atrial mechanical function.

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

PubMed Central

Michailidou, Z.; Carter, R. N.; Marshall, E.; Sutherland, H. G.; Brownstein, D. G.; Owen, E.; Cockett, K.; Kelly, V.; Ramage, L.; Al-Dujaili, E. A. S.; Ross, M.; Maraki, I.; Newton, K.; Holmes, M. C.; Seckl, J. R.; Morton, N. M.; Kenyon, C. J.; Chapman, K. E.

2008-01-01

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GRβgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.—Michailidou, Z., Carter, R. N., Marshall, E., Sutherland, H. G., Brownstein, D. G., Owen, E., Cockett, K., Kelly, V., Ramage, L., Al-Dujaili, E. A. S., Ross, M., Maraki, I., Newton, K., Holmes, M. C., Seckl, J. R., Morton, N. M., Kenyon, C. J., Chapman, K. E. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet. PMID:18697839

Revealing modified gravity signals in matter and halo hierarchical clustering

NASA Astrophysics Data System (ADS)

Hellwing, Wojciech A.; Koyama, Kazuya; Bose, Benjamin; Zhao, Gong-Bo

2017-07-01

We use a set of N-body simulations employing a modified gravity (MG) model with Vainshtein screening to study matter and halo hierarchical clustering. As test-case scenarios we consider two normal branch Dvali-Gabadadze-Porrati (nDGP) gravity models with mild and strong growth rate enhancement. We study higher-order correlation functions ξn(R ) up to n =9 and associated reduced cumulants Sn(R )≡ξn(R )/σ (R )2n -2. We find that the matter probability distribution functions are strongly affected by the fifth force on scales up to 50 h-1 Mpc , and the deviations from general relativity (GR) are maximized at z =0 . For reduced cumulants Sn, we find that at small scales R ≤6 h-1 Mpc the MG is characterized by lower values, with the deviation growing from 7% in the reduced skewness up to even 40% in S5. To study the halo clustering we use a simple abundance matching and divide haloes into thee fixed number density samples. The halo two-point functions are weakly affected, with a relative boost of the order of a few percent appearing only at the smallest pair separations (r ≤5 h-1 Mpc ). In contrast, we find a strong MG signal in Sn(R )'s, which are enhanced compared to GR. The strong model exhibits a >3 σ level signal at various scales for all halo samples and in all cumulants. In this context, we find that the reduced kurtosis to be an especially promising cosmological probe of MG. Even the mild nDGP model leaves a 3 σ imprint at small scales R ≤3 h-1 Mpc , while the stronger model deviates from a GR signature at nearly all scales with a significance of >5 σ . Since the signal is persistent in all halo samples and over a range of scales, we advocate that the reduced kurtosis estimated from galaxy catalogs can potentially constitute a strong MG-model discriminatory as well as GR self-consistency test.

Differential expression of a fructose receptor gene in honey bee workers according to age and behavioral role.

PubMed

Takada, Tomoyuki; Sasaki, Taiyo; Sato, Ryoichi; Kikuta, Shingo; Inoue, Maki N

2018-02-01

Honey bee (Apis mellifera) workers contribute to the maintenance of colonies in various ways. The primary functions of workers are divided into two types depending on age: young workers (nurses) primarily engage in such behaviors as cleaning and food handling within the hive, whereas older workers (foragers) acquire floral nutrients beyond the colony. Concomitant with this age-dependent change in activity, physiological changes occur in the tissues and organs of workers. Nurses supply younger larvae with honey containing high levels of glucose and supply older larvae with honey containing high levels of fructose. Given that nurses must determine both the concentration and type of sugar used in honey, gustatory receptors (Gr) expressed in the chemosensory organs likely play a role in distinguishing between sugars. Glucose is recognized by Gr1 in honey bees (AmGr1); however, it remains unclear which Gr are responsible for fructose recognition. This study aimed to identify fructose receptors in honey bees and reported that AmGr3, when transiently expressed in Xenopus oocytes, responded only to fructose, and to no other sugars. We analyzed expression levels of AmGr3 to identify which tissues and organs of workers are involved in fructose recognition and determined that expression of AmGr3 was particularly high in the antennae and legs of nurses. Our results suggest that nurses use their antennae and legs to recognize fructose, and that AmGr3 functions as an accurate nutrient sensor used to maintain food quality in honey bee hives. © 2017 Wiley Periodicals, Inc.

Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD.

PubMed

Sabbagh, Jonathan J; Cordova, Ricardo A; Zheng, Dali; Criado-Marrero, Marangelie; Lemus, Andrea; Li, Pengfei; Baker, Jeremy D; Nordhues, Bryce A; Darling, April L; Martinez-Licha, Carlos; Rutz, Daniel A; Patel, Shreya; Buchner, Johannes; Leahy, James W; Koren, John; Dickey, Chad A; Blair, Laura J

2018-06-19

Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression.

Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera

NASA Astrophysics Data System (ADS)

Xu, Wei; Anderson, Alisha

2015-04-01

Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors.

Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

PubMed

Hudson, William H; Vera, Ian Mitchelle S de; Nwachukwu, Jerome C; Weikum, Emily R; Herbst, Austin G; Yang, Qin; Bain, David L; Nettles, Kendall W; Kojetin, Douglas J; Ortlund, Eric A

2018-04-06

Glucocorticoids (GCs) are potent repressors of NF-κB activity, making them a preferred choice for treatment of inflammation-driven conditions. Despite the widespread use of GCs in the clinic, current models are inadequate to explain the role of the glucocorticoid receptor (GR) within this critical signaling pathway. GR binding directly to NF-κB itself-tethering in a DNA binding-independent manner-represents the standing model of how GCs inhibit NF-κB-driven transcription. We demonstrate that direct binding of GR to genomic NF-κB response elements (κBREs) mediates GR-driven repression of inflammatory gene expression. We report five crystal structures and solution NMR data of GR DBD-κBRE complexes, which reveal that GR recognizes a cryptic response element between the binding footprints of NF-κB subunits within κBREs. These cryptic sequences exhibit high sequence and functional conservation, suggesting that GR binding to κBREs is an evolutionarily conserved mechanism of controlling the inflammatory response.

Modulation of Kalirin-7 Expression by Hippocampal CA1 5-HT1B Receptors in Spatial Memory Consolidation.

PubMed

Zhou, Meng-He; Sun, Fang-Fang; Xu, Chang; Chen, Hui-Bin; Qiao, Hui; Cai, Xiang; Ma, Xin-Ming; An, Shu-Cheng

2018-06-24

Serotonin 5-HT1B receptors (5-HT1BRs) are distributed in hippocampal CA1 and play a pivotal role in cognitive function. Activation of 5-HT1BRs regulates synaptic plasticity at the excitatory synapses in the hippocampus. However, the role and its underlying mechanism of 5-HT1BR activation-mediated glutamatergic synaptic plasticity in spatial memory are not fully understood. In this study, spatial memory of Sprague-Dawley (SD) rats was assessed in a Morris water maze after bilateral dorsal hippocampal CA1 infusion of the 5-HT1BR antagonist GR55562 (25 μg/μL) or agonist CP93129 (25 μg/μL). GR55562 did not affect the spatial memory acquisition but significantly increased the target quadrant preference during the memory consolidation probe performed 14 d after the training session, while CP93129 impaired the memory consolidation process. Moreover, GR55562 significantly increased, while CP93129 significantly decreased, the density of dendritic spines on the distal apical dendrites of CA1 pyramidal neurons. Furthermore, western blot experiments indicated that GR55562 significantly increased, but CP93129 significantly reduced, the expression of Kalirin-7 (Kal-7), PSD95, and GluA2/3 subunits of AMPA receptors. Our results suggest that Kal-7 and Kal-7-mediatedalteration of AMPA receptor subtype expression may play crucial roles in the impact of hippocampal CA1 5-HT1BR activation on spatial memory consolidation. Copyright © 2018. Published by Elsevier B.V.

GNU Radio Sandia Utilities v. 1.0

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

Gilbert, Jacob; Knee, Peter

This software adds a data handling module to the GNU Radio (GR) software defined radio (SDR) framework as well as some general-purpose function blocks (filters, metadata control, etc). This software is useful for processing bursty RF transmissions with GR, and serves as a base for applying SDR signal processing techniques to a whole burst of data at a time, as opposed to streaming data which GR has been primarily focused around.

Observation of Image Potential State in Oxygen Intercalated Graphene on Iridium by Two-Photon-Photoemission Spectroscopy

NASA Astrophysics Data System (ADS)

Lin, Yi; Li, Yunzhe; Sadowski, Jerzy; Dadap, Jerry; Jin, Wencan; Osgood, Richard

In this talk, we report our experimental results on the first direct observation of image potential state (IPS) in oxygen-intercalated graphene on iridium by two-photo-photoemission spectroscopy. We demonstrate how oxygen intercalation influences the IPS in Gr/Ir and decouples the interlayer interaction. We present measurements of the electronic dispersion and work function in pristine Gr/Ir, oxygen-intercalated Gr/O/Ir, and deintercalated Gr/Ir. LEED patterns are measured during the pristine, oxygen-intercalated, and deintercalated phases of the Gr/Ir sample. Based on these measurements, relative to the pristine case, the work function and the energy location of n =1 IPS relative to the Fermi level increases by 0.39 eV and 0.3 eV, respectively, due to oxygen intercalation, whereas the effective mass of n =1 IPS is hardly influenced by the intercalation process. Moreover, we achieve the quenching and restoration of the resonance from Ir Rashba states to n =1 IPS in Gr/Ir by oxygen intercalation and deintercalation. This work was supported by the DOE, Office of Basic Energy Sciences, Division of MSE under Contract No. DE-FG 02-04-ER-46157. This research used resources of the CFN, which is the U.S. DOE Office of Science User Facility, under Contract No. DE-SC0012704.

A minichaperone-based fusion system for producing insoluble proteins in soluble stable forms.

PubMed

Sharapova, Olga A; Yurkova, Maria S; Fedorov, Alexey N

2016-02-01

We have developed a fusion system for reliable production of insoluble hydrophobic proteins in soluble stable forms. A carrier is thermophilic minichaperone, GroEL apical domain (GrAD), a 15 kDa monomer able to bind diverse protein substrates. The Met-less variant of GrAD has been made for further convenient use of Met-specific CNBr chemical cleavage, if desired. The Met-less GrAD retained stability and solubility of the original protein. Target polypeptides can be fused to either C-terminus or N-terminus of GrAD. The system has been tested with two unrelated insoluble proteins fused to the C-terminus of GrAD. One of the proteins was also fused to GrAD N-terminus. The fusions formed inclusion bodies at 25°C and above and were partly soluble only at lower expression temperatures. Most importantly, however, after denaturation in urea, all fusions without exception were completely renatured in soluble stable forms that safely survived freezing-thawing as well as lyophilization. All fusions for both tested target proteins retained solubility at high concentrations for days. Functional analysis revealed that a target protein may retain functionality in the fusion. Convenience features include potential thermostability of GrAD fusions, capacity for chemical and enzymatic cleavage of a target and His6 tag for purification. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Simplicial Palatini action

NASA Astrophysics Data System (ADS)

Khatsymovsky, V. M.

2018-01-01

We consider the piecewise flat spacetime and a simplicial analog of the Palatini form of the general relativity (GR) action where the discrete Christoffel symbols are given on the tetrahedra as variables that are independent of the metric. Excluding these variables with the help of the equations of motion gives exactly the Regge action. This paper continues our previous work. Now, we include the parity violation term and the analog of the Barbero-Immirzi parameter introduced in the orthogonal connection form of GR. We consider the path integral and the functional integration over the connection. The result of the latter (for certain limiting cases of some parameters) is compared with the earlier found result of the functional integration over the connection for the analogous orthogonal connection representation of Regge action. These results, mainly as some measures on the lengths/areas, are discussed for the possibility of the diagram technique where the perturbative diagrams for the Regge action calculated using the measure obtained are finite. This finiteness is due to these measures providing elementary lengths being mostly bounded and separated from zero, just as the finiteness of a theory on a lattice with an analogous probability distribution of spacings.

Graphene-Immobilized fac-Re(bipy)(CO)3Cl for Syngas Generation from Carbon Dioxide.

PubMed

Zhou, Xin; Micheroni, Daniel; Lin, Zekai; Poon, Christopher; Li, Zhong; Lin, Wenbin

2016-02-17

We report the synthesis of fac-M(4-amino-bipy)(CO)3X (M = Mn and X = Br or M = Re and X = Cl, with bipy = 2,2'-bipyridine), their immobilization on graphene oxide (GrO) via diazonium grafting, and the use of Re-functionalized GrO for electrocatalytic syngas production. Infrared (IR) spectroscopy, X-ray absorption fine structure (XAFS) spectroscopy, and electrocatalysis indicated successful grafting of the Re catalyst onto GrO. Re-functionalized GrO was then deposited onto a glassy carbon electrode (GCE) for CO2 reduction. Investigation of the Re-functionalized GCE for syngas production was performed in a CO2-saturated acetonitrile solution with 3.1 M H2O as the proton source and 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF6) as the supporting electrolyte. Cyclic voltammetry (CV), controlled potential electrolysis (CPE), and gas chromatography (GC) were employed to determine its CO2-to-CO conversion performance. The Re catalyst shows a turnover frequency (TOF) for generating CO up to 4.44 s(-1) with a CO/H2 ratio of 7:5.

The novel GrCEP12 peptide from the plant-parasitic nematode Globodera rostochiensis suppresses flg22-mediated PTI.

PubMed

Chen, Shiyan; Chronis, Demosthenis; Wang, Xiaohong

2013-09-01

The potato cyst nematode Globodera rostochiensis is a biotrophic pathogen that secretes effector proteins into host root cells to promote successful plant parasitism. In addition to the role in generating within root tissue the feeding cells essential for nematode development, (1) nematode secreted effectors are becoming recognized as suppressors of plant immunity. (2)(-) (4) Recently we reported that the effector ubiquitin carboxyl extension protein (GrUBCEP12) from G. rostochiensis is processed into free ubiquitin and a 12-amino acid GrCEP12 peptide in planta. Transgenic potato lines overexpressing the derived GrCEP12 peptide showed increased susceptibility to G. rostochiensis and to an unrelated bacterial pathogen Streptomyces scabies, suggesting that GrCEP12 has a role in suppressing host basal defense or possibly pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) during the parasitic interaction. (3) To determine if GrCEP12 functions as a PTI suppressor we evaluated whether GrCEP12 suppresses flg22-induced PTI responses in Nicotiana benthamiana. Interestingly, we found that transient expression of GrCEP12 in N. benthamiana leaves suppressed reactive oxygen species (ROS) production and the induction of two PTI marker genes triggered by the bacterial PAMP flg22, providing direct evidence that GrCEP12 indeed has an activity in PTI suppression.

Functional Development of the Octenol Response in Aedes aegypti

DTIC Science & Technology

2013-03-07

and AgGr24 genes (Jones et al., 2007; Lu et al., 2007), the orthologs of the Drosophila melanogaster CO2 receptors Gr21a and Gr63a (Jones et al... genome with TopHat (Trapnell et al., 2009). Resulting sequence alignment files were uploaded into the Avadis NGS software (Strand Scientific...isolated following the manufacturer’s protocol and sent to the Genomic Services Lab at Hudson Alpha Institute for Biotechnology (Huntsville, Alabama

Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

PubMed

Bei, E S; Salpeas, V; Alevizos, B; Anagnostara, C; Pappa, D; Moutsatsou, P

2013-11-01

Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis. Copyright © 2013. Published by Elsevier Ltd.

5D.07: THE IMPACT OF FLAVONOL-RICH DARK CHOCOLATE ON BLOOD PRESSURE AND VASCULAR FUNCTION IN HEALTHY SUBJECTS.

PubMed

Heuten, H; Van Ackeren, K; Hoymans, V; Wouters, K; Goovaerts, I; Conraads, V; Vrints, C

2015-06-01

Flavanoids may have a beneficial effect on blood pressure (BP) and endothelial function. There is however, limited data on this effect during a longer period (8 weeks) and no data on the effect on EPC (endothelial progenitor cells) in healthy subjects. Healthy, non-smoking, male and female volunteers aged 35-65 year with no history of diabetes or cardiovascular disease and with normal or mild hypertensive blood pressure (<160/100 mmHg) were included. Subjects could not take any medication affecting blood pressure or endothelial function. The subjects were randomised (double-blind) in two groups: Group 1(n = 25): daily consuming 20 gram of high-flavanol dark chocolate (High-DC). Group 2 (n = 26): daily consuming 20 gram of low-flavanol dark chocolate (Low-DC). At week 0,4,6,7 and 8 blood pressure was assessed in all subjects, and endothelial function (FMD, flow mediated dilation) in a subgroup. A blood sample was taken in each subject at week 0 and 8 for measuring glucose, lipids and EPC. Baseline characteristics were comparable between both groups. There was a decrease in systolic and diastolic blood pressure over time in both groups, however at 8 weeks there was no statistically significant difference between groups (delta SBP -2.17  + /-8.53 mmHg in gr 1 versus -4.06 + /-8.05 mmHg in gr 2, p = 0.4; delta DBP -3.97  + /-7.1 mmHg in gr 1 versus -4.67  + /-5.99 mmHg in gr 2, p = 0.7).FMD was performed in 9 subjects from each group, no significant difference was noted between both groups over time (delta FMD gr 1: -3.50  + /- 6.00 % versus gr 2: + 0.12  + /- 2.51 %, p = 0.06). EPC values did not differ between groups at baseline (T0) and at the end of the study (T8) (ISHAGE count (T8-T0): gr1: 3.23 (-68.01 - 41.71) versus gr 2: -9.23 (-57.59 - 17.28), p = 0.4). Glucose and lipids were comparable between both groups at baseline and at the end of the study (p = ns). In this study, no beneficial effect was noticed in favour of the consumption of flavanol-rich dark chocolate during 8 weeks on blood pressure or vascular function, in healthy subjects.

Validation of the German revised version of the program in palliative care education and practice questionnaire (PCEP-GR).

PubMed

Fetz, Katharina; Wenzel-Meyburg, Ursula; Schulz-Quach, Christian

2017-12-28

The evaluation of the effectiveness of undergraduate palliative care education (UPCE) programs is an essential foundation to providing high-quality UPCE programs. Therefore, the implementation of valid evaluation tools is indispensable. Until today, there has been no general consensus regarding concrete outcome parameters and their accurate measurement. The Program in Palliative Care Education and Practice Questionnaire (German Revised Version; PCEP-GR) is a promising assessment tool for UPCE. The aim of the current study was to evaluate the psychometric properties of PCEP-GR and to demonstrate its feasibility for the evaluation of UPCE programs. The practical feasibility of the PCEP-GR and its acceptance in medical students were investigated in a pilot study with 24 undergraduate medical students at Heinrich Heine University Dusseldorf, Germany. Subsequently, the PCEP-GR was surveyed in a representative sample (N = 680) of medical students in order to investigate its psychometric properties. Factorial validity was investigated by means of principal component analysis (PCA). Reliability was examined by means of split-half-reliability analysis and analysis of internal consistency. After taking into consideration the PCA and distribution analysis results, an evaluation instruction for the PCEP-GR was developed. The PCEP-GR proved to be feasible and well-accepted in medical students. PCA revealed a four-factorial solution indicating four PCEP-GR subscales: preparation to provide palliative care, attitudes towards palliative care, self-estimation of competence in communication with dying patients and their relatives and self-estimation of knowledge and skills in palliative care. The PCEP-GR showed good split-half-reliability and acceptable to good internal consistency of subscales. Attitudes towards palliative care slightly missed the criterion of acceptable internal consistency. The evaluation instruction suggests a global PCEP-GR index and four subscales. The PCEP-GR has proven to be a feasible, economic, valid and reliable tool for the assessment of UPCE that comprises self-efficacy expectation and relevant attitudes towards palliative care.

A Glycine-Rich RNA-Binding Protein, CsGR-RBP3, Is Involved in Defense Responses Against Cold Stress in Harvested Cucumber (Cucumis sativus L.) Fruit

PubMed Central

Wang, Bin; Wang, Guang; Shen, Fei; Zhu, Shijiang

2018-01-01

Plant glycine-rich RNA-binding proteins (GR-RBPs) have been shown to play important roles in response to abiotic stresses in actively proliferating organs such as young plants, root tips, and flowers, but their roles in chilling responses of harvested fruit remains largely unknown. Here, we investigated the role of CsGR-RBP3 in the chilling response of cucumber fruit. Pre-storage cold acclimation at 10°C (PsCA) for 3 days significantly enhanced chilling tolerance of cucumber fruit compared with the control fruit that were stored at 5°C. In the control fruit, only one of the six cucumber CsGR-RBP genes, CsGR-RBP2, was enhanced whereas the other five, i.e., CsGR-RBP3, CsGR-RBP4, CsGR-RBP5, CsGR-RBP-blt801, and CsGR-RBP-RZ1A were not. However, in the fruit exposed to PsCA before storage at 5°C, CsGR-RBP2 transcript levels were not obviously different from those in the controls, whereas the other five were highly upregulated, with CsGR-RBP3 the most significantly induced. Treatment with endogenous ABA and NO biosynthesis inhibitors, tungstate and L-nitro-arginine methyl ester, respectively, prior to PsCA treatment, clearly downregulated CsGR-RBP3 expression and significantly aggravated chilling injury. These results suggest a strong connection between CsGR-RBP3 expression and chilling tolerance in cucumber fruit. Transient expression in tobacco suggests CsGR-RBP3 was located in the mitochondria, implying a role for CsGR-RBP3 in maintaining mitochondria-related functions under low temperature. Arabidopsis lines overexpressing CsGR-RBP3 displayed faster growth at 23°C, lower electrolyte leakage and higher Fv/Fm ratio at 0°C, and higher survival rate at -20°C, than wild-type plants. Under cold stress conditions, Arabidopsis plants overexpressing CsGR-RBP3 displayed lower reactive oxygen species levels, and higher catalase and superoxide dismutase expression and activities, compared with the wild-type plants. In addition, overexpression of CsGR-RBP3 significantly upregulated nine Arabidopsis genes involved in defense responses to various stresses, including chilling. These results strongly suggest CsGR-RBP3 plays a positive role in defense against chilling stress. PMID:29740470

Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex

PubMed Central

Hua, Guoqiang; Ganti, Krishna Priya; Chambon, Pierre

2016-01-01

Upon binding of a glucocorticoid (GC), the GC receptor (GR) can exert one of three transcriptional regulatory functions. We recently reported that SUMOylation of the GR at position K293 in humans (K310 in mice) within the N-terminal domain is indispensable for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression. We now demonstrate that the integrity of this GR SUMOylation site is mandatory for the formation of a GR-small ubiquitin-related modifiers (SUMOs)-SMRT/NCoR1-HDAC3 repressing complex, which is indispensable for NF-κB/AP1-mediated GC-induced tethered indirect transrepression in vitro. Using GR K310R mutant mice or mice containing the N-terminal truncated GR isoform GRα-D3 lacking the K310 SUMOylation site, revealed a more severe skin inflammation than in WT mice. Importantly, cotreatment with dexamethasone (Dex) could not efficiently suppress a 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced skin inflammation in these mutant mice, whereas it was clearly decreased in WT mice. In addition, in mice selectively ablated in skin keratinocytes for either nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors or histone deacetylase 3 (HDAC3), Dex-induced tethered transrepression and the formation of a repressing complex on DNA-bound NF-κB/AP1 were impaired. We previously suggested that GR ligands that would lack both (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression activities of GCs may preferentially exert the therapeutically beneficial GC antiinflammatory properties. Interestingly, we now identified a nonsteroidal antiinflammatory selective GR agonist (SEGRA) that selectively lacks both Dex-induced (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression functions, while still exerting a tethered indirect transrepression activity and could therefore be clinically lesser debilitating on long-term GC therapy. PMID:26712006

Micromechanical Modeling of the Thermal Expansion of Graphite/copper Composites with Nonuniform Microstructure

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Pindera, Marek-Jerzy

1994-01-01

Two micromechanical models were developed to investigate the thermal expansion of graphite/copper (Gr/Cu) composites. The models incorporate the effects of temperature-dependent material properties, matrix inelasticity, initial residual stresses due to processing history, and nonuniform fiber distribution. The first model is based on the multiple concentric cylinder geometry, with each cylinder treated as a two-phase composite with a characteristic fiber volume fractions. By altering the fiber volume fraction of the individual cylinders, unidirectional composites with radially nonuniform fiber distributions can be investigated using this model. The second model is based on the inelastic lamination theory. By varying the fiber content in the individual laminae, composites with nonuniform fiber distribution in the thickness direction can be investigated. In both models, the properties of the individual regions (cylinders or laminae) are calculated using the method of cells micromechanical model. Classical incremental plasticity theory is used to model the inelastic response of the copper matrix at the microlevel. The models were used to characterize the effects of nonuniform fiber distribution on the thermal expansion of Gr/Cu. These effects were compared to the effects of matrix plasticity, choice of stress-free temperature, and slight fiber misalignment. It was found that the radially nonuniform fiber distribution has little effect on the thermal expansion of Gr/Cu but could become significant for composites with large fiber-matrix transverse CTE and Young's modulus mismatch. The effect of nonuniform fiber distribution in the through-thickness direction of a laminate was more significant, but only approached that of the stress-free temperature for the most extreme cases that include large amounts of bending. Subsequent comparison with experimental thermal expansion data indicated the need for more accurate characterization of the graphite fiber thermomechanical properties. Correlation with cyclic data revealed the presence of a mechanism not considered in the developed models. The predicted response did, however, exhibit ratcheting behavior that has been observed experimentally in Gr/Cu. Finally, simulation of the actual fiber distribution of particular specimens had little effect on the predicted thermal expansion.

Functional anatomy and ultrasound examination of the canine penis.

PubMed

Goericke-Pesch, Sandra; Hölscher, Catharina; Failing, Klaus; Wehrend, Axel

2013-07-01

The aim of this study was to identify the functional-anatomical structures of the canine penis during and after erection to demonstrate the respective changes to provide a basis for further examinations of pathological conditions like priapism. Additionally, a gray-scale analysis was performed to quantify results from the ultrasound examination. In total, 80 dogs were examined. In group (Gr.) A, 44 intact or castrated dogs were examined, and in Gr. B, 36 dogs were examined during erection and after complete detumescence of the penis. The following parameters were assessed: (1) using physical measurements: length of the Pars longa glandis [Plg] and length of the Bulbus glandis [Bg]; and (2) using ultrasound: total penile diameter, width of the erectile tissue of the Plg, diameter of the Corpus spongiosum [Cs] including the penile bone and urethra, vertical diameter, circumference of the penis, cross-sectional area, and area of the Cs including the urethra. The mentioned parameters could be assessed in all dogs of Gr. A and Gr. B with the only exception being the urethra that could be visualized using ultrasound in some dogs only and predominantly in the erected penis (Gr. B). Concomitantly, the erectile tissue of the Plg and the Cs was more heterogenous and hypo- to anechoic during erection compared with dogs in Gr. A and Gr. B after detumescence. Comparing the results in Gr. B, the length of the Plg and the Bg were decreased approximately 40.6% and 38.0%, the total width of the penis 40.5%, the total width of the erectile tissue of the Plg 48.0%, and the width of the Cs 15.6% during detumescence compared with erection. Comparing the decrease in size at the different locations (apex penis, middle of Plg, middle of Bg) for vertical diameter, total circumference, and cross-section area, it was largest at the Bg. B-mode ultrasound is a suitable tool to investigate not only the morpho-functional structures of the resting canine penis, but also of the erected and detumescent penis, and to investigate the underlying changes during erection and detumenscence. Copyright © 2013 Elsevier Inc. All rights reserved.

Enduring, Handling-Evoked Enhancement of Hippocampal Memory Function and Glucocorticoid Receptor Expression Involves Activation of the Corticotropin-Releasing Factor Type 1 Receptor

PubMed Central

Fenoglio, Kristina A.; Brunson, Kristen L.; Avishai-Eliner, Sarit; Stone, Blake A.; Kapadia, Bhumika J.; Baram, Tallie Z.

2011-01-01

Early-life experience, including maternal care, influences hippocampus-dependent learning and memory throughout life. Handling of pups during postnatal d 2–9 (P2–9) stimulates maternal care and leads to improved memory function and stress-coping. The underlying molecular mechanisms may involve early (by P9) and enduring reduction of hypothalamic corticotropin-releasing factor (CRF) expression and subsequent (by P45) increase in hippocampal glucocorticoid receptor (GR) expression. However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF receptor activation and consequent lower plasma glucocorticoid levels, is unclear. In this study we administered selective antagonist for the type 1 CRF receptor, NBI 30775, to nonhandled rats post hoc from P10–17 and examined hippocampus-dependent learning and memory later (on P50–70), using two independent paradigms, compared with naive and vehicle-treated nonhandled, and naive and antagonist-treated handled rats. Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined. Transient, partial selective blockade of CRF1 in nonhandled rats improved memory functions on both the Morris watermaze and object recognition tests to levels significantly better than in naive and vehicle-treated controls and were indistinguishable from those in handled (naive, vehicle-treated, and antagonist-treated) rats. GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1-antagonist treated nonhandled rats to levels commensurate with those in handled cohorts. Thus, the extent of CRF1 activation, probably involving changes in hypothalamic CRF levels and release, contributes to the changes in hippocampal GR expression and learning and memory functions. PMID:15932935

Glucocorticoid receptor ligand binding in monocytic cells using a microplate assay.

PubMed

Jansen, J; Uitdehaag, B; Koper, J W; van Den Berg, T K

1999-01-01

Glucocorticoids have profound effects on macrophage function and are widely used as anti-inflammatory drugs. Glucocorticoids receptor (GR) ligand binding capacity is a major determinant of cellular glucocorticoid sensitivity. The number and affinity of GR can be measured in a whole cell binding assay using (3)H-dexamethasone. Here, we describe a rapid and simple microplate assay for GR measurement using the human promonocytic cell line THP-1. Copyright 2000 S. Karger AG, Basel.

A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease.

PubMed

Riebold, Mathias; Kozany, Christian; Freiburger, Lee; Sattler, Michael; Buchfelder, Michael; Hausch, Felix; Stalla, Günter K; Paez-Pereda, Marcelo

2015-03-01

One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotroph adenomas that excessively secrete ACTH, which leads to hypercortisolism. Mutations that impair GR function explain glucocorticoid resistance only in sporadic cases. However, the proper folding of GR depends on direct interactions with the chaperone heat shock protein 90 (HSP90, refs. 7,8). We show here that corticotroph adenomas overexpress HSP90 compared to the normal pituitary. N- and C-terminal HSP90 inhibitors act at different steps of the HSP90 catalytic cycle to regulate corticotroph cell proliferation and GR transcriptional activity. C-terminal inhibitors cause the release of mature GR from HSP90, which promotes its exit from the chaperone cycle and potentiates its transcriptional activity in a corticotroph cell line and in primary cultures of human corticotroph adenomas. In an allograft mouse model, the C-terminal HSP90 inhibitor silibinin showed anti-tumorigenic effects, partially reverted hormonal alterations, and alleviated symptoms of Cushing disease. These results suggest that the pathogenesis of Cushing disease caused by overexpression of heat shock proteins and consequently misregulated GR sensitivity may be overcome pharmacologically with an appropriate HSP90 inhibitor.

Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion

PubMed Central

McKlveen, Jessica M.; Myers, Brent; Flak, Jonathan N.; Bundzikova, Jana; Solomon, Matia B.; Seroogy, Kim B.; Herman, James P.

2013-01-01

Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation. Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field. Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyper-locomotion in the open field, but did not affect stress sensitization or helplessness behavior. Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation. PMID:23683655

Positivity bound on the imaginary part of the right-chiral tensor coupling gR in polarized top quark decay

NASA Astrophysics Data System (ADS)

Groote, S.; Körner, J. G.

2017-12-01

We derive a positivity bound on the right-chiral tensor coupling Im gR in polarized top quark decay by analyzing the angular decay distribution of the three-body polarized top quark decay t (↑)→b +ℓ++νℓ in next-to-leading order QCD. We obtain the bound -0.0420 ≤Im gR≤0.0420 .

Methylobacterium variabile sp. nov., a methylotrophic bacterium isolated from an aquatic environment.

PubMed

Gallego, Virginia; García, Maria Teresa; Ventosa, Antonio

2005-07-01

Strain GR3(T) was isolated from drinking water during a screening programme to monitor the bacterial population present in the distribution system of Seville (Spain), and it was studied phenotypically, genotypically and phylogenetically. This pink-pigmented bacterium was identified as a Methylobacterium sp. Members of this genus are distributed in a wide variety of natural habitats, including soil, dust, air, freshwater and aquatic sediments. Phylogenetic analysis of the 16S rRNA gene sequence showed that strain GR3(T) was closely related to Methylobacterium aquaticum (97.4% sequence similarity), whereas sequence similarity values with respect to the rest of the species belonging to this genus were lower than 96%. Furthermore, the DNA-DNA hybridization data and its phenotypic characteristics clearly indicate that the isolate represents a novel Methylobacterium species, for which the name Methylobacterium variabile sp. nov. is proposed. GR3(T) (=DSM 16961(T)=CCM 7281(T)=CECT 7045(T)) is the type strain; the DNA G+C content of this strain is 69.2 mol%.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

PubMed

Wilson, K S; Baily, J; Tucker, C S; Matrone, G; Vass, S; Moran, C; Chapman, K E; Mullins, J J; Kenyon, C; Hadoke, P W F; Denvir, M A

2015-10-15

Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart

PubMed Central

Wilson, K.S.; Baily, J.; Tucker, C.S.; Matrone, G.; Vass, S.; Moran, C.; Chapman, K.E.; Mullins, J.J.; Kenyon, C.; Hadoke, P.W.F.; Denvir, M.A.

2015-01-01

Background Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. PMID:26219824

Small meteoroids' major contribution to Mercury's exosphere

NASA Astrophysics Data System (ADS)

Grotheer, E. B.; Livi, S. A.

2014-01-01

The contribution of the meteoroid population to the generation of Mercury's exosphere is analyzed to determine which segment contributes most greatly to exospheric refilling via the process of meteoritic impact vaporization. For the meteoroid data, a differential mass distribution based on work by Grün et al. (Grün, E., Zook, H.A., Fechtig, H., Giese, R.H. [1985]. Icarus 62(2), 244-272) and a differential velocity distribution based on the work of Zook (Zook, H.A. [1975]. In: 6th Lunar Science Conference, vol. 2. Pergamon Press, Inc., Houston, TX, pp. 1653-1672) is used. These distributions are then evaluated using the method employed by Cintala (Cintala, M.J. [1992]. J. Geophys. Res. 97(E1), 947-974) to determine impact rates for selected mass and velocity segments of the meteoroid population.

DFT Studies of Graphene-Functionalised Derivatives of Capecitabine

NASA Astrophysics Data System (ADS)

Aramideh, Mehdi; Mirzaei, Mahmoud; Khodarahmi, Ghadamali; Gülseren, Oğuz

2017-11-01

Cancer is one of the major problems for so many people around the world; therefore, dedicating efforts to explore efficient therapeutic methodologies is very important for researchers of life sciences. In this case, nanostructures are expected to be carriers of medicinal compounds for targeted drug design and delivery purposes. Within this work, the graphene (Gr)-functionalised derivatives of capecitabine (CAP), as a representative anticancer, have been studied based on density functional theory calculations. Two different sizes of Gr molecular models have been used for the functionalisation of CAP counterparts, CAP-Gr3 and CAP-Gr5, to explore the effects of Gr-functionalisation on the original properties of CAP. All singular and functionalised molecular models have been optimised and the molecular and atomic scale properties have been evaluated for the optimised structures. Higher formation favourability has been obtained for CAP-Gr5 in comparison with CAP-Gr3 and better structural stability has been obtained in the water-solvated system than the isolated gas-phase system for all models. The CAP-Gr5 model could play a better role of electron transferring in comparison with the CAP-Gr3 model. As a concluding remark, the molecular properties of CAP changed from singular to functionalised models whereas the atomic properties remained almost unchanged, which is expected for a carrier not to use significant perturbations to the original properties of the carried counterpart.

The Grid Analysis and Display System (GrADS)

NASA Technical Reports Server (NTRS)

Kinter, James L., III

1994-01-01

During the period 1 September 1993 - 31 August 1994, further development of the Grid Analysis and Display System (GrADS) was conducted at the Center for Ocean-Land-Atmosphere Studies (COLA) of the Institute of Global Environment and Society, Inc. (IGES) under subcontract 5555-31 from the University Space Research Association (USRA) administered by The Center of Excellence in Space Data and Information Sciences (CESDIS). This final report documents progress made under this subcontract and provides directions on how to access the software and documentation developed therein. A short description of GrADS is provided followed by summary of progress completed and a summary of the distribution of the software to date and the establishment of research collaborations.

Gr-GDHP: A New Architecture for Globalized Dual Heuristic Dynamic Programming.

PubMed

Zhong, Xiangnan; Ni, Zhen; He, Haibo

2017-10-01

Goal representation globalized dual heuristic dynamic programming (Gr-GDHP) method is proposed in this paper. A goal neural network is integrated into the traditional GDHP method providing an internal reinforcement signal and its derivatives to help the control and learning process. From the proposed architecture, it is shown that the obtained internal reinforcement signal and its derivatives can be able to adjust themselves online over time rather than a fixed or predefined function in literature. Furthermore, the obtained derivatives can directly contribute to the objective function of the critic network, whose learning process is thus simplified. Numerical simulation studies are applied to show the performance of the proposed Gr-GDHP method and compare the results with other existing adaptive dynamic programming designs. We also investigate this method on a ball-and-beam balancing system. The statistical simulation results are presented for both the Gr-GDHP and the GDHP methods to demonstrate the improved learning and controlling performance.

Modeling the Solar Probe Plus Dust Environment: Comparison with MESSENGER Observations

NASA Astrophysics Data System (ADS)

Strong, S. B.; Strikwerda, T.

2009-12-01

NASA’s Solar Probe Plus mission will be the first to approach the Sun as close as 9 solar radii from the surface. This mission will provide the only in-situ observations of the Sun’s corona. In the absence of observational data (e.g. Helios, Pioneer), specifically at distances less than 0.4 AU, the precise ambient dust distributions at these distances remain unknown and limited to extrapolative models for distances < 1 AU (e.g. Mann et al. 2004). For the Solar Probe Plus mission, it has become critical to characterize the inner solar system dust environment in order to examine potential impacts on spacecraft health and attitude. We have implemented the Mann et al. (2004) and Grün et al. (1985) dust distribution theory along with Mie scattering effects to determine the magnitude of solar irradiance scattered towards an optical sensor such as a star tracker as a function of ecliptic latitude and longitude for distances 0.05 to 1 AU. Background irradiance data from NASA’s MESSENGER mission (down to 0.3 AU) reveal trends consistent with our model predictions, potentially validating Mann et al. (2004) and Grün et al. (1985) theory, but perhaps suggesting an enhancement of dust density short ward of 0.3 AU. This paper will present the scattering model and analysis of MESSENGER data gathered to date, during the phasing orbits, and includes star tracker background irradiance, irradiance distribution over the sky, and effects on star magnitude sensitivity and position accuracy.

Protic ammonium carboxylate ionic liquids: insight into structure, dynamics and thermophysical properties by alkyl group functionalization.

PubMed

Reddy, Th Dhileep N; Mallik, Bhabani S

2017-04-19

This study is aimed at characterising the structure, dynamics and thermophysical properties of five alkylammonium carboxylate ionic liquids (ILs) from classical molecular dynamics simulations. The structural features of these ILs were characterised by calculating the site-site radial distribution functions, g(r), spatial distribution functions and structure factors. The structural properties demonstrate that ILs show greater interaction between cations and anions when alkyl chain length increases on the cation or anion. In all ILs, spatial distribution functions show that the anion is close to the acidic hydrogen atoms of the ammonium cation. We determined the role of alkyl group functionalization of the charged entities, cations and anions, in the dynamical behavior and the transport coefficients of this family of ionic liquids. The dynamics of ILs are described by studying the mean square displacement (MSD) of the centres of mass of the ions, diffusion coefficients, ionic conductivities and hydrogen bonds as well as residence dynamics. The diffusion coefficients and ionic conductivity decrease with an increase in the size of the cation or anion. The effect of alkyl chain length on ionic conductivity calculated in this article is consistent with the findings of other experimental studies. Hydrogen bond lifetimes and residence times along with structure factors were also calculated, and are related to alkyl chain length.

Investigations for Thermal and Electrical Conductivity of ABS-Graphene Blended Prototypes

PubMed Central

Singh, Rupinder; Sandhu, Gurleen S.; Penna, Rosa; Farina, Ilenia

2017-01-01

The thermoplastic materials such as acrylonitrile-butadiene-styrene (ABS) and Nylon have large applications in three-dimensional printing of functional/non-functional prototypes. Usually these polymer-based prototypes are lacking in thermal and electrical conductivity. Graphene (Gr) has attracted impressive enthusiasm in the recent past due to its natural mechanical, thermal, and electrical properties. This paper presents the step by step procedure (as a case study) for development of an in-house ABS-Gr blended composite feedstock filament for fused deposition modelling (FDM) applications. The feedstock filament has been prepared by two different methods (mechanical and chemical mixing). For mechanical mixing, a twin screw extrusion (TSE) process has been used, and for chemical mixing, the composite of Gr in an ABS matrix has been set by chemical dissolution, followed by mechanical blending through TSE. Finally, the electrical and thermal conductivity of functional prototypes prepared from composite feedstock filaments have been optimized. PMID:28773244

A simple preparation of graphite/gelatin composite for electrochemical detection of dopamine.

PubMed

Rajkumar, Chellakannu; Thirumalraj, Balamurugan; Chen, Shen-Ming; Chen, His-An

2017-02-01

In this study, we demonstrate a simple preparation of graphite (GR) sheets assisted with gelatin (GLN) polypeptide composite was developed for sensitive detection of dopamine (DA) sensor. The GR/GLN composite was prepared by GR powder in GLN solution (5mg/mL) via sonication process. The prepared GR/GLN composite displays well dispersion ability in biopolymer matrix and characterized via scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy and electrochemical impedance spectroscopy (EIS) studies. The GR/GLN modified electrode showed an excellent electrocatalytic activity toward the oxidation of DA, suggesting that the successful formation of GR sheets crosslinked with the functional groups of GLN polypeptide. In addition, the GR/GLN modified electrode achieved a wide linear response ranging from 0.05 to 79.5μM with a detection limit of 0.0045μM. The calculated analytical sensitivity of the sensor was 1.36±0.02μAμM -1 cm -2 . Conversely, the modified electrode demonstrates a good storage stability, reproducibility and repeatability. In addition, the sensor manifests the determination of DA in human serum and urine samples for practical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Topological and Functional Characterization of an Insect Gustatory Receptor

PubMed Central

Zhang, Hui-Jie; Anderson, Alisha R.; Trowell, Stephen C.; Luo, A-Rong; Xiang, Zhong-Huai; Xia, Qing-You

2011-01-01

Insect gustatory receptors are predicted to have a seven-transmembrane structure and are distantly related to insect olfactory receptors, which have an inverted topology compared with G-protein coupled receptors, including mammalian olfactory receptors. In contrast, the topology of insect gustatory receptors remains unknown. Except for a few examples from Drosophila, the specificity of individual insect gustatory receptors is also unknown. In this study, the total number of identified gustatory receptors in Bombyx mori was expanded from 65 to 69. BmGr8, a silkmoth gustatory receptor from the sugar receptor subfamily, was expressed in insect cells. Membrane topology studies on BmGr8 indicate that, like insect olfactory receptors, it has an inverted topology relative to G protein-coupled receptors. An orphan GR from the bitter receptor family, BmGr53, yielded similar results. We infer, from the finding that two distantly related BmGrs have an intracellular N-terminus and an odd number of transmembrane spans, that this is likely to be a general topology for all insect gustatory receptors. We also show that BmGr8 functions independently in Sf9 cells and responds in a concentration-dependent manner to the polyalcohols myo-inositol and epi-inositol but not to a range of mono- and di-saccharides. BmGr8 is the first chemoreceptor shown to respond specifically to inositol, an important or essential nutrient for some Lepidoptera. The selectivity of BmGr8 responses is consistent with the known responses of one of the gustatory receptor neurons in the lateral styloconic sensilla of B. mori, which responds to myo-inositol and epi-inositol but not to allo-inositol. PMID:21912618

Constructing the quantum Hall system on the Grassmannians Gr2(CN)

NASA Astrophysics Data System (ADS)

Ballı, F.; Behtash, A.; Kürkçüoğlu, S.; Ünal, G.

2015-04-01

In this talk, we give the formulation of Quantum Hall Effects (QHEs) on the complex Grassmann manifolds Gr2(CN). We set up the Landau problem in Gr2(CN), solve it using group theoretical techniques and provide the energy spectrum and the eigenstates in terms of the SU(N) Wigner D-functions for charged particles on Gr2(CN) under the influence of abelian and non-abelian background magnetic monopoles or a combination of these thereof. For the simplest case of Gr2(C4) we provide explicit constructions of the single and many- particle wavefunctions by introducing the Plucker coordinates and show by calculating the two-point correlation function that the lowest Landau level (LLL) at filling factor v = 1 forms an incompressible fluid. Finally, we heuristically identify a relation between the U(1) Hall effect on Gr2(C4) and the Hall effect on the odd sphere S5, which is yet to be investigated in detail, by appealing to the already known analogous relations between the Hall effects on CP3 and CP7 and those on the spheres S4 and S8, respectively. The talk is given by S. Kürkçüoğlu at the Group 30 meeting at Ghent University, Ghent, Belgium in July 2014 and based on the article by F.Ballı, A.Behtash, S. Kürkçüoğlu, G.Ünal [1].

Synthesis of surface molecular imprinted TiO2/graphene photocatalyst and its highly efficient photocatalytic degradation of target pollutant under visible light irradiation

NASA Astrophysics Data System (ADS)

Lai, Cui; Wang, Man-Man; Zeng, Guang-Ming; Liu, Yun-Guo; Huang, Dan-Lian; Zhang, Chen; Wang, Rong-Zhong; Xu, Piao; Cheng, Min; Huang, Chao; Wu, Hai-Peng; Qin, Lei

2016-12-01

The molecular imprinted TiO2/graphene photocatalyst (MIP-TiO2/GR) was successfully prepared with bisphenol A (BPA) as the template molecule (target pollutant) and o-phenylenediamine (OPDA) as functional monomers by the surface molecular imprinting method. The combination between BPA and OPDA led to the formation of the precursor, and the subsequent polymerization of OPDA initiated by ultraviolet radiation can ensure the realization of MIP-TiO2/GR. The samples were characterized by SEM, EDS, XRD, BET, UV-vis DRS and Zeta potential. In addition, adsorption capacities, adsorption selectivity and visible light photocatalytic performances of MIP-TiO2/GR and non-imprinted TiO2/graphene (NIP-TiO2/GR) were evaluated. Moreover, the effects of pH and initial BPA concentration on removal efficiency of BPA were also investigated. The results showed that MIP-TiO2/GR exhibited better adsorption capacity and adsorption selectivity towards the template molecule compared to NIP-TiO2/GR due to the imprinted cavities on the surface of MIP-TiO2/GR. Moreover, the photocatalytic activity of MIP-TiO2/GR toward the target molecules was stronger than that of NIP-TiO2/GR as a result of large adsorption capacity to target molecules and narrow band gap energy on MIP-TiO2/GR. Therefore, modifying the photocatalyst by the surface molecular imprinting is a promising method to improve the molecule recognition and photocatalytic efficiency of photocatalyst for target pollutant.

Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1 in Bombyx mori.

PubMed

Mang, Dingze; Shu, Min; Tanaka, Shiho; Nagata, Shinji; Takada, Tomoyuki; Endo, Haruka; Kikuta, Shingo; Tabunoki, Hiroko; Iwabuchi, Kikuo; Sato, Ryoichi

2016-08-01

Insect gustatory receptors (Grs) are members of a large family of proteins with seven transmembrane domains that provide insects with the ability to detect chemical signals critical for feeding, mating, and oviposition. To date, 69 Bombyx mori Grs (BmGrs) genes have been identified via genome studies. BmGr9 has been shown to respond specifically to fructose and to function as a ligand-gated ion channel selectively activated by fructose. However, the sites where this Gr are expressed remain unclear. We demonstrated using reverse transcription (RT)-PCR that BmGr9 is widely expressed in the central nervous system (CNS), as well as oral sensory organs. Additionally, immunohistochemistry was performed using anti-BmGr9 antiserum to show that BmGr9 is expressed in cells of the oral sensory organs, including the maxillary galea, maxillary palps, labrum, and labium, as well as in putative neurosecretory cells of the CNS. Furthermore, double immunohistochemical analysis showed that most BmGr9-expressing cells co-localized with putative neuropeptide F1-expressing cells in the brain, suggesting that BmGr9 is involved in the promotion of feeding behaviors. In addition, a portion of BmGr9-expressing cells in the brain co-localized with cells expressing BmGr6, a molecule of the sugar receptor clade, suggesting that sugars other than fructose are involved in the regulation of feeding behaviors in B. mori larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feasibility analysis of using inverse modeling for estimating natural groundwater recharge from a large-scale soil moisture monitoring network

NASA Astrophysics Data System (ADS)

Wang, Tiejun; Franz, Trenton E.; Yue, Weifeng; Szilagyi, Jozsef; Zlotnik, Vitaly A.; You, Jinsheng; Chen, Xunhong; Shulski, Martha D.; Young, Aaron

2016-02-01

Despite the importance of groundwater recharge (GR), its accurate estimation still remains one of the most challenging tasks in the field of hydrology. In this study, with the help of inverse modeling, long-term (6 years) soil moisture data at 34 sites from the Automated Weather Data Network (AWDN) were used to estimate the spatial distribution of GR across Nebraska, USA, where significant spatial variability exists in soil properties and precipitation (P). To ensure the generality of this study and its potential broad applications, data from public domains and literature were used to parameterize the standard Hydrus-1D model. Although observed soil moisture differed significantly across the AWDN sites mainly due to the variations in P and soil properties, the simulations were able to capture the dynamics of observed soil moisture under different climatic and soil conditions. The inferred mean annual GR from the calibrated models varied over three orders of magnitude across the study area. To assess the uncertainties of the approach, estimates of GR and actual evapotranspiration (ETa) from the calibrated models were compared to the GR and ETa obtained from other techniques in the study area (e.g., remote sensing, tracers, and regional water balance). Comparison clearly demonstrated the feasibility of inverse modeling and large-scale (>104 km2) soil moisture monitoring networks for estimating GR. In addition, the model results were used to further examine the impacts of climate and soil on GR. The data showed that both P and soil properties had significant impacts on GR in the study area with coarser soils generating higher GR; however, different relationships between GR and P emerged at the AWDN sites, defined by local climatic and soil conditions. In general, positive correlations existed between annual GR and P for the sites with coarser-textured soils or under wetter climatic conditions. With the rapidly expanding soil moisture monitoring networks around the globe, this study may have important applications in aiding water resources management in different regions.

Baicalin Modulates APPL2/Glucocorticoid Receptor Signaling Cascade, Promotes Neurogenesis, and Attenuates Emotional and Olfactory Dysfunctions in Chronic Corticosterone-Induced Depression.

PubMed

Gao, Chong; Du, Qiaohui; Li, Wenting; Deng, Ruixia; Wang, Qi; Xu, Aimin; Shen, Jiangang

2018-04-19

Olfactory dysfunction is often accompanied with anxiety- and depressive-like behaviors in depressive patients. Impaired neurogenesis in hippocampus and subventricular zone (SVZ)-olfactory bulb (OB) contribute to anxiety- and depressive-like behaviors and olfactory dysfunctions. However, the underlying mechanisms of olfactory dysfunction remain unclear. Our previous study indicates that adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2), could affect the activity and sensitivity of glucocorticoid receptor (GR) and mediate impaired hippocampal neurogenesis, which contribute the development of depression. In the present study, we further identified the roles of APPL2 in olfactory functions. APPL2 Tg mice displayed higher GR activity and less capacity of neurogenesis at olfactory system with less olfactory sensitivity than WT mice, indicating that APPL2 could be a potential therapeutic target for depression and olfactory deficits. We then studied the effects of baicalin, a medicinal herbal compound, on modulating APPL2/GR signaling pathway for promoting neurogenesis and antidepressant as well as improving olfactory functions. Baicalin treatment inhibited APPL2/GR signaling pathway and improved neurogenesis at SVZ, OB, and hippocampus in APPL2 Tg mice and chronic corticosterone-induced depression mouse model. Behavioral tests revealed that baicalin attenuated depressive- and anxiety-like behaviors and improve olfactory functions in the chronic depression mouse model and APPL2 Tg mice. Taken together, APPL2 could be a novel therapeutic target for improving depressant-related olfactory dysfunctions and baicalin could inhibit APPL2-mediated GR hyperactivity and promote adult neurogenesis, subsequently releasing depressive and anxiety symptoms and improving olfactory functions for antidepressant therapy.

Interactions in charged colloidal suspensions: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Padidela, Uday Kumar; Behera, Raghu Nath

2017-07-01

Colloidal suspensions are extensively used in everyday life and find several applications in the pharmaceutical, chemical, food industries, etc. We present the classical molecular dynamics simulation results of the structural and transport properties of charged colloidal suspensions as a function of its size, charge and concentration. The system is viewed as a two-component (colloids and counterions) primitive model consisting of spherical colloid particle (macroion) and the counterions (micro-particles), which are treated explicitly. The solvent is treated as dielectric continuum. A systematic trend in the radial distribution functions g(r), potential of mean force W(r), different thermodynamic properties and diffusion coefficients is obtained as a function of colloid charge, size and concentration. An attractive minimum in W(r) is obtained at short interparticle distance.

Fiber post cementation strategies: effect of mechanical cycling on push-out bond strength and cement polymerization stress.

PubMed

Bergoli, Cesar Dalmolin; Amaral, Marina; Boaro, Leticia Cristina; Braga, Roberto Ruggiero; Valandro, Luiz Felipe

2012-08-01

To evaluate the effect of mechanical cycling and cementation strategies on the push-out bond strength between fiber posts and root dentin and the polymerization stresses produced using three resin cements. Eighty bovine mandibular teeth were sectioned to a length of 16 mm, prepared to 12 mm, and embedded in self-curing acrylic resin. The specimens were then distributed into 8 groups (n = 10): Gr1 - Scotchbond Multi Purpose + RelyX ARC; Gr2 - Scotchbond Multi Purpose + RelyX ARC + mechanical cycling; Gr3 - AdheSE + Multilink Automix; Gr4 - AdheSE + Multilink Automix + mechanical cycling; Gr5 - phosphoric acid + RelyX U100 (self-adhesive cement); Gr6 - phosphoric acid+ RelyX U100 + mechanical cycling; Gr7 - RelyX U100; Gr8 - RelyX U100 + mechanical cycling. The values obtained from the push-out bond strength test were submitted to two-way ANOVA and Tukey's test (p = 0.05), while the values obtained from the polymerization stress test were subjected to one-way ANOVA and Tukey's test (α = 0.05). Mechanical cycling did not affect the bond strength values (p = 0.236), while cementation strategies affected the push-out bond strength (p < 0.001). Luting with RelyX U100 and Scotch Bond Multi Purpose + RelyX ARC yielded higher push-out bond strength values. The polymerization stress results were affected by the factor "cement" (p = 0.0104): the self-adhesive cement RelyX U100 exhibited the lowest values, RelyX ARC resulted in the highest values, while Multilink Automix presented values statistically similar to the other two cements. The self-adhesive cement appears to be a good alternative for luting fiber posts due to the high push-out bond strengths and lower polymerization stress values.

The role of digestive factors in determining glycemic response in a multiethnic Asian population.

PubMed

Tan, Verena Ming Hui; Ooi, Delicia Shu Qin; Kapur, Jeevesh; Wu, Ting; Chan, Yiong Huak; Henry, Christiani Jeyakumar; Lee, Yung Seng

2016-06-01

There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals. Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (-5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva α-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR. The GR for jasmine rice was significantly higher than for basmati rice (P < 0.001). The median number of AMY1 gene copies was 6, with a range of 2-15. There was a significant positive relationship between AMY1 copy number and α-amylase activity (P = 0.002). There were no significant ethnic differences in GR. For both rice varieties, the number of chews per mouthful was positively associated with the GR (JR, P = 0.011; BR, P = 0.005), while chewing time per mouthful showed a negative association (JR, P = 0.039; BR, P = 0.016). Ethnicity, salivary α-amylase activity, particle size distribution, gastric emptying rate and AMY1 gene copy numbers were not significant contributors to GR (P > 0.05). Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control.

Mismodeling in gravitational-wave astronomy: The trouble with templates

NASA Astrophysics Data System (ADS)

Sampson, Laura; Cornish, Neil; Yunes, Nicolás

2014-03-01

Waveform templates are a powerful tool for extracting and characterizing gravitational wave signals, acting as highly restrictive priors on the signal morphologies that allow us to extract weak events buried deep in the instrumental noise. The templates map the waveform shapes to physical parameters, thus allowing us to produce posterior probability distributions for these parameters. However, there are attendant dangers in using highly restrictive signal priors. If strong field gravity is not accurately described by general relativity (GR), then using GR templates may result in fundamental bias in the recovered parameters, or even worse, a complete failure to detect signals. Here we study such dangers, concentrating on three distinct possibilities. First, we show that there exist modified theories compatible with all existing observations that would fail to be detected by the LIGO/Virgo network using searches based on GR templates, but which would be detected using a one parameter post-Einsteinian extension. Second, we study modified theories that produce departures from GR that turn on suddenly at a critical frequency, producing waveforms that do not directly fit into the simplest parametrized post-Einsteinian (ppE) scheme. We show that even the simplest ppE templates are still capable of picking up these strange signals and diagnosing a departure from GR. Third, we study whether using inspiral-only ppE waveforms for signals that include merger and ringdown can lead to problems in misidentifying a GR departure. We present a simple technique that allows us to self-consistently identify the inspiral portion of the signal, and thus remove these potential biases, allowing GR tests to be performed on higher mass signals that merge within the detector band. We close by studying a parametrized waveform model that may allow us to test GR using the full inspiral-merger-ringdown signal.

Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations

NASA Astrophysics Data System (ADS)

Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

2017-02-01

Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations.

PubMed

Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

2017-02-06

Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw.

PubMed

Sun, Yujie; Kaur, Kawaljit; Kanayama, Keiichi; Morinaga, Kenzo; Park, Sil; Hokugo, Akishige; Kozlowska, Anna; McBride, William H; Li, Jun; Jewett, Anahid; Nishimura, Ichiro

2016-09-23

Injury to the barrier tissue initiates a rapid distribution of myeloid immune cells from bone marrow, which guide sound wound healing. Bisphosphonates, a widely used anti-bone resorptive drug with minimal systemic side effects, have been linked to an abnormal wound healing in the oral barrier tissue leading to, in some cases, osteonecrosis of the jaw (ONJ). Here we report that the development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+ myeloid cells in the oral barrier tissue undergoing tooth extraction wound healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice followed by maxillary first molar extraction resulted in the development of ONJ-like lesion during the second week of wound healing. The multiplex assay of dissociated oral barrier cells exhibited the secretion of cytokines and chemokines, which was significantly modulated in ZOL mice. Tooth extraction-induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with abnormal size and morphology as well as different flow cytometric staining intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5 days during the second week of tooth extraction, CD11b+GR1(hi) cells in bone marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the development of ONJ-like lesion was significantly attenuated. This study suggests that local modulation of myeloid cell plasticity in the oral barrier tissue may provide the basis for pathogenesis and thus therapeutic as well as preventive strategy of ONJ. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Gyroscope-reduced inertial navigation system for flight vehicle motion estimation

NASA Astrophysics Data System (ADS)

Wang, Xin; Xiao, Lu

2017-01-01

In this paper, a novel configuration of strategically distributed accelerometer sensors with the aid of one gyro to infer a flight vehicle's angular motion is presented. The MEMS accelerometer and gyro sensors are integrated to form a gyroscope-reduced inertial measurement unit (GR-IMU). The motivation for gyro aided accelerometers array is to have direct measurements of angular rates, which is an improvement to the traditional gyroscope-free inertial system that employs only direct measurements of specific force. Some technical issues regarding error calibration in accelerometers and gyro in GR-IMU are put forward. The GR-IMU based inertial navigation system can be used to find a complete attitude solution for flight vehicle motion estimation. Results of numerical simulation are given to illustrate the effectiveness of the proposed configuration. The gyroscope-reduced inertial navigation system based on distributed accelerometer sensors can be developed into a cost effective solution for a fast reaction, MEMS based motion capture system. Future work will include the aid from external navigation references (e.g. GPS) to improve long time mission performance.

Inhomogeneity in barrier height at graphene/Si (GaAs) Schottky junctions.

PubMed

Tomer, D; Rajput, S; Hudy, L J; Li, C H; Li, L

2015-05-29

Graphene (Gr) interfaced with a semiconductor forms a Schottky junction with rectifying properties, however, fluctuations in the Schottky barrier height are often observed. In this work, Schottky junctions are fabricated by transferring chemical vapor deposited monolayer Gr onto n-type Si and GaAs substrates. Temperature dependence of the barrier height and ideality factor are obtained by current-voltage measurements between 215 and 350 K. An increase in the zero bias barrier height and decrease in the ideality factor are observed with increasing temperature for both junctions. Such behavior is attributed to barrier inhomogeneities that arise from interfacial disorders as revealed by scanning tunneling microscopy/spectroscopy. Assuming a Gaussian distribution of the barrier heights, mean values of 1.14 ± 0.14 eV and 0.76 ± 0.10 eV are found for Gr/Si and Gr/GaAs junctions, respectively. These findings resolve the origin of barrier height inhomogeneities in these Schottky junctions.

Characterization of an Adhesion Molecule that Mediates Leukocyte Rolling on 24 h Cytokine- or Lipopolysaccharide-stimulated Bovine Endothelial Cells under Flow Conditions

PubMed Central

Jutila, Mark A.; Wilson, Eric; Kurk, Sandy

1997-01-01

Bovine γ/δ T cells and neutrophils roll on 24 h cytokine- or lipopolysaccharide-stimulated bovine fetal umbilical cord endothelial cells in assays done under physiological flow. An antibody directed against E- and L-selectin has minimal blocking effect on this rolling interaction. mAbs were raised against the stimulated bovine endothelial cells and screened for inhibition of γ/δ T cell rolling. One mAb (GR113) was identified that recognizes an antigen (GR antigen) selectively expressed by stimulated bovine endothelial cells isolated from fetal umbilical cord, mesenteric lymph nodes, and aorta. GR113 blocked bovine γ/δ T cell as well as neutrophil rolling on the 24 h-activated endothelial cells. The GR antigen was constitutively expressed at low levels on the cell surface of platelets and its expression was not upregulated after stimulation of these cells with thrombin or phorbol myristate acetate. However, stimulated platelets released a soluble, functionally active form of the molecule that selectively bound in solution to γ/δ T cells in a mixed lymphocyte preparation. GR113 mAb blocked the binding of the soluble platelet molecule to the γ/δ T cells. Soluble GR antigen also bound a subset of human lymphocytes. Cutaneous lymphocyte-associated antigen (CLA) bright human lymphocytes exhibited the greatest capacity to bind the GR antigen, though CLA was not required for binding. Subsets of both human CD4 and CD8 T cells bound the GR antigen. Immunoprecipitation experiments showed the GR antigen to be 110-120 kD M r. The binding of soluble GR antigen was inhibited by EDTA and O-sialoglycoprotease, but not neuraminidase treatment of the target cells. PMID:9362530

Key algorithms used in GR02: A computer simulation model for predicting tree and stand growth

Treesearch

Garrett A. Hughes; Paul E. Sendak; Paul E. Sendak

1985-01-01

GR02 is an individual tree, distance-independent simulation model for predicting tree and stand growth over time. It performs five major functions during each run: (1) updates diameter at breast height, (2) updates total height, (3) estimates mortality, (4) determines regeneration, and (5) updates crown class.

Hydrogen Sulfide Attenuates the Recruitment of CD11b+Gr-1+ Myeloid Cells and Regulates Bax/Bcl-2 Signaling in Myocardial Ischemia Injury

PubMed Central

Zhang, Youen; Li, Hua; Zhao, Gang; Sun, Aijun; Zong, Nobel C.; Li, Zhaofeng; Zhu, Hongming; Zou, Yunzeng; Yang, Xiangdong; Ge, Junbo

2014-01-01

Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b+Gr-1+ myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b+Gr-1+ myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b+Gr-1+ myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling. PMID:24758901

Intracellular glucocorticoid receptors in spleen, but not skin, vary seasonally in wild house sparrows (Passer domesticus)

PubMed Central

Lattin, Christine R.; Waldron-Francis, K.; Romero, L. Michael

2013-01-01

Over the short-term and at physiological doses, acute increases in corticosterone (CORT) titres can enhance immune function. There are predictable seasonal patterns in both circulating CORT and immune function across many animal species, but whether CORT receptor density in immune tissues varies seasonally is currently unknown. Using radioligand binding assays, we examined changes in concentrations of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) in spleen and skin in wild-caught house sparrows in Massachusetts during six different life-history stages: moult, early winter, late winter, pre-egg-laying, breeding and late breeding. Splenic GR and MR binding were highest during the pre-laying period. This may help animals respond to immune threats through increased lymphocyte proliferation and/or an increase in delayed-type hypersensitivity reactions, both of which CORT can stimulate and in which spleen is involved. A decrease in splenic GR and MR during the late breeding period coincides with low baseline and stress-induced CORT, suggesting immune function in spleen may be relatively CORT-independent during this period. We saw no seasonal patterns in GR or MR in skin, suggesting skin's response to CORT is modulated primarily via changes in circulating CORT titres and/or via local production of CORT in response to wounding and other noxious stimuli. PMID:23407837

Multi-modal albedo distributions in the ablation area of the southwestern Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Moustafa, S. E.; Rennermalm, A. K.; Smith, L. C.; Miller, M. A.; Mioduszewski, J. R.; Koenig, L. S.; Hom, M. G.; Shuman, C. A.

2015-05-01

Surface albedo is a key variable controlling solar radiation absorbed at the Greenland Ice Sheet (GrIS) surface and, thus, meltwater production. Recent decline in surface albedo over the GrIS has been linked to enhanced snow grain metamorphic rates, earlier snowmelt, and amplified melt-albedo feedback from atmospheric warming. However, the importance of distinct surface types on ablation area albedo and meltwater production is still relatively unknown. In this study, we analyze albedo and ablation rates using in situ and remotely sensed data. Observations include (1) a new high-quality in situ spectral albedo data set collected with an Analytical Spectral Devices Inc. spectroradiometer measuring at 325-1075 nm along a 1.25 km transect during 3 days in June 2013; (2) broadband albedo at two automatic weather stations; and (3) daily MODerate Resolution Imaging Spectroradiometer (MODIS) albedo (MOD10A1) between 31 May and 30 August 2012 and 2013. We find that seasonal ablation area albedos in 2013 have a bimodal distribution, with snow and ice facies characterizing the two peaks. Our results show that a shift from a distribution dominated by high to low albedos corresponds to an observed melt rate increase of 51.5% (between 10-14 July and 20-24 July 2013). In contrast, melt rate variability caused by albedo changes before and after this shift was much lower and varied between ~10 and 30% in the melting season. Ablation area albedos in 2012 exhibited a more complex multimodal distribution, reflecting a transition from light to dark-dominated surface, as well as sensitivity to the so called "dark-band" region in southwest Greenland. In addition to a darkening surface from ice crystal growth, our findings demonstrate that seasonal changes in GrIS ablation area albedos are controlled by changes in the fractional coverage of snow, bare ice, and impurity-rich surface types. Thus, seasonal variability in ablation area albedos appears to be regulated primarily as a function of bare ice expansion at the expense of snow, surface meltwater ponding, and melting of outcropped ice layers enriched with mineral materials, enabling dust and impurities to accumulate. As climate change continues in the Arctic region, understanding the seasonal evolution of ice sheet surface types in Greenland's ablation area is critical to improve projections of mass loss contributions to sea level rise.

Charge-transfer channel in quantum dot-graphene hybrid materials

NASA Astrophysics Data System (ADS)

Cao, Shuo; Wang, Jingang; Ma, Fengcai; Sun, Mengtao

2018-04-01

The energy band theory of a classical semiconductor can qualitatively explain the charge-transfer process in low-dimensional hybrid colloidal quantum dot (QD)-graphene (GR) materials; however, the definite charge-transfer channels are not clear. Using density functional theory (DFT) and time-dependent DFT, we simulate the hybrid QD-GR nanostructure, and by constructing its orbital interaction diagram, we show the quantitative coupling characteristics of the molecular orbitals (MOs) of the hybrid structure. The main MOs are derived from the fragment MOs (FOs) of GR, and the Cd13Se13 QD FOs merge with the GR FOs in a certain proportion to afford the hybrid system. Upon photoexcitation, electrons in the GR FOs jump to the QD FOs, leaving holes in the GR FOs, and the definite charge-transfer channels can be found by analyzing the complex MOs coupling. The excited electrons and remaining holes can also be localized in the GR or the QD or transfer between the QD and GR with different absorption energies. The charge-transfer process for the selected excited states of the hybrid QD-GR structure are testified by the charge difference density isosurface. The natural transition orbitals, charge-transfer length analysis and 2D site representation of the transition density matrix also verify the electron-hole delocalization, localization, or coherence chacracteristics of the selected excited states. Therefore, our research enhances understanding of the coupling mechanism of low-dimensional hybrid materials and will aid in the design and manipulation of hybrid photoelectric devices for practical application in many fields.

Charge-transfer channel in quantum dot-graphene hybrid materials.

PubMed

Cao, Shuo; Wang, Jingang; Ma, Fengcai; Sun, Mengtao

2018-04-06

The energy band theory of a classical semiconductor can qualitatively explain the charge-transfer process in low-dimensional hybrid colloidal quantum dot (QD)-graphene (GR) materials; however, the definite charge-transfer channels are not clear. Using density functional theory (DFT) and time-dependent DFT, we simulate the hybrid QD-GR nanostructure, and by constructing its orbital interaction diagram, we show the quantitative coupling characteristics of the molecular orbitals (MOs) of the hybrid structure. The main MOs are derived from the fragment MOs (FOs) of GR, and the Cd 13 Se 13 QD FOs merge with the GR FOs in a certain proportion to afford the hybrid system. Upon photoexcitation, electrons in the GR FOs jump to the QD FOs, leaving holes in the GR FOs, and the definite charge-transfer channels can be found by analyzing the complex MOs coupling. The excited electrons and remaining holes can also be localized in the GR or the QD or transfer between the QD and GR with different absorption energies. The charge-transfer process for the selected excited states of the hybrid QD-GR structure are testified by the charge difference density isosurface. The natural transition orbitals, charge-transfer length analysis and 2D site representation of the transition density matrix also verify the electron-hole delocalization, localization, or coherence chacracteristics of the selected excited states. Therefore, our research enhances understanding of the coupling mechanism of low-dimensional hybrid materials and will aid in the design and manipulation of hybrid photoelectric devices for practical application in many fields.

Transcriptome analysis of reproductive-stage Arabidopsis plants exposed gamma-ray irradiation at various doses.

PubMed

Hwang, Sun-Goo; Kim, Dong Sub; Kim, Jin-Baek; Hwang, Jung Eun; Park, Hyun Mi; Kim, Jin Hyuk; Jang, Cheol Seong

2016-08-01

Gamma rays (GR) induce significant changes in the structure and expression of genes involved in the regulation of diverse biochemical and physiological processes. Arabidopsis plants exhibit different growth and development patterns in response to exposure to GR. The effects on gene expression of different radiation doses of GR (100 and 800 Gy) administered to Arabidopsis plants were examined at the reproductive stage. We irradiated 26-day-old plants with three replications [developmental stages 5.1-6.0, according to Boyes et al. ( 2001 )] using a GR irradiator (60 Co, ca. 150 TBq capacity, Atomic Energy of Canada Limited, Ontario, Canada) at the Korea Atomic Energy Research Institute. Plants were treated with 100, 200, 300, 400, 800, 1200, 1600, or 2000 Gy, and the doses were made from varying the distance to the source. We conducted a high-throughput screening analysis and detected 883 GR-responsive genes that showed significant changes; these were involved in several putative metabolic pathways related to biotic stress. Additionally, five overrepresented cis-regulatory elements were identified in the 1-kb upstream regions of GR-responsive genes by using motif enrichment analysis. We also detected three GR-responsive genes associated with stamen development and confirmed their co-regulation with functionally interacting genes. This finding suggests that a network-based analysis is a viable approach to identify significant GR-responsive genes associated with the reproductive stage of Arabidopsis. Our results provide further insights into the complex biological systems involved in the response to different doses of GR in plants.

A report on the current status of grand rounds in radiology residency programs in the United States.

PubMed

Yablon, Corrie M; Wu, Jim S; Slanetz, Priscilla J; Eisenberg, Ronald L

2011-12-01

A national needs assessment of radiology program directors was performed to characterize grand rounds (GR) programs, assess the perceived educational value of GR programs, and determine the impact of the recent economic downturn on GR. A 28-question survey was developed querying the organizational logistics of GR programs, types of speakers, content of talks, honoraria, types of speakers invited, response to the economic downturn, types of speaker interaction with residents, and perceived educational value of GR. Questions were in multiple-choice, yes-or-no, and five-point Likert-type formats. The survey was distributed to the program directors of all radiology residencies within the United States. Fifty-seven of 163 programs responded, resulting in a response rate of 36%. Thirty-eight programs (67%) were university residencies and 10 (18%) were university affiliated. Eighty-two percent of university and 60% of university-affiliated residencies had their own GR programs, while only 14% of community and no military residencies held GR. GR were held weekly in 18% of programs, biweekly in 8%, monthly in 42%, bimonthly in 16%, and less frequently than every 2 months in 16%. All 38 programs hosting GR reported a broad spectrum of presentations, including talks on medical education (66%), clinical and evidence-based medicine (55%), professionalism (45%), ethics (45%), quality assurance (34%), global health (26%), and resident presentations (26%). All programs invited speakers from outside the institution, but there was variability with regard to the frequency of visits and whether invited speakers were from out of town. As a result of recent economic events, one radiology residency (3%) completely canceled its GR program. Others decreased the number of speakers from outside their cities (40%) or decreased the number of speakers from within their own cities (16%). Honoraria were paid to speakers by 95% of responding programs. Most program directors (79%) who had their own GR programs either strongly agreed or agreed that GR are an essential component of any academic radiology department, and this opinion was shared by a majority of all respondents (68%). Almost all respondents (97%) either strongly agreed or agreed that general radiologic education of imaging subspecialists is valuable in an academic radiology department. A majority (65%) either strongly agreed or agreed that attendance at GR should be expected of all attending radiologists. GR programs among radiology residencies tend to have similar formats involving invited speakers, although the frequency, types of talks, and honoraria may vary slightly. Most programs value GR, and all programs integrate GR within resident education to some degree. The recent economic downturn has led to a decrease in the number of invited visiting speakers but not to a decrease in the amounts of honoraria. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Arabidopsis GLUTATHIONE REDUCTASE1 Plays a Crucial Role in Leaf Responses to Intracellular Hydrogen Peroxide and in Ensuring Appropriate Gene Expression through Both Salicylic Acid and Jasmonic Acid Signaling Pathways1[C][W][OA

PubMed Central

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-01-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H2O2) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H2O2 signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H2O2. Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H2O2-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H2O2 availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system. PMID:20488891

Region-specific Alterations in Glucocorticoid Receptor Expression in the Postmortem Brain of Teenage Suicide Victims

PubMed Central

Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Dwivedi, Yogesh; Palkovits, Miklós

2013-01-01

Introduction Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Methods Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. Results We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls. Conclusions These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time. PMID:23845513

Arabidopsis GLUTATHIONE REDUCTASE1 plays a crucial role in leaf responses to intracellular hydrogen peroxide and in ensuring appropriate gene expression through both salicylic acid and jasmonic acid signaling pathways.

PubMed

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-07-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H(2)O(2)) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H(2)O(2) signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H(2)O(2). Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H(2)O(2)-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H(2)O(2) availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system.

NRIP enhances HPV gene expression via interaction with either GR or E2

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

Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong

We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, inmore » a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.« less

Functional characterization of PhGR and PhGRL1 during flower senescence in the petunia.

PubMed

Yang, Weiyuan; Liu, Juanxu; Tan, Yinyan; Zhong, Shan; Tang, Na; Chen, Guoju; Yu, Yixun

2015-09-01

Petunia PhGRL1 suppression accelerated flower senescence and increased the expression of the genes downstream of ethylene signaling, whereas PhGR suppression did not. Ethylene plays an important role in flowers senescence. Homologous proteins Green-Ripe and Reversion to Ethylene sensitivity1 are positive regulators of ethylene responses in tomato and Arabidopsis, respectively. The petunia flower has served as a model for the study of ethylene response during senescence. In this study, petunia PhGR and PhGRL1 expression was analyzed in different organs, throughout floral senescence, and after exogenous ethylene treatment; and the roles of PhGR and PhGRL1 during petunia flower senescence were investigated. PhGRL1 suppression mediated by virus-induced gene silencing accelerated flower senescence and increased ethylene production; however, the suppression of PhGR did not. Taken together, these data suggest that PhGRL1 is involved in negative regulation of flower senescence, possibly via ethylene production inhibition and consequently reduced ethylene signaling activation.

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

PubMed Central

Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

2015-01-01

Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

The Multifaceted Mineralocorticoid Receptor

PubMed Central

Gomez-Sanchez, Elise; Gomez-Sanchez, Celso E.

2015-01-01

The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non-genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β-HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β-HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β-HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect. PMID:24944027

Simultaneous determination of ascorbic acid, dopamine and uric acid based on tryptophan functionalized graphene.

PubMed

Lian, Qianwen; He, Zhifang; He, Qian; Luo, Ai; Yan, Kaiwang; Zhang, Dongxia; Lu, Xiaoquan; Zhou, Xibin

2014-05-01

A new type of tryptophan-functionalized graphene nanocomposite (Trp-GR) was synthesized by utilizing a facile ultrasonic method via π-π conjugate action between graphene (GR) and tryptophan (Trp) molecule. The material as prepared had well dispersivity in water and better conductivity than pure GR. The surface morphology of Trp-GR was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The electrochemical behaviors of ascorbic acid (AA), dopamine (DA), and uric acid (UA) were investigated by cyclic voltammetry (CV) on the surface of Trp-GR. The separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 182 mV, 125 mV and 307 mV, which allowed simultaneously determining AA, DA, and UA. Differential pulse voltammetery (DPV) was used for the determination of AA, DA, and UA in their mixture. Under optimum conditions, the linear response ranges for the determination of AA, DA, and UA were 0.2-12.9 mM, 0.5-110 μM, and 10-1000 μM, with the detection limits (S/N=3) of 10.09 μM, 0.29 μM and 1.24 μM, respectively. Furthermore, the modified electrode was investigated for real sample analysis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Pollination and reproduction of an invasive plant inside and outside its ancestral range

NASA Astrophysics Data System (ADS)

Petanidou, Theodora; Price, Mary V.; Bronstein, Judith L.; Kantsa, Aphrodite; Tscheulin, Thomas; Kariyat, Rupesh; Krigas, Nikos; Mescher, Mark C.; De Moraes, Consuelo M.; Waser, Nickolas M.

2018-05-01

Comparing traits of invasive species within and beyond their ancestral range may improve our understanding of processes that promote aggressive spread. Solanum elaeagnifolium (silverleaf nightshade) is a noxious weed in its ancestral range in North America and is invasive on other continents. We compared investment in flowers and ovules, pollination success, and fruit and seed set in populations from Arizona, USA ("AZ") and Greece ("GR"). In both countries, the populations we sampled varied in size and types of present-day disturbance. Stature of plants increased with population size in AZ samples whereas GR plants were uniformly tall. Taller plants produced more flowers, and GR plants produced more flowers for a given stature and allocated more ovules per flower. Similar functional groups of native bees pollinated in AZ and GR populations, but visits to flowers decreased with population size and we observed no visits in the largest GR populations. As a result, plants in large GR populations were pollen-limited, and estimates of fecundity were lower on average in GR populations despite the larger allocation to flowers and ovules. These differences between plants in our AZ and GR populations suggest promising directions for further study. It would be useful to sample S. elaeagnifolium in Mediterranean climates within the ancestral range (e.g., in California, USA), to study asexual spread via rhizomes, and to use common gardens and genetic studies to explore the basis of variation in allocation patterns and of relationships between visitation and fruit set.

Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: effects on energy metabolism.

PubMed

Adzic, Miroslav; Lukic, Iva; Mitic, Milos; Djordjevic, Jelena; Elaković, Ivana; Djordjevic, Ana; Krstic-Demonacos, Marija; Matić, Gordana; Radojcic, Marija

2013-12-01

Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fluoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fluoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bimodal albedo distributions in the ablation zone of the southwestern Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Moustafa, S. E.; Rennermalm, A. K.; Smith, L. C.; Miller, M. A.; Mioduszewski, J. R.

2014-09-01

Surface albedo is a key variable controlling solar radiation absorbed at the Greenland Ice Sheet (GrIS) surface, and thus, meltwater production. Recent decline in surface albedo over the GrIS has been linked to enhanced snow grain metamorphic rates and amplified ice-albedo feedback from atmospheric warming. However, the importance of distinct surface types on ablation zone albedo and meltwater production is still relatively unknown, and excluded in surface mass balance models. In this study, we analyze albedo and ablation rates using in situ and remotely-sensed data. Observations include: (1) a new high-quality in situ spectral albedo dataset collected with an Analytical Spectral Devices (ASD) spectroradiometer measuring at 325-1075 nm, along a 1.25 km transect during three days in June 2013; (2) broadband albedo at two automatic weather stations; and (3) daily MODerate Resolution Imaging Spectroradiometer (MODIS) albedo (MOD10A1) between 31 May and 30 August. We find that seasonal ablation zone albedos have a bimodal distribution, with two alternate states. This suggests that an abrupt switch from high to low albedo can be triggered by a modest melt event, resulting in amplified surface ablation rates. Our results show that such a shift corresponds to an observed melt rate percent difference increase of 51.6% during peak melt season (between 10-14 and 20-24 July 2013). Furthermore, our findings demonstrate that seasonal changes in GrIS ablation zone albedo are not exclusively a function of a darkening surface from ice crystal growth, but rather are controlled by changes in the fractional coverage of snow, bare ice, and impurity-rich surface types. As the climate continues to warm, regional climate models should consider the seasonal evolution of ice surface types in Greenland's ablation zone to improve projections of mass loss contributions to sea level rise.

Bimodal Albedo Distributions in the Ablation Zone of the Southwestern Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Moustafa, S.; Rennermalm, A. K.; Smith, L. C.; Miller, M. A.; Mioduszewski, J.; Koenig, L.

2014-12-01

Surface albedo is a key variable controlling solar radiation absorbed at the Greenland Ice Sheet (GrIS) surface, and thus meltwater production. Recent decline in surface albedo over the GrIS has been linked to enhanced snow grain metamorphic rates and amplified ice-albedo feedback from atmospheric warming. However, the importance of distinct surface types on ablation zone albedo and meltwater production is still relatively unknown, and excluded in surface mass balance models. In this study, we analyze albedo and ablation rates (m d-1) using in situ and remotely-sensed data. Observations include: 1) a new high-quality in situ spectral albedo dataset collected with an Analytical Spectral Devices (ASD) spectroradiometer measuring at 325-1075 nm, along a 1.25 km transect during three days in June 2013; 2) broadband albedo at two automatic weather stations; and 3) daily MODerate Resolution Imaging Spectroradiometer (MODIS) albedo (MOD10A1) between 31 May and 30 August. We find that seasonal ablation zone albedos have a bimodal distribution, with two alternate states. This suggests that an abrupt switch from high to low albedo can be triggered by a modest melt event, resulting in amplified ablation rates. Our results show that such a shift corresponds to an observed melt rate percent difference increase of 51.6% during peak melt season (between 10-14 July and 20-24 July, 2013). Furthermore, our findings demonstrate that seasonal changes in GrIS ablation zone albedo are not exclusively a function of a darkening surface from ice crystal growth, but rather are controlled by changes in the fractional coverage of snow, bare ice, and impurity-rich surface types. As the climate continues to warm, regional climate models should consider the seasonal evolution of ice surface types in Greenland's ablation zone to improve projections of mass loss contributions to sea level rise.

Historical contingency and its biophysical basis in glucocorticoid receptor evolution.

PubMed

Harms, Michael J; Thornton, Joseph W

2014-08-14

Understanding how chance historical events shape evolutionary processes is a central goal of evolutionary biology. Direct insights into the extent and causes of evolutionary contingency have been limited to experimental systems, because it is difficult to know what happened in the deep past and to characterize other paths that evolution could have followed. Here we combine ancestral protein reconstruction, directed evolution and biophysical analysis to explore alternative 'might-have-been' trajectories during the ancient evolution of a novel protein function. We previously found that the evolution of cortisol specificity in the ancestral glucocorticoid receptor (GR) was contingent on permissive substitutions, which had no apparent effect on receptor function but were necessary for GR to tolerate the large-effect mutations that caused the shift in specificity. Here we show that alternative mutations that could have permitted the historical function-switching substitutions are extremely rare in the ensemble of genotypes accessible to the ancestral GR. In a library of thousands of variants of the ancestral protein, we recovered historical permissive substitutions but no alternative permissive genotypes. Using biophysical analysis, we found that permissive mutations must satisfy at least three physical requirements--they must stabilize specific local elements of the protein structure, maintain the correct energetic balance between functional conformations, and be compatible with the ancestral and derived structures--thus revealing why permissive mutations are rare. These findings demonstrate that GR evolution depended strongly on improbable, non-deterministic events, and this contingency arose from intrinsic biophysical properties of the protein.

Dispersal, patch Leaving, and distribution of Homalodisca vitripennis (Hemiptera: Cicadellidae)

USDA-ARS?s Scientific Manuscript database

Influences on the dispersal, distribution, and residence times of the glassy-winged sharpshooter leafhopper, Homalodisca vitripennis (Germar), were measured to establish a model of leafhopper behavior. This model aids in the management and design of cropping systems to reduce Pierce’s disease in gr...

Dopamine inhibits the function of Gr-1+CD115+ myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity.

PubMed

Wu, Jin; Zhang, Ruihua; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Chen, Kang; Cai, Wei

2015-01-01

MDSCs accumulate in tumor-bearing animals and cancer patients and are a major factor responsible for cancer-induced immunosuppression that limits effective cancer immunotherapy. Strategies aimed at effectively inhibiting the function of MDSCs are expected to enhance host anti-tumor immunity and improve cancer immunotherapy significantly. The neurotransmitter DA has been found to have anti-cancer activity, but the underlying mechanism is poorly understood. In this study, we sought to investigate the therapeutic mechanism and efficacy of DA on the inhibition of cancer development via the regulation of MDSC functions. The regulation of the suppressive function of Gr-1(+)CD115(+) MDSCs by DA was determined by use of murine syngeneic LLC and B16 graft models treated with DA in vivo, as well as Gr-1(+)CD115(+) MDSCs isolated from these model treated with DA ex vivo. Here, we show that Gr-1(+)CD115(+) monocytic MDSCs express D1-like DA receptors. DA dramatically attenuated the inhibitory function of tumor-induced monocytic MDSCs on T cell proliferation and IFN-γ production via D1-like DA receptors and retarded tumor growth. DA and other D1 receptor agonists inhibited IFN-γ-induced NO production by MDSCs from tumor-bearing mice and cancer patients. Decreased NO production was, in part, mediated via the suppression of p-ERK and p-JNK. In conclusion, the neurotransmitter DA potently inhibits the suppressive function of MDSC and enhances anti-tumor immunity. Our finding provides a mechanistic basis for the use of DA or D1-like receptor agonists to overcome tumor-induced immunosuppression in cancer immunotherapy. © Society for Leukocyte Biology.

Extracting the pair distribution function of liquids and liquid-vapor surfaces by grazing incidence x-ray diffraction mode.

PubMed

Vaknin, David; Bu, Wei; Travesset, Alex

2008-07-28

We show that the structure factor S(q) of water can be obtained from x-ray synchrotron experiments at grazing angle of incidence (in reflection mode) by using a liquid surface diffractometer. The corrections used to obtain S(q) self-consistently are described. Applying these corrections to scans at different incident beam angles (above the critical angle) collapses the measured intensities into a single master curve, without fitting parameters, which within a scale factor yields S(q). Performing the measurements below the critical angle for total reflectivity yields the structure factor of the top most layers of the water/vapor interface. Our results indicate water restructuring at the vapor/water interface. We also introduce a new approach to extract g(r), the pair distribution function (PDF), by expressing the PDF as a linear sum of error functions whose parameters are refined by applying a nonlinear least square fit method. This approach enables a straightforward determination of the inherent uncertainties in the PDF. Implications of our results to previously measured and theoretical predictions of the PDF are also discussed.

CpG Distribution and Methylation Pattern in Porcine Parvovirus

PubMed Central

Tóth, Renáta; Mészáros, István; Stefancsik, Rajmund; Bartha, Dániel; Bálint, Ádám; Zádori, Zoltán

2013-01-01

Based on GC content and the observed/expected CpG ratio (oCpGr), we found three major groups among the members of subfamily Parvovirinae: Group I parvoviruses with low GC content and low oCpGr values, Group II with low GC content and high oCpGr values and Group III with high GC content and high oCpGr values. Porcine parvovirus belongs to Group I and it features an ascendant CpG distribution by position in its coding regions similarly to the majority of the parvoviruses. The entire PPV genome remains hypomethylated during the viral lifecycle independently from the tissue of origin. In vitro CpG methylation of the genome has a modest inhibitory effect on PPV replication. The in vitro hypermethylation disappears from the replicating PPV genome suggesting that beside the maintenance DNMT1 the de novo DNMT3a and DNMT3b DNA methyltransferases can’t methylate replicating PPV DNA effectively either, despite that the PPV infection does not seem to influence the expression, translation or localization of the DNA methylases. SNP analysis revealed high mutability of the CpG sites in the PPV genome, while introduction of 29 extra CpG sites into the genome has no significant biological effects on PPV replication in vitro. These experiments raise the possibility that beyond natural selection mutational pressure may also significantly contribute to the low level of the CpG sites in the PPV genome. PMID:24392033

Reduction of halogenated ethanes by green rust.

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

O'Loughlin, E. J.; Burris, D. R.; Environmental Research

Green rusts, mixed Fe{sup II}/Fe{sup III} hydroxide minerals present in many suboxic environments, have been shown to reduce a number of organic and inorganic contaminants. The reduction of halogenated ethanes was examined in aqueous suspensions of green rust, both alone and with the addition of Ag{sup I} (AgGR) and Cu{sup II} (CuGR). Hexachloroethane (HCA), pentachloroethane (PCA), 1,1,1,2-tetrachloroethane (1,1,1,2-TeCA), 1,1,2,2-tetrachloroethane (1,1,2,2-TeCA), 1,1,1-trichloroethane (1,1,1-TCA), 1,1,2-trichloroethane (1,1,2-TCA), 1,1-dichloroethane (1,1-DCA), and 1,2-dibromoethane were reduced in the presence of green rust alone, AgGR, or CuGR; only 1,2-dichloroethane and chloroethane were nonreactive. The reduction was generally more rapid for more highly substituted ethanes than for ethanesmore » having fewer halogen groups (HCA > PCA > 1,1,1,2-TeCA > 1,1,1-TCA > 1,1,2,2-TeCA > 1,1,2-TCA > 1,1-DCA), and isomers with the more asymmetric distributions of halogen groups were more rapidly reduced than the isomer with greater symmetry (e.g., 1,1,1-TCA > 1,1,2-TCA). The addition of Ag{sup I} or Cu{sup II} to green rust suspensions resulted in a substantial increase in the rate of halogenated ethane reduction as well as significant differences in the product distributions with respect to green rust alone.« less

The role of the substrate in Graphene/Silicon photodiodes

NASA Astrophysics Data System (ADS)

Luongo, G.; Giubileo, F.; Iemmo, L.; Di Bartolomeo, A.

2018-01-01

The Graphene/Silicon (Gr/Si) junction can function as a Schottky diode with performances strictly related to the quality of the interface. Here, we focus on the substrate geometry and on its effects on Gr/Si junction physics. We fabricate and study the electrical and optical behaviour of two types of devices: one made of a Gr/Si planar junction, the second realized with graphene on an array of Si nanotips. We show that the Gr/Si flat device exhibits a reverse photocurrent higher than the forward current and achieves a photoresponsivity of 2.5 A/W. The high photoresponse is due to the charges photogenerated in Si below a parasitic graphene/SiO2/Si structure, which are injected into the Gr/Si junction region. The other device with graphene on Si-tips displays a reverse current that grows exponentially with the bias. We explain this behaviour by taking into account the tip geometry of the substrate, which magnifies the electric field and shifts the Fermi level of graphene, thus enabling fine-tuning of the Schottky barrier height. The Gr/Si-tip device achieves a higher photoresponsivity, up to 3 A/W, likely due to photocharge internal multiplication.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

PubMed

Lee, M-S; Kim, Y-H; Park, W-S; Park, O-K; Kwon, S-H; Hong, K S; Rhim, H; Shim, I; Morita, K; Wong, D L; Patel, P D; Lyons, D M; Schatzberg, A F; Her, S

2016-02-01

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

Population structure of microbial communities associated with two deep, anaerobic, alkaline aquifers.

PubMed Central

Fry, N K; Fredrickson, J K; Fishbain, S; Wagner, M; Stahl, D A

1997-01-01

Microbial communities of two deep (1,270 and 316 m) alkaline (pH 9.94 and 8.05), anaerobic (Eh, -137 and -27 mV) aquifers were characterized by rRNA-based analyses. Both aquifers, the Grande Ronde (GR) and Priest rapids (PR) formations, are located within the Columbia River Basalt Group in south-central Washington, and sulfidogenesis and methanogenesis characterize the GR and PR formations, respectively. RNA was extracted from microorganisms collected from groundwater by ultrafiltration through hollow-fiber membranes and hybridized to taxon-specific oligonucleotide probes. Of the three domains, Bacteria dominated both communities, making up to 92.0 and 64.4% of the total rRNA from the GR and PR formations, respectively. Eucarya comprised 5.7 and 14.4%, and Archaea comprised 1.8% and 2.5%, respectively. The gram-positive target group was found in both aquifers, 11.7% in GR and 7.6% in PR. Two probes were used to target sulfate- and/or metal-reducing bacteria within the delta subclass of Proteobacteria. The Desulfobacter groups was present (0.3%) only in the high-sulfate groundwater (GR). However, comparable hybridization to a probe selective for the desulfovibrios and some metal-reducing bacteria was found in both aquifers, 2.5 and 2.9% from the GR and PR formations, respectively. Selective PCR amplification and sequencing of the desulfovibrio/metal-reducing group revealed a predominance of desulfovibrios in both systems (17 of 20 clones), suggesting that their environmental distribution is not restricted by sulfate availability. PMID:9097447

Population structure of microbial communities associated with two deep, anaerobic, alkaline aquifers.

PubMed

Fry, N K; Fredrickson, J K; Fishbain, S; Wagner, M; Stahl, D A

1997-04-01

Microbial communities of two deep (1,270 and 316 m) alkaline (pH 9.94 and 8.05), anaerobic (Eh, -137 and -27 mV) aquifers were characterized by rRNA-based analyses. Both aquifers, the Grande Ronde (GR) and Priest rapids (PR) formations, are located within the Columbia River Basalt Group in south-central Washington, and sulfidogenesis and methanogenesis characterize the GR and PR formations, respectively. RNA was extracted from microorganisms collected from groundwater by ultrafiltration through hollow-fiber membranes and hybridized to taxon-specific oligonucleotide probes. Of the three domains, Bacteria dominated both communities, making up to 92.0 and 64.4% of the total rRNA from the GR and PR formations, respectively. Eucarya comprised 5.7 and 14.4%, and Archaea comprised 1.8% and 2.5%, respectively. The gram-positive target group was found in both aquifers, 11.7% in GR and 7.6% in PR. Two probes were used to target sulfate- and/or metal-reducing bacteria within the delta subclass of Proteobacteria. The Desulfobacter groups was present (0.3%) only in the high-sulfate groundwater (GR). However, comparable hybridization to a probe selective for the desulfovibrios and some metal-reducing bacteria was found in both aquifers, 2.5 and 2.9% from the GR and PR formations, respectively. Selective PCR amplification and sequencing of the desulfovibrio/metal-reducing group revealed a predominance of desulfovibrios in both systems (17 of 20 clones), suggesting that their environmental distribution is not restricted by sulfate availability.

Determination of Optimal Harvest Time of Chuchung Variety Green Rice® (Oryza sativa L.) with High Contents of GABA, γ-Oryzanol, and α-Tocopherol

PubMed Central

Kim, Hoon; Kim, Oui-Woung; Ha, Ae Wha; Park, Soojin

2016-01-01

In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice® (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as γ-aminobutyric acid, γ-oryzanol, and α-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products. PMID:27390725

Determination of Optimal Harvest Time of Chuchung Variety Green Rice(®) (Oryza sativa L.) with High Contents of GABA, γ-Oryzanol, and α-Tocopherol.

PubMed

Kim, Hoon; Kim, Oui-Woung; Ha, Ae Wha; Park, Soojin

2016-06-01

In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice(®) (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as γ-aminobutyric acid, γ-oryzanol, and α-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products.

Cysteine oxidation impairs systemic glucocorticoid responsiveness in children with difficult-to-treat asthma.

PubMed

Stephenson, Susan T; Brown, Lou Ann S; Helms, My N; Qu, Hongyan; Brown, Sheena D; Brown, Milton R; Fitzpatrick, Anne M

2015-08-01

The mechanisms underlying glucocorticoid responsiveness are largely unknown. Although redox regulation of the glucocorticoid receptor (GR) has been reported, it has not been studied in asthmatic patients. We characterized systemic cysteine oxidation and its association with inflammatory and clinical features in healthy children and children with difficult-to-treat asthma. We hypothesized that cysteine oxidation would be associated with increased markers of oxidative stress and inflammation, increased features of asthma severity, decreased clinically defined glucocorticoid responsiveness, and impaired GR function. PBMCs were collected from healthy children (n = 16) and children with asthma (n = 118) aged 6 to 17 years. Children with difficult-to-treat asthma underwent glucocorticoid responsiveness testing with intramuscular triamcinolone. Cysteine, cystine, and inflammatory chemokines and reactive oxygen species generation were quantified, and expression and activity of the GR were assessed. Cysteine oxidation was present in children with difficult-to-treat asthma and accompanied by increased reactive oxygen species generation and increased CCL3 and CXCL1 mRNA expression. Children with the greatest extent of cysteine oxidation had more features of asthma severity, including poorer symptom control, greater medication use, and less glucocorticoid responsiveness despite inhaled glucocorticoid therapy. Cysteine oxidation also modified the GR protein by decreasing available sulfhydryl groups and decreasing nuclear GR expression and activity. A highly oxidized cysteine redox state promotes a posttranslational modification of the GR that might inhibit its function. Given that cysteine oxidation is prevalent in children with difficult-to-treat asthma, the cysteine redox state might represent a potential therapeutic target for restoration of glucocorticoid responsiveness in this population. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Equation of State for Detonation Product Gases

NASA Astrophysics Data System (ADS)

Nagayama, Kunihito; Kubota, Shiro

2013-06-01

Based on the empirical linear relationship between detonation velocity and loading density, an approximate description for the Chapman-Jouguet state for detonation product gases of solid phase high explosives has been developed. Provided that the Grüneisen parameter is a function only of volume, systematic and closed system of equations for the Grüneisen parameter and CJ volume have been formulated. These equations were obtained by combining this approximation with the Jones-Stanyukovich-Manson relation together with JWL isentrope for detonation of crystal density PETN. A thermodynamic identity between the Grüneisen parameter and another non-dimensional material parameter introduced by Wu and Jing can be used to derive the enthalpy-pressure-volume equation of state for detonation gases. This Wu-Jing parameter is found to be the ratio of the Grüneisen parameter and the adiabatic index. Behavior of this parameter as a function of pressure was calculated and revealed that their change with pressure is very gradual. By using this equation of state, several isentropes down from the Chapman-Jouguet states reached by four different lower initial density PETN have been calculated and compared with available cylinder expansion tests.

Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation.

PubMed

Cho, Hana; Park, Ok Hyun; Park, Joori; Ryu, Incheol; Kim, Jeonghan; Ko, Jesang; Kim, Yoon Ki

2015-03-31

Glucocorticoid receptor (GR), which was originally known to function as a nuclear receptor, plays a role in rapid mRNA degradation by acting as an RNA-binding protein. The mechanism by which this process occurs remains unknown. Here, we demonstrate that GR, preloaded onto the 5'UTR of a target mRNA, recruits UPF1 through proline-rich nuclear receptor coregulatory protein 2 (PNRC2) in a ligand-dependent manner, so as to elicit rapid mRNA degradation. We call this process GR-mediated mRNA decay (GMD). Although GMD, nonsense-mediated mRNA decay (NMD), and staufen-mediated mRNA decay (SMD) share upstream frameshift 1 (UPF1) and PNRC2, we find that GMD is mechanistically distinct from NMD and SMD. We also identify de novo cellular GMD substrates using microarray analysis. Intriguingly, GMD functions in the chemotaxis of human monocytes by targeting chemokine (C-C motif) ligand 2 (CCL2) mRNA. Thus, our data provide molecular evidence of a posttranscriptional role of the well-studied nuclear hormone receptor, GR, which is traditionally considered a transcription factor.

Current transport in graphene/AlGaN/GaN vertical heterostructures probed at nanoscale.

PubMed

Fisichella, Gabriele; Greco, Giuseppe; Roccaforte, Fabrizio; Giannazzo, Filippo

2014-08-07

Vertical heterostructures combining two or more graphene (Gr) layers separated by ultra-thin insulating or semiconductor barriers represent very promising systems for next generation electronics devices, due to the combination of high speed operation with wide-range current modulation by a gate bias. They are based on the specific mechanisms of current transport between two-dimensional-electron-gases (2DEGs) in close proximity. In this context, vertical devices formed by Gr and semiconductor heterostructures hosting an "ordinary" 2DEG can be also very interesting. In this work, we investigated the vertical current transport in Gr/Al(0.25)Ga(0.75)N/GaN heterostructures, where Gr is separated from a high density 2DEG by a ∼ 24 nm thick AlGaN barrier layer. The current transport from Gr to the buried 2DEG was characterized at nanoscale using conductive atomic force microscopy (CAFM) and scanning capacitance microscopy (SCM). From these analyses, performed both on Gr/AlGaN/GaN and on AlGaN/GaN reference samples using AFM tips with different metal coatings, the Gr/AlGaN Schottky barrier height ΦB and its lateral uniformity were evaluated, as well as the variation of the carrier densities of graphene (ngr) and AlGaN/GaN 2DEG (ns) as a function of the applied bias. A low Schottky barrier (∼ 0.40 eV) with excellent spatial uniformity was found at the Gr/AlGaN interface, i.e., lower compared to the measured values for metal/AlGaN contacts, which range from ∼ 0.6 to ∼ 1.1 eV depending on the metal workfunction. The electrical behavior of the Gr/AlGaN contact has been explained by Gr interaction with AlGaN donor-like surface states located in close proximity, which are also responsible of high n-type Gr doping (∼ 1.3 × 10(13) cm(-2)). An effective modulation of ns by the Gr Schottky contact was demonstrated by capacitance analysis under reverse bias. From this basic understanding of transport properties in Gr/AlGaN/GaN heterostructures, novel vertical field effect transistor concepts with high operating speed and I(on)/I(off) ratio can be envisaged.

Computing Role Assignments of Proper Interval Graphs in Polynomial Time

NASA Astrophysics Data System (ADS)

Heggernes, Pinar; van't Hof, Pim; Paulusma, Daniël

A homomorphism from a graph G to a graph R is locally surjective if its restriction to the neighborhood of each vertex of G is surjective. Such a homomorphism is also called an R-role assignment of G. Role assignments have applications in distributed computing, social network theory, and topological graph theory. The Role Assignment problem has as input a pair of graphs (G,R) and asks whether G has an R-role assignment. This problem is NP-complete already on input pairs (G,R) where R is a path on three vertices. So far, the only known non-trivial tractable case consists of input pairs (G,R) where G is a tree. We present a polynomial time algorithm that solves Role Assignment on all input pairs (G,R) where G is a proper interval graph. Thus we identify the first graph class other than trees on which the problem is tractable. As a complementary result, we show that the problem is Graph Isomorphism-hard on chordal graphs, a superclass of proper interval graphs and trees.

A ubiquitin carboxyl extension protein secreted from a plant-parasitic nematode Globodera rostochiensis is cleaved in planta to promote plant parasitism.

PubMed

Chronis, Demosthenis; Chen, Shiyan; Lu, Shunwen; Hewezi, Tarek; Carpenter, Sara C D; Loria, Rosemary; Baum, Thomas J; Wang, Xiaohong

2013-04-01

Nematode effector proteins originating from esophageal gland cells play central roles in suppressing plant defenses and in formation of the plant feeding cells that are required for growth and development of cyst nematodes. A gene (GrUBCEP12) encoding a unique ubiquitin carboxyl extension protein (UBCEP) that consists of a signal peptide for secretion, a mono-ubiquitin domain, and a 12 amino acid carboxyl extension protein (CEP12) domain was cloned from the potato cyst nematode Globodera rostochiensis. This GrUBCEP12 gene was expressed exclusively within the nematode's dorsal esophageal gland cell, and was up-regulated in the parasitic second-stage juvenile, correlating with the time when feeding cell formation is initiated. We showed that specific GrUBCEP12 knockdown via RNA interference reduced nematode parasitic success, and that over-expression of the secreted Gr(Δ) (SP) UBCEP12 protein in potato resulted in increased nematode susceptibility, providing direct evidence that this secreted effector is involved in plant parasitism. Using transient expression assays in Nicotiana benthamiana, we found that Gr(Δ) (SP) UBCEP12 is processed into free ubiquitin and a CEP12 peptide (GrCEP12) in planta, and that GrCEP12 suppresses resistance gene-mediated cell death. A target search showed that expression of RPN2a, a gene encoding a subunit of the 26S proteasome, was dramatically suppressed in Gr(Δ) (SP) UBCEP12 but not GrCEP12 over-expression plants when compared with control plants. Together, these results suggest that, when delivered into host plant cells, Gr(Δ) (SP) UBCEP12 becomes two functional units, one acting to suppress plant immunity and the other potentially affecting the host 26S proteasome, to promote feeding cell formation. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

PubMed

Luo, Wen-Hui; Yang, Ya-Wun

2016-04-01

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

A mean spherical model for soft potentials: The hard core revealed as a perturbation

NASA Technical Reports Server (NTRS)

Rosenfeld, Y.; Ashcroft, N. W.

1978-01-01

The mean spherical approximation for fluids is extended to treat the case of dense systems interacting via soft-potentials. The extension takes the form of a generalized statement concerning the behavior of the direct correlation function c(r) and radial distribution g(r). From a detailed analysis that views the hard core portion of a potential as a perturbation on the whole, a specific model is proposed which possesses analytic solutions for both Coulomb and Yukawa potentials, in addition to certain other remarkable properties. A variational principle for the model leads to a relatively simple method for obtaining numerical solutions.

Capture of dengue viruses using antibody-integrated graphite-encapsulated magnetic beads produced using gas plasma technology

PubMed Central

SAKUDO, AKIKAZU; VISWAN, ANCHU; CHOU, HAN; SASAKI, TADAHIRO; IKUTA, KAZUYOSHI; NAGATSU, MASAAKI

2016-01-01

Despite significant advances in medicine, global health is threatened by emerging infectious diseases caused by a number of viruses. Dengue virus (DENV) is a mosquito-borne virus, which can be transmitted to humans via mosquito vectors. Previously, the Ministry of Health, Labour and Welfare in Japan reported the country's first domestically acquired case of dengue fever for almost 70 years. To address this issue, it is important to develop novel technologies for the sensitive detection of DENV. The present study reported on the development of plasma-functionalized, graphite-encapsulated magnetic nanoparticles (GrMNPs) conjugated with anti-DENV antibody for DENV capture. Radiofrequency wave-excited inductively-coupled Ar and ammonia gas plasmas were used to introduce amino groups onto the surface of the GrMNPs. The GrMNPs were then conjugated with an antibody against DENV, and the antibody-integrated magnetic beads were assessed for their ability to capture DENV. Beads incubated in a cell culture medium of DENV-infected mosquito cells were separated from the supernatant by applying a magnetic field and were then washed. The adsorption of DENV serotypes 1–4 onto the beads was confirmed using reverse transcription-polymerase chain reaction, which detected the presence of DENV genomic RNA on the GrMNPs. The methodology described in the present study, which employed the plasma-functionalization of GrMNPs to enable antibody-integration, represents a significant improvement in the detection of DENV. PMID:27221214

Expression map of a complete set of gustatory receptor genes in chemosensory organs of Bombyx mori.

PubMed

Guo, Huizhen; Cheng, Tingcai; Chen, Zhiwei; Jiang, Liang; Guo, Youbing; Liu, Jianqiu; Li, Shenglong; Taniai, Kiyoko; Asaoka, Kiyoshi; Kadono-Okuda, Keiko; Arunkumar, Kallare P; Wu, Jiaqi; Kishino, Hirohisa; Zhang, Huijie; Seth, Rakesh K; Gopinathan, Karumathil P; Montagné, Nicolas; Jacquin-Joly, Emmanuelle; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

2017-03-01

Most lepidopteran species are herbivores, and interaction with host plants affects their gene expression and behavior as well as their genome evolution. Gustatory receptors (Grs) are expected to mediate host plant selection, feeding, oviposition and courtship behavior. However, due to their high diversity, sequence divergence and extremely low level of expression it has been difficult to identify precisely a complete set of Grs in Lepidoptera. By manual annotation and BAC sequencing, we improved annotation of 43 gene sequences compared with previously reported Grs in the most studied lepidopteran model, the silkworm, Bombyx mori, and identified 7 new tandem copies of BmGr30 on chromosome 7, bringing the total number of BmGrs to 76. Among these, we mapped 68 genes to chromosomes in a newly constructed chromosome distribution map and 8 genes to scaffolds; we also found new evidence for large clusters of BmGrs, especially from the bitter receptor family. RNA-seq analysis of diverse BmGr expression patterns in chemosensory organs of larvae and adults enabled us to draw a precise organ specific map of BmGr expression. Interestingly, most of the clustered genes were expressed in the same tissues and more than half of the genes were expressed in larval maxillae, larval thoracic legs and adult legs. For example, BmGr63 showed high expression levels in all organs in both larval and adult stages. By contrast, some genes showed expression limited to specific developmental stages or organs and tissues. BmGr19 was highly expressed in larval chemosensory organs (especially antennae and thoracic legs), the single exon genes BmGr53 and BmGr67 were expressed exclusively in larval tissues, the BmGr27-BmGr31 gene cluster on chr7 displayed a high expression level limited to adult legs and the candidate CO 2 receptor BmGr2 was highly expressed in adult antennae, where few other Grs were expressed. Transcriptional analysis of the Grs in B. mori provides a valuable new reference for finding genes involved in plant-insect interactions in Lepidoptera and establishing correlations between these genes and vital insect behaviors like host plant selection and courtship for mating. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Involvement of STH7 in light-adapted development in Arabidopsis thaliana promoted by both strigolactone and karrikin.

PubMed

Thussagunpanit, Jutiporn; Nagai, Yuko; Nagae, Miyu; Mashiguchi, Kiyoshi; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Nakano, Takeshi; Nakamura, Hidemitsu; Asami, Tadao

2017-02-01

Strigolactones (SLs) and karrikins (KARs) regulate photomorphogenesis. GR24, a synthetic SL and KAR 1 , a KAR, inhibit the hypocotyl elongation of Arabidopsis thaliana in a weak light. GR24 and KAR 1 up-regulate the expression of STH7, encoding a transcription factor belonging to the double B-box zinc finger subfamily. In this study, we used STH7-overexpressing (STH7ox) lines and functionally defective STH7 (STH7-SRDX) mutants to investigate roles of SLs and KARs in photomorphogenesis of Arabidopsis. Hypocotyl elongation of STH7-SRDX mutants was less sensitive to both GR24 and KAR 1 treatment than that of wild-type Arabidopsis under weak light conditions. Furthermore, the chlorophyll and anthocyanin content was increased in STH7ox lines when de-etiolated with light and GR24-treated plants had enhanced anthocyanin production. GR24 and KAR 1 treatment significantly increased the expression level of photosynthesis-related genes LHCB1 and rbcS. The results strongly suggest that SL and KAR induce photomorphogenesis of Arabidopsis in an STH7-dependent manner.

A facile and scalable method to prepare carbon nanotube-grafted-graphene for high performance Li-S battery

NASA Astrophysics Data System (ADS)

Wang, Q. Q.; Huang, J. B.; Li, G. R.; Lin, Z.; Liu, B. H.; Li, Z. P.

2017-01-01

A carbon nanotube-grafted-graphene (CNT-g-Gr) is developed for enhancements of electrical conduction and polysulfide (PS) absorption to improve rate performance and cycleability of lithium-sulfur battery. The CNT-g-Gr is prepared through CNT growth on Ni-deposited graphene sheet which is fabricated via pyrolysis of glucose in a molten salt. The obtained CNT-g-Gr shows much higher specific surface area and PS adsorption capability than graphene. The in-situ formed Ni nanoparticles on graphene sheet not only serve as the catalytic sites for CNT growth, but also function as the anchor-sites for polar PS absorption. The CNT-g-Gr contributes a superb PS adsorption capability arising from graphene and CNT absorbing weakly-polar PS species, and Ni nanoparticles absorbing the species with stronger polarity. The resultant Li-S battery with the CNT-g-Gr shows excellent cycleability and rate performance. A stable discharge capacity of 900 mAh g-1 (with low capacity degradation rate) and a rate capacity of 260 mAh g-1 at 30 C discharge rate have been achieved.

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

PubMed Central

Revest, J-M; Kaouane, N; Mondin, M; Le Roux, A; Rougé-Pont, F; Vallée, M; Barik, J; Tronche, F; Desmedt, A; Piazza, P V

2010-01-01

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GRNesCre), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress. PMID:20368707

Mechanisms of Molecular Mimicry of Plant CLE Peptide Ligands by the Parasitic Nematode Globodera rostochiensis1[C][W

PubMed Central

Guo, Yongfeng; Ni, Jun; Denver, Robert; Wang, Xiaohong; Clark, Steven E.

2011-01-01

Nematodes that parasitize plant roots cause huge economic losses and have few mechanisms for control. Many parasitic nematodes infect plants by reprogramming root development to drive the formation of feeding structures. How nematodes take control of plant development is largely unknown. Here, we identify two host factors involved in the function of a receptor ligand mimic, GrCLE1, secreted by the potato cyst nematode Globodera rostochiensis. GrCLE1 is correctly processed to an active form by host plant proteases. Processed GrCLE1 peptides bind directly to the plant CLE receptors CLV2, BAM1, and BAM2. Involvement of these receptors in the ligand-mimicking process is also supported by the fact that the ability of GrCLE1 peptides to alter plant root development in Arabidopsis (Arabidopsis thaliana) is dependent on these receptors. Critically, we also demonstrate that GrCLE1 maturation can be entirely carried out by plant factors and that the availability of CLE processing activity may be essential for successful ligand mimicry. PMID:21750229

Mechanisms of molecular mimicry of plant CLE peptide ligands by the parasitic nematode Globodera rostochiensis.

PubMed

Guo, Yongfeng; Ni, Jun; Denver, Robert; Wang, Xiaohong; Clark, Steven E

2011-09-01

Nematodes that parasitize plant roots cause huge economic losses and have few mechanisms for control. Many parasitic nematodes infect plants by reprogramming root development to drive the formation of feeding structures. How nematodes take control of plant development is largely unknown. Here, we identify two host factors involved in the function of a receptor ligand mimic, GrCLE1, secreted by the potato cyst nematode Globodera rostochiensis. GrCLE1 is correctly processed to an active form by host plant proteases. Processed GrCLE1 peptides bind directly to the plant CLE receptors CLV2, BAM1, and BAM2. Involvement of these receptors in the ligand-mimicking process is also supported by the fact that the ability of GrCLE1 peptides to alter plant root development in Arabidopsis (Arabidopsis thaliana) is dependent on these receptors. Critically, we also demonstrate that GrCLE1 maturation can be entirely carried out by plant factors and that the availability of CLE processing activity may be essential for successful ligand mimicry.

Post impact compressive strength in composites

NASA Technical Reports Server (NTRS)

Demuts, Edvins; Sandhu, Raghbir S.; Daniels, John A.

1992-01-01

Presented in this paper are the plan, equipment, procedures, and findings of an experimental investigation of the tolerance to low velocity impact of a graphite epoxy (AS4/3501-6) and graphite bismaleimide (M6/CYCOM3100) advanced composites. The applied impacts were governed by the Air Force Guide Specification 87221. Specimens of each material system having a common nominal layup (10% 0 deg; 80% +/-45 deg; 10% 90 deg), a common 7 inch (17.78 cm) by 10 inch (25.40 cm) size, five different thicknesses (9, 26, 48, 74, and 96 plies), and ambient moisture content were impacted and strength tested at room temperature. Damaged areas and post impact compression strengths (PICS) were among the most significant findings obtained. While the undamaged per ply compression strength of both materials is a strong function of laminate thickness, the per ply PICS is not. The average difference in per ply PICS between the two material systems is about seven percent. Although a smaller percentage of the applied kinetic energy was absorbed by the Gr/BMI than by the Gr/Epoxy composites, larger damaged areas were produced in the Gr/BMI than in Gr/Epoxy. Within the limitations of this investigation, the Gr/BMI system seems to offer no advantage in damage tolerance over the Gr/Epoxy system examined.

Chronic stress decreases availability of heat shock proteins to glucocorticoid receptor in response to novel acute stress in Wistar rat hypothalamus.

PubMed

Simic, Iva; Mitic, Milos; Djordjevic, Jelena; Radojcic, Marija; Adzic, Miroslav

2012-05-01

Chronic psychosocial isolation (CPSI) is known to cause several maladaptive changes in the limbic brain structures, which regulate the hypothalamic-pituitary-adrenal (HPA) axis activity. In this study, we focused our investigation on CPSI effects in the hypothalamus (HT) since it is a major driver of HPA axis activity. We also investigated whether the exposure to CPSI could alter the response to subsequent acute stress (30-min immobilization). In the HT, we followed cytosolic and nuclear levels of the glucocorticoid receptor (GR), as a mediator of HPA axis feedback inhibition, and its chaperones, the heat shock proteins (HSPs), hsp70 and hsp90. The CPSI did not cause any changes in either GR or HSPs levels. However, we observed increase of the GR and hsp70 in both HT cellular compartments as a response of naïve rats to acute stress, whereas the response of CPSI rats to acute stress was associated with elevation of the GR in the cytosol and decrease of HSPs in the nucleus. Thus, our data indicated reduced availability of HSPs to GR in both cytosol and nucleus of the HT under acute stress of CPSI animals, and therefore, pointed out to potentially negative effects of CPSI on GR function in the HT.

The biomass, abundance, and distribution pattern of starfish Asterias sp. (Echinodermata: Asteroidea) in East Coast of Surabaya

NASA Astrophysics Data System (ADS)

Dewi, N. N.; Pursetyo, K. T.; Aprilianitasari, L.; Zakaria, M. H.; Ramadhan, M. R.; Triatmaja, R. A.

2018-04-01

This study aims to determine the biomass, density, and distribution patterns of Asterias sp. Samples were collected from three locations such as Wonokromo, Dadapan and Juanda, each divided into 3 zones. In each zone, samples were taken as many as 5 repetitions using swept area method. Temporarily, the highest biomass of starfish was 2.95 gr/m2 in Dadapan Zone on January. Spatially, biomass of starfish was found in Dadapan Zone (3,35 gr/m2). Similarly, the high density was also found in Dadapan Zone on January (9 ind/10 m2). In general, the distributionpattern of starfish in East Coast Surabaya throughspatial and temporal showed that the pattern of starfish was grouping distribution (Id value > 1) for Dadapan and Juanda, and uniform for Wonokromo. Oceanographic condition, antropogenic activity, and water quality in East Cost of Surabaya become important things which is affected the biomass, densityand distribution pattern of starfish. The knowledge of starfish biomass and density is very important given that this biota has ecological value as a balancing ecosystem in the waters.

A perturbative approach to the redshift space correlation function: beyond the Standard Model

NASA Astrophysics Data System (ADS)

Bose, Benjamin; Koyama, Kazuya

2017-08-01

We extend our previous redshift space power spectrum code to the redshift space correlation function. Here we focus on the Gaussian Streaming Model (GSM). Again, the code accommodates a wide range of modified gravity and dark energy models. For the non-linear real space correlation function used in the GSM we use the Fourier transform of the RegPT 1-loop matter power spectrum. We compare predictions of the GSM for a Vainshtein screened and Chameleon screened model as well as GR. These predictions are compared to the Fourier transform of the Taruya, Nishimichi and Saito (TNS) redshift space power spectrum model which is fit to N-body data. We find very good agreement between the Fourier transform of the TNS model and the GSM predictions, with <= 6% deviations in the first two correlation function multipoles for all models for redshift space separations in 50Mpch <= s <= 180Mpc/h. Excellent agreement is found in the differences between the modified gravity and GR multipole predictions for both approaches to the redshift space correlation function, highlighting their matched ability in picking up deviations from GR. We elucidate the timeliness of such non-standard templates at the dawn of stage-IV surveys and discuss necessary preparations and extensions needed for upcoming high quality data.

CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice.

PubMed

Pohl, Judith-Mira; Volke, Julia K; Thiebes, Stephanie; Brenzel, Alexandra; Fuchs, Kerstin; Beziere, Nicolas; Ehrlichmann, Walter; Pichler, Bernd J; Squire, Anthony; Gueler, Faikah; Engel, Daniel R

2018-06-01

The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1 high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS- injection, thus suggesting Gr1 high monocyte infiltration into the kidney. Indeed, the number of Gr1 high monocytes was strongly increased one day after HUS induction. Moreover, these cells expressed high levels of CD11b suggesting activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury mainly in the kidney cortex and this damage coincided with the detection of Gr1 high monocytes. Lack of Gr1 high monocytes in Ccr2-deficient animals reduced neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels. Moreover, the survival of Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that CCR2-dependent Gr1 high monocytes contribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

General Relativity solutions in modified gravity

NASA Astrophysics Data System (ADS)

Motohashi, Hayato; Minamitsuji, Masato

2018-06-01

Recent gravitational wave observations of binary black hole mergers and a binary neutron star merger by LIGO and Virgo Collaborations associated with its optical counterpart constrain deviation from General Relativity (GR) both on strong-field regime and cosmological scales with high accuracy, and further strong constraints are expected by near-future observations. Thus, it is important to identify theories of modified gravity that intrinsically possess the same solutions as in GR among a huge number of theories. We clarify the three conditions for theories of modified gravity to allow GR solutions, i.e., solutions with the metric satisfying the Einstein equations in GR and the constant profile of the scalar fields. Our analysis is quite general, as it applies a wide class of single-/multi-field scalar-tensor theories of modified gravity in the presence of matter component, and any spacetime geometry including cosmological background as well as spacetime around black hole and neutron star, for the latter of which these conditions provide a necessary condition for no-hair theorem. The three conditions will be useful for further constraints on modified gravity theories as they classify general theories of modified gravity into three classes, each of which possesses i) unique GR solutions (i.e., no-hair cases), ii) only hairy solutions (except the cases that GR solutions are realized by cancellation between singular coupling functions in the Euler-Lagrange equations), and iii) both GR and hairy solutions, for the last of which one of the two solutions may be selected dynamically.

FLRW cosmological models with quark and strange quark matters in f(R,T) gravity

NASA Astrophysics Data System (ADS)

Nagpal, Ritika; Singh, J. K.; Aygün, S.

2018-06-01

In this paper, we have studied the magnetized quark matter (QM) and strange quark matter (SQM) distributions in the presence of f(R,T) gravity in the background of Friedmann-Lemaître-Robertson-Walker (FLRW) metric. To get exact solutions of modified field equations we have used f(R,T ) = R + 2 f(T) model given by Harko et al. with two different parametrization of geometrical parameters i.e. the parametrization of the deceleration parameter q , and the scale factor a in hybrid expansion form. Also, we have obtained Einstein Static Universe (ESU) solutions for QM and SQM distributions in f(R,T) gravity and General Relativity (GR). All models in f(R,T) gravity and GR for FRW and ESU Universes with QM also SQM distributions, we get zero magnetic field. These results agree with the solutions of Aktaş and Aygün in f(R,T) gravity. However, we have also discussed the physical consequences of our obtained models.

Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis.

PubMed

Katsarou, Martha-Spyridoula; Latsi, Rosana; Papasavva, Maria; Demertzis, Nikolaos; Kalogridis, Thodoris; Tsatsakis, Aristides M; Spandidos, Demetrios A; Drakoulis, Nikolaos

2016-07-01

Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by increased dietary iron absorption. Due to the absence of an effective excretory mechanism, the excess iron in the body may accumulate resulting in toxic effects. The HFE gene also affects the activity of hepcidin, a hormone which acts as a negative regulator of iron metabolism. In this study, we performed a population-based analysis of the distribution of three hemochromatosis-related polymorphisms in the HFE gene (rs1800562, rs1799945 and rs1800730). DNA from 1,446 non‑related individuals of Greek ethnicity was collected and analyzed, either from whole blood or buccal swabs. The frequency distribution of these HFE gene polymorphisms was then determined. The results revealed that in our Greek population cohort (gr) the frequencies of each polymorphism were as follows: rs1800562: GG (wild‑type)=97.0%, GA=1.5%, AA=1.5%; rs1799945: CC (wild‑type)=74.4%, CG=23.4%, GG=2.2%; rs1800730: AA (wild‑type)=98.1%, AT=1.5% and TT=0.4%. No association between the HFE polymorphisms rs1800562, rs1799945 and rs1800730 and gender could be established. As regards the rs1800562 polymorphism, the A allele (mutant) was ~1.8‑fold more frequent in the European population (eur) than in the Greek population [(gr)=2,3%<(eur)=4%]. As for the rs1799945 polymorphism, the G allele (mutant) was 1.2‑fold more frequent in the European population than in the Greek population [(gr)=13,9%<(eur)=17%]. As regards the rs1800730 polymorphism, the T allele (mutant) was ~1.7‑fold more frequent in the European population than in the Greek population [(gr)=1.2%<(eur)=2%]. However, these pathogenic mutations were found more frequently in the Greek population compared to the global population (gl) [rs1800562: (gl)=1%<(gr)=2,3%; rs1799945: (gl)=7%<(gr)=13,9%; rs1800730: (gl)=<1%<(gr)=1.2%]. This suggests that the Greek population may differ genetically from the northern European population, due to influences from neighboring Asian and African populations. These findings also suggest that there is no gender-associated inheritance of these polymorphisms, and gender-specific symptoms appear as a result of independent biological processes. Thus, the early detection of the tendency towards iron accumulation may be achieved by the genotypic analysis of the polymorphisms that may contribute to the development of the hemochromatosis.

Quantitative Voronovskaya and Grüss-Voronovskaya type theorems for Jain-Durrmeyer operators of blending type

NASA Astrophysics Data System (ADS)

Kajla, Arun; Deshwal, Sheetal; Agrawal, P. N.

2018-05-01

In the present paper we introduce a Durrmeyer variant of Jain operators based on a function ρ (x) where ρ is a continuously differentiable function on [0,∞), ρ (0)=0 and \\inf ρ '(x)≥ a, a >0, x \\in [0,∞) . For these new operators, some indispensable auxiliary results are established first. Then, the degree of approximation with the aid of Ditzian-Totik modulus of smoothness and the rate of convergence for functions whose derivatives are of bounded variation, is obtained. Further, we focus on the study of a Voronovskaja type asymptotic theorem, quantitative Voronovskaya and Grüss-Voronovskaya type theorems.

Maximum earthquake magnitudes in the Aegean area constrained by tectonic moment release rates

NASA Astrophysics Data System (ADS)

Ch. Koravos, G.; Main, I. G.; Tsapanos, T. M.; Musson, R. M. W.

2003-01-01

Seismic moment release is usually dominated by the largest but rarest events, making the estimation of seismic hazard inherently uncertain. This uncertainty can be reduced by combining long-term tectonic deformation rates with short-term recurrence rates. Here we adopt this strategy to estimate recurrence rates and maximum magnitudes for tectonic zones in the Aegean area. We first form a merged catalogue for historical and instrumentally recorded earthquakes in the Aegean, based on a recently published catalogue for Greece and surrounding areas covering the time period 550BC-2000AD, at varying degrees of completeness. The historical data are recalibrated to allow for changes in damping in seismic instruments around 1911. We divide the area up into zones that correspond to recent determinations of deformation rate from satellite data. In all zones we find that the Gutenberg-Richter (GR) law holds at low magnitudes. We use Akaike's information criterion to determine the best-fitting distribution at high magnitudes, and classify the resulting frequency-magnitude distributions of the zones as critical (GR law), subcritical (gamma density distribution) or supercritical (`characteristic' earthquake model) where appropriate. We determine the ratio η of seismic to tectonic moment release rate. Low values of η (<0.5) corresponding to relatively aseismic deformation, are associated with higher b values (>1.0). The seismic and tectonic moment release rates are then combined to constrain recurrence rates and maximum credible magnitudes (in the range 6.7-7.6 mW where the results are well constrained) based on extrapolating the short-term seismic data. With current earthquake data, many of the tectonic zones show a characteristic distribution that leads to an elevated probability of magnitudes around 7, but a reduced probability of larger magnitudes above this value when compared with the GR trend. A modification of the generalized gamma distribution is suggested to account for this, based on a finite statistical second moment for the seismic moment distribution.

Local mechanical properties of Alloy 82/182 dissimilar weld joint between SA508 Gr.1a and F316 SS at RT and 320 °C

NASA Astrophysics Data System (ADS)

Kim, Jin Weon; Lee, Kyoungsoo; Kim, Jong Sung; Byun, Thak Sang

2009-02-01

The distributions of mechanical and microstructural properties were investigated for the dissimilar metal weld joints between SA508 Gr.1a ferritic steel and F316 austenitic stainless steel with Alloy 82/182 filler metal using small-size tensile specimens. The material properties varied significantly in different zones while those were relatively uniform within each material. In particular, significant gradient of the mechanical properties were observed near the both heat-affected zones (HAZs) of F316 SS and SA508 Gr.1a. Thus, the yield stress (YS) was under-matched with respect to the both HAZs, although, the YS of the weld metal was over-matched with respect to both base metals. The minimum ductility occurred in the HAZ of SA508 Gr.1a at both test temperatures. The plastic instability stress also varied considerably across the weld joints, with minimum values occurring in the SA508 Gr.1a base metal at RT and in the HAZ of F316 SS at 320 °C. The transmission electron micrographs showed that the strengthening in the HAZ of F316 SS was attributed to the strain hardening, induced by a strain mismatch between the weldment and the base metal, which was evidenced by high dislocation density in the HAZ of F316 SS.

Solar radiation and precipitable water modeling for Turkey using artificial neural networks

NASA Astrophysics Data System (ADS)

Şenkal, Ozan

2015-08-01

Artificial neural network (ANN) method was applied for modeling and prediction of mean precipitable water and solar radiation in a given location and given date (month), given altitude, temperature, pressure and humidity in Turkey (26-45ºE and 36-42ºN) during the period of 2000-2002. Resilient Propagation (RP) learning algorithms and logistic sigmoid transfer function were used in the network. To train the network, meteorological measurements taken by the Turkish State Meteorological Service (TSMS) and Wyoming University for the period from 2000 to 2002 from five stations distributed in Turkey were used as training data. Data from years (2000 and 2001) were used for training, while the year 2002 was used for testing and validating the model. The RP algorithm were first used for determination of the precipitable water and subsequently, computation of the solar radiation, in these stations Root Mean Square Error (RMSE) between the estimated and measured values for monthly mean daily sum for precipitable water and solar radiation values have been found as 0.0062 gr/cm2 and 0.0603 MJ/m2 (training cities), 0.5652 gr/cm2 and 3.2810 MJ/m2 (testing cities), respectively.

A hotspot in the glucocorticoid receptor DNA-binding domain susceptible to loss of function mutation

PubMed Central

Banuelos, Jesus; Shin, Soon Cheon; Lu, Nick Z.

2015-01-01

Glucocorticoids (GCs) are used to treat a variety of inflammatory disorders and certain cancers. However, GC resistance occurs in subsets of patients. We found that EL4 cells, a GC-resistant mouse thymoma cell line, harbored a point mutation in their GC receptor (GR) gene, resulting in the substitution of arginine 493 by a cysteine in the second zinc finger of the DNA-binding domain. Allelic discrimination analyses revealed that the R493C mutation occurred on both alleles. In the absence of GCs, the GR in EL4 cells localized predominantly in the cytoplasm and upon dexamethasone treatment underwent nuclear translocation, suggesting the ligand binding ability of the GR in EL4 cells was intact. In transient transfection assays, the R493C mutant could not transactivate the MMTV-luciferase reporter. Site-directed mutagenesis to revert the R493C mutation restored the transactivation activity. Cotransfection experiments showed that the R493C mutant did not inhibit the transcriptional activities of the wild-type GR. In addition, the R493C mutant did not repress either the AP-1 or NF-κB reporters as effectively as WT GR. Furthermore, stable expression of the WT GR in the EL4 cells enabled GC-mediated gene regulation, specifically upregulation of IκBα and downregulation of interferon γ and interleukin 17A. Arginine 493 is conserved among multiple species and all human nuclear receptors and its mutation has also been found in the human GR, androgen receptor, and mineralocorticoid receptor. Thus, R493 is necessary for the transcriptional activity of the GR and a hotspot for mutations that result in GC resistance. PMID:25676786

CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

PubMed

Hill, Micah J; Suzuki, Shigeru; Segars, James H; Kino, Tomoshige

2016-01-01

Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

Simulating changes in cropping practices in conventional and glyphosate-resistant maize. II. Weed impacts on crop production and biodiversity.

PubMed

Colbach, Nathalie; Darmency, Henri; Fernier, Alice; Granger, Sylvie; Le Corre, Valérie; Messéan, Antoine

2017-05-01

Overreliance on the same herbicide mode of action leads to the spread of resistant weeds, which cancels the advantages of herbicide-tolerant (HT) crops. Here, the objective was to quantify, with simulations, the impact of glyphosate-resistant (GR) weeds on crop production and weed-related wild biodiversity in HT maize-based cropping systems differing in terms of management practices. We (1) simulated current conventional and probable HT cropping systems in two European regions, Aquitaine and Catalonia, with the weed dynamics model FLORSYS; (2) quantified how much the presence of GR weeds contributed to weed impacts on crop production and biodiversity; (3) determined the effect of cultural practices on the impact of GR weeds and (4) identified which species traits most influence weed-impact indicators. The simulation study showed that during the analysed 28 years, the advent of glyphosate resistance had little effect on plant biodiversity. Glyphosate-susceptible populations and species were replaced by GR ones. Including GR weeds only affected functional biodiversity (food offer for birds, bees and carabids) and weed harmfulness when weed effect was initially low; when weed effect was initially high, including GR weeds had little effect. The GR effect also depended on cultural practices, e.g. GR weeds were most detrimental for species equitability when maize was sown late. Species traits most harmful for crop production and most beneficial for biodiversity were identified, using RLQ analyses. None of the species presenting these traits belonged to a family for which glyphosate resistance was reported. An advice table was built; the effects of cultural practices on crop production and biodiversity were synthesized, explained, quantified and ranked, and the optimal choices for each management technique were identified.

Import Manipulate Plot RELAP5/MOD3 Data

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

Jones, K. R.

1999-10-05

XMGR5 was derived from an XY plotting tool called ACE/gr, which is copyrighted by Paul J. Turner and in the public domain. The interactive version of ACE/GR is xmgr, and includes a graphical interface to the X-windows system. Enhancements to xmgr have been developed which import, manipualate, and plot data from RELAP/MOD3, MELCOR, FRAPCON, and SINDA codes, and NRC databank files. capabilities, include two-phase property table lookup functions, an equation interpreter, arithmetic library functions, and units conversion. Plot titles, labels, legends, and narrative can be displayed using Latin or Cyrillic alphabets.

Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

PubMed

Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

2013-05-01

Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural abnormalities are, in part, caused by up-regulation of dynein IC2-GR-COX-1 signaling, which may be a novel therapeutic target for NF1.

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes*

PubMed Central

Zhao, Xuan; Khurana, Simran; Charkraborty, Sharmistha; Tian, Yuqian; Sedor, John R.; Bruggman, Leslie A.; Kao, Hung-Ying

2017-01-01

Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-κB (p65) binding sites on GR-transrepressed promoters such as IL-1β, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes. PMID:27998979

Dexamethasone impairs hypoxia-inducible factor-1 function

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

Wagner, A.E.; Huck, G.; Stiehl, D.P.

2008-07-25

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of {alpha}- and {beta}-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1{alpha} levels in the cytosol of HepG2 cells, while nuclear HIF-1{alpha} levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in amore » reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients.« less

BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus.

PubMed

Jeanneteau, Freddy D; Lambert, W Marcus; Ismaili, Naima; Bath, Kevin G; Lee, Francis S; Garabedian, Michael J; Chao, Moses V

2012-01-24

Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased expression of the glucocorticoid receptor (GR) has been documented. To investigate the role of the GR in CRH neurons, we have targeted the deletion of the GR, specifically in the parventricular nucleus. Impairment of GR function in the parventricular nucleus resulted in an enhancement of CRH expression and an up-regulation of hypothalamic levels of BDNF and disinhibition of the HPA axis. BDNF is a stress and activity-dependent factor involved in many activities modulated by the HPA axis. Significantly, ectopic expression of BDNF in vivo increased CRH, whereas reduced expression of BDNF, or its receptor TrkB, decreased CRH expression and normal HPA functions. We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.

Cyanobacterial Light-Driven Proton Pump, Gloeobacter Rhodopsin: Complementarity between Rhodopsin-Based Energy Production and Photosynthesis

PubMed Central

Choi, Ah Reum; Shi, Lichi; Brown, Leonid S.; Jung, Kwang-Hwan

2014-01-01

A homologue of type I rhodopsin was found in the unicellular Gloeobacter violaceus PCC7421, which is believed to be primitive because of the lack of thylakoids and peculiar morphology of phycobilisomes. The Gloeobacter rhodopsin (GR) gene encodes a polypeptide of 298 amino acids. This gene is localized alone in the genome unlike cyanobacterium Anabaena opsin, which is clustered together with 14 kDa transducer gene. Amino acid sequence comparison of GR with other type I rhodopsin shows several conserved residues important for retinal binding and H+ pumping. In this study, the gene was expressed in Escherichia coli and bound all-trans retinal to form a pigment (λmax  = 544 nm at pH 7). The pKa of proton acceptor (Asp121) for the Schiff base, is approximately 5.9, so GR can translocate H+ under physiological conditions (pH 7.4). In order to prove the functional activity in the cell, pumping activity was measured in the sphaeroplast membranes of E. coli and one of Gloeobacter whole cell. The efficient proton pumping and rapid photocycle of GR strongly suggests that Gloeobacter rhodopsin functions as a proton pumping in its natural environment, probably compensating the shortage of energy generated by chlorophyll-based photosynthesis without thylakoids. PMID:25347537

Experimental Characterization of Aluminum-Based Hybrid Composites Obtained Through Powder Metallurgy

NASA Astrophysics Data System (ADS)

Marcu, D. F.; Buzatu, M.; Ghica, V. G.; Petrescu, M. I.; Popescu, G.; Niculescu, F.; Iacob, G.

2018-06-01

The paper presents some experimental results concerning fabrication through powder metallurgy (P/M) of aluminum-based hybrid composites - Al/Al2O3/Gr. In order to understand the mechanisms that occur during the P/M processes of obtaining Al/Al2O3/Gr composite, we correlated the physical characteristics with their micro-structural characteristics. The characterization was performed using analysis techniques specific for P/M process, SEM-EDS and XRD analyses. Micro-structural characterization of the composites has revealed fairly uniform distribution this resulting in good properties of the final composite material.

Constraints on the frequency-magnitude relation and maximum magnitudes in the UK from observed seismicity and glacio-isostatic recovery rates

NASA Astrophysics Data System (ADS)

Main, Ian; Irving, Duncan; Musson, Roger; Reading, Anya

1999-05-01

Earthquake populations have recently been shown to have many similarities with critical-point phenomena, with fractal scaling of source sizes (energy or seismic moment) corresponding to the observed Gutenberg-Richter (G-R) frequency-magnitude law holding at low magnitudes. At high magnitudes, the form of the distribution depends on the seismic moment release rate Msolar and the maximum magnitude m_max . The G-R law requires a sharp truncation at an absolute maximum magnitude for finite Msolar. In contrast, the gamma distribution has an exponential tail which allows a soft or `credible' maximum to be determined by negligible contribution to the total seismic moment release. Here we apply both distributions to seismic hazard in the mainland UK and its immediate continental shelf, constrained by a mixture of instrumental, historical and neotectonic data. Tectonic moment release rates for the seismogenic part of the lithosphere are calculated from a flexural-plate model for glacio-isostatic recovery, constrained by vertical deformation rates from tide-gauge and geomorphological data. Earthquake focal mechanisms in the UK show near-vertical strike-slip faulting, with implied directions of maximum compressive stress approximately in the NNW-SSE direction, consistent with the tectonic model. Maximum magnitudes are found to be in the range 6.3-7.5 for the G-R law, or 7.0-8.2 m_L for the gamma distribution, which compare with a maximum observed in the time period of interest of 6.1 m_L . The upper bounds are conservative estimates, based on 100 per cent seismic release of the observed vertical neotectonic deformation. Glacio-isostatic recovery is predominantly an elastic rather than a seismic process, so the true value of m_max is likely to be nearer the lower end of the quoted range.

Local modulation of carrier density in graphene-ferroelectric field effect transistors through flexoelectric switching

NASA Astrophysics Data System (ADS)

Gura, Anna; Hsing, Hsiang C.; Yusuf, Mohammed; Du, Xu; Dawber, Mattew

We use a ferroelectric (FE) material to harness the electric functionalities of graphene (Gr) by engineering Gr-FE Field Effect Transistors. In these devices, the underlying FE superlattice layer is used to control the charge state of the Gr channel. By using artificially layered FE superlattices and optimizing parameters during growth and Gr deposition, we have obtained ideal interfaces that result in hysteretic devices. However, our successful devices using PbTiO3/SrTiO3 as the FE layer display a shift of the gating and C-V curves towards positive gate voltages, making the polarization state unstable. We believe this is caused by ordered structural defects that arise during growth of the superlattice. To overcome this obstacle we have designed a hybrid superlattice system consisting of PbTiO3/SrTiO3/PbTiO3/SrRuO3 alternating layers. In these samples the C-V measurements are centered on 0V, providing retention of the polarization state without any applied compensation bias and enabling non-volatile polarization switching as a result of strain applied by an AFM Tip. We studied local changes in conductivity of the Gr and demonstrate the use this technique to design re-writable circuit elements on the graphene-FE hybrid devices. This work was funded by NSF DMR-1105202 and NSF DMR-1334867. Part of this research was carried out at the Center for Functional Nanomaterials at BNL, supported by DOE under Contract No. DE-AC02-98CH10886.

Equation of state of Mo from shock compression experiments on preheated samples

NASA Astrophysics Data System (ADS)

Fat'yanov, O. V.; Asimow, P. D.

2017-03-01

We present a reanalysis of reported Hugoniot data for Mo, including both experiments shocked from ambient temperature (T) and those preheated to 1673 K, using the most general methods of least-squares fitting to constrain the Grüneisen model. This updated Mie-Grüneisen equation of state (EOS) is used to construct a family of maximum likelihood Hugoniots of Mo from initial temperatures of 298 to 2350 K and a parameterization valid over this range. We adopted a single linear function at each initial temperature over the entire range of particle velocities considered. Total uncertainties of all the EOS parameters and correlation coefficients for these uncertainties are given. The improved predictive capabilities of our EOS for Mo are confirmed by (1) better agreement between calculated bulk sound speeds and published measurements along the principal Hugoniot, (2) good agreement between our Grüneisen data and three reported high-pressure γ ( V ) functions obtained from shock-compression of porous samples, and (3) very good agreement between our 1 bar Grüneisen values and γ ( T ) at ambient pressure recalculated from reported experimental data on the adiabatic bulk modulus K s ( T ) . Our analysis shows that an EOS constructed from shock compression data allows a much more accurate prediction of γ ( T ) values at 1 bar than those based on static compression measurements or first-principles calculations. Published calibrations of the Mie-Grüneisen EOS for Mo using static compression measurements only do not reproduce even low-pressure asymptotic values of γ ( T ) at 1 bar, where the most accurate experimental data are available.

Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia

PubMed Central

Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

2012-01-01

Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses. PMID:23181019

Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

PubMed

Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

2012-01-01

Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

Postnatal glucocorticoid-induced hypomyelination, gliosis, neurologic deficits are dose-dependent, preparation-specific, and reversible

PubMed Central

Zia, Muhammad TK; Vinukonda, Govindaiah; Vose, Linnea; Bhimavarapu, Bala B.R.; Iacobas, Sanda; Pandey, Nishi K.; Beall, Ann Marie; Dohare, Preeti; LaGamma, Edmund F.; Iacobas, Dumitru A.; Ballabh, Praveen

2014-01-01

Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurological function in GC-treated animals. Additionally, GC-induced hypomyelination and neurological deficit might be transient. To test our hypotheses, we treated prematurely delivered rabbit pups with high (0.5 mg/kg/day) or low (0.2 mg/kg/day) doses of dexamethasone or betamethasone. Myelin basic protein (MBP), oligodendrocyte proliferation and maturation, astrocytes, transcriptomic profile, and neurobehavioral functions were evaluated. We found that high-dose GC treatment, but not low-dose, reduced MBP expression and impaired motor function at postnatal day 14. High-dose dexamethasone induced astrogliosis, betamethasone did not. Mifepristone, a GR antagonist, reversed dexamethasone-induced myelination, but not astrogliosis. Both GCs inhibited oligodendrocyte proliferation and maturation. Moreover, high-dose dexamethasone altered genes associated with myelination, cell-cycle, GR, and Mitogen-activated protein kinase. Importantly, GC-induced hypomyelination, gliosis, and motor-deficit, observed at day 14, completely recovered by day 21. Hence, high-dose, but not low-dose, postnatal GC causes reversible reductions in myelination and motor functions. GC treatment induces hypomyelination by GR-dependent genomic mechanisms, but astrogliosis by non-genomic mechanisms. GC-induced motor impairment and neurodevelopmental delay might be transient and recover spontaneously in premature infants. PMID:25263581

Formation of Supported Graphene Oxide: Evidence for Enolate Species.

PubMed

Novotny, Zbynek; Nguyen, Manh-Thuong; Netzer, Falko P; Glezakou, Vassiliki-Alexandra; Rousseau, Roger; Dohnálek, Zdenek

2018-04-18

Graphene oxides are promising materials for novel electronic devices or anchoring of the active sites for catalytic applications. Here we focus on understanding the atomic oxygen (AO) binding and mobility on different regions of graphene (Gr) on Ru(0001). Differences in the Gr/Ru lattices result in the superstructure, which offers an array of distinct adsorption sites. We employ scanning tunneling microscopy and density functional theory to map out the chemical identity and stability of prepared AO functionalities in different Gr regions. The AO diffusion is utilized to establish that in the regions that are close to the metal substrate the terminally bonded enolate groups are strongly preferred over bridge-bonded epoxy groups. No oxygen species are observed on the graphene regions that are far from the underlying Ru, indicating their low relative stability. This study provides a clear fundamental basis for understanding the local structural, electronic factors and C-Ru bond strengthening/weakening processes that affect the stability of enolate and epoxy species.

DNA-templated synthesis of PtAu bimetallic nanoparticle/graphene nanocomposites and their application in glucose biosensor

PubMed Central

2014-01-01

In this paper, single-stranded DNA (ss-DNA) is demonstrated to functionalize graphene (GR) and to further guide the growth of PtAu bimetallic nanoparticles (PtAuNPs) on GR with high densities and dispersion. The obtained nanocomposites (PtAuNPs/ss-DNA/GR) were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectrometer (EDS), and electrochemical techniques. Then, an enzyme nanoassembly was prepared by self-assembling glucose oxidase (GOD) on PtAuNP/ss-DNA/GR nanocomposites (GOD/PtAuNPs/ss-DNA/GR). The nanocomposites provided a suitable microenvironment for GOD to retain its biological activity. The direct and reversible electron transfer process between the active site of GOD and the modified electrode was realized without any extra electron mediator. Thus, the prepared GOD/PtAuNP/ss-DNA/GR electrode was proposed as a biosensor for the quantification of glucose. The effects of pH, applied potential, and temperature on the performance of the biosensor were discussed in detail and were optimized. Under optimal conditions, the biosensor showed a linearity with glucose concentration in the range of 1.0 to 1,800 μM with a detection limit of 0.3 μM (S/N = 3). The results demonstrate that the developed approach provides a promising strategy to improve the sensitivity and enzyme activity of electrochemical biosensors. PMID:24572068

In vitro and in silico assessment of the structure-dependent binding of bisphenol analogues to glucocorticoid receptor.

PubMed

Zhang, Jie; Zhang, Tiehua; Guan, Tianzhu; Yu, Hansong; Li, Tiezhu

2017-03-01

Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein. A fluorescein-labeled dexamethasone derivative (Dex-fl) was employed as tracer. Competitive displacement of Dex-fl from GR by BPs showed that the binding affinities of bisphenol analogues were largely dependent on their characteristic functional groups. In order to further understand the relationship between BPs structures and their GR-mediated activities, molecular docking was utilized to explore the binding modes at the atomic level. The results confirmed that structural variations of bisphenol analogues contributed to different interactions of BPs with GR, potentially causing distinct toxic effects. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (R 2  = 0.8266), which might be helpful for the design of environmentally benign materials with reduced toxicities. In addition, the established FP assay based on GR exhibited the potential to offer an alternative to traditional methods for the detection of bisphenols.

Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

PubMed Central

Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

2015-01-01

A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

PubMed

Hay, Colin W; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J; MacKenzie, Alasdair

2014-09-01

Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones

PubMed Central

Hay, Colin W.; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J.; MacKenzie, Alasdair

2014-01-01

Summary Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. PMID:25001955

Melatonin and nitric oxide modulate glutathione content and glutathione reductase activity in sunflower seedling cotyledons accompanying salt stress.

PubMed

Kaur, Harmeet; Bhatla, Satish C

2016-09-30

The present findings demonstrate significant modulation of total glutathione content, reduced glutathione (GSH) content, oxidized glutathione (GSSG) content, GSH/GSSG ratio and glutathione reductase (GR; EC 1.6.4.2) activity in dark-grown seedling cotyledons in response to salt-stress (120 mM NaCl) in sunflower (Helianthus annuus L.) seedlings. A differential spatial distribution of GR activity (monitored by confocal laser scanning microscopic (CLSM) imaging) is also evident. Melatonin and nitric oxide (NO) differentially ameliorate salt stress effect by modulating GR activity and GSH content in seedling cotyledons. Total glutathione content (GSH + GSSG) exhibit a seedling age-dependent increase in the cotyledons, more so in salt-stressed conditions and when subjected to melatonin treatment. Seedlings raised in presence of 15 μM of melatonin exhibit significant increase in GR activity in cotyledon homogenates (10,000 g supernatant) coinciding with significant increase in GSH content. GSSG content and GSH/GSSG ratio also increased due to melatonin treatment. A correlation is thus evident in NaCl-sensitized modulation of GSH content and GR activity by melatonin. GSH content is down regulated by NO provided as 250 μM of sodium nitroprusside (SNP) although total glutathione content remained in similar range. A reversal of response (enhanced total glutathione accumulation) by NO scavenger (cPTIO) highlights the critical role of NO in modulating glutathione homeostasis. SNP lowers the activity of hydroxyindole-O-methyltransferase (HIOMT) - a regulatory enzyme in melatonin biosynthesis in control seedlings whereas its activity is upregulated in salt-stressed seedling cotyledons. Melatonin content of seedling cotyledons is also modulated by NO. NO and melatonin thus seem to modulate GR activity and GSH content during seedling growth under salt stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantifying ocean and ice sheet contributions to nutrient fluxes in Sermilik Fjord, Southeast Greenland

NASA Astrophysics Data System (ADS)

Cape, M. R.; Straneo, F.; Beaird, N.; Bundy, R.; Charette, M. A.

2016-12-01

Meltwater discharged at the margins of the Greenland Ice Sheet (GrIS) represents a potential source of nutrients to biological communities downstream. In Greenland's glacial fjords, this discharge occurs at depth below and along the face of deeply grounded marine-terminating glaciers. This process drives vigorous circulation and mixing between melt and ambient waters at the ice-ocean margins, giving rise to a new glacially modified water mass (GMW) which constitutes the primary vehicle for transport of meltwater in the marine environment. While previous field studies have noted nutrient enrichment in GMW with respect to unmodified waters along the shelf, the source of this enrichment, whether due to entrainment of deep ambient waters or input by meltwater, remains poorly understood. This knowledge is however critical in order to evaluate the current and future contributions of the GrIS to marine biogeochemical cycling. Here we shed light on the distribution, composition, and properties of GMW along the GrIS margin by analyzing integrated physical and chemical measurements collected in August 2015 in Sermilik Fjord, a major glacial freshwater export pathway. Our results document up to a doubling of nutrient concentrations (nitrate, silicate, phosphate, and iron) in GMW, which is distributed in the top 300 m of the water column throughout the fjord. Partitioning of ocean and ice sheet contributions to GMW nutrient load demonstrates that upwelled waters are the primary source of macro-nutrients to GMW. We expand on these results to discuss the magnitude of fluxes in context of previous observations along the GrIS margins, export pathways of GMW to the shelf, and knowledge gaps needed to be addressed to better constrain ice sheet contributions to marine ecosystem processes.

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

Chen, Juncheng; Wang, Xiaofeng; Li, Junzheng

We present extensive optical observations of the normal Type Ic supernova (SN) 2007gr, spanning from about one week before maximum light to more than one year thereafter. The optical light and color curves of SN 2007gr are very similar to those of the broad-lined Type Ic SN 2002ap, but the spectra show remarkable differences. The optical spectra of SN 2007gr are characterized by unusually narrow lines, prominent carbon lines, and slow evolution of the line velocity after maximum light. The earliest spectrum (taken at t = –8 days) shows a possible signature of helium (He I λ5876 at a velocitymore » of ∼19,000 km s{sup –1}). Moreover, the larger intensity ratio of the [O I] λ6300 and λ6364 lines inferred from the early nebular spectra implies a lower opacity of the ejecta shortly after the explosion. These results indicate that SN 2007gr perhaps underwent a less energetic explosion of a smaller-mass Wolf-Rayet star (∼8-9 M{sub ☉}) in a binary system, as favored by an analysis of the progenitor environment through pre-explosion and post-explosion Hubble Space Telescope images. In the nebular spectra, asymmetric double-peaked profiles can be seen in the [O I] λ6300 and Mg I] λ4571 lines. We suggest that the two peaks are contributed by the blueshifted and rest-frame components. The similarity in velocity structure and the different evolution of the strength of the two components favor an aspherical explosion with the ejecta distributed in a torus or disk-like geometry, but inside the ejecta the O and Mg have different distributions.« less

A perturbative approach to the redshift space correlation function: beyond the Standard Model

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

Bose, Benjamin; Koyama, Kazuya, E-mail: benjamin.bose@port.ac.uk, E-mail: kazuya.koyama@port.ac.uk

We extend our previous redshift space power spectrum code to the redshift space correlation function. Here we focus on the Gaussian Streaming Model (GSM). Again, the code accommodates a wide range of modified gravity and dark energy models. For the non-linear real space correlation function used in the GSM we use the Fourier transform of the RegPT 1-loop matter power spectrum. We compare predictions of the GSM for a Vainshtein screened and Chameleon screened model as well as GR. These predictions are compared to the Fourier transform of the Taruya, Nishimichi and Saito (TNS) redshift space power spectrum model whichmore » is fit to N-body data. We find very good agreement between the Fourier transform of the TNS model and the GSM predictions, with ≤ 6% deviations in the first two correlation function multipoles for all models for redshift space separations in 50Mpc h ≤ s ≤ 180Mpc/ h . Excellent agreement is found in the differences between the modified gravity and GR multipole predictions for both approaches to the redshift space correlation function, highlighting their matched ability in picking up deviations from GR. We elucidate the timeliness of such non-standard templates at the dawn of stage-IV surveys and discuss necessary preparations and extensions needed for upcoming high quality data.« less

Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape.

PubMed

Stortz, Martin; Presman, Diego M; Bruno, Luciana; Annibale, Paolo; Dansey, Maria V; Burton, Gerardo; Gratton, Enrico; Pecci, Adali; Levi, Valeria

2017-07-24

The distribution of the transcription machinery among different sub-nuclear domains raises the question on how the architecture of the nucleus modulates the transcriptional response. Here, we used fluorescence fluctuation analyses to quantitatively explore the organization of the glucocorticoid receptor (GR) in the interphase nucleus of living cells. We found that this ligand-activated transcription factor diffuses within the nucleus and dynamically interacts with bodies enriched in the coregulator NCoA-2, DNA-dependent foci and chromatin targets. The distribution of the receptor among the nuclear compartments depends on NCoA-2 and the conformation of the receptor as assessed with synthetic ligands and GR mutants with impaired transcriptional abilities. Our results suggest that the partition of the receptor in different nuclear reservoirs ultimately regulates the concentration of receptor available for the interaction with specific targets, and thus has an impact on transcription regulation.

Dissolution kinetics as a function of the Gibbs free energy of reaction: An experimental study based on albite feldspar

NASA Astrophysics Data System (ADS)

Hellmann, Roland; Tisserand, Delphine

2006-01-01

Here we report on an experimental investigation of the relation between the dissolution rate of albite feldspar and the Gibbs free energy of reaction, Δ Gr. The experiments were carried out in a continuously stirred flow-through reactor at 150 °C and pH (150 °C) 9.2. The dissolution rates R are based on steady-state Si and Al concentrations and sample mass loss. The overall relation between Δ Gr and R was determined over a free energy range of -150 < Δ Gr < -15.6 kJ mol -1. The data define a continuous and highly non-linear, sigmoidal relation between R and Δ Gr that is characterized by three distinct free energy regions. The region furthest from equilibrium, delimited by -150 < Δ Gr < -70 kJ mol -1, represents an extensive dissolution rate plateau with an average rate R¯=1.0×10-8molm-2s-1. In this free energy range the rates of dissolution are constant and independent of Δ Gr, as well as [Si] and [Al]. The free energy range delimited by -70 ⩽ Δ Gr ⩽ -25 kJ mol -1, referred to as the 'transition equilibrium' region, is characterized by a sharp decrease in dissolution rates with increasing Δ Gr, indicating a very strong inverse dependence of the rates on free energy. Dissolution nearest equilibrium, defined by Δ Gr > -25 kJ mol -1, represents the 'near equilibrium' region where the rates decrease as chemical equilibrium is approached, but with a much weaker dependence on Δ Gr. The lowest rate measured in this study, R = 6.2 × 10 -11 mol m -2 s -1 at Δ Gr = -16.3 kJ mol -1, is more than two orders of magnitude slower than the plateau rate. The data have been fitted to a rate equation (adapted from Burch et al. [Burch, T. E., Nagy, K. L., Lasaga, A. C., 1993. Free energy dependence of albite dissolution kinetics at 80 °C and pH 8.8. Chem. Geol.105, 137-162]) that represents the sum of two parallel reactions R=k1[1-exp(-ng)]+k2[1-exp(-g)], where k1 and k2 are rate constants that have been determined by regression, with values 1.02 × 10 -8 and 1.80 × 10 -10 mol m -2 s -1, g ≡ |Δ Gr|/R T is a dimensionless number, and n, m1, and m2 are adjustable fitted parameters ( n = 7.98 × 10 -5, m1 = 3.81 and m2 = 1.17). Based on measurements of the temporal evolution of RSi and RAl for each experiment, steady-state dissolution rates appear to be congruent at all Δ Gr. In contrast, non-steady-state dissolution is incongruent, and is related to Δ Gr. Scanning electron microscopy (SEM) images of post-reaction grain surfaces indicate that dissolution close to equilibrium (Δ Gr > -25 kJ mol -1) resulted in the precipitation of a secondary crystalline phase, but there are no indications that this altered the measured R-Δ Gr relation.

Beyond δ : Tailoring marked statistics to reveal modified gravity

NASA Astrophysics Data System (ADS)

Valogiannis, Georgios; Bean, Rachel

2018-01-01

Models that seek to explain cosmic acceleration through modifications to general relativity (GR) evade stringent Solar System constraints through a restoring, screening mechanism. Down-weighting the high-density, screened regions in favor of the low density, unscreened ones offers the potential to enhance the amount of information carried in such modified gravity models. In this work, we assess the performance of a new "marked" transformation and perform a systematic comparison with the clipping and logarithmic transformations, in the context of Λ CDM and the symmetron and f (R ) modified gravity models. Performance is measured in terms of the fractional boost in the Fisher information and the signal-to-noise ratio (SNR) for these models relative to the statistics derived from the standard density distribution. We find that all three statistics provide improved Fisher boosts over the basic density statistics. The model parameters for the marked and clipped transformation that best enhance signals and the Fisher boosts are determined. We also show that the mark is useful both as a Fourier and real-space transformation; a marked correlation function also enhances the SNR relative to the standard correlation function, and can on mildly nonlinear scales show a significant difference between the Λ CDM and the modified gravity models. Our results demonstrate how a series of simple analytical transformations could dramatically increase the predicted information extracted on deviations from GR, from large-scale surveys, and give the prospect for a much more feasible potential detection.

Cluster functions and scattering amplitudes for six and seven points

DOE PAGES

Harrington, Thomas; Spradlin, Marcus

2017-07-05

Scattering amplitudes in planar super-Yang-Mills theory satisfy several basic physical and mathematical constraints, including physical constraints on their branch cut structure and various empirically discovered connections to the mathematics of cluster algebras. The power of the bootstrap program for amplitudes is inversely proportional to the size of the intersection between these physical and mathematical constraints: ideally we would like a list of constraints which determine scattering amplitudes uniquely. Here, we explore this intersection quantitatively for two-loop six- and seven-point amplitudes by providing a complete taxonomy of the Gr(4, 6) and Gr(4, 7) cluster polylogarithm functions of [15] at weight 4.

Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages

PubMed Central

Zhang, Leying; Gao, Hang; Song, Yanyan; Ren, Hui; Ouyang, Mao; Wu, Xiwei; D’Apuzzo, Massimo; Badie, Behnam

2016-01-01

Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors. PMID:27936099

Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages.

PubMed

Zhang, Ian; Alizadeh, Darya; Liang, Junling; Zhang, Leying; Gao, Hang; Song, Yanyan; Ren, Hui; Ouyang, Mao; Wu, Xiwei; D'Apuzzo, Massimo; Badie, Behnam

2016-01-01

Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.

Integrating Distributed Homogeneous and Heterogeneous Databases: Prototypes. Volume 3.

DTIC Science & Technology

1987-12-01

Integrating Distributed3 Institute of Teholg Homogeneous and -Knowledge-Based eeokn usDtb e: Integrated Information Pooye Systems Engineering Pooye (KBIISE...Transportation Systems Center, December 1987 Broadway, NIA 02142 13. NUMBER OF PAGES IT ~ *n~1~ ArFre 218 Pages 14. kW rSi dTfrn front N Gr~in Office) IS...SECURITY CLASS. (of thie report) Transportation Systems Center, Unclassified Broadway, MA 02142 I5a. DECLASSIFICATION/ DOWNGRADING SCHEDULE 16. DISTRIBUTION

Confined Li ion migration in the silicon-graphene complex system: An ab initio investigation

NASA Astrophysics Data System (ADS)

Wang, Guoqing; Xu, Bo; Shi, Jing; Lei, Xueling; Ouyang, Chuying

2018-04-01

Silicon-Carbon complex systems play an important role in enhancing the performance of Si-based anode materials for Li ion batteries. In this work, the Li migration property of the Silicon-Graphene (Si-Gr) complex systems are investigated by using first-principles calculations. Especially, the effects of graphene coating on the migration of Li ions are discussed in detail. The distance between Si surface and graphene in the Si-Gr system significantly affects the lateral migration of Li ions. With the decrease of the distance from 4.715 to 3.844 Å, the energy barrier of Li ion migration also decreases from 0.115 to 0.067 eV, which are all lower than that of the case without graphene d(0.135 eV). However, smaller distance (3.586 Å) brings the high energy barrier (0.237 eV). Through AIMD calculations, it is found that the graphene coating in the Si-Gr complex system would result in the larger intercalation depths, more uniform distributions, and higher migration coefficients of Li ions. Further calculations of migration coefficients of Li ions at different temperature are used to obtained the activation energy for Li ions migration in the Si-Gr system, which is as low as 0.028 eV. This low activation energy shows that it is easy for Li ions migrating in the Si-Gr system. Our study provided the basically information to understand the migration mechanism of Li ions in Si-C system.

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

Nagayama, K., E-mail: nagayama@aero.kyushu-u.ac.jp

The dimensionless material parameter R introduced by Wu and Jing into the Rice-Walsh equation of state (EOS) has been deduced from the LASL shock Hugoniot data for porous Al and Cu. It was found that the parameter R/p decays smoothly with shock pressure p and displays small experimental scatter in the high pressure region. This finding led to the conclusion that the parameter has only a weak temperature dependence and is well approximated by a function of pressure alone, and the Grüneisen parameter should be temperature dependent under compression. The thermodynamic formulation of the Rice-Walsh EOS for Al and Cumore » was realized using the empirically determined function R(p) for each material and their known shock Hugoniot. It was then possible to reproduce porous shock Hugoniot for these metals. For most degrees of porosity, agreement between the porous data and the calculated Hugoniots using the empirical function described was very good. However, slight discrepancies were seen for Hugoniots with very high porosity. Two new thermal variables were introduced after further analysis, which enabled the calculation of the cold compression curve for these metals. The Grüneisen parameters along full-density and porous Hugoniot curve were calculated using a thermodynamic identity connecting R and the Grüneisen parameter. It was shown that the Grüneisen parameter is strongly temperature dependent. The present analysis suggested that the Rice-Walsh type EOS is a preferable choice for the analysis with its simple form, pressure-dependent empirical Wu-Jing parameter, and its compatibility with porous shock data.« less

The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease.

PubMed

Fries, Gabriel R; Gassen, Nils C; Rein, Theo

2017-12-05

Among the chaperones and co-chaperones regulating the glucocorticoid receptor (GR), FK506 binding protein (FKBP) 51 is the most intensely investigated across different disciplines. This review provides an update on the role of the different co-chaperones of Hsp70 and Hsp90 in the regulation of GR function. The development leading to the focus on FKBP51 is outlined. Further, a survey of the vast literature on the mechanism and function of FKBP51 is provided. This includes its structure and biochemical function, its regulation on different levels-transcription, post-transcription, and post-translation-and its function in signaling pathways. The evidence portraying FKBP51 as a scaffolding protein organizing protein complexes rather than a chaperone contributing to the folding of individual proteins is collated. Finally, FKBP51's involvement in physiology and disease is outlined, and the promising efforts in developing drugs targeting FKBP51 are discussed.

Holocene distribution of woody taxa at the westernmost limit of the Circumboreal/Mediterranean boundary: Evidence from wood remains

NASA Astrophysics Data System (ADS)

Rubiales, Juan M.; Ezquerra, Javier; Muñoz Sobrino, Castor; Génova, María M.; Gil, Luis; Ramil-Rego, Pablo; Gómez Manzaneque, Fernando

2012-02-01

Macrofossils and megafossils of different genera, which were found in twelve localities in the mountains of northwest Iberia, provide spatially precise evidence of their distribution in the region during the Holocene. Macrofossils were recovered from mires, eroded peat bogs and lakes, identified by their wood anatomy and dated using radiocarbon methods. Conifers (Pinus), deciduous trees (Betula, Salix, Quercus) and shrubs (Erica, Fabaceae) were identified. The findings of Pinus gr. sylvestris/nigra have special biogeographical significance. The available palaeoecological data from the Cantabrian Range and nearby mountains (Ancares and Courel) indicate that pines have grown during the Holocene over the highlands of the western part of the Cantabrian Range area as a natural vegetation element. Nevertheless, Pinus sylvestris is the only pine species that is currently present in the Cantabrian Mountains, and its natural distribution area is now limited to a few enclaves. In this study, we provide a number of conclusive findings demonstrating that the past distribution of Pinus gr. sylvestris/nigra in this region suffered an important range contraction during the last two millennia. Historical data also support this idea, as they strongly suggest that this species survived well into the historical period.

Sea Buckthorn Pomace Supplementation in the Diet of Growing Pigs-Effects on Fatty Acid Metabolism, HPA Activity and Immune Status.

PubMed

Dannenberger, Dirk; Tuchscherer, Margret; Nürnberg, Gerd; Schmicke, Marion; Kanitz, Ellen

2018-02-21

There is evidence that sea buckthorn, as a source of n -3 polyunsaturated fatty acids ( n -3 PUFA), possesses health-enhancing properties and may modulate neuroendocrine and immune functions. In the present study, we investigated the effect of sea buckthorn pomace (SBP) supplementation in the diet of growing German Landrace pigs on fatty acids in the blood and hypothalamus, peripheral immune parameters and mRNA expression of corticotropin-releasing hormone (CRH), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hypothalamus and spleen. Pigs were fed diets supplemented with 12% of dried SBP or 0% SBP (control group) over an intervention period of eight weeks. The fatty acid profiles in blood plasma were significantly affected by SBP supplementation only for C18:2 n -6 and n -6/ n -3 PUFA ratio compared with the control group. SBP supplementation did not significantly affect the fatty acid concentrations in the hypothalamus. Furthermore, there were no significant differences in mRNA expression of CRH, MR and GR in the hypothalamus or of GR mRNA expression in the spleen. Concerning the immune status, the plasma IgG levels tended to be higher in SBP pigs, whereas the leukocyte distribution, mitogen-stimulated lymphocyte proliferation, and serum IgM levels remained unchanged. In conclusion, the SBP supplementation of the diet only caused moderate effects on fatty acid metabolism, but no significant effects on hypothalamic-pituitary-adrenal (HPA) activity and immunity in growing pigs. It seems that a beneficial effect of dietary n -3 PUFA on health and welfare is more likely to be expected during stressful situations.

Sea Buckthorn Pomace Supplementation in the Diet of Growing Pigs—Effects on Fatty Acid Metabolism, HPA Activity and Immune Status

PubMed Central

Dannenberger, Dirk; Tuchscherer, Margret; Nürnberg, Gerd; Kanitz, Ellen

2018-01-01

There is evidence that sea buckthorn, as a source of n-3 polyunsaturated fatty acids (n-3 PUFA), possesses health-enhancing properties and may modulate neuroendocrine and immune functions. In the present study, we investigated the effect of sea buckthorn pomace (SBP) supplementation in the diet of growing German Landrace pigs on fatty acids in the blood and hypothalamus, peripheral immune parameters and mRNA expression of corticotropin-releasing hormone (CRH), mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hypothalamus and spleen. Pigs were fed diets supplemented with 12% of dried SBP or 0% SBP (control group) over an intervention period of eight weeks. The fatty acid profiles in blood plasma were significantly affected by SBP supplementation only for C18:2n-6 and n-6/n-3 PUFA ratio compared with the control group. SBP supplementation did not significantly affect the fatty acid concentrations in the hypothalamus. Furthermore, there were no significant differences in mRNA expression of CRH, MR and GR in the hypothalamus or of GR mRNA expression in the spleen. Concerning the immune status, the plasma IgG levels tended to be higher in SBP pigs, whereas the leukocyte distribution, mitogen-stimulated lymphocyte proliferation, and serum IgM levels remained unchanged. In conclusion, the SBP supplementation of the diet only caused moderate effects on fatty acid metabolism, but no significant effects on hypothalamic–pituitary–adrenal (HPA) activity and immunity in growing pigs. It seems that a beneficial effect of dietary n-3 PUFA on health and welfare is more likely to be expected during stressful situations. PMID:29466282

A highly sensitive and selective sensor based on a graphene-coated carbon paste electrode modified with a computationally designed boron-embedded duplex molecularly imprinted hybrid membrane for the sensing of lamotrigine.

PubMed

Wang, Hongjuan; Qian, Duo; Xiao, Xilin; Gao, Shuqin; Cheng, Jianlin; He, Bo; Liao, Lifu; Deng, Jian

2017-08-15

An innovative electrochemical sensor, based on a carbon paste electrode (CPE) modified with graphene (GR) and a boron-embedded duplex molecularly imprinted hybrid membrane (B-DMIHM), was fabricated for the highly sensitive and selective determination of lamotrigine (LMT). Density functional theory (DFT) was employed to study the interactions between the template and monomers to screen appropriate functional monomers for rational design of the B-DMIHM. The distinct synergic effect of GR and B-DMIHM was evidenced by the positive shift of the reduction peak potential of LMT at B-DMIHM/GR modified CPE (B-DMIHM/GR/CPE) by about 300mV, and the 13-fold amplification of the peak current, compared to a bare carbon paste electrode (CPE). The electrochemical reduction mechanism of lamotrigine was investigated by different voltammetric techniques. It was illustrated that square wave voltammetry (SWV) was more sensitive than different pulse voltammetry (DPV) for the quantitative analysis of LMT. Thereafter, a highly sensitive electroanalytical method for LMT was established by SWV at B-DMIHM/GR/CPE with a good linear relationship from 5.0×10 -8 to 5.0×10 -5 and 5.0×10 -5 to 3.0×10 -4 molL -1 with a lower detection limit (1.52×10 -9 molL -1 ) based on the lower linear range(S/N=3). The practical application of the sensor was demonstrated by determining the concentration of LMT in pharmaceutical and biological samples with good precision (RSD 1.04-4.41%) and acceptable recoveries (92.40-107.0%). Copyright © 2017 Elsevier B.V. All rights reserved.

Individual Muscle use in Hamstring Exercises by Soccer Players Assessed using Functional MRI.

PubMed

Fernandez-Gonzalo, R; Tesch, P A; Linnehan, R M; Kreider, R B; Di Salvo, V; Suarez-Arrones, L; Alomar, X; Mendez-Villanueva, A; Rodas, G

2016-06-01

This study used functional magnetic resonance imaging (fMRI) to compare individual muscle use in exercises aimed at preventing hamstring injuries. Thirty-six professional soccer players were randomized into 4 groups, each performing either Nordic hamstring, flywheel leg curl, Russian belt or conic-pulley exercise. MRIs were performed before and immediately after a bout of 4 sets of 8 repetitions. Pre-post exercise differences in contrast shift (T2) were analyzed for the long (BFLh) and short head (BFSh) of biceps femoris, semitendinosus (ST), semimembranosus (SM) and gracilis (GR) muscles. Flywheel leg curl increased (P<0.001) T2 of GR (95%), ST (65%), BFSh (51%) and BFLh (14%). After the Nordic hamstring, GR (39%), ST (16%) and BFSh (14%) showed increased T2 (P<0.001). Russian belt and conic-pulley exercise produced subtle (P<0.02) T2 increases of ST (9 and 6%, respectively) and BFLh (7 and 6%, respectively). Russian belt increased T2 of SM (7%). Among exercises examined, flywheel leg curl showed the most substantial hamstring and GR muscle use. However, no single exercise executed was able to increase T2 of all hamstring and synergist muscles analyzed. It is therefore suggested that multiple exercises must be carried out to bring in, and fully activate all knee flexors and hip extensors. © Georg Thieme Verlag KG Stuttgart · New York.

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A.

PubMed

Otsuka, M; Yoshioka, K; Yanagisawa, M; Suzuki, H; Zhao, F Y; Guo, J Z; Hosoki, R; Kurihara, T

1995-07-01

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.

Effects of comprehensive function of factors on retention behavior of microparticles in gravitational field-flow fractionation.

PubMed

Guo, Shuang; Qiu, Bai-Ling; Zhu, Chen-Qi; Yang, Ya-Ya Gao; Wu, Di; Liang, Qi-Hui; Han, Nan-Yin

2016-09-15

Gravitational field-flow fractionation (GrFFF) is a useful technique for separation and characterization for micrometer-sized particles. Elution behavior of micrometer-sized particles in GrFFF was researched in this study. Particles in GrFFF channel are subject to hydrodynamic lift forces (HLF), fluid inertial forces and gravity, which drive them to different velocities by carrier flow, resulting in a size-based separation. Effects of ionic strength, flow rate and viscosity as well as methanol were investigated using polystyrene latex beads as model particles. This study is devoted to experimental verification of the effect of every factor and their comprehensive function. All experiments were performed to show isolated influence of every variable factor. The orthogonal design test was used to evaluate various factors comprehensively. Results suggested that retention ratio of particles increases with increasing flow rate or the viscosity of carrier liquid by adjusting external forces acting on particles. In addition, retention ratio increases as ionic strength decreases because of decreased electrostatic repulsion between particles and channel accumulation wall. As far as methanol, there is no general trend due to the change of both density and viscosity. On the basis of orthogonal design test it was found that viscosity of carrier liquid plays a significant role in determining resolution of micrometer-sized particles in GrFFF. Copyright © 2016 Elsevier B.V. All rights reserved.

Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity.

PubMed

Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

2014-01-01

In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed "biomimetic". Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells.

High level of reduced glutathione contributes to detoxification of lipid peroxide-derived reactive carbonyl species in transgenic Arabidopsis overexpressing glutathione reductase under aluminum stress.

PubMed

Yin, Lina; Mano, Jun'ichi; Tanaka, Kiyoshi; Wang, Shiwen; Zhang, Meijuan; Deng, Xiping; Zhang, Suiqi

2017-10-01

Lipid peroxide-derived reactive carbonyl species (RCS), generated downstream of reactive oxygen species (ROS), are critical damage-inducing species in plant aluminum (Al) toxicity. In mammals, RCS are scavenged primarily by glutathione (reduced form of glutathione, GSH), but in plant Al stress, contribution of GSH to RCS detoxification has not been evaluated. In this study, Arabidopsis plants overexpressing the gene AtGR1 (accession code At3g24170), encoding glutathione reductase (GR), were generated, and their performance under Al stress was examined. These transgenic plants (GR-OE plants) showed higher GSH levels and GSH/GSSG (oxidized form of GSH) ratio, and an improved Al tolerance as they suffered less inhibition of root growth than wild-type under Al stress. Exogenous application of 4-hydroxy-2-nonenal, an RCS responsible for Al toxicity in roots, markedly inhibited root growth in wild-type plants. GR-OE plants suffered significantly smaller inhibition, indicating that the enhanced GSH level increased the capacity of RCS detoxification. The generation of H 2 O 2 due to Al stress in GR-OE plants was lower by 26% than in wild-type. Levels of various RCS, such as malondialdehyde, butyraldehyde, phenylacetaldehyde, (E)-2-heptenal and n-octanal, were suppressed by more than 50%. These results indicate that high levels of GSH and GSH/GSSG ratio by GR overexpression contributed to the suppression of not only ROS, but also RCS. Thus, the maintenance of GSH level by overexpressing GR reinforces dual detoxification functions in plants and is an efficient approach to enhance Al tolerance. © 2017 Scandinavian Plant Physiology Society.

Highly selective colorimetric and electrochemical sensing of iron (III) using Nile red functionalized graphene film.

PubMed

Sadak, Omer; Sundramoorthy, Ashok K; Gunasekaran, Sundaram

2017-03-15

We report a highly selective method for identification and detection of iron (III) (ferric iron, Fe 3+ ) using Nile red (NR) as a complexing agent. Fe 3+ preferentially binds with NR in dimethylformamide (DMF)/water (1:1) solution over other cations such as Fe 2+ , Cu 2+ , Pb 2+ , Hg 2+ , Mn 2+ , Ni 2+ , Zn 2+ , Co 2+ and Cd 2+ at room temperature. In the presence of Fe 3+ , the color of NR solution changes from purple to dark brown, which is detectable with bare eyes. Using UV-vis spectroscopy, we could measure the amount of Fe 3+ in the sample solution by monitoring changes in absorption from 540 to 580nm; the linear range and the limit of detection are 30-1000µM and 24.9µM, respectively. Taking advantage of the NR selectivity, we treated partially oxidized graphene sheets (po-Gr) with NR to obtain po-Gr-NR dispersion by ultrasonication. The NR-treated po-Gr flakes (po-Gr-NR) were characterized by UV-vis, FT-IR, and Raman spectroscopies and FE-SEM, which indicated attachment of NR on po-Gr sheets. The po-Gr-NR hybrid film deposited glassy carbon electrode (po-Gr-NR/GCE) served as the Fe 3+ sensor. Differential pulse voltammetry was used to investigate the detection of Fe 3+ in 0.05M HCl+0.05M KCl solution. The linear range and the limit of detection of Fe 3+ were from 37.5nM to 21.53µM and 18.7nM, respectively. Furthermore, this sensor was successfully used to measure Fe 3+ content in red wine samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of gramicidin-A on the adsorption of phospholipids to the air–water interface

PubMed Central

Biswas, Samares C.; Rananavare, Shankar B.; Hall, Stephen B.

2012-01-01

Prior studies suggest that the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of the lipids in pulmonary surfactant to an air–water interface by stabilizing a negatively curved rate-limiting structure that is intermediate between bilayer vesicles and the surface film. This model predicts that other peptides capable of stabilizing negative curvature should also promote lipid adsorption. Previous reports have shown that under appropriate conditions, gramicidin-A (GrA) induces dioleoyl phosphatidylcholine (DOPC), but not dimyristoyl phosphatidylcholine (DMPC), to form the negatively curved hexagonal-II (HII) phase. The studies reported here determined if GrA would produce the same effects on adsorption of DMPC and DOPC that the hydrophobic surfactant proteins have on the surfactant lipids. Small angle X-ray scattering and 31P-nuclear magnetic resonance confirmed that at the particular conditions used to study adsorption, GrA induced DOPC to form the HII phase, but DMPC remained lamellar. Measurements of surface tension showed that GrA in vesicles produced a general increase in the rate of adsorption for both phospholipids. When restricted to the interface, however, in preexisting films, GrA with DOPC, but not with DMPC, replicated the ability of the surfactant proteins to promote adsorption of vesicles containing only the lipids. The correlation between the structural and functional effects of GrA with the two phospholipids, and the similar effects on adsorption of GrA with DOPC and the hydrophobic surfactant proteins with the surfactant lipids fit with the model in which SP-B and SP-C facilitate adsorption by stabilizing a rate-limiting intermediate with negative curvature. PMID:16242116

Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

PubMed Central

Fujii, Hideki; Yagi, Kazuma; Suzuki, Shoji; Hegab, Ahmed E.; Tasaka, Sadatomo; Nakamoto, Nobuhiro; Iwata, Satoshi; Honda, Kenya; Kanai, Takanori; Hasegawa, Naoki; Betsuyaku, Tomoko

2018-01-01

Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides. PMID:29621339

Dexamethasone-Mediated Changes in Adipose Triacylglycerol Metabolism Are Exaggerated, Not Diminished, in the Absence of a Functional GR Dimerization Domain

PubMed Central

Roohk, Donald J.; Mascharak, Smita; Khambatta, Cyrus; Leung, Ho; Hellerstein, Marc

2013-01-01

The glucocorticoid (GC) receptor (GR) has multiple effector mechanisms, including dimerization-mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein-protein interactions. Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti-inflammatory effects. The GRdim/dim mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression. To understand the role of GR dimerization-dependent targets in multiple tissues, we measured metabolic fluxes through several disease-relevant GC target pathways using heavy water labeling and mass spectrometry in wild-type and GRdim/dim mice administered the potent GC dexamethasone (DEX). Absolute triglyceride synthesis was increased in both wild-type and GRdim/dim mice by DEX in the inguinal and epididymal fat depots. GRdim/dim mice showed an exaggerated response to DEX in both depots. De novo lipogenesis was also greatly increased in both depots in response to DEX in GRdim/dim, but not wild-type mice. In contrast, the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild-type compared with GRdim/dim mice. Wild-type mice were more sensitive to DEX-dependent decreases in insulin sensitivity than GRdim/dim mice. Wild-type and GRdim/dim mice were equally sensitive to DEX-dependent decreases in muscle protein synthesis. Chronic elevation of GCs in GRdim/dim mice results in severe runting and lethality. In conclusion, some metabolic effects of GC treatment are exaggerated in adipose tissue of GRdim/dim mice, suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully. PMID:23493372

Molecular characterization and expression analysis of a glycine-rich RNA-binding protein gene from Malus hupehensis Rehd.

PubMed

Wang, Shuncai; Wang, Rongchao; Liang, Dong; Ma, Fengwang; Shu, Huairui

2012-04-01

Members of the plant glycine-rich RNA-binding protein (GR-RBP) family play diverse roles in regulating RNA metabolism for various cellular processes. To understand better their function at the molecular level in stress responses, we cloned a GR-RBP gene, MhGR-RBP1, from Malus hupehensis. Its full-length cDNA is 558 bp long, with a 495-bp open reading frame, and it encodes 164 amino acids. The deduced amino acid sequence contains an RNA-recognition motif (RRM) at the amino terminal and a glycine-rich domain at the carboxyl terminal; these are highly homologous with those from other plant species. Multiple alignment and phylogenetic analyses show that the deduced protein is a novel member of the plant GR-RBP family. To characterize this gene, we also applied a model for predicting its homology of protein structure with other species. Both organ-specific and stress-related expression were detected by quantitative real-time PCR and semi-quantitative RT-PCR, indicating that MhGR-RBP1 is expressed abundantly in young leaves but weakly in roots and shoots. Transcript levels in the leaves were increased markedly by drought, hydrogen peroxide (H(2)O(2)), and mechanical wounding, slightly by salt stress. Furthermore, the transcript is initially up- and down-regulated rapidly within 24 h of abscisic acid (ABA) treatment. After 24 h of ABA and jasmonic acid (JA) treatments with different concentrations, the transcript levels of MhGR-RBP1 were significantly repressed. These results suggest that MhGR-RBP1 may be involved in the responses to abiotic stresses, H(2)O(2), ABA, or JA.

Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity

PubMed Central

Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

2014-01-01

In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed “biomimetic”. Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells. PMID:24648728

Ectoderm-targeted overexpression of the glucocorticoid receptor induces hypohidrotic ectodermal dysplasia.

PubMed

Cascallana, Jose Luis; Bravo, Ana; Donet, Eva; Leis, Hugo; Lara, Maria Fernanda; Paramio, Jesús M; Jorcano, José L; Pérez, Paloma

2005-06-01

Hypohidrotic ectodermal dysplasia is a human syndrome defined by maldevelopment of one or more ectodermal-derived tissues, including the epidermis and cutaneous appendices, teeth, and exocrine glands. The molecular bases of this pathology converge in a dysfunction of the transcription factor nuclear factor of the kappa-enhancer in B cells (NF-kappaB), which is essential to epithelial homeostasis and development. A number of mouse models bearing disruptions in NF-kappaB signaling have been reported to manifest defects in ectodermal derivatives. In ectoderm-targeted transgenic mice overexpressing the glucocorticoid receptor (GR) [keratin 5 (K5)-GR mice], the NF-kappaB activity is greatly decreased due to functional antagonism between GR and NF-kappaB. Here, we report that K5-GR mice exhibit multiple epithelial defects in hair follicle, tooth, and palate development. Additionally, these mice lack Meibomian glands and display underdeveloped sweat and preputial glands. These phenotypic features appear to be mediated specifically by ligand-activated GR because the synthetic analog dexamethasone induced similar defects in epithelial morphogenesis, including odontogenesis, in wild-type mice. We have focused on tooth development in K5-GR mice and found that an inhibitor of steroid synthesis partially reversed the abnormal phenotype. Immunostaining revealed reduced expression of the inhibitor of kappaB kinase subunits, IKKalpha and IKKgamma, and diminished p65 protein levels in K5-GR embryonic tooth, resulting in a significantly reduced kappaB-binding activity. Remarkably, altered NF-kappaB activity elicited by GR overexpression correlated with a dramatic decrease in the protein levels of DeltaNp63 in tooth epithelia without affecting Akt, BMP4, or Foxo3a. Given that many of the 170 clinically distinct ectodermal dysplasia syndromes still remain without cognate genes, deciphering the molecular mechanisms of this mouse model with epithelial NF-kappaB and p63 dysfunction may provide important clues to understanding the basis of other ectodermal dysplasia syndromes.

Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the Vitamin D receptor in 24(OH)ase transcription.

PubMed

Dhawan, Puneet; Christakos, Sylvia

2010-08-15

Glucocorticoid-induced bone loss has been proposed to involve direct effects on bone cells as well as alterations in calcium absorption and excretion. Since vitamin D is important for the maintenance of calcium homeostasis, in the present study the effects of glucocorticoids on vitamin D metabolism through the expression of 24(OH)ase, an enzyme involved in the catabolism of 1,25(OH)(2)D(3), were examined. Injection of vitamin D replete mice with dexamethasone (dex) resulted in a significant induction in 24(OH)ase mRNA in kidney, indicating a regulatory effect of glucocorticoids on vitamin D metabolism. Whether glucocorticoids can affect 24(OH)ase transcription is not known. Here we demonstrate for the first time a glucocorticoid receptor (GR) dependent enhancement of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. Dex treatment of GR and vitamin D receptor (VDR) transfected COS-7 cells and dex treatment of osteoblastic cells (in which VDR and GR are present endogenously) potentiated 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. In addition, GR was found to cooperate with C/EBP beta to enhance VDR-mediated 24(OH)ase transcription. Using the rat 24(OH)ase promoter with the C/EBP site mutated, GR-mediated potentiation of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription was inhibited. Immunoprecipitation indicated that that GR can interact with C/EBP beta and ChIP/re-ChIP analysis showed that C/EBP beta and GR bind simultaneously to the 24(OH)ase promoter. These findings indicate a novel mechanism whereby glucocorticoids can alter VDR-mediated 24(OH)ase transcription through functional cooperation between C/EBP beta and GR that results in an enhanced ability of C/EBP beta to cooperate with VDR in the regulation of 24(OH)ase. (c) 2010 Wiley-Liss, Inc.

Recruitment of bone marrow CD11b+Gr-1+ cells by polymeric nanoparticles for antigen cross-presentation

NASA Astrophysics Data System (ADS)

Yang, Ya-Wun; Luo, Wen-Hui

2017-03-01

The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr-1+ myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chigh and CD11b+Gr-1highLy-6Clow subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+ cells. Co-culture of OT-I CD8+ T cells with PLGA/OVA NPs-primed CD11b+Gr-1+ subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+ T cells and differentiation into effector cytotoxic T lymphocytes (CTLs). In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr-1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells.

Ice Core Records of West Greenland Melt and Climate Forcing

NASA Astrophysics Data System (ADS)

Graeter, K. A.; Osterberg, E. C.; Ferris, D. G.; Hawley, R. L.; Marshall, H. P.; Lewis, G.; Meehan, T.; McCarthy, F.; Overly, T.; Birkel, S. D.

2018-04-01

Remote sensing observations and climate models indicate that the Greenland Ice Sheet (GrIS) has been losing mass since the late 1990s, mostly due to enhanced surface melting from rising summer temperatures. However, in situ observational records of GrIS melt rates over recent decades are rare. Here we develop a record of frozen meltwater in the west GrIS percolation zone preserved in seven firn cores. Quantifying ice layer distribution as a melt feature percentage (MFP), we find significant increases in MFP in the southernmost five cores over the past 50 years to unprecedented modern levels (since 1550 CE). Annual to decadal changes in summer temperatures and MFP are closely tied to changes in Greenland summer blocking activity and North Atlantic sea surface temperatures since 1870. However, summer warming of 1.2°C since 1870-1900, in addition to warming attributable to recent sea surface temperature and blocking variability, is a critical driver of high modern MFP levels.

Microscopic mechanisms of graphene electrolytic delamination from metal substrates

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

Fisichella, G.; Department of Electronic Engineering, University of Catania, Viale A. Doria, 6 – 95125 Catania; Di Franco, S.

In this paper, hydrogen bubbling delamination of graphene (Gr) from copper using a strong electrolyte (KOH) water solution was performed, focusing on the effect of the KOH concentration (C{sub KOH}) on the Gr delamination rate. A factor of ∼10 decrease in the time required for the complete Gr delamination from Cu cathodes with the same geometry was found increasing C{sub KOH} from ∼0.05 M to ∼0.60 M. After transfer of the separated Gr membranes to SiO{sub 2} substrates by a highly reproducible thermo-compression printing method, an accurate atomic force microscopy investigation of the changes in Gr morphology as a function of C{submore » KOH} was performed. Supported by these analyses, a microscopic model of the delamination process has been proposed, where a key role is played by graphene wrinkles acting as nucleation sites for H{sub 2} bubbles at the cathode perimeter. With this approach, the H{sub 2} supersaturation generated at the electrode for different electrolyte concentrations was estimated and the inverse dependence of t{sub d} on C{sub KOH} was quantitatively explained. Although developed in the case of Cu, this analysis is generally valid and can be applied to describe the electrolytic delamination of graphene from several metal substrates.« less

The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

PubMed Central

Wazir, Javed Fayyaz; Brahmi, Urmil Prabha; Fakhro, Abdul Rahman

2017-01-01

The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs) are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs) in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC) for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal) carcinoma, particularly HER-2-negative cancers. PMID:29348941

Southern San Andreas Fault seismicity is consistent with the Gutenberg-Richter magnitude-frequency distribution

USGS Publications Warehouse

Page, Morgan T.; Felzer, Karen

2015-01-01

The magnitudes of any collection of earthquakes nucleating in a region are generally observed to follow the Gutenberg-Richter (G-R) distribution. On some major faults, however, paleoseismic rates are higher than a G-R extrapolation from the modern rate of small earthquakes would predict. This, along with other observations, led to formulation of the characteristic earthquake hypothesis, which holds that the rate of small to moderate earthquakes is permanently low on large faults relative to the large-earthquake rate (Wesnousky et al., 1983; Schwartz and Coppersmith, 1984). We examine the rate difference between recent small to moderate earthquakes on the southern San Andreas fault (SSAF) and the paleoseismic record, hypothesizing that the discrepancy can be explained as a rate change in time rather than a deviation from G-R statistics. We find that with reasonable assumptions, the rate changes necessary to bring the small and large earthquake rates into alignment agree with the size of rate changes seen in epidemic-type aftershock sequence (ETAS) modeling, where aftershock triggering of large earthquakes drives strong fluctuations in the seismicity rates for earthquakes of all magnitudes. The necessary rate changes are also comparable to rate changes observed for other faults worldwide. These results are consistent with paleoseismic observations of temporally clustered bursts of large earthquakes on the SSAF and the absence of M greater than or equal to 7 earthquakes on the SSAF since 1857.

AB INITIO Molecular Dynamics Simulations on Local Structure and Electronic Properties in Liquid Sb from 913 K to 1193 K

NASA Astrophysics Data System (ADS)

Hao, Qing-Hai; Li, Y. D.; Kong, Xiang-Shan; Liu, C. S.

2013-02-01

Ab initio molecular dynamics simulations on liquid Sb have been carried out at five different temperatures from 913 K to 1193 K. We have investigated the temperature dependence of structure properties including structural factor S(Q), pair correlation function g(r), bond-angle distribution function g3(θ), cluster properties and bond order parameter Q4 and Q6. A shoulder was reproduced in the high wave number side of the first peak in the S(Q) implying that the residual structure units of crystalline Sb remain in liquid Sb. There is a noticeable bend at around 1023 K in the temperature dependence of the first-peak height of S(Q), the cluster properties and bond order parameter Q4, respectively, indicating that an abnormal structural change may occur at 973-1023 K.

Solvation of fluoro-acetonitrile in water by 2D-IR spectroscopy: A combined experimental-computational study

NASA Astrophysics Data System (ADS)

Cazade, Pierre-André; Tran, Halina; Bereau, Tristan; Das, Akshaya K.; Kläsi, Felix; Hamm, Peter; Meuwly, Markus

2015-06-01

The solvent dynamics around fluorinated acetonitrile is characterized by 2-dimensional infrared spectroscopy and atomistic simulations. The lineshape of the linear infrared spectrum is better captured by semiempirical (density functional tight binding) mixed quantum mechanical/molecular mechanics simulations, whereas force field simulations with multipolar interactions yield lineshapes that are significantly too narrow. For the solvent dynamics, a relatively slow time scale of 2 ps is found from the experiments and supported by the mixed quantum mechanical/molecular mechanics simulations. With multipolar force fields fitted to the available thermodynamical data, the time scale is considerably faster—on the 0.5 ps time scale. The simulations provide evidence for a well established CF-HOH hydrogen bond (population of 25%) which is found from the radial distribution function g(r) from both, force field and quantum mechanics/molecular mechanics simulations.

Strong interfacial polarization in graphene/ZnO nanocomposite for high-performance miniscule permittivity materials

NASA Astrophysics Data System (ADS)

Shoeb, Mohd; Mobin, Mohammad; Naqvi, Alim H.

2018-05-01

In the 21st century evolution of microelectronics industries, consumptions of integrated circuits (IC's) increases, so the demand of miniscule permittivity (MP) material with minimum loss factor arises in the electronics industries. Graphene embedded ZnO Nanoparticle (Gr/ZnO NCs) is synthesized and studied their dielectric properties In the studied frequency range 75 kHz to 7 MHz. In the sample Gr/ZnO NCs dielectric permittivity decrease gradually from 7.2 to 6.7 as the frequency increases, whereas dielectric permittivity of ZnO NPs shows also diminishing behavior in the range 75 to 20 as the frequency increases. In the Gr/ZnO NCs, Maxwell-Wagner polarization model explains strong interfacial polarization to presence of functionalization group and lattice defects on graphene sheet.

T -odd correlations in polarized top quark decays in the sequential decay t (↑)→Xb+W+(→ℓ++νℓ) and in the quasi-three-body decay t (↑)→ Xb+ℓ++νℓ

NASA Astrophysics Data System (ADS)

Fischer, M.; Groote, S.; Körner, J. G.

2018-05-01

We identify the T -odd structure functions that appear in the description of polarized top quark decays in the sequential decay t (↑)→Xb+W+(→ℓ++νℓ) (two structure functions) and the quasi-three-body decay t (↑)→X b+ℓ++νℓ (one structure function). A convenient measure of the magnitude of the T -odd structure functions is the contribution of the imaginary part Im gR of the right-chiral tensor coupling gR to the T -odd structure functions which we work out. Contrary to the case of QCD, the NLO electroweak corrections to polarized top quark decays admit absorptive one-loop vertex contributions. We analytically calculate the imaginary parts of the relevant four electroweak one-loop triangle vertex diagrams and determine their contributions to the T -odd helicity structure functions that appear in the description of polarized top quark decays.

Gröbner Bases and Generation of Difference Schemes for Partial Differential Equations

NASA Astrophysics Data System (ADS)

Gerdt, Vladimir P.; Blinkov, Yuri A.; Mozzhilkin, Vladimir V.

2006-05-01

In this paper we present an algorithmic approach to the generation of fully conservative difference schemes for linear partial differential equations. The approach is based on enlargement of the equations in their integral conservation law form by extra integral relations between unknown functions and their derivatives, and on discretization of the obtained system. The structure of the discrete system depends on numerical approximation methods for the integrals occurring in the enlarged system. As a result of the discretization, a system of linear polynomial difference equations is derived for the unknown functions and their partial derivatives. A difference scheme is constructed by elimination of all the partial derivatives. The elimination can be achieved by selecting a proper elimination ranking and by computing a Gröbner basis of the linear difference ideal generated by the polynomials in the discrete system. For these purposes we use the difference form of Janet-like Gröbner bases and their implementation in Maple. As illustration of the described methods and algorithms, we construct a number of difference schemes for Burgers and Falkowich-Karman equations and discuss their numerical properties.

IL-33 expands suppressive CD11b+ Gr-1int and regulatory T cells (Treg), including ST2L+ Foxp3+ cells, and mediates Treg-dependent promotion of cardiac allograft survival

PubMed Central

Turnquist, Hēth R.; Zhao, Zhenlin; Rosborough, Brian R.; Liu, Quan; Castellaneta, Antonino; Isse, Kumiko; Wang, Zhiliang; Lang, Megan; Stolz, Donna Beer; Zheng, Xin Xiao; Demetris, A. Jake; Liew, Foo Y.; Wood, Kathryn J.; Thomson, Angus W.

2011-01-01

IL-33 administration is associated with facilitation of Th type-2 (Th2) responses and cardioprotective properties in rodent models. However, in heart transplantation, the mechanism by which IL-33, signaling through ST2L, the membrane-bound form of ST2, promotes transplant survival is unclear. We report that IL-33 administration, while facilitating Th2 responses, also increases immunoregulatory myeloid cells and CD4+ Foxp3+ regulatory T cells (Treg) in mice. IL-33 expands functional myeloid-derived suppressor cells (MDSC), -CD11b+ cells that exhibit intermediate (int) levels of Gr-1 and potent T cell suppressive function. Furthermore, IL-33 administration causes a St2-dependent expansion of suppressive CD4+ Foxp3+ Treg, including a ST2L+ population. IL-33 monotherapy following fully allogeneic mouse heart transplantation resulted in significant graft prolongation, associated with increased Th2-type responses and decreased systemic CD8+ IFN-γ+ cells. Also, despite reducing overall CD3+ cell infiltration of the graft, IL-33 administration markedly increased intragraft Foxp3+ cells. Whereas control graft recipients displayed increases in systemic CD11b+ Gr-1hi cells, IL-33-treated recipients exhibited increased CD11b+ Gr-1int cells. Enhanced ST2 expression was observed in the myocardium and endothelium of rejecting allografts, however the therapeutic effect of IL-33 required recipient St2 expression and was dependent on Treg. These findings reveal a new immunoregulatory property of IL-33. Specifically, in addition to supporting Th2 responses, IL-33 facilitates regulatory cells, particularly functional CD4+ Foxp3+ Treg that underlie IL-33-mediated cardiac allograft survival. PMID:21949025

Expression and Regulation of the Fkbp5 Gene in the Adult Mouse Brain

PubMed Central

Scharf, Sebastian H.; Liebl, Claudia; Binder, Elisabeth B.

2011-01-01

Background Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR). The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5). Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. Methodology/Principal Findings In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN) and the central amygdala (CeA). Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. Conclusions/Significance Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain. PMID:21347384

Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs.

PubMed

Rupniak, N M; Carlson, E J; Webb, J K; Harrison, T; Porsolt, R D; Roux, S; de Felipe, C; Hunt, S P; Oates, B; Wheeldon, A

2001-11-01

The phenotype of NK1R-/- mice was compared with that of acute pharmacological blockade of the tachykinin NK1 receptor on sensorimotor function and in assays relevant to depressive illness and anxiety. The dose range for L-760735 and GR205171 that was associated with functional blockade of central NK1 receptors in the target species was established by antagonism of the behavioural effects of intracerebroventricular NK1 agonist challenge in gerbils, mice and rats. The caudal grooming and scratching response to GR73632 was absent in NK1R-/- mice, confirming that the receptor had been genetically ablated. There was no evidence of sedation or motor impairment in NK1R-/- mice or following administration of L-760735 to gerbils, even at doses in excess of those required for central NK1 receptor occupancy. In the resident-intruder and forced swim test, the behaviour of NK1R-/- mice, or animals treated acutely with L-760735 or GR205171, resembled that seen with the clinically used antidepressant drug fluoxetine. However, the effects of GR205171 were not clearly enantioselective in mice. In contrast, although NK1R-/- mice also exhibited an increase in the duration of struggle behaviour in the tail suspension test, this was not observed following pharmacological blockade with L-760735 in gerbils or GR205171 in mice, suggesting that this may reflect a developmental alteration in the knockout mouse. There was no effect of NK1 receptor blockade with L-760735 in guinea-pigs or GR205171 in rats, or deletion of the NK1 receptor in mice, on behaviour in the elevated plus-maze test for anxiolytic activity. These findings extend previous observations on the phenotype of the NK1R-/- mouse and establish a broadly similar profile following acute pharmacological blockade of the receptor. These studies also serve to underscore the limitations of currently available antagonists that are suitable for use in rat and mouse behavioural assays.

Receptor-selective, peptidase-resistant agonists at neurokinin NK-1 and NK-2 receptors: new tools for investigating neurokinin function.

PubMed

Hagan, R M; Ireland, S J; Jordan, C C; Beresford, I J; Deal, M J; Ward, P

1991-06-01

The pharmacological profiles of two novel neurokinin agonists have been investigated. delta Ava[L-Pro9,N-MeLeu10]SP(7-11) (GR73632) and [Lys3,Gly8-R-gamma-lactam-Leu9] NKA(3-10) (GR64349) are potent and selective agonists at NK-1 and NK-2 receptors respectively. In the guinea-pig isolated trachea preparation, contractions induced by these agonists were largely unaffected by inclusion of peptidase inhibitors in the bathing medium, indicating that these agonists are resistant to metabolism by peptidases. In the anaesthetised guinea-pig, both agonists were more potent bronchoconstrictor agents than either NKA or the SP analogue, SP methylester. In the anaesthetised rat, the NK-1 agonist, GR73632 was more potent than SP, NKA or NKB at causing the histamine-independent extravasation of plasma proteins into the skin after intradermal administration. The NK-2 agonist, GR64349 and the NK-3 agonist, senktide were without significant effect in this model. These agonists are useful tools for characterizing neurokinin receptor-mediated actions both in vitro and in vivo.

A X-Ray Diffraction Study of the Structure of Fluid Argon.

NASA Astrophysics Data System (ADS)

Yan, Kam-Leung

X-ray diffraction patterns of liquid argon were measured and analyzed at six thermodynamic states, all above the critical pressure. These states were on the isotherms T = 105.4K ((rho) = 1.43, 1.36, & 1.30 g/cm('3)) and T = 152.0K ((rho) = 1.30, 1.15, & 1.00 g/cm('3)), with pressures between 70 and 765 kg/cm('2). Samples of fluid argon confined in a beryllium cell were irradiated by monochromatized Mo x-radiation. The scattered intensities were detected with a NaI scintillation counter using step-scanning technique. A total resolution of 0.06(DEGREES) in the scattering plane allowed the scanning process to be performed in uniform step-increments of 0.125(DEGREES). Cooling of the Be cell was accomplished with a two-stage N(,2)-He cooling system. Static structure factors S(k) were obtained from the diffraction data. Refinement of these factors and determination of the radial distribution function g(r) were performed by iterative Fourier analysis. The efficacy of this method was exemplified by the overall improvement in the general form as well as the fine details of both functions. The principal features in S(k) and g(r) were located below k = 9 (ANGSTROM)('-1) and r = 16 (ANGSTROM), respectively. The first three maxima in S(k) were approximately at 1.98, 3.66, and 5.28 (ANGSTROM)('-1), respectively, and their respective averaged heights were 2.19, 1.23, and 1.07. In g(r), the positions of the first three coordinate shells were consistently at 3.37, 7.11, and 10.31 (ANGSTROM), respectively; their respective averaged magnitudes were 2.41, 1.20, and 1.07. Both functions were examined for their response to variations of (rho) and T. The main structures in both functions were found to be strongly dependent of the bulk density of the fluid, and relatively insensitive to temperature changes. g(r) for the state of (rho) = 1.43 g/cm('3) presently studied was compared with the results of computer simulation studies of Lennard-Jones fluids (Verlet 1968). The excellent overall agreement inferred from the comparison was apparently indicative of the appropriateness of the Lennard-Jones (6:12) potential as an effective pair potential for classical monatomic fluids. Anomalies in the form of subsidiary peaks were present in g(r) for four states of argon. These secondary features were observed at or near the first major minimum, in between the first two principal coordinate shells. Their position and degree of prominence exhibit little evidence of state-dependence. The triplet correlation function g(,3)(r,s,t) of argon was studied with the modified Kirkwood superposition approximation (Egelstaff et al 1969, 1971) which included a correction term H(r,s,t). The corresponding term of H(r,s,t) in momentum space, H(k),(' )has presently been calculated for argon at six thermodynamic states on the two said isotherms. The structure in(' )H(k) was apparent of a short range nature, and varied smoothly and continuously with the thermodynamic parameters of the fluid. The small -k behavior of(' )H(k) was indicative of the long range form of its real space transform. H(k)(' )for the state of (rho) = 1.08 g/cm('3) showed a substantial increase in the prominence of secondary features. Although no attempt has yet been made to examine the nature of this phenomenon, the implied increase in the significance of the pressure effect might conceivably be caused by the fact that this state was the closest to the critical point. The strong state-dependence of(' )H(k) supported the theoretical prediction that H(k)(' )(--->) 0 for all k as the critical point was approached.

[Control of postoperative hemorrhage in isolated coronary bypass surgery: comparison of tranexamic acid effects in off-pump surgery with aprotinin effects in conventional surgery].

PubMed

Bordalo, Alvaro D B; Nobre, Angelo L; Silva, Fernanda; Serpa, Carlos; Cravino, João

2011-01-01

In spite of the strong criticism elicited thereafter, the results of a multicentric study on the consequences of several perioperative anti-hemorrhagic strategies in cardiac surgery, published five years ago, led to the aprotinin (Aprot) withdrawal from the market and its progressive replacement by tranexamic acid (TrAc) in many surgical departments. To evaluate the hemostatic effects and clinical consequences of TrAc use or non-use in off-pump coronary bypass surgery (CABG) and compare them with those of Aprot use or non-use in conventional (conv) CABG. Retrospective analysis of 2 groups (Gr) of patients (pts): GrA - 252 pts undergoing isolated conv CABG (GrA1 - 185 pts submitted to an intra-operative full-dose Aprot protocol; GrA2 - 67 pts operated without Aprot); GrB - 383 pts undergoing isolated off-pump CABG (GrB1 - 136 pts submitted to an intra-operative low-dose TrAc protocol; GrB2 - 247 pts operated in absence of TrAc). Pre-operative clinical characteristics (GrA1 vs GrA2, GrB1 vs GrB2): mean age (years) - 65 vs 64 (NS), 64 vs 64; female gender - 20% vs 21% (NS), 23% vs 20% (NS); logistic Euroscore - 5.1% vs 6.2% (NS), 6.3% vs 5.5% (NS); chronic renal failure - 21% vs 27% (NS), 27% vs 25% (NS); diffuse coronary artery disease - 34% vs 42% (NS), 36% vs 30% (NS); pre-operative betablocker treatment - 64% vs 55% (NS), 74% vs 71% (NS); statin therapy for > 3 months - 78% vs 82% (NS), 81% vs 85% (NS). Pts have been operated by 4 surgeons largely experienced in both CABG modalities. Antiplatelet therapy was stopped => 4 days prior to surgery (but aspirin was maintained in high-risk pts). Results (GrA1 vs GrA2, GrB1 vs GrB2): 1) Bleeding (mL/pt - mean): 783 vs 1375 (p < 0.001), 1061 vs 1368 (p < 0.001); blood loss > 1500 mL (%pts) - 5.4% vs 34% (p < 0.0001), 12% vs 28% (p < 0.001); surgical re-exploration for bleeding - 1.1% vs 3.0% (NS), 2.2% vs 2.0% (NS). 2) Transfusion of blood products (U/pt - mean): plasma - 0.56 vs 2.19 (p < 0.001), 1.45 vs 1.03 (p < 0.05); platelets - 0.09 vs 0.22 (p < 0.02), 0.24 vs 0.15 (NS). 3) Renal function (%pts): increased serum cre- atinine - 56% vs 56%, 55% vs 38% (p < 0.001); hemofiltration use - 1.1% vs 1.5% (NS), 1.5% vs 0.4% (NS). 4) Perioperative myocardial infarction - 21.6% vs 17.9% (NS), 17.6% vs 14.6% (NS); other ischemic events - 3.2% vs 3.0% (NS), 1.5% vs 1.2% (NS). 5) Hospital mortality: 4.8% vs 4.5% (NS), 4.4% vs 1.6% (NS). 1) TrAc does not reduce the risk of surgical re-exploration for bleeding. 2) Taking into account the differences between conv CABG and off-pump CABG, TrAc hemostatic effect seems to be inferior to that of Aprot, without offering a better safety profile in terms of lesser renal or ischemic risk as a counterpart.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.

PubMed

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-09-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA-spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients.

Testing Modified Gravity Theories via Wide Binaries and GAIA

NASA Astrophysics Data System (ADS)

Pittordis, Charalambos; Sutherland, Will

2018-06-01

The standard ΛCDM model based on General Relativity (GR) including cold dark matter (CDM) is very successful at fitting cosmological observations, but recent non-detections of candidate dark matter (DM) particles mean that various modified-gravity theories remain of significant interest. The latter generally involve modifications to GR below a critical acceleration scale ˜10-10 m s-2. Wide-binary (WB) star systems with separations ≳ 5 kAU provide an interesting test for modified gravity, due to being in or near the low-acceleration regime and presumably containing negligible DM. Here, we explore the prospects for new observations pending from the GAIA spacecraft to provide tests of GR against MOND or TeVes-like theories in a regime only partially explored to date. In particular, we find that a histogram of (3D) binary relative velocities, relative to equilibrium circular velocity predicted from the (2D) projected separation predicts a rather sharp feature in this distribution for standard gravity, with an 80th (90th) percentile value close to 1.025 (1.14) with rather weak dependence on the eccentricity distribution. However, MOND/TeVeS theories produce a shifted distribution, with a significant increase in these upper percentiles. In MOND-like theories without an external field effect, there are large shifts of order unity. With the external field effect included, the shifts are considerably reduced to ˜0.04 - 0.08, but are still potentially detectable statistically given reasonably large samples and good control of contaminants. In principle, followup of GAIA-selected wide binaries with ground-based radial velocities accurate to ≲ 0.03 { km s^{-1}} should be able to produce an interesting new constraint on modified-gravity theories.

Effect of different cements on the biomechanical behavior of teeth restored with cast dowel-and-cores-in vitro and FEA analysis.

PubMed

Soares, Carlos José; Raposo, Luís Henrique Araújo; Soares, Paulo Vinícius; Santos-Filho, Paulo César Freitas; Menezes, Murilo Sousa; Soares, Priscilla Barbosa Ferreira; Magalhães, Denildo

2010-02-01

To test the hypothesis that the type of cement used for fixation of cast dowel-and-cores might influence fracture resistance, fracture mode, and stress distribution of single-rooted teeth restored with this class of metallic dowels. The coronal portion was removed from 40 bovine incisors, leaving a 15 mm root. After endodontic treatment and standardized root canal relief at 10 mm, specimens were embedded in polystyrene resin, and the periodontal ligament was simulated with polyether impression material. The specimens were randomly divided into four groups (n = 10), and restored with Cu-Al cast dowel-and-cores cemented with one of four options: conventional glass ionomer cement (GI); resin-modified glass ionomer cement (GR); dual-cure resin cement (RC); or zinc-phosphate cement (ZP). Sequentially, fracture resistance of the specimens was tested with a tangential load at a 135 degrees angle with a 0.5 mm/min crosshead speed. Data were analyzed using one-way analysis of variance (ANOVA) and the Fisher test. Two-dimensional finite element analysis (2D-FEA) was then performed with representative models of each group simulating a 100 microm cement layer. Results were analyzed based on von Mises stress distribution criteria. The mean fracture resistance values were (in N): RC, 838.2 +/- 135.9; GI, 772.4 +/- 169.8; GR, 613.4 +/- 157.5; ZP, 643.6 +/- 106.7. FEA revealed that RC and GR presented lower stress values than ZP and GI. The higher stress concentration was coincident with more catastrophic failures, and consequently, with lower fracture resistance values. The type of cement influenced fracture resistance, failure mode, and stress distribution on teeth restored with cast dowel-and-cores.

Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine

PubMed Central

Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik

2015-01-01

Abdominal aortic aneurysms (AAAs) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between AAAs and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on AAAs specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the AAA. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA–spine interaction is accounted for using a penalty method when the AAA surface meets the spine surface. The simulation results show that, while the radial growth of the AAA wall is prevented on the posterior side due to the spine acting as a constraint, the AAA expands faster on the anterior side, leading to higher curvature and asymmetry in the AAA configuration compared to the simulation excluding the spine. Accordingly, the AAA wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA–spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of AAAs but also provides a framework to account for the interactions between an enlarging AAA and the spine for a better rupture potential assessment and management of AAA patients. PMID:26158885

Recent advances in synthesis of three-dimensional porous graphene and its applications in construction of electrochemical (bio)sensors for small biomolecules detection.

PubMed

Lu, Lu

2018-07-01

Electrochemical (bio)sensors have attracted much attention due to their high sensitivity, fast response time, biocompatibility, low cost and easy miniaturization. Specially, ever-growing necessity and interest have given rise to the fast development of electrochemical (bio)sensors for the detection of small biomolecules. They play enormous roles in the life processes with various biological function, such as life signal transmission, genetic expression and metabolism. Moreover, their amount in body can be used as an indicator for diagnosis of many diseases. For example, an abnormal concentration of blood glucose can indicate hyperglycemia or hypoglycemia. Graphene (GR) shows great applications in electrochemical (bio)sensors. Compared with two-dimensional (2D) GR that is inclined to stack together due to the strong π-π interaction, monolithic 3D porous GR has larger specific area, superior mechanical strength, better stability, higher conductivity and electrocatalytic activity. So they attracted more and increasing attention as sensing materials for small biomolecules. This review focuses on the recent advances and strategies in the fabrication methods of 3D porous GR and the development of various electrochemical (bio)sensors based on porous GR and its nanocomposites for the detection of small biomolecules. The challenges and future efforts direction of high-performance electrochemical (bio)sensors based on 3D porous GR for more sensitive analysis of small biomolecules are discussed and proposed. It will give readers an overall understanding of their progress and provide some theoretical guidelines for their future efforts and development. Copyright © 2018 Elsevier B.V. All rights reserved.

Chimeric Proton-Pumping Rhodopsins Containing the Cytoplasmic Loop of Bovine Rhodopsin

PubMed Central

Sasaki, Kengo; Yamashita, Takahiro; Yoshida, Kazuho; Inoue, Keiichi; Shichida, Yoshinori; Kandori, Hideki

2014-01-01

G-protein-coupled receptors (GPCRs) transmit stimuli to intracellular signaling systems. Rhodopsin (Rh), which is a prototypical GPCR, possesses an 11-cis retinal. Photoisomerization of 11-cis to all-trans leads to structural changes in the protein of cytoplasmic loops, activating G-protein. Microbial rhodopsins are similar heptahelical membrane proteins that function as bacterial sensors, light-driven ion-pumps, or light-gated channels. They possess an all-trans retinal, and photoisomerization to 13-cis triggers structural changes in protein. Despite these similarities, there is no sequence homology between visual and microbial rhodopsins, and microbial rhodopsins do not activate G-proteins. In this study, new chimeric proton-pumping rhodopsins, proteorhodopsin (PR) and Gloeobacter rhodopsin (GR) were designed by replacing cytoplasmic loops with bovine Rh loops. Although G-protein was not activated by the PR chimeras, all 12 GR chimeras activated G-protein. The GR chimera containing the second cytoplasmic loop of bovine Rh did not activate G-protein. However, the chimera with a second and third double-loop further enhanced G-protein activation. Introduction of an E132Q mutation slowed the photocycle 30-fold and enhanced activation. The highest catalytic activity of the GR chimera was still 3,200 times lower than bovine Rh but only 64 times lower than amphioxus Go-rhodopsin. This GR chimera showed a strong absorption change of the amide-I band on a light-minus-dark difference FTIR spectrum which could represent a larger helical opening, important for G-protein activation. The light-dependent catalytic activity of this GR chimera makes it a potential optogenetic tool for enzymatic activation by light. PMID:24621599

Zuogui Jiangtang Jieyu Formulation Prevents Hyperglycaemia and Depressive-Like Behaviour in Rats by Reducing the Glucocorticoid Level in Plasma and Hippocampus

PubMed Central

Wang, YuHong; Yang, Hui; Li, Wei; Meng, Pan; Han, YuanShan; Zhang, Xiuli; Cao, DeLiang; Tan, Yuansheng

2015-01-01

Aim. To determine whether Zuogui Jiangtang Jieyu prescription (ZGJTJY) has hypoglycemic and antidepressant effects which are mediated by corticosterone through adjustment of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and glucocorticoid (GR) levels. Materials and Methods. The diabetes-related depression rats were randomly divided into four groups: the model group, metformin (1.8 mg/kg) combined with fluoxetine (10.8 mg/kg) group, and ZGJTJY high and low dose groups. Four weeks after modeling, blood glucose, behavior, and cognitive function of depression were detected. The expressions of 11β-HSD1 and GR in hippocampus were measured by western blotting and immunohistochemical experiments. Results. We found that (1) the treatment with ZGJTJY (10.26 g/kg) increases the motor activities and improves cognition ability. (2) ZGJTJY (10.26 g/kg) significantly relieves the disorder in blood and the relative indexes. (3) ZGJTJY (10.26 g/kg) can reduce hippocampal corticosterone expression levels and further improve hippocampus pathological changes. (4) ZGJTJY increased the expression of GR accompanied with decreasing 11β-HSD1 in hippocampus. Conclusions. ZGJTJY inhibits the expression of 11β-HSD1 and increases GR in hippocampus and subsequently modulates blood glucose levels, and therefore it is potential property that ZGJTJY could be of benefit for the treatment of behavior and cognitive function of diabetes-related depression. PMID:26273311

Next-generation Lunar Laser Retroreflectors for Precision Tests of General Relativity

NASA Astrophysics Data System (ADS)

Ciocci, Emanuele; dell'Agnello, Simone; Delle Monache, Giovanni; Martini, Manuele; Contessa, Stefania; Porcelli, Luca; Tibuzzi, Mattia; Salvatori, Lorenzo; Patrizi, Giordano; Maiello, Mauro; Intaglietta, Nicola; Mondaini, Chiara; Currie, Douglas; Chandler, John; Bianco, Giuseppe; Murphy, Tom

2016-04-01

Since 1969, Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflectors (CCRs) has supplied almost all significant tests of General Relativity (GR). When first installed in the 1970s, the Apollo CCRs geometry contributed only a negligible fraction of the ranging error budget. Today, because of lunar librations, this contribution dominates the error budget, limiting the precision of the experimental tests of gravitational theories. The new MoonLIGHT-2 (Moon Laser Instrumentation for General relativity High-accuracy Tests) apparatus is a new-generation LLR payload developed by the SCF_Lab (http://www.lnf.infn.it/esperimenti/etrusco/) at INFN-LNF in collaboration with the Maryland University. With the unique design of a single large CCR unaffected by librations, MoonLIGHT-2 can increase up to a factor 100 the precision of the measurement of the lunar geodetic precession and other General Relativity (GR) tests respect to Apollo CCRs. MoonLIGHT-2 is approved to be launched with the Moon Express mission MEX-1 and will be deployed on the Moon surface in 2018. MoonLIGHT-2 is also proposed for the Roscosmos mission Luna-27. To validate/optimize MoonLIGHT-2 for MEX-1, the SCF_Lab is carrying out a unique experimental test called SCF-Test: the concurrent measurement of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of the CCR under thermal conditions produced with a close-match solar simulator and simulated space environment. We perform test of GR with current LLR data and also different GR simulation of the expected improvement in GR test provided by MoonLIGHT-2, using the Planetary Ephemeris Program in collaboration with CfA. Our ultimate goal is to improve GR tests by a factor up to 100, and provide constraints on the new gravitational theories like non-miminally coupled gravity and spacetime torision.

[Analysis of cis-regulatory element distribution in gene promoters of Gossypium raimondii and Arabidopsis thaliana].

PubMed

Sun, Gao-Fei; He, Shou-Pu; Du, Xiong-Ming

2013-10-01

Cotton genomic studies have boomed since the release of Gossypium raimondii draft genome. In this study, cis-regulatory element (CRE) in 1 kb length sequence upstream 5' UTR of annotated genes were selected and scanned in the Arabidopsis thaliana (At) and Gossypium raimondii (Gr) genomes, based on the database of PLACE (Plant cis-acting Regulatory DNA Elements). According to the definition of this study, 44 (12.3%) and 57 (15.5%) CREs presented "peak-like" distribution in the 1 kb selected sequences of both genomes, respectively. Thirty-four of them were peak-like distributed in both genomes, which could be further categorized into 4 types based on their core sequences. The coincidence of TATABOX peak position and their actual position ((-) -30 bp) indicated that the position of a common CRE was conservative in different genes, which suggested that the peak position of these CREs was their possible actual position of transcription factors. The position of a common CRE was also different between the two genomes due to stronger length variation of 5' UTR in Gr than At. Furthermore, most of the peak-like CREs were located in the region of -110 bp-0 bp, which suggested that concentrated distribution might be conductive to the interaction of transcription factors, and then regulate the gene expression in downstream.

Functionalized graphene with polymer toughener as novel interface modifier for property-tailored poly(lactic acid)/graphene nanocomposites

USDA-ARS?s Scientific Manuscript database

In this work, an effective strategy for engineering the interfacial compatibility between graphene and polylactic acid (PLA) was developed by manipulating the functionalization of graphene and introducing an epoxy-containing elastomer modifier. Curing between the functional groups of the modified gr...

Intracellular colocalization of HAP1/STBs with steroid hormone receptors and its enhancement by a proteasome inhibitor

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

Fujinaga, Ryutaro; Takeshita, Yukio; Yoshioka, Kazuhiro

2011-07-15

The stigmoid body (STB) is a cytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), and HAP1/STB formation is induced by transfection of the HAP1 gene into cultured cells. In the present study, we examined the intracellular colocalization of HAP1/STBs with steroid hormone receptors (SHRs), including the androgen receptor (AR), estrogen receptor, glucocorticoid receptor (GR), and mineralocorticoid receptor, in COS-7 cells cotransfected with HAP1 and each receptor. We found that C-terminal ligand-binding domains of all SHRs had potential for colocalization with HAP1/STBs, whereas only AR and GR were clearly colocalized with HAP1/STBs when each full-length SHR was coexpressed with HAP1. In addition,more » it appeared that HAP1/STBs did not disrupt GR and AR functions because the receptors on HAP1/STBs maintained nuclear translocation activity in response to their specific ligands. When the cells were treated with a proteasome inhibitor, GR and AR localized outside HAP1/STBs translocated into the nucleus, whereas the receptors colocalized with HAP1/STBs persisted in their colocalization even after treatment with their ligands. Therefore, HAP1/STBs may be involved in cytoplasmic modifications of the nuclear translocation of GR and AR in a ubiquitin-proteasome system.« less

Aldosterone induces clonal β-cell failure through glucocorticoid receptor

PubMed Central

Chen, Fang; Liu, Jia; Wang, Yanyang; Wu, Tijun; Shan, Wei; Zhu, Yunxia; Han, Xiao

2015-01-01

Aldosterone excess causes insulin resistance in peripheral tissues and directly impairs the function of clonal β-cell. The aim of this study was to investigate the molecular mechanisms involved in the aldosterone-induced impairment of clonal β-cells. As expected, aldosterone induced apoptosis and β-cell dysfunction, including impairment of insulin synthesis and secretion, which were reversed by Glucocorticoid receptor (GR) antagonists or GR-specific siRNA. However, mineralocorticoid receptor (MR) antagonists or MR-specific siRNA had no effect on impairment of clonal β-cells induced by aldosterone. Besides, aldosterone significantly decreased expression and activity of MafA, while activated JNK and p38 MAPK in a GR-dependent manner. In addition, JNK inhibitors (SP600125) and/or p38 inhibitors (SB203580) could abolish the effect of aldosterone on MafA expression and activity. Importantly, overexpression of JNK1 or p38 reversed the protective effect of a GR antagonist on the decrease of MafA expression and activity. Furthermore, aldosterone inhibits MafA expression at the transcriptional and post-transcriptional level through activation of JNK and p38, respectively. Consequently, overexpression of MafA increased synthesis and secretion of insulin, and decreased apoptosis in clonal β-cells exposed to aldosterone. These findings identified aldosterone as an inducer of clonal β-cell failure that operates through the GR-MAPK-MafA signaling pathway. PMID:26287126

The effects of crushing speed on the energy-absorption capability of composite material

NASA Technical Reports Server (NTRS)

Farley, Gary L.

1987-01-01

The energy-absorption capability as a function of crushing speed was determined for Thornel 300/Fiberite 934 (Gr/E) and Kevlar-49/Fiberite 934 (K/E) composite material. Circular cross section tube specimens were crushed at quasi-static, 6 m/sec, and 12 m/sec speeds. Ply orientations of the tube specimens were (0/+ or - theta) sub 2 and (+ or - theta) sub 3 where theta=15, 45, and 75 degress. Based on the results of these tests the energy-absortion capability of Gr/E and K/E was determined to be a function of crushing speed. The crushing modes based on exterior appearance of the crushed tubes were unchanged for either material. However, the interlaminar crushing behavior changed with crushing speed.

Associations between DNA methylation of a glucocorticoid receptor promoter and acute stress responses in a large healthy adult population are largely explained by lifestyle and educational differences.

PubMed

de Rooij, Susanne R; Costello, Paula M; Veenendaal, Marjolein V E; Lillycrop, Karen A; Gluckman, Peter D; Hanson, Mark A; Painter, Rebecca C; Roseboom, Tessa J

2012-06-01

Glucocorticoids are the key regulators of the biological stress response and act by binding to glucocorticoid receptors (GR). Expression of GR is altered by DNA methylation. Methylation patterns in GR promoters have been shown to be highly variable between individuals, but little is known about the functional consequences of this variation for the acute stress response. The present study investigated associations between methylation status of the GR 1-C promoter and cortisol, cardiovascular and perceived stress responses to a psychosocial stress protocol in a large healthy adult population. A total of 725 overall healthy men and women, aged 55-60 years, participated in a standardized psychosocial stress protocol consisting of three different stressors. At different stages during the stress protocol, salivary cortisol levels, continuous blood pressure and heart rate (HR) levels as well as perceived stress were measured. Stress reactivity was calculated as the increase between basal and peak measurements. Methylation status of the GR 1-C promoter was assessed in DNA isolated from peripheral blood samples using a methylation sensitive PCR assay for 675 of the 725 participants. A decrease in methylation of the GR 1-C promoter was associated with a decrease in stress reactivity as indicated by lower cortisol and lower HR reactivity. A 1% decrease in GR 1-C methylation corresponded with a cortisol decrease by 0.14% (95% CI: 0.03-0.25, p=0.02) and an HR decrease by 0.10 bpm (0.03-0.16, p=0.003). Adjusting for sex, lifestyle and education largely abolished these associations. A decrease in methylation of the GR 1-C promoter was also associated with an increase in stress perception as indicated by higher perceived stress (0.03 points [0.00-0.06, p=0.05]), lower perceived performance (-0.03 points [-0.05 to -0.01], p=0.02), and lower perceived control (-0.03 points [-0.05 to 0.00], p=0.04). After adjusting for sex and educational level the associations were no longer statistically significant. GR 1-C methylation status was not associated with blood pressure responses to the stress protocol. Although effects were small, variation in methylation status in the GR 1-C promoter was associated with physical and perceived acute stress responses. Interestingly, these associations could largely be explained by differences in lifestyle and education. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

NASA Astrophysics Data System (ADS)

Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

2016-02-01

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

Rapid corticosteroid-dependent regulation of mineralocorticoid receptor protein expression in rat brain.

PubMed

Kalman, Brian A; Spencer, Robert L

2002-11-01

Corticosteroid hormones regulate many aspects of neural function via mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Although GR expression is negatively regulated by endogenous corticosteroids, the autologous regulation of MR expression has been less well studied, partly due to limitations of receptor binding assays that cannot measure the ligand-activated form of MR. Using MR-reactive antibodies and Western blot, we examined relative MR protein expression in rat brain and its potential autoregulation by corticosteroids. We found that MR protein expression is autoregulated in a negative fashion by adrenal steroids. Compared with GR, we see a more rapid regulation of MR, such that there is a substantial increase in MR protein within 12 h after adrenalectomy, whereas GR levels show very little increase until more than 24 h after adrenalectomy. Also, in contrast to GR, which has been found to be regulated by both MR and GR, adrenalectomy-induced increase in MR was prevented by treatment with the MR selective agonist, aldosterone, but not the GR selective agonist, RU28362. Interestingly, acute treatment of adrenalectomized rats with corticosterone produced a significant decrease in whole-cell MR protein within 45 min, suggesting ligand-induced rapid degradation of MR. Chronic high levels of corticosterone also produced a significant decrease in MR protein levels below adrenal-intact rat levels. These results have important implications for previous studies that estimated the proportion of MR that are occupied in vivo by various circulating levels of corticosterone. Those studies compared available MR binding levels in adrenal-intact rats with 24-h adrenalectomized rats, with the assumption that there were no differences between the various conditions in total receptor expression. Those studies concluded that MR is nearly fully occupied by even the lowest circulating corticosterone levels. Given the 2- to 3-fold increase in MR protein that we have observed within 24 h after adrenalectomy, it is likely that those studies significantly overestimated the proportion of MR that were occupied by low basal corticosterone levels. These results support the prospect that MR as well as GR can participate in the transduction of phasic corticosteroid signals.

General Relativistic Precession in Small Solar System Bodies

NASA Astrophysics Data System (ADS)

Sekhar, Aswin; Werner, Stephanie; Hoffmann, Volker; Asher, David; Vaubaillon, Jeremie; Hajdukova, Maria; Li, Gongjie

2016-10-01

Introduction: One of the greatest successes of the Einstein's General Theory of Relativity (GR) was the correct prediction of the precession of perihelion of Mercury. The closed form expression to compute this precession tells us that substantial GR precession would occur only if the bodies have a combination of both moderately small perihelion distance and semi-major axis. Minimum Orbit Intersection Distance (MOID) is a quantity which helps us to understand the closest proximity of two orbits in space. Hence evaluating MOID is crucial to understand close encounters and collision scenarios better. In this work, we look at the possible scenarios where a small GR precession in argument of pericentre (ω) can create substantial changes in MOID for small bodies ranging from meteoroids to comets and asteroids.Analytical Approach and Numerical Integrations: Previous works have looked into neat analytical techniques to understand different collision scenarios and we use those standard expressions to compute MOID analytically. We find the nature of this mathematical function is such that a relatively small GR precession can lead to drastic changes in MOID values depending on the initial value of ω. Numerical integrations were done with package MERCURY incorporating the GR code to test the same effects. Numerical approach showed the same interesting relationship (as shown by analytical theory) between values of ω and the peaks/dips in MOID values. Previous works have shown that GR precession suppresses Kozai oscillations and this aspect was verified using our integrations. There is an overall agreement between both analytical and numerical methods.Summary and Discussion: We find that GR precession could play an important role in the calculations pertaining to MOID and close encounter scenarios in the case of certain small solar system bodies (depending on their initial orbital elements). Previous works have looked into impact probabilities and collision scenarios on planets from different small body populations. This work aims to find certain sub-sets of orbits where GR could play an interesting role. Certain parallels are drawn between the cases of asteroids, comets and small perihelion distance meteoroid streams.

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis.

PubMed

Saberi, Shahram; Stauffer, Jennifer E; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

2018-03-01

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically related and clinically unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically related areas compared to unrelated areas (p < 0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p < 0.0001). While most poly-GR dendritic inclusions were pTDP-43 positive, only 4% of pTDP-43 dendritic inclusions were poly-GR positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to dendrites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites.

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat expanded C9orf72 amyotrophic lateral sclerosis

PubMed Central

Saberi, Shahram; Stauffer, Jennifer E.; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L.; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

2018-01-01

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically-related and clinically-unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically-related areas compared to unrelated areas (p<0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p<0.0001). While most poly-GR dendritic inclusions were pTDP-43-positive, only 4% of pTDP-43 dendritic inclusions were poly-GR-positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically-related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to neurites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites. PMID:29196813

Reliability, validity and minimal detectable change of the Mini-BESTest in Greek participants with chronic stroke.

PubMed

Lampropoulou, Sofia I; Billis, Evdokia; Gedikoglou, Ingrid A; Michailidou, Christina; Nowicky, Alexander V; Skrinou, Dimitra; Michailidi, Fotini; Chandrinou, Danae; Meligkoni, Margarita

2018-02-23

This study aimed to investigate the psychometric characteristics of reliability, validity and ability to detect change of a newly developed balance assessment tool, the Mini-BESTest, in Greek patients with stroke. A prospective, observational design study with test-retest measures was conducted. A convenience sample of 21 Greek patients with chronic stroke (14 male, 7 female; age of 63 ± 16 years) was recruited. Two independent examiners administered the scale, for the inter-rater reliability, twice within 10 days for the test-retest reliability. Bland Altman Analysis for repeated measures assessed the absolute reliability and the Standard Error of Measurement (SEM) and the Minimum Detectable Change at 95% confidence interval (MDC 95% ) were established. The Greek Mini-BESTest (Mini-BESTest GR ) was correlated with the Greek Berg Balance Scale (BBS GR ) for assessing the concurrent validity and with the Timed Up and Go (TUG), the Functional Reach Test (FRT) and the Greek Falls Efficacy Scale-International (FES-I GR ) for the convergent validity. The Mini-BESTestGR demonstrated excellent inter-rater reliability (ICC (95%CI) = 0.997 (0.995-0.999, SEM = 0.46) with the scores of two raters within the limits of agreement (mean dif  = -0.143 ± 0.727, p > 0.05) and test-retest reliability (ICC (95%CI) = 0.966 (0.926-0.988), SEM = 1.53). Additionally, the Mini-BESTest GR yielded very strong to moderate correlations with BBS GR (r = 0.924, p < 0.001), TUG (r = -0.823, p < 0.001), FES-I GR (r = -0.734, p < 0.001) and FRT (r = 0.689, p < 0.001). MDC 95 was 4.25 points. The exceptionally high reliability and the equally good validity of the Mini-BESTest GR , strongly support its utility in Greek people with chronic stroke. Its ability to identify clinically meaningful changes and falls risk need further investigation.

An Application of Gröbner Basis in Differential Equations of Physics

NASA Astrophysics Data System (ADS)

Chaharbashloo, Mohammad Saleh; Basiri, Abdolali; Rahmany, Sajjad; Zarrinkamar, Saber

2013-11-01

We apply the Gröbner basis to the ansatz method in quantum mechanics to obtain the energy eigenvalues and the wave functions in a very simple manner. There are important physical potentials such as the Cornell interaction which play significant roles in particle physics and can be treated via this technique. As a typical example, the algorithm is applied to the semi-relativistic spinless Salpeter equation under the Cornell interaction. Many other applications of the idea in a wide range of physical fields are listed as well.

Relationship of patient volume and service concentration with outcome in geriatric rehabilitation.

PubMed

Holstege, Marije S; Zekveld, Ineke G; Caljouw, Monique A A; Peerenboom, Peter Bob; van Balen, Romke; Gussekloo, Jacobijn; Achterberg, Wilco P

2013-10-01

Although geriatric rehabilitation (GR) is beneficial for restoration of activities and participation after hospitalization of vulnerable older persons, little is known about the optimal organization of care of these postacute facilities. This study examines the relationship of patient volume and service concentration with successful GR (short length of stay and discharge home) in skilled nursing facilities (SNFs). A national multicenter retrospective cohort study. All patients indicated for GR in a Dutch SNF. Nurses filled out digital registration forms from patient records. Patients were studied in 3 predefined diagnostic groups: total joint replacement, traumatic injuries, and stroke. Facility characteristics were obtained by structured telephone interviews with facility managers. Volume was based on the number of discharges in a 3-month period and categorized in low-, medium-, and high-volume facilities. Concentration was defined at the organizational level in which the population consists of 80% or more of 1 or 2 diagnostic groups, with the prerequisite of having a minimum of 10 rehabilitation beds. From 88 facilities, 2269 GR patients (mean age 78.2 years [SD 9.7]; 68.2% female) were included. The median length of stay in the SNF was 45 days (interquartile range 23-81), 57% of the patients were discharged home, and 9.8% died during GR. Of patients with total joint replacement (n = 501), concentration was related to successful rehabilitation (odds ratio 5.7; 95% confidence interval 1.3-24.3; P = .020, adjusted for age and gender); this relationship was not found for patients with traumatic injuries or stroke. Volume showed no relation with successful rehabilitation in any of the 3 diagnostic groups. This study may indicate that concentration in an SNF, as a proxy for specialization, favors successful GR in total joint replacement. This relationship was not found for the traumatic injuries or stroke groups, or for volume. The relation on functional outcome in GR needs further investigation. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

Change in Minimum Orbit Intersection Distance due to General Relativistic Precession in Small Solar System Bodies

NASA Astrophysics Data System (ADS)

Sekhar, Aswin; Valsecchi, Giovanni B.; Asher, David; Werner, Stephanie; Vaubaillon, Jeremie; Li, Gongjie

2017-06-01

One of the greatest successes of Einstein's General Theory of Relativity (GR) was the correct prediction of the perihelion precession of Mercury. The closed form expression to compute this precession tells us that substantial GR precession would occur only if the bodies have a combination of both moderately small perihelion distance and semi-major axis. Minimum Orbit Intersection Distance (MOID) is a quantity which helps us to understand the closest proximity of two orbits in space. Hence evaluating MOID is crucial to understand close encounters and collision scenarios better. In this work, we look at the possible scenarios where a small GR precession in argument of pericentre can create substantial changes in MOID for small bodies ranging from meteoroids to comets and asteroids.Previous works have looked into neat analytical techniques to understand different collision scenarios and we use those standard expressions to compute MOID analytically. We find the nature of this mathematical function is such that a relatively small GR precession can lead to drastic changes in MOID values depending on the initial value of argument of pericentre. Numerical integrations were done with the MERCURY package incorporating GR code to test the same effects. A numerical approach showed the same interesting relationship (as shown by analytical theory) between values of argument of pericentre and the peaks or dips in MOID values. There is an overall agreement between both analytical and numerical methods.We find that GR precession could play an important role in the calculations pertaining to MOID and close encounter scenarios in the case of certain small solar system bodies (depending on their initial orbital elements) when long term impact risk possibilities are considered. Previous works have looked into impact probabilities and collision scenarios on planets from different small body populations. This work aims to find certain sub-sets of small bodies where GR could play an interesting role. Certain parallels are drawn between the cases of asteroids, comets and small perihelion distance meteoroid streams.

Placental glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase-2 recruitment indicates impact of prenatal adversity upon postnatal development in mice.

PubMed

Gross, Moshe; Romi, Hava; Gilimovich, Yelena; Drori, Elyashiv; Pinhasov, Albert

2018-04-12

Prenatal stress may increase concentrations of maternal glucocorticoids, which restrict fetal growth, with variable impact upon postnatal development. Among key regulators of stress hormone effects are the glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase-2 (11βHSD2), the enzyme that inactivates glucocorticoid. This study utilized mice selectively bred for social dominance (Dom) or submissiveness (Sub), respectively exhibiting resilience or sensitivity to stress, to test whether stress-induced alterations in placental GR and 11βHSD2 protein expression may mediate divergent effects of prenatal adversity upon postnatal development. Pregnant Dom and Sub dams underwent prenatal restraint stress (PRS) for 45 min on gestational days (GD) 15-17. PRS induced a similar spike in serum corticosterone concentrations of dams from each strain on GD15 (p < .001, n = 8), and impaired fetal growth (p < .01, n = 5 litters), although Dom placentae were larger than Sub placentae (p < .01). Among placentae from Dom dams, PRS elevated protein contents of both GR (p < .05, n = 5 litters) and 11βHSD2 (p < .01) on GD19. In contrast, GR contents were reduced among placentae from PRS-exposed Sub mice (p < .01), without changes in 11βHSD2 content. Correspondingly, Dom PRS pup growth recovered by PND14, yet Sub PRS pups remained underweight into adolescence (p < .0001, n = 40 pups). Thus, prenatal stress more strongly increased placental GR and 11βHSD2 levels among Dom mice than in Subs. Increased GR may improve placental function and up-regulate 11βHSD2 expression, protecting fetuses from effects of prenatal stress upon postnatal development. Placental recruitment of GR and 11βHSD2 are potential markers of stress-induced developmental disorders, in accordance with maternal resilience or sensitivity to stress.

Running Out of Steam.

ERIC Educational Resources Information Center

Kumar, Promod

2000-01-01

Explains why schools should evaluate whether their older steam-heating systems are still cost-effective, or need to be repaired or replaced. The symptoms of deterioration are listed along with discussions on repair or replacement decision making on three areas of steam heating systems: boilers; distribution system; and terminal equipment. (GR)

Exploring the functional diversity of the supraglacial environment: Microbial degradation of the pesticide 2,4-D on the Greenland Ice Sheet

NASA Astrophysics Data System (ADS)

Stibal, M.; Bælum, J.; Holben, W. E.; Jacobsen, C. S.

2012-12-01

The surface of the Greenland ice sheet (GrIS) harbours a diverse community of heterotrophic microorganisms. Organic compounds of anthropogenic origin, including pesticides, are deposited on the GrIS; however, the fate of these compounds in the ice is currently unknown. In this study we determine the potential of the microbial community from the surface of the GrIS to mineralise the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). It is one of the most easily degraded compounds among the phenoxyacetic acid pesticides, and the ability to mineralise 2,4-D has been found to be widespread in microbial communities around the globe. Functional genes involved in the degradation pathway have also been characterised. Thus, 2,4-D represents a very suitable model compound to use in order to gain an insight into pollutant degradation dynamics in the rapidly changing Arctic region. We collected surface ice cores on the GrIS and incubated them for up to 529 days in microcosms simulating in situ conditions. We measured mineralisation of side-chain- and ring-labelled 14C-2,4-D in the samples and performed quantitative PCR targeting the tfdA gene, encoding an enzyme catalysing the first step in the degradation pathway of 2,4-D, in the DNA extracted from the ice after the experiments. We show that the microbial community on the surface of the GrIS is of low diversity, but contains microbes capable of degrading 2,4-D. The low diversity of the community and the similarity of the detected clones to those from other icy environment clones suggest that the bacterial community on the GrIS is selected from a pool of propagules deposited on the surface of the ice sheet, based on the level of adaptation to the conditions in the surface ice. The 2,4-D degraders are likely present in very low numbers, and they can mineralise 2,4-D at a rate of up to 1 nmol per m2 per day, equivalent to ~26 ng C m-2 d-1. We contend that the surface of the GrIS should not be considered to be a mere reservoir of all atmospheric contaminants, as it is likely that some deposited compounds will be removed from the system via biodegradation processes before their potential release due to the accelerated melting of the ice sheet.

A selective phenomenology of the seismicity of Southern California.

PubMed Central

Knopoff, L

1996-01-01

Predictions of earthquakes that are based on observations of precursory seismicity cannot depend on the average properties of the seismicity, such as the Gutenberg-Richter (G-R) distribution. Instead it must depend on the fluctuations in seismicity. We summarize the observational data of the fluctuations of seismicity in space, in time, and in a coupled space-time regime over the past 60 yr in Southern California, to provide a basis for determining whether these fluctuations are correlated with the times and locations of future strong earthquakes in an appropriate time- and space-scale. The simple extrapolation of the G-R distribution must lead to an overestimate of the risk due to large earthquakes. There may be two classes of earthquakes: the small earthquakes that satisfy the G-R law and the larger and large ones. Most observations of fluctuations of seismicity are of the rate of occurrence of smaller earthquakes. Large earthquakes are observed to be preceded by significant quiescence on the faults on which they occur and by an intensification of activity at distance. It is likely that the fluctuations are due to the nature of fractures on individual faults of the network of faults. There are significant inhomogeneities on these faults, which we assume will have an important influence on the nature of self-organization of seismicity. The principal source of the inhomogeneity on the large scale is the influence of geometry--i.e., of the nonplanarity of faults and the system of faults. PMID:11607661

Runoff simulations from the Greenland ice sheet at Kangerlussuaq from 2006-2007 to 2007/08. West Greenland

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

Mernild, Sebastian Haugard; Hasholt, Bent; Van Den Broeke, Michiel

2009-01-01

This study focuses on runoff from a large sector of the Greenland Ice Sheet (GrIS) - the Kangerlussuaq drainage area, West Greenland - for the runoff observation period 2006/07 to 2007/08. SnowModel, a state-of-the-art snow-evolution modeling system, was used to simulate winter accumulation and summer ablation processes, including runoff. Independent in situ end-of-winter snow depth and high-resolution runoff observations were used for validation of simulated accumulation and ablation processes. Runoff was modeled on both daily and hourly time steps, filling a data gap of runoff exiting part of the GrIS. Using hourly meteorological driving data instead of smoothed daily-averaged datamore » produced more realistic meteorological conditions in relation to snow and melt threshold surface processes, and produced 6-17% higher annual cumulative runoff. The simulated runoff series yielded useful insights into the present conditions of inter-seasonal and inter-annual variability of Kangerlussuaq runoff, and provided an acceptable degree of agreement between simulated and observed runoff. The simulated spatial runoff distributions, in some areas of the GrIS terminus, were as high as 2,750 mm w.eq. of runoff for 2006/07, while only 900 mm w.eq was simulated for 2007/08. The simulated total runoff from Kangerlussuaq was 1.9 km{sup 3} for 2006/07 and 1.2 km{sup 3} for 2007/08, indicating a reduction of 35-40% caused by the climate conditions and changes in the GrIS freshwater storage. The reduction in runoff from 2006/07 to 2007/08 occurred simultaneously with the reduction in the overall pattern of satellite-derived GrIS surface melt from 2007 to 2008.« less

Nonlinear Elastic Effects on the Energy Flux Deviation of Ultrasonic Waves in GR/EP Composites

NASA Technical Reports Server (NTRS)

Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

1992-01-01

In isotropic materials, the direction of the energy flux (energy per unit time per unit area) of an ultrasonic plane wave is always along the same direction as the normal to the wave front. In anisotropic materials, however, this is true only along symmetry directions. Along other directions, the energy flux of the wave deviates from the intended direction of propagation. This phenomenon is known as energy flux deviation and is illustrated. The direction of the energy flux is dependent on the elastic coefficients of the material. This effect has been demonstrated in many anisotropic crystalline materials. In transparent quartz crystals, Schlieren photographs have been obtained which allow visualization of the ultrasonic waves and the energy flux deviation. The energy flux deviation in graphite/epoxy (gr/ep) composite materials can be quite large because of their high anisotropy. The flux deviation angle has been calculated for unidirectional gr/ep composites as a function of both fiber orientation and fiber volume content. Experimental measurements have also been made in unidirectional composites. It has been further demonstrated that changes in composite materials which alter the elastic properties such as moisture absorption by the matrix or fiber degradation, can be detected nondestructively by measurements of the energy flux shift. In this research, the effects of nonlinear elasticity on energy flux deviation in unidirectional gr/ep composites were studied. Because of elastic nonlinearity, the angle of the energy flux deviation was shown to be a function of applied stress. This shift in flux deviation was modeled using acoustoelastic theory and the previously measured second and third order elastic stiffness coefficients for T300/5208 gr/ep. Two conditions of applied uniaxial stress were considered. In the first case, the direction of applied uniaxial stress was along the fiber axis (x3) while in the second case it was perpendicular to the fiber axis along the laminate stacking direction (x1).

Northeast sector of the Greenland Ice Sheet to undergo the greatest inland expansion of supraglacial lakes during the 21st century

NASA Astrophysics Data System (ADS)

Ignéczi, Ádám.; Sole, Andrew J.; Livingstone, Stephen J.; Leeson, Amber A.; Fettweis, Xavier; Selmes, Nick; Gourmelen, Noel; Briggs, Kate

2016-09-01

The formation and rapid drainage of supraglacial lakes (SGL) influences the mass balance and dynamics of the Greenland Ice Sheet (GrIS). Although SGLs are expected to spread inland during the 21st century due to atmospheric warming, less is known about their future spatial distribution and volume. We use GrIS surface elevation model and regional climate model outputs to show that at the end of the 21st century (2070-2099) approximately 9.8 ± 3.9 km3 (+113% compared to 1980-2009) and 12.6 ± 5 km3 (+174%) of meltwater could be stored in SGLs under moderate and high representative concentration pathways (RCP 4.5 and 8.5), respectively. The largest increase is expected in the northeastern sector of the GrIS (191% in RCP 4.5 and 320% in RCP 8.5), whereas in west Greenland, where the most SGLs are currently observed, the future increase will be relatively moderate (55% in RCP 4.5 and 68% in RCP 8.5).

Materials and Mechanics of Metamaterial Enhanced MEMS for Terahertz Technology

DTIC Science & Technology

2013-12-23

raveritt@physics.bu.edu Major Ph.D. students who have worked on this project: Hu Tao, Kebin Fan, Huseyin Seren Major postdoctoral researchers who have...please contact Prof. Xin Zhang at the address given above. DISTRIBUTION A: Distribution approved for public release. 2 Huseyin Seren will...Title: Optically Tunable Terahertz Metamaterials on Highly Flexible Substrates * With K. Fan, X. Zhao, J. Zhang, G.R. Keiser, H.R. Seren , G.D. Metcalfe

Utility of 222Rn as a passive tracer of subglacial distributed system drainage

NASA Astrophysics Data System (ADS)

Linhoff, Benjamin S.; Charette, Matthew A.; Nienow, Peter W.; Wadham, Jemma L.; Tedstone, Andrew J.; Cowton, Thomas

2017-03-01

Water flow beneath the Greenland Ice Sheet (GrIS) has been shown to include slow-inefficient (distributed) and fast-efficient (channelized) drainage systems, in response to meltwater delivery to the bed via both moulins and surface lake drainage. This partitioning between channelized and distributed drainage systems is difficult to quantify yet it plays an important role in bulk meltwater chemistry and glacial velocity, and thus subglacial erosion. Radon-222, which is continuously produced via the decay of 226Ra, accumulates in meltwater that has interacted with rock and sediment. Hence, elevated concentrations of 222Rn should be indicative of meltwater that has flowed through a distributed drainage system network. In the spring and summer of 2011 and 2012, we made hourly 222Rn measurements in the proglacial river of a large outlet glacier of the GrIS (Leverett Glacier, SW Greenland). Radon-222 activities were highest in the early melt season (10-15 dpm L-1), decreasing by a factor of 2-5 (3-5 dpm L-1) following the onset of widespread surface melt. Using a 222Rn mass balance model, we estimate that, on average, greater than 90% of the river 222Rn was sourced from distributed system meltwater. The distributed system 222Rn flux varied on diurnal, weekly, and seasonal time scales with highest fluxes generally occurring on the falling limb of the hydrograph and during expansion of the channelized drainage system. Using laboratory based estimates of distributed system 222Rn, the distributed system water flux generally ranged between 1-5% of the total proglacial river discharge for both seasons. This study provides a promising new method for hydrograph separation in glacial watersheds and for estimating the timing and magnitude of distributed system fluxes expelled at ice sheet margins.

Short-term withdrawal from developmental exposure to cocaine activates the glucocorticoid receptor and alters spine dynamics.

PubMed

Caffino, Lucia; Giannotti, Giuseppe; Malpighi, Chiara; Racagni, Giorgio; Fumagalli, Fabio

2015-10-01

Although glucocorticoid receptors (GRs) contribute to the action of cocaine, their role following developmental exposure to the psychostimulant is still unknown. To address this issue, we exposed adolescent male rats to cocaine (20mg/kg/day) from post-natal day (PND) 28 to PND 42 and sacrificed them at PND 45 or 90. We studied the medial prefrontal cortex (mPFC), a brain region that is still developing during adolescence. In PND 45 rats we found enhanced GR transcription and translation as well as increased trafficking toward the nucleus of the receptor, with no alteration in plasma corticosterone levels. We also showed reduced expression of the GR co-chaperone FKBP51, that normally keeps the receptor in the cytoplasm, and increased expression of Src1, which cooperates in the activation of GR transcriptional activity, revealing that short withdrawal alters the finely tuned mechanisms regulating GR action. Since activation of GRs regulate dendritic spine morphology, we next investigated spine dynamics in cocaine-withdrawn rats. We found that PSD95, cofilin and F-actin, molecules regulating spine actin network, are reduced in the mPFC of PND 45 rats suggesting reduced spine density, confirmed by confocal imaging. Further, formation of filopodia, i.e. the inactive spines, is enhanced suggesting the formation of non-functional spines. Of note, no changes were found in molecules related to GR machinery or spine dynamics following long-term abstinence, i.e. in adult rats (PND 90). These findings demonstrate that short withdrawal promotes plastic changes in the developing brain via the dysregulation of the GR system and alterations in the spine network. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of Intracellular Proteases for Targeted Cytotoxicity.

PubMed

Ho, Patrick; Ede, Christopher; Chen, Yvonne Y

2017-08-18

Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity. COVERT molecules consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N-terminal peptide, which can be removed by researcher-specified proteases to activate GrB function. We demonstrate that fusion of a small ubiquitin-like modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB selectively triggers apoptotic phenotypes in HEK293T cells that overexpress SENP1, and it is highly sensitive to different SENP1 levels across cell lines. We further demonstrate the rational design of additional COVERT molecules responsive to enterokinase (EK) and tobacco etch virus protease (TEVp), highlighting the COVERT platform's modularity and adaptability to diverse protease targets. As an initial step toward engineering COVERT-T cells for adoptive T-cell therapy, we verified that primary human T cells can express, package, traffic, and deliver engineered GrB molecules in response to antigen stimulation. Our findings set the foundation for future intracellular-antigen-responsive therapeutics that can complement surface-targeted therapies.

Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes.

PubMed

Vyas, Sheela; Maatouk, Layal

2013-12-01

Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells.

PubMed

Somasagara, Ranganatha R; Deep, Gagan; Shrotriya, Sangeeta; Patel, Manisha; Agarwal, Chapla; Agarwal, Rajesh

2015-04-01

Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcitabine-resistant (GR) and gemcitabine-sensitive (GS) PanC cells and underlying molecular mechanisms, together with efficacy of a natural agent bitter melon juice (BMJ). GR PanC cells showed distinct morphological features including spindle-shaped morphology and a decrease in E-cadherin expression. GR cells also showed higher ATP production with an increase in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Molecular studies showed higher expression of glucose transporters (GLUT1 and 4) suggesting an increase in glucose uptake by GR cells. Importantly, GR cells showed a significant increase in Akt and ERK1/2 phosphorylation and their inhibition decreased cell viability, suggesting their role in survival and drug resistance of these cells. Recently, we reported strong efficacy of BMJ against a panel of GS cells in culture and nude mice, which we expanded here and found that BMJ was also effective in decreasing both Akt and ERK1/2 phosphorylation and viability of GR PanC cells. Overall, we have identified novel mechanisms of gemcitabine resistance in PanC cells which are targeted by BMJ. Considering the short survival in PanC patients, our findings could have high translational potential in controlling this deadly malignancy.

Anharmonic interatomic force constants and thermal conductivity from Grüneisen parameters: An application to graphene

NASA Astrophysics Data System (ADS)

Lee, Ching Hua; Gan, Chee Kwan

2017-07-01

Phonon-mediated thermal conductivity, which is of great technological relevance, arises due fundamentally to anharmonic scattering from interatomic potentials. Despite its prevalence, accurate first-principles calculations of thermal conductivity remain challenging, primarily due to the high computational cost of anharmonic interatomic force constant (IFC) calculations. Meanwhile, the related anharmonic phenomenon of thermal expansion is much more tractable, being computable from the Grüneisen parameters associated with phonon frequency shifts due to crystal deformations. In this work, we propose an approach for computing the largest cubic IFCs from the Grüneisen parameter data. This allows an approximate determination of the thermal conductivity via a much less expensive route. The key insight is that although the Grüneisen parameters cannot possibly contain all the information on the cubic IFCs, being derivable from spatially uniform deformations, they can still unambiguously and accurately determine the largest and most physically relevant ones. By fitting the anisotropic Grüneisen parameter data along judiciously designed deformations, we can deduce (i.e., reverse-engineer) the dominant cubic IFCs and estimate three-phonon scattering amplitudes. We illustrate our approach by explicitly computing the largest cubic IFCs and thermal conductivity of graphene, especially for its out-of-plane (flexural) modes that exhibit anomalously large anharmonic shifts and thermal conductivity contributions. Our calculations on graphene not only exhibit reasonable agreement with established density-functional theory results, but they also present a pedagogical opportunity for introducing an elegant analytic treatment of the Grüneisen parameters of generic two-band models. Our approach can be readily extended to more complicated crystalline materials with nontrivial anharmonic lattice effects.

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

PubMed Central

Menke, Andreas; Arloth, Janine; Pütz, Benno; Weber, Peter; Klengel, Torsten; Mehta, Divya; Gonik, Mariya; Rex-Haffner, Monika; Rubel, Jennifer; Uhr, Manfred; Lucae, Susanne; Deussing, Jan M; Müller-Myhsok, Bertram; Holsboer, Florian; Binder, Elisabeth B

2012-01-01

Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N=18 cases/18 controls) and a test cohort (N=11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes. PMID:22237309

Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells.

PubMed

Li, Qing; Kobayashi, Maiko; Kawada, Tomoyuki

2015-09-01

We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37°C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ≒ GrA ≒ GrB. © The Author(s) 2015.

The Interactome of the Glucocorticoid Receptor and Its Influence on the Actions of Glucocorticoids in Combatting Inflammatory and Infectious Diseases

PubMed Central

Petta, Ioanna; Dejager, Lien; Ballegeer, Marlies; Lievens, Sam; Tavernier, Jan; Libert, Claude

2016-01-01

SUMMARY Glucocorticoids (GCs) have been widely used for decades as a first-line treatment for inflammatory and autoimmune diseases. However, their use is often hampered by the onset of adverse effects or resistance. GCs mediate their effects via binding to glucocorticoid receptor (GR), a transcription factor belonging to the family of nuclear receptors. An important aspect of GR's actions, including its anti-inflammatory capacity, involves its interactions with various proteins, such as transcription factors, cofactors, and modifying enzymes, which codetermine receptor functionality. In this review, we provide a state-of-the-art overview of the protein-protein interactions (PPIs) of GR that positively or negatively affect its anti-inflammatory properties, along with mechanistic insights, if known. Emphasis is placed on the interactions that affect its anti-inflammatory effects in the presence of inflammatory and microbial diseases. PMID:27169854

Semi-empirical anzatz for Helmholtz free energy calculation: Thermal properties of silver along shock Hugoniot

NASA Astrophysics Data System (ADS)

Joshi, R. H.; Thakore, B. Y.; Bhatt, N. K.; Vyas, P. R.; Jani, A. R.

2018-02-01

A density functional theory along with electronic contribution is used to compute quasiharmonic total energy for silver, whereas explicit phonon anharmonic contribution is added through perturbative term in temperature. Within the Mie-Grüneisen approach, we propose a consistent computational scheme for calculating various thermophysical properties of a substance, in which the required Grüneisen parameter γth is calculated from the knowledge of binding energy. The present study demonstrates that no separate relation for volume dependence for γth is needed, and complete thermodynamics under simultaneous high-temperature and high-pressure condition can be derived in a consistent manner. We have calculated static and dynamic equation of states and some important thermodynamic properties along the shock Hugoniot. A careful examination of temperature dependence of Grüneisen parameter reveals the importance of temperature-effect on various thermal properties.

Kid's Play.

ERIC Educational Resources Information Center

Whalen, Susan L.

1998-01-01

Examines the use of fabric mesh knitting as canopies for children's playgrounds. Its benefits and drawbacks are addressed as are how innovative design and choice of materials can help eliminate function difficulties. (GR)

Distributed Algorithms for Probabilistic Solution of Computational Vision Problems.

DTIC Science & Technology

1988-03-01

34 targets. Legters and Young (1982) developed an operator-based approach r% using foreground and background models and solved a least-squares minimiza...1960), "Finite Markov Chains", Van Nostrand, , - New York. Legters , G.R., and Young, T.Y. (1982), "A Mathematical Model for Computer Image Tracking

Groundwater surface water interactions and the role of phreatophytes in identifying recharge zones

USDA-ARS?s Scientific Manuscript database

Groundwater and surface water interactions within riparian corridors impact the distribution of phreatophytes that tap into groundwater stores. The changes in canopy area of phreatophytes over time is related to changes in depth to groundwater, distance from a stream or river, and hydrologic soil gr...

A facile method for synthesis of graphene-coated hexagonal ZnO photocatalyst with enhanced photodegradation activity

NASA Astrophysics Data System (ADS)

Zhang, Yunlong; Zhang, Yuzhi

2017-12-01

A kind of hexagonal ZnO (HZO) was synthesized in N-methyl-2-pyrrolidone (NMP)/H2O mixed solvent for a high exposure of polar ±(0001) facets to get a high-efficiency photocatalyst. The amine-functionalized HZO particles were coated with graphene oxide (GO) by electrostatic force-induced self-assemby and thermal reduction to form HZO@Gr core/shell structure. The as-prepared HZO and HZO@Gr were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy and UV-visible diffuse reflectance spectroscopy (UV-vis/DRS). The results indicate that the graphene on HZO@Gr remains high quality and the optical properties of the composite change a lot with sunlight absorption improving, bandgap and photoluminescence (PL) intensity decreasing. The obtained HZO photocatalyst shows good photocatalytic activity for methylene blue (MB) under UV-visible irradiation. Furthermore, the HZO@Gr photocatalyst exhibits the best photodegradation rate of MB reaching up to 98.2% within 50 minutes. The graphene-coated HZO structure could offer new directions which would further extend the scope for synthesis of various ZnO/graphene composites with improved properties useful for various applications.

Identification of a sugar gustatory receptor and its effect on fecundity of the brown planthopper Nilaparvata lugens.

PubMed

Chen, Wei-Wen; Kang, Kui; Yang, Pan; Zhang, Wen-Qing

2017-11-27

In insects, the gustatory system plays a crucial role in multiple physiological behaviors, including feeding, toxin avoidance, courtship, mating and oviposition. Gustatory stimuli from the environment are recognized by gustatory receptors. To date, little is known about the function of gustatory receptors in agricultural pest insects. In this study, we cloned a sugar gustatory receptor gene, NlGr11, from the brown planthopper (BPH), Nilaparvata lugens (Stål), a serious pest of rice in Asia; we then identified its ligands, namely, fructose, galactose and arabinose, by calcium imaging assay. After injection of NlGr11 double-stranded RNA, we found that the number of eggs laid by BPH decreased. Moreover, we found that NlGr11 inhibited the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and promoted the phosphorylation of protein kinase B (AKT). These findings demonstrated that NlGr11 could accelerate the fecundity of BPH through AMPK- and AKT-mediated signaling pathways. This is the first report to indicate that a gustatory receptor modulates the fecundity of insects and that the receptor could be a potential target for pest control. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Poly(methylene blue) functionalized graphene modified carbon ionic liquid electrode for the electrochemical detection of dopamine.

PubMed

Sun, Wei; Wang, Yuhua; Zhang, Yuanyuan; Ju, Xiaomei; Li, Guangjiu; Sun, Zhenfan

2012-11-02

An ionic liquid 1-butylpyridinium hexafluorophosphate based carbon ionic liquid electrode (CILE) was used as the substrate electrode and a poly(methylene blue) (PMB) functionalized graphene (GR) composite film was co-electrodeposited on CILE surface by cyclic voltammetry. The PMB-GR/CILE exhibited better electrochemical performances with higher conductivity and lower electron transfer resistance. Electrochemical behavior of dopamine (DA) was further investigated by cyclic voltammetry and a pair of well-defined redox peaks appeared with the peak-to-peak separation (ΔE(p)) as 0.058V in 0.1 mol L(-1) pH 6.0 phosphate buffer solution, which proved a fast quasi-reversible electron transfer process on the modified electrode. Electrochemical parameters of DA on PMB-GR/CILE were calculated with the electron transfer number as 1.83, the charge transfer coefficients as 0.70, the apparent heterogeneous electron transfer rate constant as 1.72 s(-1) and the diffusional coefficient (D) as 3.45×10(-4) cm(2) s(-1), respectively. Under the optimal conditions with differential pulse voltammetric measurement, the linear relationship between the oxidation peak current of DA and its concentration was obtained in the range from 0.02 to 800.0 μmol L(-1) with the detection limit as 5.6 nmol L(-1) (3σ). The coexisting substances exhibited no interference and PMB-GR/CILE was applied to the detection of DA injection samples and human urine samples with satisfactory results. Copyright © 2012 Elsevier B.V. All rights reserved.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2010-10-01

count < 15,000 > 7 days or need for > 3 plt transfusions in 30 days • Gr 4 neutropenia > 7 days • Febrile neutropenia • Attributable Gr > 3...11% No febrile neutropenia (no growth factor use) • Transaminitis Transient Gr 1 AST 29% (1 Gr 2) Need for transfusions 6 pts...No pts had significant bleeding; 2 received plt transfusions (cohort 6) • Neutropenia Gr 0 = 40%; Gr 1-2 = 32%; Gr 3 = 29%; Gr 4

airGRteaching: an R-package designed for teaching hydrology with lumped hydrological models

NASA Astrophysics Data System (ADS)

Thirel, Guillaume; Delaigue, Olivier; Coron, Laurent; Andréassian, Vazken; Brigode, Pierre

2017-04-01

Lumped hydrological models are useful and convenient tools for research, engineering and educational purposes. They propose catchment-scale representations of the precipitation-discharge relationship. Thanks to their limited data requirements, they can be easily implemented and run. With such models, it is possible to simulate a number of hydrological key processes over the catchment with limited structural and parametric complexity, typically evapotranspiration, runoff, underground losses, etc. The Hydrology Group at Irstea (Antony) has been developing a suite of rainfall-runoff models over the past 30 years. This resulted in a suite of models running at different time steps (from hourly to annual) applicable for various issues including water balance estimation, forecasting, simulation of impacts and scenario testing. Recently, Irstea has developed an easy-to-use R-package (R Core Team, 2016), called airGR (Coron et al., 2016, 2017), to make these models widely available. Although its initial target public was hydrological modellers, the package is already used for educational purposes. Indeed, simple models allow for rapidly visualising the effects of parameterizations and model components on flows hydrographs. In order to avoid the difficulties that students may have when manipulating R and datasets, we developed (Delaigue and Coron, 2016): - Three simplified functions to prepare data, calibrate a model and run a simulation - Simplified and dynamic plot functions - A shiny (Chang et al., 2016) interface that connects this R-package to a browser-based visualisation tool. On this interface, the students can use different hydrological models (including the possibility to use a snow-accounting model), manually modify their parameters and automatically calibrate their parameters with diverse objective functions. One of the visualisation tabs of the interface includes observed precipitation and temperature, simulated snowpack (if any), observed and simulated discharges, which are updated immediately (a calibration only needs a couple of seconds or less, a simulation is almost immediate). In addition, time series of internal variables, live-visualisation of internal variables evolution and performance statistics are provided. This interface allows for hands-on exercises that can include for instance the analysis by students of: - The effects of each parameter and model components on simulated discharge - The effects of objective functions based on high flows- or low flows-focused criteria on simulated discharge - The seasonality of the model components. References Winston Chang, Joe Cheng, JJ Allaire, Yihui Xie and Jonathan McPherson (2016). shiny: Web Application Framework for R. R package version 0.13.2. https://CRAN.R-project.org/package=shiny Coron L., Thirel G., Perrin C., Delaigue O., Andréassian V., airGR: a suite of lumped hydrological models in an R-package, Environmental Modelling and software, 2017, submitted. Coron, L., Perrin, C. and Michel, C. (2016). airGR: Suite of GR hydrological models for precipitation-runoff modelling. R package version 1.0.3. https://webgr.irstea.fr/airGR/?lang=en. Olivier Delaigue and Laurent Coron (2016). airGRteaching: Tools to simplify the use of the airGR hydrological package by students. R package version 0.0.1. https://webgr.irstea.fr/airGR/?lang=en R Core Team (2016). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.

Nine Steps to a Successful Lighting Retrofit.

ERIC Educational Resources Information Center

Ries, Jack

1998-01-01

Presents the steps needed to successfully design a lighting retrofit of school classrooms. Tips cover budgeting, technology, financing, contractor selection, assessing area function, and choosing a light source. (GR)

Electrochemical sensors and biosensors based on less aggregated graphene.

PubMed

Bo, Xiangjie; Zhou, Ming; Guo, Liping

2017-03-15

As a novel single-atom-thick sheet of sp 2 hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

The neuronal and molecular basis of quinine-dependent bitter taste signaling in Drosophila larvae

PubMed Central

Apostolopoulou, Anthi A.; Mazija, Lorena; Wüst, Alexander; Thum, Andreas S.

2014-01-01

The sensation of bitter substances can alert an animal that a specific type of food is harmful and should not be consumed. However, not all bitter compounds are equally toxic and some may even be beneficial in certain contexts. Thus, taste systems in general may have a broader range of functions than just in alerting the animal. In this study we investigate bitter sensing and processing in Drosophila larvae using quinine, a substance perceived by humans as bitter. We show that behavioral choice, feeding, survival, and associative olfactory learning are all directly affected by quinine. On the cellular level, we show that 12 gustatory sensory receptor neurons that express both GR66a and GR33a are required for quinine-dependent choice and feeding behavior. Interestingly, these neurons are not necessary for quinine-dependent survival or associative learning. On the molecular receptor gene level, the GR33a receptor, but not GR66a, is required for quinine-dependent choice behavior. A screen for gustatory sensory receptor neurons that trigger quinine-dependent choice behavior revealed that a single GR97a receptor gene expressing neuron located in the peripheral terminal sense organ is partially necessary and sufficient. For the first time, we show that the elementary chemosensory system of the Drosophila larva can serve as a simple model to understand the neuronal basis of taste information processing on the single cell level with respect to different behavioral outputs. PMID:24478653

CD40 dependent exacerbation of immune mediated hepatitis by hepatic CD11b+ Gr-1+ myeloid derived suppressor cells in tumor bearing mice

PubMed Central

Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M.; Wiltrout, Robert H.; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A.; Manns, Michael P.; Wang, Ena; Marincola, Francesco M.; Korangy, Firouzeh; Greten, Tim F.

2015-01-01

Immunosuppressive CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) accumulate in the livers of tumor-bearing mice. We studied hepatic MDSC in two murine models of immune mediated hepatitis. Unexpectedly, treatment of tumor bearing mice with Concanavalin A or α-Galactosylceramide resulted in increased ALT and AST serum levels in comparison to tumor free mice. Adoptive transfer of hepatic MDSC into naïve mice exacerbated Concanavalin A induced liver damage. Hepatic CD11b+Gr-1+ cells revealed a polarized pro-inflammatory gene signature after Concanavalin A treatment. An interferon gamma- dependent up-regulation of CD40 on hepatic CD11b+Gr-1+ cells along with an up-regulation of CD80, CD86, and CD1d after Concanavalin A treatment was observed. Concanavalin A treatment resulted in a loss of suppressor function by tumor-induced CD11b+Gr-1+ MDSC as well as enhanced reactive oxygen species-mediated hepatotoxicity. CD40 knockdown in hepatic MDSC led to increased arginase activity upon Concanavalin A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40−/− tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased reactive oxygen species production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSC act as pro-inflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. PMID:25616156

Phylogeography and population diversity of Simulium hirtipupa Lutz (Diptera: Simuliidae) based on mitochondrial COI sequences

PubMed Central

Silva, Janisete G.; Hamada, Neusa

2017-01-01

High morphological homogeneity and cryptic speciation may cause the diversity within Simuliidae to be underestimated. Recent molecular studies on population genetics and phylogeography have contributed to reveal which factors influenced the diversity within this group. This study aimed at examining the genetic diversity of Simulium hirtipupa Lutz, 1910 in populations from the biomes Caatinga, Cerrado, and Atlantic Forest. In this study, we carried out phylogeographic and population genetic analyses using a fragment of the mitochondrial gene COI. The 19 populations studied were clustered into seven groups, most of which are associated with geography indicating certain genetic structure. The northern region of the state of Minas Gerais is most likely the center of origin of this species. The average intergroup genetic distance was 3.7%, indicating the presence of cryptic species. The species tree as well as the haplotype network recovered all groups forming two major groups: the first comprises groups Gr-Bahia (in which the São Francisco river has not acted as geographical barrier), Gr-Pernambuco, and Gr-Mato Grosso do Sul. The second included groups comprising populations of the states of Goiás, Tocantins, Minas Gerais, Bahia, São Paulo, and Espírito Santo. The mismatch distribution for groups was consistent with the model of demographic expansion, except for the Gr-Central-East_1 group. The diversification in this group occurred about 1.19 Mya during the Pleistocene, influenced by paleoclimatic oscillations during the Quaternary glacial cycles. PMID:29281704

MODULATION OF RAT LEYDIG CELL STEROIDOGENIC FUNCTION BY DI(2-ETHYLHEXYL)PHTHALATE

EPA Science Inventory

Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate.

Akingbemi BT, Youker RT, Sottas CM, Ge R, Katz E, Klinefelter GR, Zirkin BR, Hardy MP.

Center for Biomedical Research, Population Council, New York, New York 10021, USA. benson@popcbr...

A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the Drosophila brain

PubMed Central

Miyazaki, Takaaki; Lin, Tzu-Yang; Ito, Kei; Lee, Chi-Hon; Stopfer, Mark

2016-01-01

Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons in Drosophila. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate gustatory second-order neurons (G2Ns) we screened ~5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of Gr5a-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single cell analysis by FLPout recombination, revealed a pair of neurons that contact Gr5a axon terminals in both brain hemispheres, and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to Gr5a neurons, while presynaptic sites were broadly distributed throughout the neurons’ arborizations. GRASP analysis and further tests with the Syb-GRASP method suggested that the identified G2Ns receive synaptic inputs from Gr5a-expressing GSNs, but not Gr66a-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from Gr5a-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system. PMID:26004543

A gustatory second-order neuron that connects sucrose-sensitive primary neurons and a distinct region of the gnathal ganglion in the Drosophila brain.

PubMed

Miyazaki, Takaaki; Lin, Tzu-Yang; Ito, Kei; Lee, Chi-Hon; Stopfer, Mark

2015-01-01

Although the gustatory system provides animals with sensory cues important for food choice and other critical behaviors, little is known about neural circuitry immediately following gustatory sensory neurons (GSNs). Here, we identify and characterize a bilateral pair of gustatory second-order neurons (G2Ns) in Drosophila. Previous studies identified GSNs that relay taste information to distinct subregions of the primary gustatory center (PGC) in the gnathal ganglia (GNG). To identify candidate G2Ns, we screened ∼5,000 GAL4 driver strains for lines that label neural fibers innervating the PGC. We then combined GRASP (GFP reconstitution across synaptic partners) with presynaptic labeling to visualize potential synaptic contacts between the dendrites of the candidate G2Ns and the axonal terminals of Gr5a-expressing GSNs, which are known to respond to sucrose. Results of the GRASP analysis, followed by a single-cell analysis by FLP-out recombination, revealed a pair of neurons that contact Gr5a axon terminals in both brain hemispheres and send axonal arborizations to a distinct region outside the PGC but within the GNG. To characterize the input and output branches, respectively, we expressed fluorescence-tagged acetylcholine receptor subunit (Dα7) and active-zone marker (Brp) in the G2Ns. We found that G2N input sites overlaid GRASP-labeled synaptic contacts to Gr5a neurons, while presynaptic sites were broadly distributed throughout the neurons' arborizations. GRASP analysis and further tests with the Syb-GRASP method suggested that the identified G2Ns receive synaptic inputs from Gr5a-expressing GSNs, but not Gr66a-expressing GSNs, which respond to caffeine. The identified G2Ns relay information from Gr5a-expressing GSNs to distinct regions in the GNG, and are distinct from other, recently identified gustatory projection neurons, which relay information about sugars to a brain region called the antennal mechanosensory and motor center (AMMC). Our findings suggest unexpected complexity for taste information processing in the first relay of the gustatory system.

Relationships between elastic anisotropy and thermal expansion in A 2Mo 3O 12 materials

DOE PAGES

Romao, Carl P.; Donegan, S. P.; Zwanziger, J. W.; ...

2016-10-24

Here, we report calculated elastic tensors, axial Grüneisen parameters, and thermal stress distributions in Al 2Mo 3O 12, ZrMgMo 3O 12, Sc 2Mo 3O 12, and Y 2Mo 3O 12, a series of isomorphic materials for which the coefficients of thermal expansion range from low-positive to negative. Thermal stress in polycrystalline materials arises from interactions between thermal expansion and mechanical properties, and both can be highly anisotropic. Thermal expansion anisotropy was found to be correlated with elastic anisotropy: axes with negative thermal expansion were less compliant. Calculations of axial Grüneisen parameters revealed that the thermal expansion anisotropy in these materialsmore » is in part due to the Poisson effect. Models of thermal stress due to thermal expansion anisotropy in polycrystals following cooling showed thermal stresses of sufficient magnitude to cause microcracking in all cases. The thermal expansion anisotropy was found to couple to elastic anisotropy, decreasing the bulk coefficient of thermal expansion and leading to lognormal extremes of the thermal stress distributions.« less

Relationships between elastic anisotropy and thermal expansion in A 2Mo 3O 12 materials

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

Romao, Carl P.; Donegan, S. P.; Zwanziger, J. W.

Here, we report calculated elastic tensors, axial Grüneisen parameters, and thermal stress distributions in Al 2Mo 3O 12, ZrMgMo 3O 12, Sc 2Mo 3O 12, and Y 2Mo 3O 12, a series of isomorphic materials for which the coefficients of thermal expansion range from low-positive to negative. Thermal stress in polycrystalline materials arises from interactions between thermal expansion and mechanical properties, and both can be highly anisotropic. Thermal expansion anisotropy was found to be correlated with elastic anisotropy: axes with negative thermal expansion were less compliant. Calculations of axial Grüneisen parameters revealed that the thermal expansion anisotropy in these materialsmore » is in part due to the Poisson effect. Models of thermal stress due to thermal expansion anisotropy in polycrystals following cooling showed thermal stresses of sufficient magnitude to cause microcracking in all cases. The thermal expansion anisotropy was found to couple to elastic anisotropy, decreasing the bulk coefficient of thermal expansion and leading to lognormal extremes of the thermal stress distributions.« less

Mutiple Stellar Populations in Blanco DECam Bulge Survey Globular Clusters

NASA Astrophysics Data System (ADS)

Miller, Doryan; Pilachowski, C. A.; Johnson, C. I.; Rich, R. Michael; Clarkson, William I.; Young, M.; Michael, S.

2018-01-01

Preliminary SDSS ugrizY photometric observations of globular cluster stars included in the Blanco DECam Bulge Survey (BDBS) were examined to determine the suitability of these data to characterize stellar populations within clusters. The BDBS fields include around two dozen globular clusters, including the iron-complex cluster M22 and the pulsar-rich cluster Terzan 5. Many globular clusters show evidence for multiple stellar populations as a spread in the u-g color of stars in a given phase of stellar evolution, and in some clusters, the populations have different radial distributions. BDBS clusters with low and/or non-variable reddening and long dynamical mixing time scales were selected for study, and photometry for RGB and main sequence stars within two half-light radii from the center of each cluster was extracted from the BDBS preliminary catalog. Field contamination was reduced in each candidate cluster by removing all stars more than a tenth of a magnitude from the best-fit fiducial curves following the g-r vs r color-magnitude diagram. The remaining stars were split into separate populations based on u-g color, and effective cumulative distribution functions vs. half-light radius were compared to identify differences in the populations’ radial distributions.

Sandpile-based model for capturing magnitude distributions and spatiotemporal clustering and separation in regional earthquakes

NASA Astrophysics Data System (ADS)

Batac, Rene C.; Paguirigan, Antonino A., Jr.; Tarun, Anjali B.; Longjas, Anthony G.

2017-04-01

We propose a cellular automata model for earthquake occurrences patterned after the sandpile model of self-organized criticality (SOC). By incorporating a single parameter describing the probability to target the most susceptible site, the model successfully reproduces the statistical signatures of seismicity. The energy distributions closely follow power-law probability density functions (PDFs) with a scaling exponent of around -1. 6, consistent with the expectations of the Gutenberg-Richter (GR) law, for a wide range of the targeted triggering probability values. Additionally, for targeted triggering probabilities within the range 0.004-0.007, we observe spatiotemporal distributions that show bimodal behavior, which is not observed previously for the original sandpile. For this critical range of values for the probability, model statistics show remarkable comparison with long-period empirical data from earthquakes from different seismogenic regions. The proposed model has key advantages, the foremost of which is the fact that it simultaneously captures the energy, space, and time statistics of earthquakes by just introducing a single parameter, while introducing minimal parameters in the simple rules of the sandpile. We believe that the critical targeting probability parameterizes the memory that is inherently present in earthquake-generating regions.

Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings

PubMed Central

Bharti, Niharika; Bhatla, Satish C

2015-01-01

Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca2+]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca2+] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development. PMID:26076049

Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings.

PubMed

Bharti, Niharika; Bhatla, Satish C

2015-01-01

Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca(2+)]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca(2+)] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development.

Addition of Lubiprostone to polyethylene glycol(PEG) enhances the quality & efficacy of colonoscopy preparation: a randomized, double-blind, placebo controlled trial.

PubMed

Banerjee, Rupa; Chaudhari, Hrushikesh; Shah, Nirish; Saravanan, Arjunan; Tandan, Manu; Reddy, D Nageshwar

2016-10-13

Adequate bowel preparation is an essential prerequisite for complete mucosal visualization during colonoscopy. Polyethylene glycol (PEG) solutions are commonly used. However the large volume of the solution is often poorly tolerated. Addition of Lubiprostone (LB) could improve the adequacy of standard PEG preparation & reduce requirement. The aims to assess adequacy of PEG preparation with addition of single dose LB (24mcg) vs placebo and efficacy of reduced dose PEG + LB compared with full dose PEG + LB. Single center prospective double blind randomized controlled trial. Part I: 442 patients for colonoscopy randomized to receive placebo (GrA) or single dose of LB (GrB) prior to PEG preparation. Quality of bowel preparation graded 0-9 according to Boston Bowel Preparation Scale (BBPS). BBPS-9: excellent and BBPS 0-4: repeat procedure. Part II: 146 patients randomized to receive LB + 1.5 L PEG (GrC; 75) or LB + 1 L PEG (GrD; 71). BBPS score compared with GrB (2 L PEG). Part I: 442 patients (221 GrA & 221 Gr B). LB resulted in significant improvement in total BBPS (7.44 + 0.14 vs. 6.36 + 0.16, p < 0.0001). 66.5 % Gr B vs 38 % Gr A had excellent prep; 42.5 % GrB vs 24 % GrA had adequate prep. Repeat procedure needed 9.5 % Gr B vs 16.7 % Gr A (P < 0.01). Part II: No difference in BBPS scores with lower doses (Gr C&D) compared to standard (GrB) (Mean BBPS 7.44 + 0.14 GrA,7.30 + 0.25 GrC;7.25 + 0.26 GrD;p >0.05). Single dose LB prior to PEG significantly enhanced bowel preparation compared to PEG alone. There was no significant difference in quality of preparation with lower doses of PEG when combined with LB. The study protocol was approved by institutional review board and the trial was registered on March 22, 2011 with clinicaltrials.gov ( NCT01324284 ).

Long-Term Use of Probiotic-Containing Yogurts Is a Safe Way to Prevent Helicobacter pylori: Based on a Mongolian Gerbil's Model

PubMed Central

Kuo, Chao-Hung; Wang, Sophie S. W.; Lu, Chien-Yu; Hu, Huang-Ming; Kuo, Fu-Chen; Weng, Bi-Chuang; Wu, Chun-Chieh; Liu, Chung-Jung; Tsai, Pei-Yun; Lee, Tsung-Cheng; Chen, Li-Wei; Cheng, Kuang-Hung; Chang, Lin-Li; Wu, Deng-Chyang

2013-01-01

Background. The suppression of Helicobacter pylori (H. pylori) decreases H. pylori-related diseases. The probiotics have an inhibitory effect on H. pylori. Aim. We investigated the effects of long-term use of yogurt on H. pylori based on Mongolian gerbils' model. Materials and Methods. Yogurt (containing a supplement of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six gerbils were divided into five groups. All groups were inoculated with H. pylori for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from 5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was evaluated according to the Sydney system. Results. The positive rates of H. pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E). Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal metaplasia. Gr. D showed higher IL-10 and lower TNF-α expression than Gr. E. Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The long-term use of yogurt would be an alternative strategy to manage H. pylori infection. PMID:24349780

Biogenic hydroxysulfate green rust, a potential electron acceptor for SRB activity

NASA Astrophysics Data System (ADS)

Zegeye, Asfaw; Huguet, Lucie; Abdelmoula, Mustapha; Carteret, Cédric; Mullet, Martine; Jorand, Frédéric

2007-11-01

Microbiological reduction of a biogenic sulfated green rust (GR2(SO42-)), was examined using a sulfate reducing bacterium ( Desulfovibrio alaskensis). Experiments investigated whether GR2(SO42-) could serve as a sulfate source for D. alaskensis anaerobic respiration by analyzing mineral transformation. Batch experiments were conducted using lactate as the electron donor and biogenic GR2(SO42-) as the electron acceptor, at circumneutral pH in unbuffered medium. GR2(SO42-) transformation was monitored with time by X-ray diffraction (XRD), Transmission Mössbauer Spectroscopy (TMS), Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). The reduction of sulfate anions and the formation of iron sulfur mineral were clearly identified by XPS analyses. TMS showed the formation of additional mineral as green rust (GR) and vivianite. XRD analyses discriminated the type of the newly formed GR as GR1. The formed GR1 was GR1(CO32-) as indicated by DRIFTS analysis. Thus, the results presented in this study indicate that D. alaskensis cells were able to use GR2(SO42-) as an electron acceptor. GR1(CO32-), vivianite and an iron sulfur compound were formed as a result of GR2(SO42-) reduction by D. alaskensis. Hence, in environments where geochemical conditions promote biogenic GR2(SO42-) formation, this mineral could stimulate the anaerobic respiration of sulfate reducing bacteria.

Inositol-requiring enzyme 1α is required for gut development in Xenopus lavies embryos

PubMed Central

Guo, Jing; Li, Xin-Xin; Feng, Jiao-Jiao; Yin, Chen-Yang; Wang, Xue-Jun; Wang, Ning; Yuan, Li

2013-01-01

AIM: To investigate the role of inositol-requiring enzyme 1α (IRE1α) in gut development of Xenopus lavies embryos. METHODS: Xenopus embryos were obtained with in vitro fertilization and cultured in 0.1 × MBSH. One and half nanogram of IRE1α, 1 ng of IRE1α-GR mRNA, 1 ng of IRE1αΔC-GR mRNA, and 50 ng of IRE1α morpholino oligonucleotide (MO) or XBP1(C)MO were injected into four blastomeres at 4-cell stage for scoring the phenotype and marker gene analysis. To rescue the effect of IRE1α MO, 1 ng of IRE1α-GR mRNA was co-injected with 50 ng of MO. For the activation of the GR-fusion proteins, dexamethasone was prepared as 5 mmol/L stock solutions in 100% ethanol and applied to the mRNA injected embryos at desired stages in a concentration of 10 μmol/L in 0.1 × MBSH. Embryos were kept in dexamethasone up to stage 41. Whole-mount in situ hybridization was used to determine specific gene expression, such as IRE1α, IRE1β, Xbra and Xsox17α. IRE1α protein expression during Xenopus embryogenesis was detected by Western blotting. RESULTS: In the whole-mount in situ hybridization analysis, xenopus IRE1α and IRE1β showed quite different expression pattern during tadpole stage. The relatively higher expression of IRE1α was observed in the pancreas, and significant transcription of IRE1β was found in the liver. IRE1α protein could be detected at all developmental stages analyzed, from stage 1 to stage 42. Gain-of-function assay showed that IRE1α mRNA injected embryos at tailbud stage were nearly normal and the expression of the pan-mesodermal marker gene Xbra and the endodermal gene Xsox17α at stage 10.5 was not significantly changed in embryos injected with IRE1α mRNA as compared to uninjected control embryos. And at tadpole stage, the embryos injected with IRE1α-GR mRNA did not display overt phenotype, such as gut-coiling defect. Loss-of-function assay demonstrated that the IRE1α MO injected embryos were morphologically normal before the tailbud stages. We did not observe a significant change of mesodermal and endodermal marker gene expression, while after stage 40, about 80% of the MO injected embryos exhibited dramatic gut defects in which the guts did not coil, but other structures outside the gastrointestinal tract were relatively normal. To test if the phenotypes were specifically caused by the knockdown of IRE1α, a rescue experiment was performed by co-injection of IRE1α-GR mRMA with IRE1α MO. The data obtained demonstrated that the gut coiling defect was rescued. The deletion mutant of IRE1α was constructed, consisting of the N-terminal part without the C-terminal kinase and RNase domains named IRE1αΔC, to investigate the functional domain of IRE1α. Injection of IRE1αΔC-GR mRNA caused similar morphological alterations with gut malformation by interfering with the function of endogenous xIRE1α. In order to investigate if IRE1α/XBP1 pathway was involved in gut development, 50 ng of XBP1 MO was injected and the results showed that knockdown of XBP1 resulted in similar morphological alterations with gut-coiling defect at tadpole stage. CONCLUSION: IRE1α is not required for germ layer formation but for gut development in Xenopus lavies and it may function via XBP1-dependent pathway. PMID:23345945

Inositol-requiring enzyme 1α is required for gut development in Xenopus lavies embryos.

PubMed

Guo, Jing; Li, Xin-Xin; Feng, Jiao-Jiao; Yin, Chen-Yang; Wang, Xue-Jun; Wang, Ning; Yuan, Li

2013-01-14

To investigate the role of inositol-requiring enzyme 1α (IRE1α) in gut development of Xenopus lavies embryos. Xenopus embryos were obtained with in vitro fertilization and cultured in 0.1 × MBSH. One and half nanogram of IRE1α, 1 ng of IRE1α-GR mRNA, 1 ng of IRE1αΔC-GR mRNA, and 50 ng of IRE1α morpholino oligonucleotide (MO) or XBP1(C)MO were injected into four blastomeres at 4-cell stage for scoring the phenotype and marker gene analysis. To rescue the effect of IRE1α MO, 1 ng of IRE1α-GR mRNA was co-injected with 50 ng of MO. For the activation of the GR-fusion proteins, dexamethasone was prepared as 5 mmol/L stock solutions in 100% ethanol and applied to the mRNA injected embryos at desired stages in a concentration of 10 μmol/L in 0.1 × MBSH. Embryos were kept in dexamethasone up to stage 41. Whole-mount in situ hybridization was used to determine specific gene expression, such as IRE1α, IRE1β, Xbra and Xsox17α. IRE1α protein expression during Xenopus embryogenesis was detected by Western blotting. In the whole-mount in situ hybridization analysis, xenopus IRE1α and IRE1β showed quite different expression pattern during tadpole stage. The relatively higher expression of IRE1α was observed in the pancreas, and significant transcription of IRE1β was found in the liver. IRE1α protein could be detected at all developmental stages analyzed, from stage 1 to stage 42. Gain-of-function assay showed that IRE1α mRNA injected embryos at tailbud stage were nearly normal and the expression of the pan-mesodermal marker gene Xbra and the endodermal gene Xsox17α at stage 10.5 was not significantly changed in embryos injected with IRE1α mRNA as compared to uninjected control embryos. And at tadpole stage, the embryos injected with IRE1α-GR mRNA did not display overt phenotype, such as gut-coiling defect. Loss-of-function assay demonstrated that the IRE1α MO injected embryos were morphologically normal before the tailbud stages. We did not observe a significant change of mesodermal and endodermal marker gene expression, while after stage 40, about 80% of the MO injected embryos exhibited dramatic gut defects in which the guts did not coil, but other structures outside the gastrointestinal tract were relatively normal. To test if the phenotypes were specifically caused by the knockdown of IRE1α, a rescue experiment was performed by co-injection of IRE1α-GR mRMA with IRE1α MO. The data obtained demonstrated that the gut coiling defect was rescued. The deletion mutant of IRE1α was constructed, consisting of the N-terminal part without the C-terminal kinase and RNase domains named IRE1αΔC, to investigate the functional domain of IRE1α. Injection of IRE1αΔC-GR mRNA caused similar morphological alterations with gut malformation by interfering with the function of endogenous xIRE1α. In order to investigate if IRE1α/XBP1 pathway was involved in gut development, 50 ng of XBP1 MO was injected and the results showed that knockdown of XBP1 resulted in similar morphological alterations with gut-coiling defect at tadpole stage. IRE1α is not required for germ layer formation but for gut development in Xenopus lavies and it may function via XBP1-dependent pathway.

Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development

PubMed Central

Caldwell, Katharine E.; Labrecque, Matthew T.; Solomon, Benjamin R.; Ali, Abdulmehdi; Allan, Andrea M.

2015-01-01

The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50 ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of arsenic results in altered fetal programming of the glucocorticoid system. PMID:25459689

New Functions for New Demands.

ERIC Educational Resources Information Center

Wrobleski, Diane

1995-01-01

Explores areas to consider when planning and designing libraries/media centers. Examines wiring capabilities to meet future needs, ergonomics and furniture durability for workstations, and color and lighting schemes to enhance the indoor environment. (GR)

AMPA GluA1-flip targeted oligonucleotide therapy reduces neonatal seizures and hyperexcitability

PubMed Central

Lykens, Nicole M.; Reddi, Jyoti M.

2017-01-01

Glutamate-activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) mediate the majority of excitatory neurotransmission in brain and thus are major drug targets for diseases associated with hyperexcitability or neurotoxicity. Due to the critical nature of AMPA-Rs in normal brain function, typical AMPA-R antagonists have deleterious effects on cognition and motor function, highlighting the need for more precise modulators. A dramatic increase in the flip isoform of alternatively spliced AMPA-R GluA1 subunits occurs post-seizure in humans and animal models. GluA1-flip produces higher gain AMPA channels than GluA1-flop, increasing network excitability and seizure susceptibility. Splice modulating oligonucleotides (SMOs) bind to pre-mRNA to influence alternative splicing, a strategy that can be exploited to develop more selective drugs across therapeutic areas. We developed a novel SMO, GR1, which potently and specifically decreased GluA1-flip expression throughout the brain of neonatal mice lasting at least 60 days after single intracerebroventricular injection. GR1 treatment reduced AMPA-R mediated excitatory postsynaptic currents at hippocampal CA1 synapses, without affecting long-term potentiation or long-term depression, cellular models of memory, or impairing GluA1-dependent cognition or motor function in mice. Importantly, GR1 demonstrated anti-seizure properties and reduced post-seizure hyperexcitability in neonatal mice, highlighting its drug candidate potential for treating epilepsies and other neurological diseases involving network hyperexcitability. PMID:28178321

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

Li, Qun-Yi; Zhang, Meng; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai

Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids formore » the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.« less

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

Neelgund, Gururaj M.; Oki, Aderemi, E-mail: aroki@pvamu.edu; Luo, Zhiping

Graphical abstract: A facile chemical precipitation method is reported for effective in situ deposition of hydroxyapatite on graphene nanosheets. Prior to grafting of hydroxyapatite, chemically modified graphene nanosheets were obtained by the reduction of graphene oxide in presence of ethylenediamine. Display Omitted Highlights: ► It is a facile and effective method for deposition of HA on GR nanosheets. ► It avoids the use of harmful reducing agents like hydrazine, NaBH{sub 4} etc. ► GR nanosheets were produced using bio-compatible, ethylenediamine. ► The graphitic structure of synthesized GR nanosheets was high ordered. ► The ratio of Ca to P in HAmore » was 1.64, which is close to ratio in natural bone. -- Abstract: Graphene nanosheets were effectively functionalized by in situ deposition of hydroxyapatite through a facile chemical precipitation method. Prior to grafting of hydroxyapatite, chemically modified graphene nanosheets were obtained by the reduction of graphene oxide in presence of ethylenediamine. The resulting hydroxyapatite functionalized graphene nanosheets were characterized by attenuated total reflection IR spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, X-ray energy dispersive spectroscopy, Raman spectroscopy and thermogravimetric analysis. These characterization techniques revealed the successful grafting of hydroxyapatite over well exfoliated graphene nanosheets without destroying their structure.« less

Granulocytic myeloid-derived suppressor cells from human cord blood modulate T-helper cell response towards an anti-inflammatory phenotype.

PubMed

Köstlin, Natascha; Vogelmann, Margit; Spring, Bärbel; Schwarz, Julian; Feucht, Judith; Härtel, Christoph; Orlikowsky, Thorsten W; Poets, Christian F; Gille, Christian

2017-09-01

Infections are a leading cause of perinatal morbidity and mortality. The outstandingly high susceptibility to infections early in life is mainly attributable to the compromised state of the neonatal immune system. One important difference to the adult immune system is a bias towards T helper type 2 (Th2) responses in newborns. However, mechanisms regulating neonatal T-cell responses are incompletely understood. Granulocytic myeloid-derived suppressor cells (GR-MDSC) are myeloid cells with a granulocytic phenotype that suppress various functions of other immune cells and accumulate under physiological conditions during pregnancy in maternal and fetal blood. Although it has been hypothesized that GR-MDSC accumulation during fetal life could be important for the maintenance of maternal-fetal tolerance, the influence of GR-MDSC on the immunological phenotype of neonates is still unclear. Here, we investigated the impact of GR-MDSC isolated from cord blood (CB-MDSC) on the polarization of Th cells. We demonstrate that CB-MDSC inhibit Th1 responses and induced Th2 responses and regulatory T (Treg) cells. Th1 inhibition was cell-contact dependent and occurred independent of other cell types, while Th2 induction was mediated independently of cell contact through expression of ArgI and reactive oxygen species by CB-MDSC and partially needed the presence of monocytes. Treg cell induction by CB-MDSC also occurred cell-contact independently but was partially mediated through inducible nitric oxide synthase. These results point towards a role of MDSC in regulating neonatal immune responses. Targeting MDSC function in neonates could be a therapeutic opportunity to improve neonatal host defence. © 2017 John Wiley & Sons Ltd.

Environmental Enrichment Increases Glucocorticoid Receptors and Decreases GluA2 and Protein Kinase M Zeta (PKMζ) Trafficking During Chronic Stress: A Protective Mechanism?

PubMed Central

Zanca, Roseanna M.; Braren, Stephen H.; Maloney, Brigid; Schrott, Lisa M.; Luine, Victoria N.; Serrano, Peter A.

2015-01-01

Environmental enrichment (EE) housing paradigms have long been shown beneficial for brain function involving neural growth and activity, learning and memory capacity, and for developing stress resiliency. The expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2, which is important for synaptic plasticity and memory, is increased with corticosterone (CORT), undermining synaptic plasticity and memory. Thus, we determined the effect of EE and stress on modulating GluA2 expression in Sprague-Dawley male rats. Several markers were evaluated which include: plasma CORT, the glucocorticoid receptor (GR), GluA2, and the atypical protein kinase M zeta (PKMζ). For 1 week standard-(ST) or EE-housed animals were treated with one of the following four conditions: (1) no stress; (2) acute stress (forced swim test, FST; on day 7); (3) chronic restraint stress (6 h/day for 7 days); and (4) chronic + acute stress (restraint stress 6 h/day for 7 days + FST on day 7). Hippocampi were collected on day 7. Our results show that EE animals had reduced time immobile on the FST across all conditions. After chronic + acute stress EE animals showed increased GR levels with no change in synaptic GluA2/PKMζ. ST-housed animals showed the reverse pattern with decreased GR levels and a significant increase in synaptic GluA2/PKMζ. These results suggest that EE produces an adaptive response to chronic stress allowing for increased GR levels, which lowers neuronal excitability reducing GluA2/PKMζ trafficking. We discuss this EE adaptive response to stress as a potential underlying mechanism that is protective for retaining synaptic plasticity and memory function. PMID:26617502

Molecular Basis for Glucocorticoid Induction of the Krüppel-Like Factor 9 Gene in Hippocampal Neurons

PubMed Central

Bagamasbad, Pia; Ziera, Tim; Borden, Steffen A.; Bonett, Ronald M.; Rozeboom, Aaron M.; Seasholtz, Audrey

2012-01-01

Stress has complex effects on hippocampal structure and function, which consequently affects learning and memory. These effects are mediated in part by circulating glucocorticoids (GC) acting via the intracellular GC receptor (GR) and mineralocorticoid receptor (MR). Here, we investigated GC regulation of Krüppel-like factor 9 (KLF9), a transcription factor implicated in neuronal development and plasticity. Injection of corticosterone (CORT) in postnatal d 6 and 30 mice increased Klf9 mRNA and heteronuclear RNA by 1 h in the hippocampal region. Treatment of the mouse hippocampal cell line HT-22 with CORT caused a time- and dose-dependent increase in Klf9 mRNA. The CORT induction of Klf9 was resistant to protein synthesis inhibition, suggesting that Klf9 is a direct CORT-response gene. In support of this hypothesis, we identified two GR/MR response elements (GRE/MRE) located −6.1 and −5.3 kb relative to the transcription start site, and we verified their functionality by enhancer-reporter, gel shift, and chromatin immunoprecipitation assays. The −5.3-kb GRE/MRE is largely conserved across tetrapods, but conserved orthologs of the −6.1-kb GRE/MRE were only detected in therian mammals. GC treatment caused recruitment of the GR, histone hyperacetylation, and nucleosome removal at Klf9 upstream regions. Our findings support a predominant role for GR, with a minor contribution of MR, in the direct regulation of Klf9 acting via two GRE/MRE located in the 5′-flanking region of the gene. KLF9 may play a key role in GC actions on hippocampal development and plasticity. PMID:22962255

Are we missing a mineralocorticoid in teleost fish? Effects of cortisol, deoxycorticosterone and aldosterone on osmoregulation, gill Na+,K+-ATPase activity and isoform mRNA levels in Atlantic salmon

USGS Publications Warehouse

McCormick, S.D.; Regish, A.; O'Dea, M. F.; Shrimpton, J.M.

2008-01-01

It has long been held that cortisol, acting through a single receptor, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. The recent finding that fish express a gene with high sequence similarity to the mammalian mineralocorticoid receptor (MR) suggests the possibility that a hormone other than cortisol carries out some mineralocorticoid functions in fish. To test for this possibility, we examined the effect of in vivo cortisol, 11-deoxycorticosterone (DOC) and aldosterone on salinity tolerance, gill Na+,K+-ATPase (NKA) activity and mRNA levels of NKA α1a and α1b in Atlantic salmon. Cortisol treatment for 6–14 days resulted in increased, physiological levels of cortisol, increased gill NKA activity and improved salinity tolerance (lower plasma chloride after a 24 h seawater challenge), whereas DOC and aldosterone had no effect on either NKA activity or salinity tolerance. NKA α1a and α1b mRNA levels, which increase in response to fresh water and seawater acclimation, respectively, were both upregulated by cortisol, whereas DOC and aldosterone were without effect. Cortisol, DOC and aldosterone had no effect on gill glucocorticoid receptor GR1, GR2 and MR mRNA levels, although there was some indication of possible upregulation of GR1 by cortisol (p = 0.07). The putative GR blocker RU486 inhibited cortisol-induced increases in salinity tolerance, NKA activity and NKA α1a and α1b transcription, whereas the putative MR blocker spironolactone had no effect. The results provide support that cortisol, and not DOC or aldosterone, is involved in regulating the mineralocorticoid functions of ion uptake and salt secretion in teleost fish.

Depletion of the cellular levels of Bag-1 proteins attenuates phorbol ester-induced downregulation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B

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

Maier, Jana V., E-mail: Jana.maier@kit.edu; Volz, Yvonne; Berger, Caroline

2010-10-22

Research highlights: {yields}Bag-1 depletion only marginally affects the action of the glucocorticoid receptor but strongly regulates the activity of NF-{kappa}B. {yields}Bag-1 depletion attenuates phosphorylation and degradation of I{kappa}B{alpha} and nuclear accumulation of NF-{kappa}B p65 and p50. {yields}Bag-1 interacts with I{kappa}B{alpha} and partially restores I{kappa}B{alpha} and NF-{kappa}B activation in Bag-1 depleted cells. -- Abstract: Bag-1 consists in humans of four isoforms generated from the same RNA by alternative translation. Overexpression of single Bag-1 isoforms has identified Bag-1 as a negative regulator of action of many proteins including the glucocorticoid receptor (GR). Here we have analysed the ability of Bag-1 to regulatemore » the transrepression function of the GR. Silencing Bag-1 expression only marginally affects the transrepression action of the GR but decreased the action of the transcription factor NF-{kappa}B. Furthermore phosphorylation and degradation of the inhibitor protein I{kappa}B{alpha} and nuclear accumulation of p65 and p50 NF-{kappa}B proteins in response to phorbol ester was attenuated following Bag-1 depletion in HeLa cells. Reconstitution of Bag-1 in depleted cells partially restored I{kappa}B{alpha} and NF-{kappa}B activation. Knock-down of Bag-1 expression also did not significantly alter GR-mediated transactivation but affected the basal transcription of some of the target genes. Thus Bag-1 proteins function as regulators of the action of selective transcription factors.« less

Understanding how long‐acting β2‐adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids in asthma – an update

PubMed Central

Giembycz, Mark A

2016-01-01

In moderate‐to‐severe asthma, adding an inhaled long‐acting β2‐adenoceptor agonist (LABA) to an inhaled corticosteroid (ICS) provides better disease control than simply increasing the dose of ICS. Acting on the glucocorticoid receptor (GR, gene NR3C1), ICSs promote anti‐inflammatory/anti‐asthma gene expression. In vitro, LABAs synergistically enhance the maximal expression of many glucocorticoid‐induced genes. Other genes, including dual‐specificity phosphatase 1(DUSP1) in human airways smooth muscle (ASM) and epithelial cells, are up‐regulated additively by both drug classes. Synergy may also occur for LABA‐induced genes, as illustrated by the bronchoprotective gene, regulator of G‐protein signalling 2 (RGS2) in ASM. Such effects cannot be produced by either drug alone and may explain the therapeutic efficacy of ICS/LABA combination therapies. While the molecular basis of synergy remains unclear, mechanistic interpretations must accommodate gene‐specific regulation. We explore the concept that each glucocorticoid‐induced gene is an independent signal transducer optimally activated by a specific, ligand‐directed, GR conformation. In addition to explaining partial agonism, this realization provides opportunities to identify novel GR ligands that exhibit gene expression bias. Translating this into improved therapeutic ratios requires consideration of GR density in target tissues and further understanding of gene function. Similarly, the ability of a LABA to interact with a glucocorticoid may be suboptimal due to low β2‐adrenoceptor density or biased β2‐adrenoceptor signalling. Strategies to overcome these limitations include adding‐on a phosphodiesterase inhibitor and using agonists of other Gs‐coupled receptors. In all cases, the rational design of ICS/LABA, and derivative, combination therapies requires functional knowledge of induced (and repressed) genes for therapeutic benefit to be maximized. PMID:27646470

The effect of various concentration of tilapia (Oreochromis sp.) surimi for edible coating on the shelf-life of Pangasius sp. fillets

NASA Astrophysics Data System (ADS)

Purnama, M. A. P.; Agustono; Sahidu, A. M.

2018-04-01

Pangasius sp. fillets prone to deterioration the quality that will affect the appearance and the shelf life of fillets. The effort to extend the shelf life of fish fillet that is by using an edible coating. Surimi can be used as a protein-based edible coating because they have superior inhibitory and mechanical properties compared to the polysaccharides based material. Surimi can be made from freshwater tilapia (Oreochromis sp.) fish. The experimental design used was Completely Randomized Design (CRD) with five treatments of surimi (0 gr, 2 gr, 4 gr, 6 gr, 8 gr) with four replications. The results showed that Pangasius sp. fillets with an edible coating 8 gr surimi have the highest value in the organoleptic test. The pH testing on Pangasius sp. fillets with edible coating 2 gr, 4 gr, 6 gr, and 8 gr surimi from the 0th hour to 18th hour have increased but slower than Pangasius sp. fillets without edible coating surimi. The best value of Total Plate Count (TPC) test is in edible coating 6 gr and 8 gr surimi as it is in accordance with SNI 2696:2013 at room temperature storage until the 18th hours.

SDSS (g--r) colors of isolated galaxies

NASA Astrophysics Data System (ADS)

Fernández Lorenzo, M.; Sulentic, J.; Verdes-Montenegro, L.; Ruiz, J. E.; Sabater, J.; Sánchez-Expósito, S.

2013-05-01

Several processes can affect a galaxy over its lifetime. If effects of interaction with companions are minimized, it is possible to focus on secular evolutionary processes. We present a study of the SDSS (g--r) colors of isolated galaxies in the AMIGA project (Analysis of the interstellar Medium of Isolated GAlaxies; http://www.amiga.iaa.es). Assuming that color is an indicator of the star formation history, this work better records the signature of passive star formation via pure secular evolution. We focused on median values for the main morphological subtypes found in the AMIGA sample (66% Sb--Sc and 14% E/S0) and compared them with equivalent measures of galaxies in denser environments. The main results of this study include: 1) a tendency for AMIGA spiral galaxies to be redder than similar type galaxies in close pairs, but 2) no clear difference when we compare with galaxies in other (e.g. group) environments; 3) a Gaussian distribution of the (g--r) color of isolated galaxies, as might be expected in the case of pure secular evolution; and 4) a smaller median absolute deviation in colors for isolated galaxies compared to both wide and close pairs.

Regional variation of stress level in the Himalayas after the 25 April 2015 Gorkha earthquake (Nepal) estimated using b-values

NASA Astrophysics Data System (ADS)

Ramesh, Pudi; Martha, Tapas R.; Vinod Kumar, K.

2018-06-01

The Gutenberg-Richter (G-R) relation and its parameters reflect the distribution of magnitude and frequency of earthquakes in a seismically active region. Different segments of the Himalayas from west to east behave differently in their G-R relation. In this study, b-values from the G-R relation were computed for the four different seismic zones of the Himalayas, in order to understand the regional variation of stress levels. It was found that the b-value of the Eastern zone is relatively lower than that of the other zones. The b-values before and after the Gorkha (25 April 2015) and Dolakha (12 May 2015) earthquakes were compared for the Central-II seismic zone, where the epicentres of both earthquakes were located. It was observed that the b-value has increased gradually in this region since stress was released episodically. It was also observed that b-values in adjacent zones are lower than that in the source region of the 25 April 2015 earthquake, implying high-stress accumulation. This indicates that the recurrence period of a large earthquake will be high in adjacent zones, particularly in the Eastern zone.

Adaptive Modulation for DFIG and STATCOM With High-Voltage Direct Current Transmission.

PubMed

Tang, Yufei; He, Haibo; Ni, Zhen; Wen, Jinyu; Huang, Tingwen

2016-08-01

This paper develops an adaptive modulation approach for power system control based on the approximate/adaptive dynamic programming method, namely, the goal representation heuristic dynamic programming (GrHDP). In particular, we focus on the fault recovery problem of a doubly fed induction generator (DFIG)-based wind farm and a static synchronous compensator (STATCOM) with high-voltage direct current (HVDC) transmission. In this design, the online GrHDP-based controller provides three adaptive supplementary control signals to the DFIG controller, STATCOM controller, and HVDC rectifier controller, respectively. The mechanism is to observe the system states and their derivatives and then provides supplementary control to the plant according to the utility function. With the GrHDP design, the controller can adaptively develop an internal goal representation signal according to the observed power system states, therefore, to achieve more effective learning and modulating. Our control approach is validated on a wind power integrated benchmark system with two areas connected by HVDC transmission lines. Compared with the classical direct HDP and proportional integral control, our GrHDP approach demonstrates the improved transient stability under system faults. Moreover, experiments under different system operating conditions with signal transmission delays are also carried out to further verify the effectiveness and robustness of the proposed approach.

Introduction to bifactor polytomous item response theory analysis.

PubMed

Toland, Michael D; Sulis, Isabella; Giambona, Francesca; Porcu, Mariano; Campbell, Jonathan M

2017-02-01

A bifactor item response theory model can be used to aid in the interpretation of the dimensionality of a multifaceted questionnaire that assumes continuous latent variables underlying the propensity to respond to items. This model can be used to describe the locations of people on a general continuous latent variable as well as on continuous orthogonal specific traits that characterize responses to groups of items. The bifactor graded response (bifac-GR) model is presented in contrast to a correlated traits (or multidimensional GR model) and unidimensional GR model. Bifac-GR model specification, assumptions, estimation, and interpretation are demonstrated with a reanalysis of data (Campbell, 2008) on the Shared Activities Questionnaire. We also show the importance of marginalizing the slopes for interpretation purposes and we extend the concept to the interpretation of the information function. To go along with the illustrative example analyses, we have made available supplementary files that include command file (syntax) examples and outputs from flexMIRT, IRTPRO, R, Mplus, and STATA. Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.jsp.2016.11.001. Data needed to reproduce analyses in this article are available as supplemental materials (online only) in the Appendix of this article. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Strong magnetization and Chern insulators in compressed graphene/CrI 3 van der Waals heterostructures

NASA Astrophysics Data System (ADS)

Zhang, Jiayong; Zhao, Bao; Zhou, Tong; Xue, Yang; Ma, Chunlan; Yang, Zhongqin

2018-02-01

Graphene-based heterostructures are a promising material system for designing the topologically nontrivial Chern insulating devices. Recently, a two-dimensional monolayer ferromagnetic insulator CrI3 was successfully synthesized in experiments [B. Huang et al., Nature (London) 546, 270 (2017), 10.1038/nature22391]. Here, these two interesting materials are proposed to build a heterostructure (Gr /CrI3). Our first-principles calculations show that the system forms a van der Waals (vdW) heterostructure, which is relatively facilely fabricated in experiments. A Chern insulating state is acquired in the Gr /CrI3 heterostructure if the vdW gap is compressed to a distance between about 3.3 and 2.4 Å, corresponding to a required external pressure between about 1.4 and 18.3 GPa. Amazingly, very strong magnetization (about 150 meV) is found in graphene, induced by the substrate CrI3, despite the vdW interactions between them. A low-energy effective model is employed to understand the mechanism. The work functions, contact types, and band alignments of the Gr /CrI3 heterostructure system are also studied. Our work demonstrates that the Gr /CrI3 heterostructure is a promising system to observe the quantum anomalous Hall effect at high temperatures (up to 45 K) in experiments.

Taste-independent detection of the caloric content of sugar in Drosophila

PubMed Central

Dus, Monica; Min, SooHong; Keene, Alex C.; Lee, Ga Young; Suh, Greg S. B.

2011-01-01

Feeding behavior is influenced primarily by two factors: nutritional needs and food palatability. However, the role of food deprivation and metabolic needs in the selection of appropriate food is poorly understood. Here, we show that the fruit fly, Drosophila melanogaster, selects calorie-rich foods following prolonged food deprivation in the absence of taste-receptor signaling. Flies mutant for the sugar receptors Gr5a and Gr64a cannot detect the taste of sugar, but still consumed sugar over plain agar after 15 h of starvation. Similarly, pox-neuro mutants that are insensitive to the taste of sugar preferentially consumed sugar over plain agar upon starvation. Moreover, when given a choice between metabolizable sugar (sucrose or d-glucose) and nonmetabolizable (zero-calorie) sugar (sucralose or l-glucose), starved Gr5a; Gr64a double mutants preferred metabolizable sugars. These findings suggest the existence of a taste-independent metabolic sensor that functions in food selection. The preference for calorie-rich food correlates with a decrease in the two main hemolymph sugars, trehalose and glucose, and in glycogen stores, indicating that this sensor is triggered when the internal energy sources are depleted. Thus, the need to replenish depleted energy stores during periods of starvation may be met through the activity of a taste-independent metabolic sensing pathway. PMID:21709242

Taste-independent detection of the caloric content of sugar in Drosophila.

PubMed

Dus, Monica; Min, SooHong; Keene, Alex C; Lee, Ga Young; Suh, Greg S B

2011-07-12

Feeding behavior is influenced primarily by two factors: nutritional needs and food palatability. However, the role of food deprivation and metabolic needs in the selection of appropriate food is poorly understood. Here, we show that the fruit fly, Drosophila melanogaster, selects calorie-rich foods following prolonged food deprivation in the absence of taste-receptor signaling. Flies mutant for the sugar receptors Gr5a and Gr64a cannot detect the taste of sugar, but still consumed sugar over plain agar after 15 h of starvation. Similarly, pox-neuro mutants that are insensitive to the taste of sugar preferentially consumed sugar over plain agar upon starvation. Moreover, when given a choice between metabolizable sugar (sucrose or D-glucose) and nonmetabolizable (zero-calorie) sugar (sucralose or L-glucose), starved Gr5a; Gr64a double mutants preferred metabolizable sugars. These findings suggest the existence of a taste-independent metabolic sensor that functions in food selection. The preference for calorie-rich food correlates with a decrease in the two main hemolymph sugars, trehalose and glucose, and in glycogen stores, indicating that this sensor is triggered when the internal energy sources are depleted. Thus, the need to replenish depleted energy stores during periods of starvation may be met through the activity of a taste-independent metabolic sensing pathway.

Temperature and pressure dependent thermodynamic behavior of 2H-CuInO2

NASA Astrophysics Data System (ADS)

Bhamu, K. C.

2018-05-01

Density functional theory and quasi-harmonic Debye model has been used to study the thermodynamic properties of 2H-CuInO2. At the optimized structural parameters, pressure (0 to 80 GPa) dependent variation in the various thermodynamic properties, i.e. unit cell volume (V), bulk modulus (B), specific heat (Cv), Debye temperature (θD), Grüneisen parameter (γ) and thermal expansion coefficient (α) are calculated for various temperature values. The results predict that the pressure has significant effect on unit cell volume and bulk modulus while the temperature shows negligible effect on both parameters. With increasing temperature thermal expansion coefficient increase while with increasing pressure it decreases. The specific heat remains close to zero for ambient pressure and temperature values and it increases with increasing temperature. It is observed that the pressure has high impact on Debye temperature and Grüneisen parameter instead of temperature. Debye temperature and Grüneisen parameter both remains almost constant for the temperature range (0-300K) while Grüneisen parameter decrease with increasing pressure at constant temperature and Debye temperature increases rapidly with increasing pressure. An increase in Debye temperature with respect to pressure shows that the thermal vibration frequency changes rapidly.

Mini-invasive treatment of abdominal aortic aneurysms: current roles of endovascular, laparoscopic, and open techniques.

PubMed

Coscas, Raphaël; Maumias, Thibault; Capdevila, Clément; Javerliat, Isabelle; Goëau-Brissonnière, Olivier; Coggia, Marc

2014-01-01

Endovascular aortic repair (EVAR), laparoscopic aortic surgery (LAS), and open surgery (OS) are three established treatment methods of abdominal aortic aneurysms (AAA). While these techniques are often percieved as competitive between them, they are complementary for the vascular surgeon, whose goal is to provide a treatment adapted to each case that is noninvasive and durable. The objective of this study was to report our results of AAA repair to better define the roles of the three techniques. From January 2009 to December 2011, we operated on 235 patients for AAAs. Patients for whom the three technical methods were discussed preoperatively were selected. Cases where the three techniques were not discussed were excluded (ruptured AAA, technique not available). One hundred seventy-five (75%) patients were included. Four groups were established based on the surgical risk and the anatomic EVAR criteria of the French Health Authority (Haute Autorité de Santé [HAS]), including: (1) good risk and favorable anatomy (GR-FA); (2) good risk and unfavorable anatomy (GR-UA); (3) high-risk and favorable anatomy (HR-FA); and (4) high-risk and unfavorable anatomy (HR-UA). Data collection was prospective. The numerical data were expressed as median and range. There were 166 (95%) men, aged 74 years (range 38-97 years). AAA diameter was 51 mm (range 30-81 mm). Mini-invasive treatment (EVAR or LAS) was chosen in 156 (89%) cases. Mortality at 30 days was 3.4% (6 patients, 1 EVAR, 1 LAS, and 4 OS), including 3 patients presenting with a "shaggy aorta." There were 58, 19, 65, and 33 patients in groups GR-FA (33%), GR-UA (11%), HR-FA (37%), and HR-UA (19%), respectively. The distribution of the three techniques (EVAR, LAS, OS) according to the groups was as follows: GR-FA (9, 46, 3); GR-UA (0, 13, 6); HR-FA (50, 13, 2); and HR-UA (12, 13, 8), respectively. The results by subgroups are presented. Based on our results, we present a new algorithm for AAA treatment. Among GR-FA patients, EVAR and LAS should be discussed according to life expectancy and wish of the patient. In GR-UA patients, LAS and OS can be proposed. For HR-FA patients, EVAR remains the first choice, but LAS can be used in cases with good life expectancy. In the HR-UA patients, LAS is the best choice because of the late complications of EVAR, but a broader use of fenestrated stent grafts or the chimney technique may be beneficial. Last, the surgical threshold should be pushed back among AAA patients presenting with a shaggy aorta. Copyright © 2014 Elsevier Inc. All rights reserved.

Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner.

PubMed

Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M; Wiltrout, Robert H; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A; Manns, Michael P; Wang, Ena; Marincola, Francesco M; Korangy, Firouzeh; Greten, Tim F

2015-04-01

Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs) accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α-galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+) cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN-γ-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor-induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)-mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40(-/-) tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Complete Genome Sequence of the Alfalfa Symbiont Sinorhizobium/Ensifer meliloti Strain GR4.

PubMed

Martínez-Abarca, Francisco; Martínez-Rodríguez, Laura; López-Contreras, José Antonio; Jiménez-Zurdo, José Ignacio; Toro, Nicolás

2013-01-01

We present the complete nucleotide sequence of the multipartite genome of Sinorhizobium/Ensifer meliloti GR4, a predominant rhizobial strain in an agricultural field site. The genome (total size, 7.14 Mb) consists of five replicons: one chromosome, two expected symbiotic megaplasmids (pRmeGR4c and pRmeGR4d), and two accessory plasmids (pRmeGR4a and pRmeGR4b).

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

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activatedmore » GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.« less

Electrostatic and hydrodynamics effects in a sedimented magnetorheological suspension.

PubMed

Domínguez-García, P; Pastor, J M; Melle, Sonia; Rubio, Miguel A

2009-08-01

We present experimental results on the equilibrium microstructure of a sedimented magnetorheological suspension, namely, an aqueous suspension of micron-sized superparamagnetic particles. We develop a study of the electrical interactions on the suspension by processing video-microscopy images of the sedimented particles. We calculate the pair distribution function, g(r), which yields the electrostatic pair potential u(r), showing an anomalous attractive interaction for distances on the order of twice the particle diameter, with characteristic parameters whose values show a dependence with the two-dimensional concentration of particles. The repulsive body of the potential is adjusted to a DLVO expression in order to calculate the Debye screening length and the effective surface charge density. Influence of confinement and variations on the Boltzmann sedimentation profile because of the electrostatic interactions appear to be essential for the interpretation of experimental results.

Cytosolic glucocorticoid receptor in the testis of Bufo arenarum: seasonal changes in its binding parameters.

PubMed

Denari, Daniela; Ceballos, Nora R

2006-07-01

Glucocorticoids (GC) are the hormonal mediators of stress. In mammals, high levels of GC have negative effects on reproductive physiology. For instance, GC can inhibit testicular testosterone synthesis by acting via glucocorticoid receptors (GR), the extent of the inhibition being dependent on GC levels. However, the effect of GC on testicular function and even the presence of GR in amphibians are still unclear. The purpose of this work was to characterise testicular cytosolic GR in Bufo arenarum, determining the seasonal changes in its binding parameters as well as the intratesticular localisation. The binding assays were performed in testis cytosol with [3H]dexamethasone (DEX) and [3H]corticosterone (CORT). Binding kinetics of DEX and CORT fitted to a one-site model. Results were expressed as means +/- standard error. Apparent number of binding sites (Bapp) was similar for both steroids (Bapp DEX = 352.53 +/- 72.08 fmol/mg protein; Bapp CORT = 454.24 +/- 134.97 fmol/mg protein) suggesting that both hormones bind to the same site. Competition studies with different steroids showed that the order of displacement of [3H]DEX and [3H]CORT specific binding is: DEX approximately RU486 approximately deoxycorticosterone (DOC) > CORT > aldosterone > RU28362 > progesterone > 11-dehydroCORT. The affinity of GR for DEX (Kd = 11.2 +/- 1.5 nM) remained constant throughout the year while circulating CORT clearly increased during the reproductive season. Therefore, testis sensitivity to GC action would depend mainly on inactivating mechanisms (11beta-hydroxysteroid dehydrogenase type 2) and CORT plasma levels. Since total and free CORT are higher in the reproductive than in the non-reproductive period, the magnitude of GC actions could be higher during the breeding season. The intratesticular localisation of the GR was determined after separation of cells by a Percoll density gradient followed by binding assays in each fraction. DEX binds to two different fractions corresponding to Leydig and Sertoli cells. In conclusion, in the testis of B. arenarum GC could regulate the function of both cellular types particularly during breeding when CORT reaches the highest plasma concentration.

Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

PubMed

Guzeloglu Kayisli, Ozlem; Kayisli, Umit A; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J

2015-01-01

Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription. The resultant PR and/or GR-mediated functional withdrawal may contribute to associated endometrial inflammation, aberrant angiogenesis, and bleeding.

A family of metric gravities

NASA Astrophysics Data System (ADS)

Shuler, Robert

2018-04-01

The goal of this paper is to take a completely fresh approach to metric gravity, in which the metric principle is strictly adhered to but its properties in local space-time are derived from conservation principles, not inferred from a global field equation. The global field strength variation then gains some flexibility, but only in the regime of very strong fields (2nd-order terms) whose measurement is now being contemplated. So doing provides a family of similar gravities, differing only in strong fields, which could be developed into meaningful verification targets for strong fields after the manner in which far-field variations were used in the 20th century. General Relativity (GR) is shown to be a member of the family and this is demonstrated by deriving the Schwarzschild metric exactly from a suitable field strength assumption. The method of doing so is interesting in itself because it involves only one differential equation rather than the usual four. Exact static symmetric field solutions are also given for one pedagogical alternative based on potential, and one theoretical alternative based on inertia, and the prospects of experimentally differentiating these are analyzed. Whether the method overturns the conventional wisdom that GR is the only metric theory of gravity and that alternatives must introduce additional interactions and fields is somewhat semantical, depending on whether one views the field strength assumption as a field and whether the assumption that produces GR is considered unique in some way. It is of course possible to have other fields, and the local space-time principle can be applied to field gravities which usually are weak-field approximations having only time dilation, giving them the spatial factor and promoting them to full metric theories. Though usually pedagogical, some of them are interesting from a quantum gravity perspective. Cases are noted where mass measurement errors, or distributions of dark matter, can cause one theory to mimic another implying that such estimates or distributions should be first obtained from weakfield measurements before being used to discriminate verification candidates. By this method theorists gain insight into the local constraints on space-time, and GR verification gains strong-field comparative objectives.

Purification and properties of glutathione reductase from liver of the anoxia-tolerant turtle, Trachemys scripta elegans.

PubMed

Willmore, William G; Storey, Kenneth B

2007-03-01

Glutathione reductase (GR) is a homodimeric flavoprotein that catalyzes the reduction of oxidized glutathione (GSSG) using NADPH as a cofactor. The enzyme is a major component of cellular defense mechanisms against oxidative injury. In this study, GR was purified from the liver of the anoxia-tolerant turtle, Trachemys scripta elegans. The overall fold purifications were 13.3- and 12.1-fold with final specific activities of 5.5 and 1.44 U/mg of protein for control and anoxic turtle GR, respectively. SDS-PAGE of purified turtle liver GR showed a single protein band at approximately 55 kDa. Reverse phase HPLC of turtle GR revealed a single peak that had the same retention time as yeast GR. No new isoform of GR was detected in liver of T. s. elegans during anoxia. The K (m) values of turtle GR for GSSG and NADPH was 44.6 and 6.82 microM, respectively, suggesting a substantially higher affinity of turtle GR toward GSSG than most other vertebrates. Unlike other human GR, NADP(+ )did not inhibit turtle GR activity. The activation energy of turtle GR, calculated from the slope of the Arrhenius plot, was 32.2 +/- 2.64 kJ/mol. Turtle GR had high activity under a broad pH range (having activity between pHs 4 and 10; optimal activity at pH 6.5) and the enzyme maintains activity under the pH drop that occurs under anoxic conditions. The high affinity of turtle GR suggests that turtles have high redox buffering capacity of tissues to protect against oxidative stress encountered during anoxia/reoxygenation.

Intracellular Serine Protease Inhibitor SERPINB4 Inhibits Granzyme M-Induced Cell Death

PubMed Central

de Koning, Pieter J. A.; Kummer, J. Alain; de Poot, Stefanie A. H.; Quadir, Razi; Broekhuizen, Roel; McGettrick, Anne F.; Higgins, Wayne J.; Devreese, Bart; Worrall, D. Margaret; Bovenschen, Niels

2011-01-01

Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular expression of SERPINB9 by tumor cells renders them resistant to GrB-induced apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors are known for the other four human granzymes. In the present study, we show that SERPINB4 formed a typical serpin-protease SDS-stable complex with both recombinant and native human GrM. Mutation of the P2-P1-P1′ triplet in the SERPINB4 reactive center loop completely abolished complex formation with GrM and N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4 inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent second order rate constant of 1.3×104 M−1s−1. SERPINB4 abolished cleavage of the macromolecular GrM substrates α-tubulin and nucleophosmin. Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as well as NK cell-mediated cell death and this inhibition depended on the reactive center loop of the serpin. As SERPINB4 is highly expressed by squamous cell carcinomas, our results may represent a novel mechanism by which these tumor cells evade cytotoxic lymphocyte-induced GrM-mediated cell death. PMID:21857942

Engineering the unique 2D mat of graphene to achieve graphene-TiO2 nanocomposite for photocatalytic selective transformation: what advantage does graphene have over its forebear carbon nanotube?

PubMed

Zhang, Yanhui; Tang, Zi-Rong; Fu, Xianzhi; Xu, Yi-Jun

2011-09-27

Increasing interest has been devoted to synthesizing graphene (GR)-semiconductor nanocomposites as photocatalysts for potential applications, which is very similar to its forebear carbon nanotube (CNT)-semiconductor photocatalysts. Unfortunately, a thoughtful and inevitable comparison between GR- and CNT-semiconductors as photocatalysts is often neglected in literature. This situation may give incomplete or exaggerated information on the contribution role of GR to enhance the semiconductor photocatalytic activity, as compared to CNT. Thus, our knowledge regarding the specific advantage of GR over CNT on how to design more efficient GR-semiconductor nanocomposites and understanding the origin of their enhanced photocatalytic performance is far from satisfactory. By taking the TiO(2) semiconductor as an example, we conceptually demonstrate how to synthesize a more efficient GR-TiO(2) nanocomposite as a visible light photocatalyst toward selective oxidation of alcohols under mild conditions. Comparison between GR-TiO(2) and CNT-TiO(2) discloses the prominent advantage of GR over CNT on both controlling the morphology of GR-TiO(2) nanocomposite and enhancing the photocatalytic activity of TiO(2). This work clearly highlights the importance and necessity for a comparison investigation between GR- and CNT-semiconductors as photocatalysts, which will promote our in-depth fundamental understanding on the analogy and difference between GR and CNT on controlling the morphology of GR (or CNT)-semiconductor nanocomposites and enhancing the photocatalytic performance. Therefore, we appeal the photocatalysis community to pay attention to this respect rather than separately imposing hype on the miracle of GR in much the same way as its carbon forebears, which could significantly advance our rational fabrication of smart GR-semiconductor nanocomposites for artificial photosynthesis. © 2011 American Chemical Society

Cleaning Up.

ERIC Educational Resources Information Center

Musgrave, Chuck; Spencer-Workman, Sarah

2000-01-01

Provides a nine-step process in designing athletic facility laundry rooms that are attractive and functional. Steps include determining the level of laundry services needed, ensuring adequate storage and compatible delivery systems, selecting laundry equipment, and choosing suitable flooring. (GR)

Molecular dissection of the response of the rice Systemic Acquired Resistance Deficient 1 (SARD1) gene to different types of ionizing radiation.

PubMed

Jung, In Jung; Hwang, Jung Eun; Han, Sung Min; Kim, Dong Sub; Ahn, Joon-Woo; Choi, Hong-Il; Kwon, Soon-Jae; Kang, Si-Yong; Kim, Jin-Baek

2017-07-01

Exposure to ionizing radiation induces plant defenses by regulating the expression of response genes. The systemic acquired resistance deficient 1 (SARD1) is a key gene in plant defense response. In this study, the function of Oryza sativa SARD1 (OsSARD1) was investigated after exposure of seeds/plants to ionizing radiation, jasmonic acid (JA) or salicylic acid (SA). Rice seeds exposed to two types of ionizing radiations (gamma ray [GR] and ion beam [IB]) were analyzed by quantitative reverse transcription PCR (qRT-PCR) to identify the genes that are altered in response to ionizing radiation. Then, OsSARD1-overexpressing homozygous Arabidopsis plants were generated to assess the effects of OsSARD1 in the response to irradiation. The phenotypes of these transgenic plants, as well as control plants, were monitored after GR irradiation at doses of 200 and 300 Gray (Gy). The OsSARD1 transcript was strongly downregulated after exposure to GR and IB irradiation. Previous phylogenetic analysis showed that the Arabidopsis SARD1 (AtSARD1) protein is closely related to Arabidopsis calmodulin-binding protein 60g (AtCBP60g), which is known to be required for activation of SA biosynthesis. In this study, phylogenetic analysis showed that OsSARD1 was grouped with AtSARD1. The OsSARD1 gene was induced after exposure to SA and JA. The biological phenotype of OsSARD1-overexpressing Arabidopsis plants was examined. OsSARD1-overexpressing plants displayed resistance to GR; in comparison with wild-type plants, the height and weight of OsSARD1-overexpressing plants were significantly greater after GR irradiation. In addition, OsSARD1 protein was abundantly accumulated in the nucleus. The results indicate that OsSARD1 plays an important role in the regulation of the defense responses to GR and IB irradiation and exhibits phytohormone induced expression.

Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway.

PubMed

Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

2015-11-01

Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+) CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-) cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in TLR2(-/-) mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1(+) CD11b(+) MDSCs. © 2015 John Wiley & Sons Ltd.

Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders

PubMed Central

Tyrka, A R; Parade, S H; Welch, E S; Ridout, K K; Price, L H; Marsit, C; Philip, N S; Carpenter, L L

2016-01-01

Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic–pituitary–adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene. PMID:27378548

Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders.

PubMed

Tyrka, A R; Parade, S H; Welch, E S; Ridout, K K; Price, L H; Marsit, C; Philip, N S; Carpenter, L L

2016-07-05

Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic-pituitary-adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene.

Complete Genome Sequence of the Alfalfa Symbiont Sinorhizobium/Ensifer meliloti Strain GR4

PubMed Central

Martínez-Abarca, Francisco; Martínez-Rodríguez, Laura; López-Contreras, José Antonio; Jiménez-Zurdo, José Ignacio

2013-01-01

We present the complete nucleotide sequence of the multipartite genome of Sinorhizobium/Ensifer meliloti GR4, a predominant rhizobial strain in an agricultural field site. The genome (total size, 7.14 Mb) consists of five replicons: one chromosome, two expected symbiotic megaplasmids (pRmeGR4c and pRmeGR4d), and two accessory plasmids (pRmeGR4a and pRmeGR4b). PMID:23409262

Investigation of thermal energy transport interface of hybrid graphene-carbon nanotube/polyethylene nanocomposites.

PubMed

Liu, Feng; Liu, Xuyang; Hu, Ning; Ning, Huiming; Atobe, Satoshi; Yan, Cheng; Mo, Fuhao; Fu, Shaoyun; Zhang, Jianyu; Wang, Yu; Mu, Xiaojing

2017-10-31

It is well known the thermal properties of three-dimensional (3-D) hybrid graphene (GR)-carbon nanotube (CNT) structures are not superior to that of the individual GR and CNT, however, the 3-D hybrid GR-CNT structures can effectively improve the thermal properties of polymer matrix. Therefore, understanding the thermal energy transport in the interface between polymer matrix and 3-D hybrid GR-CNT structure is essential. Here, the enhancement mechanism of interfacial thermal transport of hybrid GR-CNT structure was explored by applying non-equilibrium molecular dynamics (NEMD) simulations. Three different types of hybrid GR-CNT structures were built. The influences of CNT radius and CNT type for the hybrid GR-CNT on the interfacial thermal properties were also analyzed. Computational results show that among the three different types of hybrid GR-CNT structures, the Model-I, i.e., the covalent bond hybrid GR-CNT structures are of the best interfacial thermal properties. Meanwhile, the CNT radius of hybrid GR-CNT structure has a great influence on the interfacial thermal properties.

Electromagnetic Wave Absorption Property of Graphene with FeO4 Nanoparticles.

PubMed

Yang, Cheng; Dai, Shenglong; Zhang, Xiaoyan; Zhao, Tianyu; Yan, Shaojiu; Zhao, Xiuying

2016-02-01

Nanomaterials consisting of various ratios of Fe3O4 and graphene (defined C-Fe3O4/GR) were pre- pared by an in situ coordination complex hydro-thermal synthesis method. The structure and morphology of the nanomaterials C-Fe3O4/GR obtained were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). It was found that the Fe3O4 nanoparticles distributed on the surfaces of graphene, and had a spinel structure and a uniform chemical phase when the weight ratios of Fe3O4 to graphene oxide (GO) were 9:1 or 9:2. It was suggested that GO had been successfully reduced to graphene and the Fe3O4 nanoparticles were chemically bonded to graphene. The SQUID vibrating sample magnetometer (SQUID-VSM) indicated that the maximum of the saturation magnetization was 83.6 emmicro g(-1) when the mass ratio of Fe3O4 to GO was 9:2. Electromagnetic wave absorption showed that the chemical compound of Fe3O4 and graphene had a better electromagnetic property than the mechanical blend of Fe3O4 and graphene (M-Fe3O4/GR). The C-Fe3O4/GR had a reflection loss larger than -10 dB in the frequency range 12.9-17.0 GHz for an absorber thickness of 3 mm, and a maximum reflection loss of -12.3 dB at 14.8 GHz and a maximum reflection loss of -31.2 dB at 10.5 GHz for an absorber thickness of 10 mm. Theoretical analysis showed that the electromagnetic wave absorption behavior obeyed the quarter-wave principles. These results showed that the C-Fe3O4/GR nanomaterials can meet the requirements for some engineering applications, showing great application potential in electromagnetic wave absorption.

High residue cover crops alone or with strategic tillage to manage glyphosate-resistant palmer amaranth (amaranthus palmeri) in Southeastern cotton (gossypium hirsutum)

USDA-ARS?s Scientific Manuscript database

Glyphosate-resistant (GR) Palmer amaranth (Amaranthus palmeri S. Wats) is redefining row crop weed management in the Southeast due to its widespread distribution, high competitive ability, copious seed production, and resilience to standard weed management programs. Herbicides alone are failing to p...

Glyphosate Effects on Plant Mineral Nutrition, Crop Rhizosphere Microbiota, and Plant Disease in Glyphosate-Resistant Crops

PubMed Central

2012-01-01

Claims have been made recently that glyphosate-resistant (GR) crops sometimes have mineral deficiencies and increased plant disease. This review evaluates the literature that is germane to these claims. Our conclusions are: (1) although there is conflicting literature on the effects of glyphosate on mineral nutrition on GR crops, most of the literature indicates that mineral nutrition in GR crops is not affected by either the GR trait or by application of glyphosate; (2) most of the available data support the view that neither the GR transgenes nor glyphosate use in GR crops increases crop disease; and (3) yield data on GR crops do not support the hypotheses that there are substantive mineral nutrition or disease problems that are specific to GR crops. PMID:23013354

A physically-based Mie–Gruneisen equation of state to determine hot spot temperature distributions

DOE PAGES

Kittell, David Erik; Yarrington, Cole Davis

2016-07-14

Here, a physically-based form of the Mie–Grüneisen equation of state (EOS) is derived for calculating 1d planar shock temperatures, as well as hot spot temperature distributions from heterogeneous impact simulations. This form utilises a multi-term Einstein oscillator model for specific heat, and is completely algebraic in terms of temperature, volume, an integrating factor, and the cold curve energy. Moreover, any empirical relation for the reference pressure and energy may be substituted into the equations via the use of a generalised reference function. The complete EOS is then applied to calculations of the Hugoniot temperature and simulation of hydrodynamic pore collapsemore » using data for the secondary explosive, hexanitrostilbene (HNS). From these results, it is shown that the choice of EOS is even more significant for determining hot spot temperature distributions than planar shock states. The complete EOS is also compared to an alternative derivation assuming that specific heat is a function of temperature alone, i.e. cv(T). Temperature discrepancies on the order of 100–600 K were observed corresponding to the shock pressures required to initiate HNS (near 10 GPa). Overall, the results of this work will improve confidence in temperature predictions. By adopting this EOS, future work may be able to assign physical meaning to other thermally sensitive constitutive model parameters necessary to predict the shock initiation and detonation of heterogeneous explosives.« less

Proton beam radiosurgery for vestibular schwannoma: tumor control and cranial nerve toxicity.

PubMed

Weber, Damien C; Chan, Annie W; Bussiere, Marc R; Harsh, Griffith R; Ancukiewicz, Marek; Barker, Fred G; Thornton, Allan T; Martuza, Robert L; Nadol, Joseph B; Chapman, Paul H; Loeffler, Jay S

2003-09-01

We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery. Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5-35 mm), and the median tumor volume was 1.4 cm(3) (range, 0.1-15.9 cm(3)). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were normal in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10-18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period was 38.7 months (range, 12-102.6 mo). The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9-99.9%) and 93.6% (95% CI, 88.3-99.3%). Salvage radiosurgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95% CI, 81.2-98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation rates were 91.1% (95% CI, 85-97.6%) and 89.4% (95% CI, 82-96.7%). Univariate analysis revealed that prescribed dose (P = 0.005), maximum dose (P = 0.006), and the inhomogeneity coefficient (P = 0.03) were associated with a significant risk of long-term facial neuropathy. No other cranial nerve deficits or cancer relapses were observed. Proton beam stereotactic radiosurgery has been shown to be an effective means of tumor control. A high radiological response rate was observed. Excellent facial and trigeminal nerve function preservation rates were achieved. A reduced prescribed dose is associated with a significant decrease in facial neuropathy.

Simulation of heavy precipitation episode over eastern Peninsular Malaysia using MM5: sensitivity to cumulus parameterization schemes

NASA Astrophysics Data System (ADS)

Salimun, Ester; Tangang, Fredolin; Juneng, Liew

2010-06-01

A comparative study has been conducted to investigate the skill of four convection parameterization schemes, namely the Anthes-Kuo (AK), the Betts-Miller (BM), the Kain-Fritsch (KF), and the Grell (GR) schemes in the numerical simulation of an extreme precipitation episode over eastern Peninsular Malaysia using the Pennsylvania State University—National Center for Atmospheric Research Center (PSU-NCAR) Fifth Generation Mesoscale Model (MM5). The event is a commonly occurring westward propagating tropical depression weather system during a boreal winter resulting from an interaction between a cold surge and the quasi-stationary Borneo vortex. The model setup and other physical parameterizations are identical in all experiments and hence any difference in the simulation performance could be associated with the cumulus parameterization scheme used. From the predicted rainfall and structure of the storm, it is clear that the BM scheme has an edge over the other schemes. The rainfall intensity and spatial distribution were reasonably well simulated compared to observations. The BM scheme was also better in resolving the horizontal and vertical structures of the storm. Most of the rainfall simulated by the BM simulation was of the convective type. The failure of other schemes (AK, GR and KF) in simulating the event may be attributed to the trigger function, closure assumption, and precipitation scheme. On the other hand, the appropriateness of the BM scheme for this episode may not be generalized for other episodes or convective environments.

Ray-tracing in pseudo-complex General Relativity

NASA Astrophysics Data System (ADS)

Schönenbach, T.; Caspar, G.; Hess, P. O.; Boller, T.; Müller, A.; Schäfer, M.; Greiner, W.

2014-07-01

Motivated by possible observations of the black hole candidate in the centre of our Galaxy and the galaxy M87, ray-tracing methods are applied to both standard General Relativity (GR) and a recently proposed extension, the pseudo-complex GR (pc-GR). The correction terms due to the investigated pc-GR model lead to slower orbital motions close to massive objects. Also the concept of an innermost stable circular orbit is modified for the pc-GR model, allowing particles to get closer to the central object for most values of the spin parameter a than in GR. Thus, the accretion disc, surrounding a massive object, is brighter in pc-GR than in GR. Iron Kα emission-line profiles are also calculated as those are good observables for regions of strong gravity. Differences between the two theories are pointed out.

Autoregulation of human relaxin-2 gene expression critically involves relaxin and glucocorticoid receptor binding to glucocorticoid response half-sites in the relaxin-2 promoter.

PubMed

Dschietzig, Thomas; Bartsch, Cornelia; Wessler, Silja; Baumann, Gert; Stangl, Karl

2009-06-05

Relaxin peptides act in brain, reproductive and cardiovascular systems, kidneys, and connective tissue through different G protein-coupled receptors. We reported that human relaxin-2 and porcine relaxin are both agonists at the human glucocorticoid receptor (GR). Here, we investigated the possible auto-regulation of relaxin-2 gene expression via recently discovered GR-binding sites in the relaxin-2 promoter. We found that porcine relaxin increased the secretion of human relaxin-like immunoreactivity in HeLa and THP-1 cells. Silencing of GR gene expression completely abolished this effect whereas transfection of wild-type GR into naturally GR-devoid HT-29 cells established relaxin sensitivity. Relaxin was shown to stimulate CAT expression driven by different deletion constructs of the 5'-flanking region of the relaxin-2 promoter. In chromatin immunoprecipitation assays, we detected both GR and relaxin binding to the relaxin-2 promoter. Gel shift assays indicated binding of relaxin-activated GR to half-GREs located between 160 and 200 bp upstream of transcription start but not to the GRE at -900 bp. Relaxin bound to human GR and displaced established GR agonists. Immunofluorescence experiments visualized nuclear co-localization of relaxin and GR in response to relaxin. In conclusion, we have identified a positive auto-regulatory loop of human relaxin-2 expression which involves GR and relaxin/GR binding to half-GREs in the relaxin-2 promoter.

Improving the photocatalytic performance of graphene-TiO2 nanocomposites via a combined strategy of decreasing defects of graphene and increasing interfacial contact.

PubMed

Zhang, Yanhui; Zhang, Nan; Tang, Zi-Rong; Xu, Yi-Jun

2012-07-07

Incessant interest has been shown in the synthesis of graphene (GR)-semiconductor nanocomposites as photocatalysts aiming to utilize the excellent electron conductivity of GR to lengthen the lifetime of photoexcited charge carriers in the semiconductor and, hence, improve the photoactivity. However, research works focused on investigating how to make sufficient use of the unique electron conductivity of GR to design a more efficient GR-semiconductor photocatalyst have been quite lacking. Here, we show a proof-of-concept study on improving the photocatalytic performance of GR-TiO(2) nanocomposites via a combined strategy of decreasing defects of GR and improving the interfacial contact between GR and the semiconductor TiO(2). The GR-TiO(2) nanocomposite fabricated by this approach is able to make more sufficient use of the electron conductivity of GR, by which the lifetime and transfer of photoexcited charge carriers of GR-TiO(2) upon visible light irradiation will be improved more efficiently. This in turn leads to the enhancement of visible-light-driven photoactivity of GR-TiO(2) toward selective transformation of alcohols to corresponding aldehydes using molecular oxygen as a benign oxidant under ambient conditions. It is anticipated that our current work would inform ongoing efforts to exploit the rational design of smart, more efficient GR-semiconductor photocatalysts for conversion of solar to chemical energy by heterogeneous photocatalysis.

A New Curriculum: Energy Outsourcing Brings Cost and Efficiency Benefits.

ERIC Educational Resources Information Center

Dickerman, Robert N.

2002-01-01

Considers the value of colleges and universities upgrading their energy infrastructure and using outsourcing energy management functions to save money and gain greater control of energy operations without substantial investments in staff and resources. (GR)

Team Needs.

ERIC Educational Resources Information Center

Cohen, Andrew

1998-01-01

Explores locker-room design concepts that can be used to accommodate multipurpose athletic facilities and make the locker room more efficient and user friendly. Spaces are described that can be added to the typical locker room that will complement expanding facility functions. (GR)

Preventing Chaos.

ERIC Educational Resources Information Center

Pineda, Ernest M.

1999-01-01

Discusses ways to help resolve the Y2K problem and avoid disruptions in school security and safety. Discusses computer software testing and validation to determine its functionality after year's end, and explores system remediation of non-compliant fire and security systems. (GR)

The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo

PubMed Central

Riggs, Daniel L.; Roberts, Patricia J.; Chirillo, Samantha C.; Cheung-Flynn, Joyce; Prapapanich, Viravan; Ratajczak, Thomas; Gaber, Richard; Picard, Didier; Smith, David F.

2003-01-01

Hsp90 is required for the normal activity of steroid receptors, and in steroid receptor complexes it is typically bound to one of the immunophilin-related co-chaperones: the peptidylprolyl isomerases FKBP51, FKBP52 or CyP40, or the protein phosphatase PP5. The physiological roles of the immunophilins in regulating steroid receptor function have not been well defined, and so we examined in vivo the influences of immunophilins on hormone-dependent gene activation in the Saccharomyces cerevisiae model for glucocorticoid receptor (GR) function. FKBP52 selectively potentiates hormone-dependent reporter gene activation by as much as 20-fold at limiting hormone concentrations, and this potentiation is readily blocked by co-expression of the closely related FKBP51. The mechanism for potentiation is an increase in GR hormone-binding affinity that requires both the Hsp90-binding ability and the prolyl isomerase activity of FKBP52. PMID:12606580

Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line.

PubMed

Peeters, B W M M; Ruigt, G S F; Craighead, M; Kitchener, P

2008-12-01

Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist-GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021-012 and RTI3021-022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone-induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 x 10(-7) M) did not induce GR translocation, but was able to block corticosterone (3 x 10(-8) M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.

Xenobiotics and the Glucocorticoid Receptor

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

Gulliver, Linda S M, E-mail: linda.gulliver@otago.

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmunemore » processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid Receptor. • Involvement of Glucocorticoid Receptor in multiple pathologies. • Novel xenobiotic ligands for Glucocorticoid Receptor. • Potential for multifaceted Glucocorticoid Receptor-targeted pharmacological interventions.« less

Low serum albumin may predict the need for gastric resection in patients with perforated peptic ulcer.

PubMed

Seow, J G; Lim, Y R; Shelat, V G

2017-06-01

Perforated peptic ulcer (PPU) is a common surgical emergency and treatment involves omental patch repair (PR). Gastric resection (GR) is reserved for difficult pathologies. We audit the outcomes of GR at our institution and evaluate the pre-operative factors predicting the need for GR. This is a single-institution, retrospective study of patients with PPU who underwent surgery from 2004 to 2012. Demographics, clinical presentation and intra-operative findings were studied to identify factors predicting the need for GR in PPU. An audit of clinical outcomes and mortality for all patients with GR is reported. 537 (89.6 %) patients underwent PR and 62 (10.4 %) patients GR. Old age (p < 0.0001), female sex (p = 0.0123), non-steroidal anti-inflammatory drugs (NSAIDs) usage (p = 0.0008), previous history of peptic ulcer disease (PUD) (p = 0.0159), low hemoglobin (p < 0.0001), low serum albumin (p < 0.0001), high serum creatinine (p = 0.0030), high urea (p = 0.0006) and large ulcer size (p < 0.0001) predict the need for GR. On multivariate analysis only low serum albumin (OR 5.57, 95 % CI 1.56-19.84, p = 0.008) predicted the need for GR. The presence of Helicobacter pylori infection was protective against GR (OR 0.25, 95 %CI 0.14-0.44, p < 0.0001). Morbidity and mortality of GR was 27.7 and 24.2 %, respectively. GR is needed in one in ten cases of PPU. Low serum albumin predicted the need for GR on multivariate analysis. Morbidity and mortality of GR remains high.

Comparison of Notch Strength between Gr/PEEK (APC-1 and APC-2) and Gr/Epoxy Composite Materials at Elevated Temperature.

DTIC Science & Technology

1985-12-01

J ub. we Jr. Captain, USARt Z712 AFIT/GAE/AA/85D- 12 Iv COMPARISON OF NOTCH STRENGTH BETWEEN GR/PEEK (APC-1 AND APC-2) AND GR/EPOXY COMPOSITE ...85D-12 COMPARISON OF NOTCH STRENGTH BETWEEN GR/PEEK _ (APC-1 AND APC-2) AND GR/EPOXY COMPOSITE MATERIAL AT ELEVATED TEMPERATURE THESIS Presented to the...unlimited Preface In this experimental investigation, the reduction of strength for notched composite laminates of Aromatic Polymer Composite , APC-2

Cobalt nanoparticles/nitrogen-doped graphene with high nitrogen doping efficiency as noble metal-free electrocatalysts for oxygen reduction reaction.

PubMed

Liang, Jingwen; Hassan, Mehboob; Zhu, Dongsheng; Guo, Liping; Bo, Xiangjie

2017-03-15

Nitrogen-doped graphene (N/GR) has been considered as active metal-free electrocatalysts for oxygen reduction reaction (ORR). However, the nitrogen (N) doping efficiency is very low and only few N atoms are doped into the framework of GR. To boost the N doping efficiency, in this work, a confined pyrolysis method with high N doping efficiency is used for the preparation of cobalt nanoparticles/nitrogen-doped GR (Co/N/GR). Under the protection of SiO 2 , the inorganic ligand NH 3 in cobalt amine complex ([Co(NH 3 ) 6 ] 3+ ) is trapped in the confined space and then can be effectively doped into the framework of GR without the introduction of any carbon residues. Meanwhile, due to the redox reaction between the cobalt ions and carbon atoms of GR, Co nanoparticles are supported into the framework of N/GR. Due to prevention of GR layer aggregation with SiO 2 , the Co/N/GR with high dispersion provides sufficient surface area and maximum opportunity for the exposure of Co nanoparticles and active sites of N dopant. By combination of enhanced N doping efficiency, Co nanoparticles and high dispersion of GR sheets, the Co/N/GR is remarkably active, cheap and selective noble-metal free catalysts for ORR. Copyright © 2016 Elsevier Inc. All rights reserved.

Selected physico-mechanical characteristics of cryogenic and ambient ground turmeric

NASA Astrophysics Data System (ADS)

Barnwal, Pradyuman; Mohite, Ashish M.; Singh, Krishna K.; Kumar, Pankaj

2014-03-01

In this communication, selected physicomechanical characteristics of ground turmeric (cv. Prabha) were investigated for cryogenic and ambient grinding conditions of turmeric at different moisture contents (4, 6, 8 and 10% w.b.). A cryogenic grinder (Model: 100 UPZ, Hosokawa Alpine, Germany) and a micro pulverizer (hammer mill) were used for cryogenic and ambient grinding, respectively. The ground turmeric was graded in three grades viz. Gr-I, Gr-II and Gr-III with a sieve shaker using BSS Nos. 40, 85 and pan, respectively. Tap densities for cryogenic and ambient ground turmeric decreased from 678.7 (Gr-I) to 546.7 kgm-3 (Gr-III) and from 642.3 (Gr-I) to 468.6 kgm-3 (Gr-III), respectively, with the moisture increase. The angle of repose for cryogenic and ambient ground turmeric increased linearly from 26.85 (Gr-I) to 34.0° (Gr-III) and from 23.10 (Gr-I) to 28.06° (Gr-III), respectively with the increase in moisture content. The static coefficient of friction was the highest on plywood surface followed by mild steel sheet and galvanized iron sheet. The cryoground samples were found better in colour. Thermal conductivity of cryo-ground samples was higher than that of ambient ground samples. These physico-mechanical characteristics of cryogenic and ambient ground turmeric will be helpful for packaging, handling, and storage.

Montmorillonite dissolution kinetics: Experimental and reactive transport modeling interpretation

NASA Astrophysics Data System (ADS)

Cappelli, Chiara; Yokoyama, Shingo; Cama, Jordi; Huertas, F. Javier

2018-04-01

The dissolution kinetics of K-montmorillonite was studied at 25 °C, acidic pH (2-4) and 0.01 M ionic strength by means of well-mixed flow-through experiments. The variations of Si, Al and Mg over time resulted in high releases of Si and Mg and Al deficit, which yielded long periods of incongruent dissolution before reaching stoichiometric steady state. This behavior was caused by simultaneous dissolution of nanoparticles and cation exchange between the interlayer K and released Ca, Mg and Al and H. Since Si was only involved in the dissolution reaction, it was used to calculate steady-state dissolution rates, RSi, over a wide solution saturation state (ΔGr ranged from -5 to -40 kcal mol-1). The effects of pH and the degree of undersaturation (ΔGr) on the K-montmorillonite dissolution rate were determined using RSi. Employing dissolution rates farthest from equilibrium, the catalytic pH effect on the K-montmorillonite dissolution rate was expressed as Rdiss = k·aH0.56±0.05 whereas using all dissolution rates, the ΔGr effect was expressed as a non-linear f(ΔGr) function Rdiss = k · [1 - exp(-3.8 × 10-4 · (|ΔGr|/RT)2.13)] The functionality of this expression is similar to the equations reported for dissolution of Na-montmorillonite at pH 3 and 50 °C (Metz, 2001) and Na-K-Ca-montmorillonite at pH 9 and 80 °C (Cama et al., 2000; Marty et al., 2011), which lends support to the use of a single f(ΔGr) term to calculate the rate over the pH range 0-14. Thus, we propose a rate law that also accounts for the effect of pOH and temperature by using the pOH-rate dependence and the apparent activation energy proposed by Rozalén et al. (2008) and Amram and Ganor (2005), respectively, and normalizing the dissolution rate constant with the edge surface area of the K-montmorillonite. 1D reactive transport simulations of the experimental data were performed using the Crunchflow code (Steefel et al., 2015) to quantitatively interpret the evolution of the released cations and to elucidate the stoichiometry of the reaction. After the implementation of (i) the obtained f(ΔGr) term in the K-montmorillonte dissolution rate law, (ii) a fraction of highly reactive particles and surfaces and (iii) the cation exchange reactions between the interlayer K+ and the released Al3+, Mg2+, Ca2+ and H+, the simulations agreed with the experimental concentrations at the outlet. This match indicates that fast dissolution of fine particles and highly reactive sites and exchange between the interlayer K and dissolved structural cations (Al and Mg) and protons are responsible for the temporary incongruency of the K-montmorillonite dissolution reaction. As long as dissolution of the bulk sample predominates, the reaction is stoichiometric.

Evolution of hormone signaling in elasmobranchs by exploitation of promiscuous receptors.

PubMed

Carroll, Sean Michael; Bridgham, Jamie T; Thornton, Joseph W

2008-12-01

Specific interactions among proteins, nucleic acids, and metabolites drive virtually all cellular functions and underlie phenotypic complexity and diversity. Despite the fundamental importance of interactions, the mechanisms and dynamics by which they evolve are poorly understood. Here we describe novel interactions between a lineage-specific hormone and its receptors in elasmobranchs, a subclass of cartilaginous fishes, and infer how these associations evolved using phylogenetic and protein structural analyses. The hormone 1alpha-hydroxycorticosterone (1alpha-B) is a physiologically important steroid synthesized only in elasmobranchs. We show that 1alpha-B modulates gene expression in vitro by activating two paralogous intracellular transcription factors, the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), in the little skate Leucoraja erinacea; MR serves as a high-sensitivity and GR as a low-sensitivity receptor. Using functional analysis of extant and resurrected ancestral proteins, we show that receptor sensitivity to 1alpha-B evolved millions of years before the hormone itself evolved. The 1alpha-B differs from more ancient corticosteroids only by the addition of a hydroxyl group; the three-dimensional structure of the ancestral receptor shows that the ligand pocket contained ample unoccupied space to accommodate this moiety. Our findings indicate that the interactions between 1alpha-B and elasmobranch GR and MR proteins evolved by molecular exploitation: a novel hormone recruited into new functional partnerships two ancient receptors that had previously interacted with other ligands. The ancestral receptor's promiscuous capacity to fortuitously bind compounds that are slight structural variants of its original ligands set the stage for the evolution of this new interaction.

Imprints of the Molecular Electronic Structure in the Photoelectron Spectra of Strong-Field Ionized Asymmetric Triatomic Model Molecules

NASA Astrophysics Data System (ADS)

Paul, Matthias; Yue, Lun; Gräfe, Stefanie

2018-06-01

We examine the circular dichroism in the angular distribution of photoelectrons of triatomic model systems ionized by strong-field ionization. Following our recent work on this effect [Paul, Yue, and Gräfe, J. Mod. Opt. 64, 1104 (2017), 10.1080/09500340.2017.1299883], we demonstrate how the symmetry and electronic structure of the system is imprinted into the photoelectron momentum distribution. We use classical trajectories to reveal the origin of the threefolded pattern in the photoelectron momentum distribution, and show how an asymmetric nuclear configuration of the triatomic system effects the photoelectron spectra.

Steroid receptor profiling of vinclozolin and its primary metabolites.

PubMed

Molina-Molina, José-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernández, Mariana-Fátima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolás; Balaguer, Patrick

2006-10-01

Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

Cerebellar learning properties are modulated by the CRF receptor in granular cells.

PubMed

Ezra-Nevo, Gili; Prestori, Francesca; Locatelli, Francesca; Soda, Teresa; Ten Brinke, Michiel M; Engel, Mareen; Boele, Henk-Jan; Botta, Laura; Leshkowitz, Dena; Ramot, Assaf; Tsoory, Michael; Biton, Inbal E; Deussing, Jan; D'Angelo, Egidio; De Zeeuw, Chris I; Chen, Alon

2018-06-22

Corticotropin-releasing factor (CRF) and its type 1 receptor (CRFR 1 ) play an important role in the responses to stressful challenges. Despite the well-established expression of CRFR 1 in granular cells (GrCs), its role in procedural motor performance and memory formation remains elusive. To investigate the role of CRFR 1 expression in cerebellar GrCs, we used a mouse model depleted of CRFR 1 in these cells. We detected changes in the cellular learning mechanisms in GrCs depleted of CRFR 1 in that they showed changes in intrinsic excitability and long-term synaptic plasticity. Moreover, male mice depleted of CRFR 1 specifically in GrCs showed accelerated Pavlovian associative eye-blink conditioning, but no differences in baseline motor performance, locomotion or fear and anxiety-related behaviors. Last, we analyzed cerebella transcriptome of KO and control mice and detected prominent alterations in the expression of calcium signaling pathways components. Our findings shed light on the interplay between stress-related central mechanisms and cerebellar motor conditioning, highlighting the role of the CRF system in regulating particular forms of cerebellar learning. SIGNIFICANCE STATEMENT Although it is known that CRFR 1 is highly expressed in the cerebellum, little attention has been given to its role in cerebellar functions in the behaving animal. Moreover, most of the attention was directed to the effect of CRF on Purkinje cells at the cellular level, and to this date, almost no data exist on the role of this stress-related receptor in other cerebellar structures. Here, we explored the behavioral and cellular effect of GrCs specific ablation of CRFR 1 We found a profound effect on learning, both at the cellular and behavioral levels, without affecting baseline motor skills. Copyright © 2018 the authors.

Progesterone and the Repression of Myometrial Inflammation: The Roles of MKP-1 and the AP-1 System

PubMed Central

Lei, K.; Georgiou, E. X.; Chen, L.; Yulia, A.; Sooranna, S. R.; Brosens, J. J.; Bennett, P. R.

2015-01-01

Progesterone (P4) maintains uterine quiescence during pregnancy and its functional withdrawal is associated with increased prostaglandin synthesis and the onset of labor. In primary human myometrial cells, the glucocorticoid receptor (GR) rather than the P4 receptor mediates P4 antagonism of IL-1β-induced cyclooxygenase-2 (COX-2) expression, the rate-limiting enzyme in prostaglandin synthesis. We now report that P4 also acts via GR to induce MAPK phosphatase (MKP)-1 and knockdown of MKP-1 impairs the ability of P4 to repress IL-1β-dependent COX-2 induction. Microarray analysis revealed that P4 repressed preferentially activator protein-1-responsive genes in response to IL-1β. Consistent with these observations, we found that the ability of P4 to reduce c-Jun activation was lost upon GR as well as MKP-1 knockdown. Interestingly, c-Jun levels in human myometrial cells declined upon GR and MKP-1 knockdown, which suggests the presence of an activator protein-1 feedback loop. This is supported by our observation that c-Jun levels declined after an initial rise in primary myometrial cells treated with phorbol 12-myrisatate 13-acetate, a potent activator of c-Jun N-terminal kinase. Finally, we show that MKP-1 is an intermediate in P4-mediated repression of some but not all IL-1β-responsive genes. For example, P4 repression of IL11 and IRAK3 was maintained upon MKP-1 knockdown. Taken together, the data show that P4 acts via GR to drive MKP-1 expression, which in turn inhibits IL-1β-dependent c-Jun activation and COX-2 expression. PMID:26280733

Circular RNA Signature Predicts Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma.

PubMed

Shao, Feng; Huang, Mei; Meng, Futao; Huang, Qiang

2018-01-01

Gemcitabine resistance is currently the main problem of chemotherapy for advanced pancreatic cancer patients. The resistance is thought to be caused by altered drug metabolism or reduced apoptosis of cancer cells. However, the underlying mechanism of Gemcitabine resistance in pancreatic cancer remains unclear. In this study, we established Gemcitabine resistant PANC-1 (PANC-1-GR) cell lines and compared the circular RNAs (circRNAs) profiles between PANC-1 cells and PANC-1-GR cells by RNA sequencing. Differentially expressed circRNAs were demonstrated using scatter plot and cluster heatmap analysis. Gene ontology and pathway analysis were performed to systemically map the genes which are functionally associated to those differentially expressed circRNAs identified from our data. The expression of the differentially expressed circRNAs picked up by RNAseq in PANC-1-GR cells was further validated by qRT-PCR and two circRNAs were eventually identified as the most distinct targets. Consistently, by analyzing plasma samples form pancreatic ductal adenocarcinoma (PDAC) patients, the two circRNAs showed more significant expression in the Gemcitabine non-responsive patients than the responsive ones. In addition, we found that silencing of the two circRNAs could restore the sensitivity of PANC-1-GR cells to Gemcitabine treatment, while over-expression of them could increase the resistance of normal PANC-1 and MIA PACA-2 cells, suggesting that they might serve as drug targets for Gemcitabine resistance. Furthermore, the miRNA interaction networks were also explored based on the correlation analysis of the target microRNAs of these two circRNAs. In conclusion, we successfully established new PANC-1-GR cells, systemically characterized the circRNA and miRNA profiles, and identified two circRNAs as novel biomarkers and potential therapeutic targets for Gemcitabine non-responsive PDAC patients.

Comparative performances of a bare graphite-polyurethane composite electrode unmodified and modified with graphene and carbon nanotubes in the electrochemical determination of escitalopram.

PubMed

Baccarin, Marina; Cervini, Priscila; Cavalheiro, Eder Tadeu Gomes

2018-02-01

A bare composite graphite-polyurethane electrode (EGPU) and two other modified with graphene (EGPU-GR) and functionalized multi-walled carbon nanotubes (EGPU-CNTs) were prepared and compared regarding their voltammetric response to escitalopran (EST). The modifiers were characterized by Raman spectroscopy and the resulting electrode materials by contact angle measurements with a hydrophilicity character in the ascending order for the composites: GPU > GPU-GR > GPU-CNTs and scanning electron microscopy (SEM). The electroactive areas of the EGPU, EGPU-GR, and EGPU-CNTs were 0.065, 0.080, and 0.092cm 2 , respectively, calculated from the chronocoulometry using K 3 [Fe(CN) 6 ] as a probe and the Cottrell equation. The cyclic voltammograms obtained for EST indicated irreversible electrochemical behavior, with an anodic peak at ca. +0.80V (νs. SCE). These measurements were carried out with the three electrodes, and comparison of the analytical responses led to the EGPU-GR electrode being selected for use in the subsequent experiments. Under optimal conditions, square wave and differential pulse voltammetry at EGPU-GR presented linear dynamic ranges between 1.5 × 10 -6 and 1.2 × 10 -5 mol L -1 , with a detection limit of 2.5 × 10 -7 molL -1 (SWV) and 1.5 × 10 -6 and 1.2 × 10 -5 molL -1 , with a detection limit of 3.2 × 10 -7 molL -1 (DPV) for EST. The proposed method was applied for the quantification of EST in synthetic urine and cerebrospinal fluid samples, offering advantages including simplicity of fabrication, no requirement for analyte preconcentration and surface renewal, fast response, and selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Corticosteroid receptor gene expression is related to sex and social behaviour in a social fish.

PubMed

O'Connor, Constance M; Rodela, Tammy M; Mileva, Viktoria R; Balshine, Sigal; Gilmour, Kathleen M

2013-03-01

Circulating corticosteroids have been related to social status in a variety of species. However, our understanding of corticosteroid receptor expression and its relationship with sociality is still in its infancy. Knowledge of variation in receptor expression is critical to understand the physiological relevance of differences in circulating corticosteroid concentrations. In this study, we examined corticosteroid receptor gene expression in relation to dominance rank, sex, and social behaviour in the highly social cichlid fish, Neolamprologus pulcher. We examined the relative gene expression of the three known teleost corticosteroid receptors: glucocorticoid receptor 1 (GR1), glucocorticoid receptor 2 (GR2), and the mineralocorticoid receptor (MR) in liver and brain tissue of dominant and subordinate N. pulcher males and females. Phylogenetic analysis revealed the N. pulcher gene originally described as GR2, clustered with other teleost GR1 genes, while the originally-described N. pulcher GR1 gene clustered with the GR2 genes of other teleosts. Therefore we propose a change in the original nomenclature of the N. pulcher GRs: GR1 (formerly GR2) and GR2 (formerly GR1) and adopt this new nomenclature throughout this manuscript. Liver MR transcript levels were higher in males than females, and positively related to submissive behaviour. Liver GR2 (formerly GR1) transcript levels were also higher in males than females. Collectively, the results demonstrate sex differences in corticosteroid receptor abundance, and suggest tissue- and receptor-specific roles for corticosteroid receptors in mediating aspects of social behaviour. Copyright © 2012. Published by Elsevier Inc.

Pseudo and true visible light photocatalytic activity of nanotube titanic acid/graphene composites

NASA Astrophysics Data System (ADS)

Wang, Xiaodong; Liu, Xiaogang; Xue, Xiaoxiao; Pan, Hui; Zhang, Min; Li, Qiuye; Yu, Laigui; Yang, Jianjun; Zhang, Zhijun

2013-09-01

Nanotube titanic acid/graphene (NTA/Gr) composites were prepared by an easy hydrothermal treatment of graphene oxide (GO) and NTA in a mixed solvent of ethanol-water. As-prepared NTA/Gr composites and GO were characterized by means of Fourier transform infrared spectrometry, X-ray diffraction, diffuse-reflection spectrometry, thermal analysis, and transmission electron microscopy. Besides, the photocatalytic activities of as-prepared NTA/Gr composites were evaluated by monitoring the degradation of methyl orange (MO) under visible light irradiation. It has been found that extending hydrothermal reaction time (24 h instead of 3 h) leads to great changes in the morphology and crystal structure of as-prepared composites. Namely, the orthorhombic NTA (ca. 10 nm in diameter) in the composite transformed to anatase TiO2 particle (ca. 20-30 nm in diameter) while the Gr sheets (with micrometers-long wrinkles) in it transformed to a few Gr fragments (ca. 50 nm in diameter). Correspondingly, the NTA/Gr composite transformed to titanium dioxide/graphene (TiO2/Gr) composite. In the meantime, pure GO only has adsorption effect but it has no photocatalytic activity in the visible light region. Nevertheless, increasing Gr ratio results in enhanced visible light absorption capability and photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites. This demonstrates that the true visible light photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites for the degradation of MO is not as excellent as expected, and their high apparent activity is attributed to the strong adsorption of MO on the composites.

Meat quality, proximate composition and muscle fatty acid profile of young llamas (Lama glama) supplemented with hay or concentrate during the dry season.

PubMed

Mamani-Linares, L W; Gallo, C B

2014-01-01

Thirty llamas were used to study the effect of a 90 day feed supplementation on meat quality, chemical composition and muscle fatty acid profile. Treatments were: GR=llama on native pasture until slaughter; GR+SH=like GR, but with overnight free access to barley/alfalfa hay; and GR+SC=like GR, but with overnight free access to a wheat bran/sorghum grain concentrate. The supplementation had no effect on postmortem pH and temperature decline in the Longissimus lumborum muscle (LLM), cooking losses nor Warner-Bratzler shear force values (P>0.05). Meat from GR+SC llama had higher fat content in LLM (P<0.05) compared to GR and GR+SH llama. Intramuscular fat from GR+SH llama showed higher (P<0.01) proportions of polyunsaturated fatty acids, higher (P<0.05) polyunsaturated fatty acids/saturated fatty acids and desirable fatty acids ratio, lower (P<0.05) omega-6/omega-3 (n-6/n-3) ratio, and higher (P<0.01) conjugated linoleic acid. © 2013.

Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

PubMed Central

Zhao, Li-Hua; Zhou, X Edward; Yi, Wei; Wu, Zhongshan; Liu, Yue; Kang, Yanyong; Hou, Li; de Waal, Parker W; Li, Suling; Jiang, Yi; Scaffidi, Adrian; Flematti, Gavin R; Smith, Steven M; Lam, Vinh Q; Griffin, Patrick R; Wang, Yonghong; Li, Jiayang; Melcher, Karsten; Xu, H Eric

2015-01-01

Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the α/β-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCFD3 that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process. PMID:26470846

Numerical simulation and characterization of trapping noise in InGaP-GaAs heterojunctions devices at high injection

NASA Astrophysics Data System (ADS)

Nallatamby, Jean-Christophe; Abdelhadi, Khaled; Jacquet, Jean-Claude; Prigent, Michel; Floriot, Didier; Delage, Sylvain; Obregon, Juan

2013-03-01

Commercially available simulators present considerable advantages in performing accurate DC, AC and transient simulations of semiconductor devices, including many fundamental and parasitic effects which are not generally taken into account in house-made simulators. Nevertheless, while the TCAD simulators of the public domain we have tested give accurate results for the simulation of diffusion noise, none of the tested simulators perform trap-assisted GR noise accurately. In order to overcome the aforementioned problem we propose a robust solution to accurately simulate GR noise due to traps. It is based on numerical processing of the output data of one of the simulators available in the public-domain, namely SENTAURUS (from Synopsys). We have linked together, through a dedicated Data Access Component (DAC), the deterministic output data available from SENTAURUS and a powerful, customizable post-processing tool developed on the mathematical SCILAB software package. Thus, robust simulations of GR noise in semiconductor devices can be performed by using GR Langevin sources associated to the scalar Green functions responses of the device. Our method takes advantage of the accuracy of the deterministic simulations of electronic devices obtained with SENTAURUS. A Comparison between 2-D simulations and measurements of low frequency noise on InGaP-GaAs heterojunctions, at low as well as high injection levels, demonstrates the validity of the proposed simulation tool.

An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs

PubMed Central

Fyfe, John C.; Hemker, Shelby L.; Venta, Patrick J.; Fitzgerald, Caitlin A.; Outerbridge, Catherine A.; Myers, Sherry L.; Giger, Urs

2013-01-01

Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9 Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome. PMID:23746554

Triboelectric charging of volcanic ash from the 2011 Grímsvötn eruption.

PubMed

Houghton, Isobel M P; Aplin, Karen L; Nicoll, Keri A

2013-09-13

The plume from the 2011 eruption of Grímsvötn was highly electrically charged, as shown by the considerable lightning activity measured by the United Kingdom Met Office's low-frequency lightning detection network. Previous measurements of volcanic plumes have shown that ash particles are electrically charged up to hundreds of kilometers away from the vent, which indicates that the ash continues to charge in the plume [R. G. Harrison, K. A. Nicoll, Z. Ulanowski, and T. A. Mather, Environ. Res. Lett. 5, 024004 (2010); H. Hatakeyama J. Meteorol. Soc. Jpn. 27, 372 (1949)]. In this Letter, we study triboelectric charging of different size fractions of a sample of volcanic ash experimentally. Consistently with previous work, we find that the particle size distribution is a determining factor in the charging. Specifically, our laboratory experiments demonstrate that the normalized span of the particle size distribution plays an important role in the magnitude of charging generated. The influence of the normalized span on plume charging suggests that all ash plumes are likely to be charged, with implications for remote sensing and plume lifetime through scavenging effects.

Triboelectric Charging of Volcanic Ash from the 2011 Grímsvötn Eruption

NASA Astrophysics Data System (ADS)

Houghton, Isobel M. P.; Aplin, Karen L.; Nicoll, Keri A.

2013-09-01

The plume from the 2011 eruption of Grímsvötn was highly electrically charged, as shown by the considerable lightning activity measured by the United Kingdom Met Office’s low-frequency lightning detection network. Previous measurements of volcanic plumes have shown that ash particles are electrically charged up to hundreds of kilometers away from the vent, which indicates that the ash continues to charge in the plume [R. G. Harrison, K. A. Nicoll, Z. Ulanowski, and T. A. Mather, Environ. Res. Lett. 5, 024004 (2010)1748-932610.1088/1748-9326/5/2/024004; H. Hatakeyama J. Meteorol. Soc. Jpn. 27, 372 (1949)JMSJAU0026-1165]. In this Letter, we study triboelectric charging of different size fractions of a sample of volcanic ash experimentally. Consistently with previous work, we find that the particle size distribution is a determining factor in the charging. Specifically, our laboratory experiments demonstrate that the normalized span of the particle size distribution plays an important role in the magnitude of charging generated. The influence of the normalized span on plume charging suggests that all ash plumes are likely to be charged, with implications for remote sensing and plume lifetime through scavenging effects.

The Efficacy of a Social Skills Group Intervention for Improving Social Behaviors in Children with High Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

DeRosier, Melissa E.; Swick, Danielle C.; Davis, Naomi Ornstein; McMillen, Janey Sturtz; Matthews, Rebecca

2011-01-01

This study tested the efficacy of a new social skills intervention, "S ocial S kills GR oup IN tervention-High Functioning Autism" ("S.S.GRIN-HFA"), designed to improve social behaviors in children with high functioning autism spectrum disorders. Fifty-five children were randomly assigned to "S.S.GRIN-HFA" treatment (n = 27) or control (i.e.,…

Global Precipitation Measurement (GPM) Validation Network

NASA Technical Reports Server (NTRS)

Schwaller, Mathew; Moris, K. Robert

2010-01-01

The method averages the minimum TRMM PR and Ground Radar (GR) sample volumes needed to match-up spatially/temporally coincident PR and GR data types. PR and GR averages are calculated at the geometric intersection of the PR rays with the individual Ground Radar(GR)sweeps. Along-ray PR data are averaged only in the vertical, GR data are averaged only in the horizontal. Small difference in PR & GR reflectivity high in the atmosphere, relatively larger differences. Version 6 TRMM PR underestimates rainfall in the case of convective rain in the lower part of the atmosphere by 30 to 40 percent.

Structure of Greyhound hemoglobin: origin of high oxygen affinity.

PubMed

Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

2011-05-01

This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation

PubMed Central

Huska, Matthew R.; Jurk, Marcel; Schöpflin, Robert; Starick, Stephan R.; Schwahn, Kevin; Cooper, Samantha B.; Yamamoto, Keith R.; Thomas-Chollier, Morgane; Vingron, Martin

2017-01-01

Abstract The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter–proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined. PMID:27903902

Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain.

PubMed

Tolcos, Mary; McDougall, Annie; Shields, Amy; Chung, Yoonyoung; O'Dowd, Rachael; Turnley, Ann; Wallace, Megan; Rees, Sandra

2018-01-01

Intrauterine growth restriction (IUGR) can lead to adverse neurodevelopmental sequelae in postnatal life. However, the effects of IUGR on the cerebellum are still to be fully elucidated. A major determinant of growth and development of the cerebellum is proliferation and subsequent migration of cerebellar granule cells. Our objective was to determine whether IUGR, induced by chronic placental insufficiency (CPI) in guinea pigs, results in abnormal cerebellar development due to deficits suggestive of impaired granule cell proliferation and/or migration. CPI was induced by unilateral ligation of the uterine artery at mid-gestation, producing growth-restricted (GR) foetuses at 52 and 60 days of gestation (dg), and neonates at 1 week postnatal age (term approx. 67 dg). Controls were from sham-operated animals. In GR foetuses compared with controls at 52 dg, the external granular layer (EGL) width and internal granular layer (IGL) area were similar. In GR foetuses compared with controls at 60 dg: (a) the EGL width was greater (p < 0.005); (b) the IGL area was smaller (p < 0.005); (c) the density of Ki67-negative (postmitotic) granule cells in the EGL was greater (p < 0.01); (d) the somal area of Purkinje cells was reduced (p < 0.005), and (e) the linear density of Bergmann glia was similar. The EGL width in GR foetuses at 60 dg was comparable to that of 52 dg control and GR foetuses. The pattern of p27-immunoreactivity in the EGL was the inverse of Ki67-immunoreactivity at both foetal ages; there was no difference between control and GR foetuses at either age in the width of p27-immunoreactivity, or in the percentage of the EGL width that it occupied. In the molecular layer of GR neonates compared with controls there was an increase in the areal density of granule cells (p < 0.05) and in the percentage of migrating to total number of granule cells (p < 0.01) at 1 week but not at 60 dg (p > 0.05). Thus, we found no specific evidence that IUGR affects granule cell proliferation, but it alters the normal program of migration to the IGL and, in addition, the development of Purkinje cells. Such alterations will likely affect the development of appropriate circuitry and have implications for cerebellar function. © 2018 S. Karger AG, Basel.

Modeling the Solar Dust Environment at 9.5 Solar Radii: Revealing Radiance Trends with MESSENGER Star Tracker Data

NASA Astrophysics Data System (ADS)

Strong, S. B.; Strikwerda, T.; Lario, D.; Raouafi, N.; Decker, R.

2010-12-01

The main components of interplanetary dust are created through destruction, erosion, and collision of asteroids and comets (e.g. Mann et al. 2006). Solar radiation forces distribute these interplanetary dust particles throughout the solar system. The percent contribution of these source particulates to the net interplanetary dust distribution can reveal information about solar nebula conditions, within which these objects are formed. In the absence of observational data (e.g. Helios, Pioneer), specifically at distances less than 0.3 AU, the precise dust distributions remain unknown and limited to 1 AU extrapolative models (e.g. Mann et al. 2003). We have developed a model suitable for the investigation of scattered dust and electron irradiance incident on a sensor for distances inward of 1 AU. The model utilizes the Grün et al. (1985) and Mann et al. (2004) dust distribution theory combined with Mie theory and Thomson electron scattering to determine the magnitude of solar irradiance scattered towards an optical sensor as a function of helio-ecliptic latitude and longitude. MESSENGER star tracker observations (launch to 2010) of the ambient celestial background combined with Helios data (Lienert et al. 1982) reveal trends in support of the model predictions. This analysis further emphasizes the need to characterize the inner solar system dust environment in anticipation of near-Solar missions.

Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Yang, Liling; Mao, Jianren

2007-09-01

Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.

Blueberry extracts protect testis from hypobaric hypoxia induced oxidative stress in rats.

PubMed

Zepeda, Andrea; Aguayo, Luis G; Fuentealba, Jorge; Figueroa, Carolina; Acevedo, Alejandro; Salgado, Perla; Calaf, Gloria M; Farías, Jorge

2012-01-01

Exposure to hypobaric hypoxia causes oxidative damage to male rat reproductive function. The aim of this study was to evaluate the protective effect of a blueberry extract (BB-4) in testis of rats exposed to hypobaric hypoxia. Morphometric analysis, cellular DNA fragmentation, glutathione reductase (GR), and superoxide dismutase (SOD) activities were evaluated. Our results showed that supplementation of BB-4 reduced lipid peroxidation, decreased apoptosis, and increased GR and SOD activities in rat testis under hypobaric hypoxia conditions (P < 0.05). Therefore, this study demonstrates that blueberry extract significantly reduced the harmful effects of oxidative stress caused by hypobaric hypoxia in rat testis by affecting glutathione reductase and superoxide dismutase activities.

Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility

PubMed Central

Machev, N; Saut, N; Longepied, G; Terriou, P; Navarro, A; Levy, N; Guichaoua, M; Metzler-Guillemai..., C; Collignon, P; Frances, A; Belougne, J; Clemente, E; Chiaroni, J; Chevillard, C; Durand, C; Ducourneau, A; Pech, N; McElreavey, K; Mattei, M; Mitchell, M

2004-01-01

Background: Complete deletion of the complete AZFc interval of the Y chromosome is the most common known genetic cause of human male infertility. Two partial AZFc deletions (gr/gr and b1/b3) that remove some copies of all AZFc genes have recently been identified in infertile and fertile populations, and an association study indicates that the resulting gene dose reduction represents a risk factor for spermatogenic failure. Methods: To determine the incidence of various partial AZFc deletions and their effect on fertility, we combined quantitative and qualitative analyses of the AZFc interval at the DAZ and CDY1 loci in 300 infertile men and 399 control men. Results: We detected 34 partial AZFc deletions (32 gr/gr deletions), arising from at least 19 independent deletion events, and found gr/gr deletion in 6% of infertile and 3.5% of control men (p>0.05). Our data provide evidence for two large AZFc inversion polymorphisms, and for relative hot and cold spots of unequal crossing over within the blocks of homology that mediate gr/gr deletion. Using SFVs (sequence family variants), we discriminate DAZ1/2, DAZ3/4, CDY1a (proximal), and CDY1b (distal) and define four types of DAZ-CDY1 gr/gr deletion. Conclusions: The only deletion type to show an association with infertility was DAZ3/4-CDY1a (p = 0.042), suggesting that most gr/gr deletions are neutral variants. We see a stronger association, however, between loss of the CDY1a SFV and infertility (p = 0.002). Thus, loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility. PMID:15520406

Glyphosate-Resistant and Conventional Canola (Brassica napus L.) Responses to Glyphosate and Aminomethylphosphonic Acid (AMPA) Treatment.

PubMed

Corrêa, Elza Alves; Dayan, Franck E; Owens, Daniel K; Rimando, Agnes M; Duke, Stephen O

2016-05-11

Glyphosate-resistant (GR) canola contains two transgenes that impart resistance to the herbicide glyphosate: (1) the microbial glyphosate oxidase gene (gox) encoding the glyphosate oxidase enzyme (GOX) that metabolizes glyphosate to aminomethylphosphonic acid (AMPA) and (2) cp4 that encodes a GR form of the glyphosate target enzyme 5-enolpyruvylshikimic acid-3-phosphate synthase. The objectives of this research were to determine the phytotoxicity of AMPA to canola, the relative metabolism of glyphosate to AMPA in GR and conventional non-GR (NGR) canola, and AMPA pool sizes in glyphosate-treated GR canola. AMPA applied at 1.0 kg ha(-1) was not phytotoxic to GR or NGR. At this AMPA application rate, NGR canola accumulated a higher concentration of AMPA in its tissues than GR canola. At rates of 1 and 3.33 kg ae ha(-1) of glyphosate, GR canola growth was stimulated. This stimulatory effect is similar to that of much lower doses of glyphosate on NGR canola. Both shikimate and AMPA accumulated in tissues of these glyphosate-treated plants. In a separate experiment in which young GR and NGR canola plants were treated with non-phytotoxic levels of [(14)C]-glyphosate, very little glyphosate was metabolized in NGR plants, whereas most of the glyphosate was metabolized to AMPA in GR plants at 7 days after application. Untreated leaves of GR plants accumulated only metabolites (mostly AMPA) of glyphosate, indicating that GOX activity is very high in the youngest leaves. These data indicate that more glyphosate is transformed to AMPA rapidly in GR canola and that the accumulated AMPA is not toxic to the canola plant.

Monoclonal antibodies against the rat liver glucocorticoid receptor.

PubMed Central

Okret, S; Wikström, A C; Wrange, O; Andersson, B; Gustafsson, J A

1984-01-01

Splenic cells from one BALB/c mouse and one C57/BL mouse, immunized with purified rat liver glucocorticoid receptor (GR), were fused with the mouse myeloma cell line Sp 2/0-Ag 14. Screening for production of anti-GR-antibodies by the hybridomas was carried out with an enzyme-linked immunosorbent assay, using partially purified rat liver GR as antigen. Further screening was by a second-antibody immunoprecipitation assay using [3H]triamcinolone acetonide-GR complex from rat liver cytosol as tracer. Hybridomas from 10 different microplate wells, positive in both assays, were successfully cloned by the limiting dilution method to monoclonality. The different origins of the monoclonal antibodies were confirmed by their various isoelectric points when analyzed by isoelectric focusing. Four of the monoclonal hybridoma cell lines secreted IgM antibodies; two, IgG1; three, IgG2a; and one, IgG2b. The GR-antibody complex was identified in glycerol density gradients by a shift of the 4S GR to an 8.5S or 19S GR-antibody complex when incubated with monoclonal IgG or IgM antibody, respectively. The 10 monoclonal antibodies recognized different determinants on the GR, all situated on that domain of the receptor that is separate from the ligand and DNA-binding domains. Also, the cross-reactivity to the mouse liver GR varied among the monoclonal antibodies. No cross-reactivity was observed to the human lymphocytic GR. NaDodSO4 electrophoresis of a 0.5% pure GR preparation followed by immunoblotting using one of the monoclonal antibodies identified a single peptide with a molecular weight of 94,000, identical to the purified rat liver GR. Images PMID:6200880

Twin Crystal Induced near Zero Thermal Expansion in SnO2 Nanowires.

PubMed

Zhu, He; Li, Qiang; Yang, Chao; Zhang, Qinghua; Ren, Yang; Gao, Qilong; Wang, Na; Lin, Kun; Deng, Jinxia; Chen, Jun; Gu, Lin; Hong, Jiawang; Xing, Xianran

2018-06-20

Knowledge of controllable thermal expansion is a fundamental issue in the field of materials science and engineering. Direct blocking of the thermal expansions in positive thermal expansion materials is a challenging but fascinating task. Here we report a near zero thermal expansion (ZTE) of SnO 2 achieved from twin crystal nanowires, which is highly correlated to the twin boundaries. Local structural evolutions followed by pair distribution function revealed a remarkable thermal local distortion along the twin boundary. Lattice dynamics investigated by Raman scattering evidenced the hardening of phonon frequency induced by the twin crystal compressing, giving rise to the ZTE of SnO 2 nanowires. Further DFT calculation of Grüneisen parameters confirms the key role of compressive stress on ZTE. Our results provide an insight into the thermal expansion behavior regarding to twin crystal boundaries, which could be beneficial to the applications.

Coordination number constraint models for hydrogenated amorphous Si deposited by catalytic chemical vapour deposition

NASA Astrophysics Data System (ADS)

Kawahara, Toshio; Tabuchi, Norikazu; Arai, Takashi; Sato, Yoshikazu; Morimoto, Jun; Matsumura, Hideki

2005-02-01

We measured structure factors of hydrogenated amorphous Si by x-ray diffraction and analysed the obtained structures using a reverse Monte Carlo (RMC) technique. A small shoulder in the measured structure factor S(Q) was observed on the larger Q side of the first peak. The RMC results with an unconstrained model did not clearly show the small shoulder. Adding constraints for coordination numbers 2 and 3, the small shoulder was reproduced and the agreement with the experimental data became better. The ratio of the constrained coordination numbers was consistent with the ratio of Si-H and Si-H2 bonds which was estimated by the Fourier transformed infrared spectra of the same sample. This shoulder and the oscillation of the corresponding pair distribution function g(r) at large r seem to be related to the low randomness of cat-CVD deposited a-Si:H.

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice

PubMed Central

Percopo, Caroline M.; Brenner, Todd A.; Ma, Michelle; Kraemer, Laura S.; Hakeem, Reem M. A.; Lee, James J.; Rosenberg, Helene F.

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45+CD11c−SiglecF+Gr1hi). SiglecF+Gr1hi eosinophils, distinct from the canonical SiglecF+Gr1− eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX−/− and MBP-1−/−) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1+ neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF+Gr1hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G+. Although indistinguishable from the more-numerous SiglecF+Gr1− eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF+Gr1hi eosinophil population (at 3.9 and 4.8 pg/106 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/106 cells). Interestingly, bone marrow-derived (SiglecF+), cultured eosinophils include a more substantial Gr1+ subpopulation (∼50%); Gr1+ bmEos includes primarily a single Ly6C+ and a smaller, double-positive (Ly6C+Ly6G+) population. Taken together, our findings characterize a distinct SiglecF+Gr1hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF+Gr1hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. PMID:27531929

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

PubMed

Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

Age related differences of selected Hatha yoga practices on anthropometric characteristics, muscular strength and flexibility of healthy individuals

PubMed Central

Halder, Kaushik; Chatterjee, Abhirup; Pal, Rameshwar; Tomer, Omveer S; Saha, Mantu

2015-01-01

Background: Physiological benefits of yoga on volunteers of a particular age group are available. However, reports on efficacy of a specific yoga package on the populace of different age groups from similar occupational background is still very limited. Therefore, the present study was conducted to appraise the effect of a specific Hatha yoga package on anthropometric characteristics, flexibility and muscular strength of healthy individuals of different age groups from similar occupational trade. Materials and Methods: A total of 71 participants (Group All) from Indian Air Force ground personnel volunteered and age wise divided into 3 groups - (i) Group I (Gr. - I) (n1 = 27, 20-29 years), (ii) Group II (Gr. - II) (n2 = 21, 30-39 years) and (iii) Group III (Gr. - III) (n3 = 23, 40-49 years). All the participants undergone selected Hatha yoga training for 1 h daily for a period of 12 weeks. Parameters were recorded before and after the training. Pre and post training differences were assessed by Student's t-test. Results: Body weight (All, Gr. - II and Gr. - III [all P < 0.05]), body mass index (Gr. - II and Gr. - III [both P < 0.01]) and fat% (Gr. - II and III [both P < 0.05]) were decreased significantly. Neck circumference was increased significantly in Gr. - I (P < 0.05) but decreased significantly in Gr. - III (P < 0.05). Chest circumference (All (P < 0.001), in Gr. - I and II [both P < 0.05]), grip strength (All [left: P < 0.01 and right: P < 0.05], in Gr. - I [left: P < 0.05 and right: P < 0.01], in Gr. - II [right: P < 0.05] and in Gr. - III [left: P < 0.05 and right: P < 0.01]), back leg strength (group wise P < 0.001, P < 0.05, P < 0.01 and P < 0.05 respectively) and flexibility (all P < 0.001) were increased significantly. Summary and Conclusion: Hatha yoga can improve anthropometric characteristics, muscular strength and flexibility among volunteers of different age group and can also be helpful in preventing and attenuating age related deterioration of these parameters. PMID:25558132

Role of Pro-637 and Gln-642 in human glucocorticoid receptors and Ser-843 and Leu-848 in mineralocorticoid receptors in their differential responses to cortisol and aldosterone.

PubMed

Mani, Orlando; Nashev, Lyubomir G; Livelo, Christopher; Baker, Michael E; Odermatt, Alex

2016-05-01

Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are descended from a common ancestral corticoid receptor. The basis for specificities of human MR for aldosterone and human GR for glucocorticoids, such as cortisol, bearing 17α-hydroxyl-groups, is incompletely understood. Differences in MR at S843 and L848 and GR at the corresponding P637 and Q642 have been proposed as important in their different responses to glucocorticoids with 17α-hydroxyl-groups. We investigated the impact of these residues on binding affinity (Ki) and transcriptional activation (EC50) of mutants MR-S843P, MR-L848Q and MR-S843P/L848Q and mutants GR-P637S, GR-Q642L and GR-P637S/Q642L in the presence of different corticosteroids. Aldosterone, cortisol and corticosterone had similar affinities for wild-type MR and all mutants, while dexamethasone had increased affinity for the three mutants. However, transactivation of MR-S843P and MR-S843P/L848Q by all four steroids was significantly lower than for wild-type MR. In contrast, transactivation of MR-L848Q tended to be 3-fold higher for cortisol and corticosterone and increased 7-fold for dexamethasone, indicating that MR-L848Q has an increased response to glucocorticoids, while retaining a strong response to aldosterone. Compared to wild-type GR, GR-P637S and GR-Q642L had increased affinities and significantly increased transcriptional activity with aldosterone and corticosterone, and GR-P637S had similar transcriptional activity with cortisol and dexamethasone, while GR-Q642L and GR-P637S/Q642L had a significant decrease in transcriptional activity with cortisol and dexamethasone. 3D-models of these MR and GR mutants revealed that dexamethasone and aldosterone, respectively, fit nicely into the steroid-binding pocket, consistent with the affinity of dexamethasone for MR mutants and aldosterone for GR mutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Slip Activity in Single Grains Extracted from Polycrystalline Specimen by X-Ray Line Broadening (Preprint)

DTIC Science & Technology

2010-01-01

4 6 8 0.005 0.010 -101-3 -110-2 1-10-2F W H M [ 1 /n m ] K [ 1/nm ] Gr #44 Gr #50 Gr #72 -101-1 1-101 (a...0 2 4 6 0.000 0.005 0.010 (b) K2Ccalc [ 1/nm ] FW H M [ 1 /n m ] Gr #44 Gr #50 Gr #72 17 Figure 5. The FWHM (in 1/nm scales) in...Preprint 01 January 2010 – 01 January 2010 4 . TITLE AND SUBTITLE SLIP ACTIVITY IN SINGLE GRAINS EXTRACTED FROM POLYCRYSTALLINE SPECIMEN BY X-RAY

Development of glyphosate-resistant alfalfa (Medicago sativa L.) upon transformation with the GR79Ms gene encoding 5-enolpyruvylshikimate-3-phosphate synthase.

PubMed

Yi, Dengxia; Ma, Lin; Lin, Min; Li, Cong

2018-07-01

The glyphosate-resistant gene, GR79Ms, was successfully introduced into the genome of alfalfa. The transgenic events may serve as novel germplasm resources in alfalfa breeding. Weed competition can reduce the alfalfa yield, generating new alfalfa germplasm with herbicide resistance is essential. To obtain transgenic alfalfa lines with glyphosate resistance, a new synthetic glyphosate-resistant gene GR79Ms encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) was introduced into alfalfa germplasm by Agrobacterium tumefaciens-mediated transformation. In total, 67 transformants were obtained. PCR and Southern blot analyses confirmed that GR79Ms was successfully inserted into the genome of alfalfa. Reverse transcription-PCR and western blot analyses further demonstrated the expression of GR79Ms and its product, GR79Ms EPSPS. Moreover, two homozygous transgenic lines were developed in the T 2 generation by means of molecular-assisted selection. Herbicide tolerance spray tests showed that the transgenic plants T 0 -GR1, T 0 -GR2, T 0 -GR3 and two homozygous lines were able to tolerate fourfold higher commercial usage of glyphosate than non-transgenic plants.

An 8.68% efficiency chemically-doped-free graphene-silicon solar cell using silver nanowires network buried contacts.

PubMed

Yang, Lifei; Yu, Xuegong; Hu, Weidan; Wu, Xiaolei; Zhao, Yan; Yang, Deren

2015-02-25

Graphene-silicon (Gr-Si) heterojunction solar cells have been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the high sheet resistance of chemical vapor deposited (CVD) Gr films is still the most important limiting factor for the improvement of the power conversion efficiency of Gr-Si solar cells, especially in the case of large device-active area. In this work, we have fabricated a novel transparent conductive film by hybriding a monolayer Gr film with silver nanowires (AgNWs) network soldered by the graphene oxide (GO) flakes. This Gr-AgNWs hybrid film exhibits low sheet resistance and larger direct-current to optical conductivity ratio, quite suitable for solar cell fabrication. An efficiency of 8.68% has been achieved for the Gr-AgNWs-Si solar cell, in which the AgNWs network acts as buried contacts. Meanwhile, the Gr-AgNWs-Si solar cells have much better stability than the chemically doped Gr-Si solar cells. These results show a new route for the fabrication of high efficient and stable Gr-Si solar cells.

On the fractional Eulerian numbers and equivalence of maps with long term power-law memory (integral Volterra equations of the second kind) to Grünvald-Letnikov fractional difference (differential) equations.

PubMed

Edelman, Mark

2015-07-01

In this paper, we consider a simple general form of a deterministic system with power-law memory whose state can be described by one variable and evolution by a generating function. A new value of the system's variable is a total (a convolution) of the generating functions of all previous values of the variable with weights, which are powers of the time passed. In discrete cases, these systems can be described by difference equations in which a fractional difference on the left hand side is equal to a total (also a convolution) of the generating functions of all previous values of the system's variable with the fractional Eulerian number weights on the right hand side. In the continuous limit, the considered systems can be described by the Grünvald-Letnikov fractional differential equations, which are equivalent to the Volterra integral equations of the second kind. New properties of the fractional Eulerian numbers and possible applications of the results are discussed.

Chronic Inflammatory Diseases and Green Tea Polyphenols

PubMed Central

Oz, Helieh S.

2017-01-01

Chronic inflammatory diseases affect millions of people globally and the incidence rate is on the rise. While inflammation contributes to the tissue healing process, chronic inflammation can lead to life-long debilitation and loss of tissue function and organ failure. Chronic inflammatory diseases include hepatic, gastrointestinal and neurodegenerative complications which can lead to malignancy. Despite the millennial advancements in diagnostic and therapeutic modalities, there remains no effective cure for patients who suffer from inflammatory diseases. Therefore, patients seek alternatives and complementary agents as adjunct therapies to relieve symptoms and possibly to prevent consequences of inflammation. It is well known that green tea polyphenols (GrTPs) are potent antioxidants with important roles in regulating vital signaling pathways. These comprise transcription nuclear factor-kappa B mediated I kappa B kinase complex pathways, programmed cell death pathways like caspases and B-cell lymphoma-2 and intervention with the surge of inflammatory markers like cytokines and production ofcyclooxygenase-2. This paper concisely reviews relevant investigations regarding protective effects of GrTPs and some reported adverse effects, as well as possible applications for GrTPs in the treatment of chronic and inflammatory complications. PMID:28587181

Evaluation of pulmonary and systemic toxicity following lung exposure to graphite nanoplates: a member of the graphene-based nanomaterial family.

PubMed

Roberts, Jenny R; Mercer, Robert R; Stefaniak, Aleksandr B; Seehra, Mohindar S; Geddam, Usha K; Chaudhuri, Ishrat S; Kyrlidis, Angelos; Kodali, Vamsi K; Sager, Tina; Kenyon, Allison; Bilgesu, Suzan A; Eye, Tracy; Scabilloni, James F; Leonard, Stephen S; Fix, Natalie R; Schwegler-Berry, Diane; Farris, Breanne Y; Wolfarth, Michael G; Porter, Dale W; Castranova, Vincent; Erdely, Aaron

2016-06-21

Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. Three sizes of graphite nanoplates [20 μm lateral (Gr20), 5 μm lateral (Gr5), and <2 μm lateral (Gr1)] ranging from 8-25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 μg/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m(2). At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently elevated in Gr5 and Gr20, relative to Gr1. Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates > 5 μm laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1-2 μm graphite nanoplate.

Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis

PubMed Central

Robben, Paul M.; LaRegina, Marie; Kuziel, William A.; Sibley, L. David

2005-01-01

Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1−/CCR2−/CX3CR1high) or responding to sites of inflammation (Gr-1+/CCR2+/CX3CR1lo). Gr-1+ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1+ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1+ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2−/− and MCP-1−/− mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1+ monocytes. The failure to recruit Gr-1+ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-α, and IFN-γ. The profound susceptibility of CCR2−/− mice establishes Gr-1+ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1+ monocytes may be an important general mechanism for resistance to intracellular pathogens. PMID:15928200

Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension.

PubMed

Peotta, Veronica; Rahmouni, Kamal; Segar, Jeffrey L; Morgan, Donald A; Pitz, Kate M; Rice, Olivia M; Roghair, Robert D

2016-08-01

Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors. We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration. nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion. nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension.

Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation.

PubMed

Love, Michael I; Huska, Matthew R; Jurk, Marcel; Schöpflin, Robert; Starick, Stephan R; Schwahn, Kevin; Cooper, Samantha B; Yamamoto, Keith R; Thomas-Chollier, Morgane; Vingron, Martin; Meijsing, Sebastiaan H

2017-02-28

The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter-proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Predator stress-induced persistent emotional arousal is associated with alterations of plasma corticosterone and hippocampal steroid receptors in rat.

PubMed

Wang, Qingsong; Yu, Ke; Wang, Jun; Lin, Hang; Wu, Yuxian; Wang, Weiwen

2012-04-21

To investigate the long-term effects of psychological stress on emotionality, the emotional arousal of rats in 4 months after predator stress was assessed in both an open field environment and elevated plus maze. We also assessed the levels of plasma corticosterone (CORT) by radioimmunoassay, the distributions of brain glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by immunohistochemistry, and the expressions of GR and MR by Western blot. The results showed that intense predator stress, which was adjusted to ensure consistent stressor intensity using rat tonic immobility behavior, successfully induced lasting decreased locomotor activity and habituation to novel environments, suppressed exploratory behavior, and increased anxiety-like behavior. The plasma CORT levels dramatically increased 1h after stress, then returned to basal levels at 1wk, decreased 1 month later, and remained significantly lower than control levels 4 months after exposure to stress. Immunohistochemical analysis showed that GR was markedly increased in the hippocampus and frontal cortexes of stressed rats and that the changes in the hippocampus were more pronounced. In contrast, MR expression was significantly decreased in both brain regions. Western analysis confirmed these dramatically elevated levels of GR expression and lower levels of MR expression in the hippocampus 4 months after stress. We conclude that acute severe psychological stress may induce long-term emotional behavioral changes, and that different patterns in plasma CORT, alterations in brain corticoid receptors, and increased hippocampal vulnerability to the effects of predator stress may play important roles in the persistent emotional arousal induced by intense psychological stress. Copyright © 2012 Elsevier B.V. All rights reserved.

Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China.

PubMed

Ye, Jun-jie; Ma, Li; Yang, Li-juan; Wang, Jin-huan; Wang, Yue-li; Guo, Hai; Gong, Ning; Nie, Wen-hui; Zhao, Shu-hua

2013-09-01

There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/-) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.

airGR: a suite of lumped hydrological models in an R-package

NASA Astrophysics Data System (ADS)

Coron, Laurent; Perrin, Charles; Delaigue, Olivier; Andréassian, Vazken; Thirel, Guillaume

2016-04-01

Lumped hydrological models are useful and convenient tools for research, engineering and educational purposes. They propose catchment-scale representations of the precipitation-discharge relationship. Thanks to their limited data requirements, they can be easily implemented and run. With such models, it is possible to simulate a number of hydrological key processes over the catchment with limited structural and parametric complexity, typically evapotranspiration, runoff, underground losses, etc. The Hydrology Group at Irstea (Antony) has been developing a suite of rainfall-runoff models over the past 30 years with the main objectives of designing models as efficient as possible in terms of streamflow simulation, applicable to a wide range of catchments and having low data requirements. This resulted in a suite of models running at different time steps (from hourly to annual) applicable for various issues including water balance estimation, forecasting, simulation of impacts and scenario testing. Recently, Irstea has developed an easy-to-use R-package (R Core Team, 2015), called airGR, to make these models widely available. It includes: - the water balance annual GR1A (Mouehli et al., 2006), - the monthly GR2M (Mouehli, 2003) models, - three versions of the daily model, namely GR4J (Perrin et al., 2003), GR5J (Le Moine, 2008) and GR6J (Pushpalatha et al., 2011), - the hourly GR4H model (Mathevet, 2005), - a degree-day snow module CemaNeige (Valéry et al., 2014). The airGR package has been designed to facilitate the use by non-expert users and allow the addition of evaluation criteria, models or calibration algorithms selected by the end-user. Each model core is coded in FORTRAN to ensure low computational time. The other package functions (i.e. mainly the calibration algorithm and the efficiency criteria) are coded in R. The package is already used for educational purposes. The presentation will detail the main functionalities of the package and present a case study application. References: - Le Moine, N. (2008), Le bassin versant de surface vu par le souterrain : une voie d'amélioration des performances et du réalisme des modèles pluie-débit ?, PhD thesis (in French), UPMC, Paris, France. - Mathevet, T. (2005), Quels modèles pluie-débit globaux pour le pas de temps horaire ? Développement empirique et comparaison de modèles sur un large échantillon de bassins versants, PhD thesis (in French), ENGREF - Cemagref (Antony), Paris, France. - Mouelhi S. (2003), Vers une chaîne cohérente de modèles pluie-débit conceptuels globaux aux pas de temps pluriannuel, annuel, mensuel et journalier, PhD thesis (in French), ENGREF - Cemagref Antony, Paris, France. - Mouelhi, S., C. Michel, C. Perrin and V. Andréassian (2006), Stepwise development of a two-parameter monthly water balance model, Journal of Hydrology, 318(1-4), 200-214, doi:10.1016/j.jhydrol.2005.06.014. - Perrin, C., C. Michel and V. Andréassian (2003), Improvement of a parsimonious model for streamflow simulation, Journal of Hydrology, 279(1-4), 275-289, doi:10.1016/S0022-1694(03)00225-7. - Pushpalatha, R., C. Perrin, N. Le Moine, T. Mathevet and V. Andréassian (2011), A downward structural sensitivity analysis of hydrological models to improve low-flow simulation, Journal of Hydrology, 411(1-2), 66-76, doi:10.1016/j.jhydrol.2011.09.034. - R Core Team (2015). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/ - Valéry, A., V. Andréassian and C. Perrin (2014), "As simple as possible but not simpler": What is useful in a temperature-based snow-accounting routine? Part 2 - Sensitivity analysis of the Cemaneige snow accounting routine on 380 catchments, Journal of Hydrology, doi:10.1016/j.jhydrol.2014.04.058.

Fracture and earthquake physics in a non extensive view

NASA Astrophysics Data System (ADS)

Vallianatos, F.

2009-04-01

It is well known that the Gutenberg-Richter (G-R) power law distribution has to be modified for large seismic moments because of energy conservation and geometrical reasons. Several models have been proposed, either in terms of a second power law with a larger b value beyond a crossover magnitude, or based on a magnidute cut-off using an exponential taper. In the present work we point out that the non extensivity viewpoint is applicable to seismic processes. In the frame of a non-extensive approach which is based on Tsallis entropy we construct a generalized expression of Gutenberg-Richter (GGR) law. The existence of lower or/and upper bound to magnitude is discussed and the conditions under which GGR lead to classical GR law are analysed. For the lowest earthquake size (i.e., energy level) the correlation between the different parts of elements involved in the evolution of an earthquake are short-ranged and GR can be deduced on the basis of the maximum entropy principle using BG statistics. As the size (i.e., energy) increases, long range correlation becomes much more important, implying the necessity of using Tsallis entropy as an appropriate generalization of BG entropy. The power law behaviour is derived as a special case, leading to b-values being functions of the non-extensivity parameter q. Furthermore a theoretical analysis of similarities presented in stress stimulated electric and acoustic emissions and earthquakes are discussed not only in the frame of GGR but taking into account a universality in the description of intrevent times distribution. Its particular form can be well expressed in the frame of a non extensive approach. This formulation is very different from an exponential distribution expected for simple random Poisson processes and indicates the existence of a nontrivial universal mechanism in the generation process. All the aforementioned similarities within stress stimulated electrical and acoustic emissions and seismicity suggests a connection with fracture phenomena at much larger scales implying that a basic general mechanism is "actively hidden" behind all this phenomena. Acknowledgements: This work is partially supported by the Greek General Secretariat of Research and Technology in the frame of Crete Regional Project 2000- 2006 (M1.2): "TALOS: An integrated system of seismic hazard monitoring and management in the front of the Hellenic Arc", CRETE PEP 7 (KP 7). [1] F. Vallianatos and A. Tzanis, Phys. Chem. Earth 23, 933 (1998). [2] A. Tzanis and F. Vallianatos, Natural Hazards and Earth Syst, Sciences 3 (2003). [3] F. Vallianatos, D. Triantis, A. Tzanis, C. Anastasiadis and I. Stavrakas, Phys. Chem. Earth 29, 339 (2004). [4] C. Anastasiadis, D. Triantis, I. Stavrakas and F. Vallianatos, Ann. Geophys. 47, 21 (2004). [5] F. Vallianatos Proc., 2nd WSEAS Int. Conference on Seismology, (Cambridge, UK, 2008). [6] F. Vallianatos, Natural Hazards and Earth Syst, Sciences (2009).

Twistor interpretation of slice regular functions

NASA Astrophysics Data System (ADS)

Altavilla, Amedeo

2018-01-01

Given a slice regular function f : Ω ⊂ H → H, with Ω ∩ R ≠ ∅, it is possible to lift it to surfaces in the twistor space CP3 of S4 ≃ H ∪ { ∞ } (see Gentili et al., 2014). In this paper we show that the same result is true if one removes the hypothesis Ω ∩ R ≠ ∅ on the domain of the function f. Moreover we find that if a surface S ⊂CP3 contains the image of the twistor lift of a slice regular function, then S has to be ruled by lines. Starting from these results we find all the projective classes of algebraic surfaces up to degree 3 in CP3 that contain the lift of a slice regular function. In addition we extend and further explore the so-called twistor transform, that is a curve in Gr2(C4) which, given a slice regular function, returns the arrangement of lines whose lift carries on. With the explicit expression of the twistor lift and of the twistor transform of a slice regular function we exhibit the set of slice regular functions whose twistor transform describes a rational line inside Gr2(C4) , showing the role of slice regular functions not defined on R. At the end we study the twistor lift of a particular slice regular function not defined over the reals. This example shows the effectiveness of our approach and opens some questions.

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

Kittell, David Erik; Yarrington, Cole Davis

Here, a physically-based form of the Mie–Grüneisen equation of state (EOS) is derived for calculating 1d planar shock temperatures, as well as hot spot temperature distributions from heterogeneous impact simulations. This form utilises a multi-term Einstein oscillator model for specific heat, and is completely algebraic in terms of temperature, volume, an integrating factor, and the cold curve energy. Moreover, any empirical relation for the reference pressure and energy may be substituted into the equations via the use of a generalised reference function. The complete EOS is then applied to calculations of the Hugoniot temperature and simulation of hydrodynamic pore collapsemore » using data for the secondary explosive, hexanitrostilbene (HNS). From these results, it is shown that the choice of EOS is even more significant for determining hot spot temperature distributions than planar shock states. The complete EOS is also compared to an alternative derivation assuming that specific heat is a function of temperature alone, i.e. cv(T). Temperature discrepancies on the order of 100–600 K were observed corresponding to the shock pressures required to initiate HNS (near 10 GPa). Overall, the results of this work will improve confidence in temperature predictions. By adopting this EOS, future work may be able to assign physical meaning to other thermally sensitive constitutive model parameters necessary to predict the shock initiation and detonation of heterogeneous explosives.« less

Modeling the growth kinetics of Bacillus cereus as a function of temperature, pH, sodium lactate and sodium chloride concentrations.

PubMed

Olmez, Hülya Kaptan; Aran, Necla

2005-02-01

Mathematical models describing the growth kinetic parameters (lag phase duration and growth rate) of Bacillus cereus as a function of temperature, pH, sodium lactate and sodium chloride concentrations were obtained in this study. In order to get a residual distribution closer to a normal distribution, the natural logarithm of the growth kinetic parameters were used in modeling. For reasons of parsimony, the polynomial models were reduced to contain only the coefficients significant at a level of p

The glucocorticoid receptor regulates the binding of C/EPBbeta on the alpha-1-acid glycoprotein promoter in vivo.

PubMed

Savoldi, G; Fenaroli, A; Ferrari, F; Rigaud, G; Albertini, A; Di Lorenzo, D

1997-12-01

A complex interaction between the Glucocorticoid Receptor (GR), C/EBPbeta, and other transcription factors activate the Alpha-1 Acid Glycoprotein (AGP) promoter in HTC(JZ-1) rat hepatoma culture cells. This effect is mediated by the so-called Steroid Responsive Unit (SRU) of the AGP promoter that contains several binding sites for C/EBP transcription factors, some of which overlap with the Glucocorticoid Responsive Element (GRE). Our in vivo footprinting experiments revealed that the GRE- and the C/EBP-binding sites were already occupied glucocorticoid dependently in HTC(JZ-1) cells 10 min after dexamethasone administration (10(-6) M). Furthermore, local changes in the chromatine structure shown by the appearance of DNAse I hypersensitive sites (HS sites) also took place. These changes were probably dependent on a tissue-specific organization of the chromatine at the SRU because they were not detectable in a different glucocorticoid-responsive cell line (PC12) that did not express AGP. Here, we have also shown that withdrawal of dexamethasone or addition of the anti-glucocorticoid RU486 were able to revert the pattern induced by dexamethasone in vivo. The disappearance of the protected region and the hypersensitive sites, typical of the hormone activated promoter, confirmed the necessity of the GR to be bound by the agonist and the inability of the GR-antagonist complex to bind the DNA. By functional assays, we showed that the occupancy of the SRU by these transcriptional proteins in vivo correlated with the activation of the AGP gene transcription. With these results, we have shown that one of the functions of the GR to activate transcription of the AGP gene is to recruit C/EBPbeta and to maintain it bound at its target DNA sequences (SRU). This process was not accomplished by RU486.

The prednisolone suppression test in depression: Dose—response and changes with antidepressant treatment

PubMed Central

Juruena, Mario F.; Cleare, Anthony J.; Papadopoulos, Andrew S.; Poon, Lucia; Lightman, Stafford; Pariante, Carmine M.

2010-01-01

Summary Depressed patients have reduced glucocorticoid receptor (GR) function, as demonstrated by resistance to the suppressive effects of the synthetic glucocorticoid hormone, and GR agonist, dexamethasone. We have developed a suppressive test with prednisolone, a synthetic glucocorticoid that is similar to cortisol in its pharmacodynamics and pharmacokinetics, and binds to both the GR and the mineralocorticoid receptor (MR). We have found that depressed patients suppress normally to prednisolone, unless they are particularly non-responsive to treatment. In the present study, we evaluated 28 inpatients with treatment-resistant depression (TRD), and compared salivary cortisol secretion (at 0900 h, 1200 h and 1700 h) after placebo or after prednisolone (5 mg), before and after an inpatient treatment admission. Half of the patients (n = 14) reached treatment response. When comparing the assessment between admission and discharge, cortisol output after placebo fell (−26% of area under the curve; p = 0.024) while the output after prednisolone did not change. Moreover, there was no change in the response to prednisolone (percentage suppression) between admission at discharge, and this was not influenced by treatment response. Finally, we could confirm and extend our previously published data with prednisolone (5 mg), showing that depressed patients (n = 12) and controls (n = 12) suppressed equally to both 5 and 10 mg doses of prednisolone. This study suggests that the response to prednisolone is similar in depressed patients and controls at different doses of prednisolone, and does not change with symptomatic improvement. This is in contrast with findings, from us and others, using other measures of hypothalamic—pituitary—adrenal axis function, such as basal cortisol levels or the response to dexamethasone. Thus, we propose that the prednisolone suppression test may offer specific biological and clinical information, related to its action at both the GR and the MR. PMID:20558006

Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway

PubMed Central

Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

2015-01-01

Gr-1+ CD11b+ myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1+ CD11b+ monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1+ CD11b+ MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1+ CD11b+ MDSCs by pAbM treatment had less ability to convert the CD4+ CD25− cells into CD4+ CD25+ phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1+ CD11b+ monocytes, nether CD8+ T cells nor CD4+ T cells. In addition to, pAbM did not inhibit tumour growth in TLR2–/– mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1+ CD11b+ MDSCs. PMID:26194418

An efficient framework for optimization and parameter sensitivity analysis in arterial growth and remodeling computations

PubMed Central

Sankaran, Sethuraman; Humphrey, Jay D.; Marsden, Alison L.

2013-01-01

Computational models for vascular growth and remodeling (G&R) are used to predict the long-term response of vessels to changes in pressure, flow, and other mechanical loading conditions. Accurate predictions of these responses are essential for understanding numerous disease processes. Such models require reliable inputs of numerous parameters, including material properties and growth rates, which are often experimentally derived, and inherently uncertain. While earlier methods have used a brute force approach, systematic uncertainty quantification in G&R models promises to provide much better information. In this work, we introduce an efficient framework for uncertainty quantification and optimal parameter selection, and illustrate it via several examples. First, an adaptive sparse grid stochastic collocation scheme is implemented in an established G&R solver to quantify parameter sensitivities, and near-linear scaling with the number of parameters is demonstrated. This non-intrusive and parallelizable algorithm is compared with standard sampling algorithms such as Monte-Carlo. Second, we determine optimal arterial wall material properties by applying robust optimization. We couple the G&R simulator with an adaptive sparse grid collocation approach and a derivative-free optimization algorithm. We show that an artery can achieve optimal homeostatic conditions over a range of alterations in pressure and flow; robustness of the solution is enforced by including uncertainty in loading conditions in the objective function. We then show that homeostatic intramural and wall shear stress is maintained for a wide range of material properties, though the time it takes to achieve this state varies. We also show that the intramural stress is robust and lies within 5% of its mean value for realistic variability of the material parameters. We observe that prestretch of elastin and collagen are most critical to maintaining homeostasis, while values of the material properties are most critical in determining response time. Finally, we outline several challenges to the G&R community for future work. We suggest that these tools provide the first systematic and efficient framework to quantify uncertainties and optimally identify G&R model parameters. PMID:23626380

Using Polymorphisms in FKBP5 to Define Biologically Distinct Subtypes of Posttraumatic Stress Disorder

PubMed Central

Mehta, Divya; Gonik, Mariya; Klengel, Torsten; Rex-Haffner, Monika; Menke, Andreas; Rubel, Jennifer; Mercer, Kristina B.; Pütz, Benno; Bradley, Bekh; Holsboer, Florian; Ressler, Kerry J.; Müller-Myhsok, Bertram; Binder, Elisabeth B.

2013-01-01

Context Polymorphisms in the gene encoding the glucocorticoid receptor (GR) regulating co-chaperone FKBP5 have been shown to alter GR sensitivity and are associated with an increased risk to develop posttraumatic stress disorder (PTSD). Objective To investigate interactions of the FKBP5 single-nucleotide polymorphism rs9296158 and PTSD symptoms on baseline cortisol level, low-dose dexamethasone suppression, and whole-blood gene expression. Design Association of FKBP5 genotypes and PTSD symptoms with endocrine measures and genome-wide expression profiles. Setting Waiting rooms of general medical and gynecological clinics of an urban hospital at Emory University. Participants The 211 participants were primarily African American (90.05%) and of low socioeconomic status and had high rates of trauma and PTSD. Main Outcome Measures Baseline and post–dexamethasone suppression cortisol measures and gene expression levels. Results In our endocrine study, we found that only risk allele A carriers of rs9296158 showed GR supersensitivity with PTSD; in contrast, baseline cortisol levels were decreased in PTSD only in patients with the GG genotype. Expression of 183 transcripts was significantly correlated with PTSD symptoms after multiple testing corrections. When adding FKBP5 genotype and its interaction with PTSD symptoms, expression levels of an additional 32 genes were significantly regulated by the interaction term. Within these 32 genes, previously reported PTSD candidates were identified, including FKBP5 and the IL18 and STAT pathways. Significant overrepresentation of steroid hormone transcription factor binding sites within these 32 transcripts was observed, highlighting the fact that the earlier-described genotype and PTSD-dependent differences in GR sensitivity could drive the observed gene expression pattern. Results were validated by reverse transcriptase–polymerase chain reaction and replicated in an independent sample (N=98). Conclusions These data suggest that the inheritance of GR sensitivity–moderating FKBP5 polymorphisms can determine specific types of hypothalamic-pituitary-adrenal axis dysfunction within PTSD, which are also reflected in gene-expression changes of a subset of GR-responsive genes. Thus, these findings indicate that functional variants in FKBP5 are associated with biologically distinct subtypes of PTSD. PMID:21536970

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2008-10-01

for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

Assimilating multi-source uncertainties of a parsimonious conceptual hydrological model using hierarchical Bayesian modeling

Treesearch

Wei Wu; James Clark; James Vose

2010-01-01

Hierarchical Bayesian (HB) modeling allows for multiple sources of uncertainty by factoring complex relationships into conditional distributions that can be used to draw inference and make predictions. We applied an HB model to estimate the parameters and state variables of a parsimonious hydrological model – GR4J – by coherently assimilating the uncertainties from the...

Investigation of Current State of Crytpography and Theoretical Implementation of a Cryptographic System for the Combat Service Support Control System.

DTIC Science & Technology

1987-05-01

34 Advances in Crypt g: Proceedings of CRYPTO 84,r o ... .. .. _ __...o ... .. ... ....... ed. by G.R. Blakely and D. Chaum . [Wagn84b] Wagner, Neal R...in Distributed Computer Systems," IEEE Trans. on Computers, Vol. C-35, No. 7, Jul. 86, pp. 583-590. Gifford, David K., "Cryptographic Sealing for

Heavy Metal.

ERIC Educational Resources Information Center

Shoemaker, W. Lee

1998-01-01

Discusses the advantages, both functional and economic, of using a standing-seam metal roof in both new roof installations and reroofing projects of educational facilities. Structural versus non-structural standing-seam roofs are described as are the types of insulation that can be added and roof finishes used. (GR)

Ontogeny of the cortisol stress response in channel catfish (Ictalurus punctatus)

USDA-ARS?s Scientific Manuscript database

Cortisol is a glucocorticoid hormone which is an endocrine signaling molecule in all vertebrates and acts through intracellular glucocorticoid receptors (GR). Cortisol affects many biological functions including immunity, stress, growth, ion homeostasis, and reproduction. The objective of this stu...

Influence of xc functional on thermal-elastic properties of Ceria: A DFT-based Debye-Grüneisen model approach

NASA Astrophysics Data System (ADS)

Lee, Ji-Hwan; Tak, Youngjoo; Lee, Taehun; Soon, Aloysius

Ceria (CeO2-x) is widely studied as a choice electrolyte material for intermediate-temperature (~ 800 K) solid oxide fuel cells. At this temperature, maintaining its chemical stability and thermal-mechanical integrity of this oxide are of utmost importance. To understand their thermal-elastic properties, we firstly test the influence of various approximations to the density-functional theory (DFT) xc functionals on specific thermal-elastic properties of both CeO2 and Ce2O3. Namely, we consider the local-density approximation (LDA), the generalized gradient approximation (GGA-PBE) with and without additional Hubbard U as applied to the 4 f electron of Ce, as well as the recently popularized hybrid functional due to Heyd-Scuseria-Ernzehof (HSE06). Next, we then couple this to a volume-dependent Debye-Grüneisen model to determine the thermodynamic quantities of ceria at arbitrary temperatures. We find an explicit description of the strong correlation (e.g. via the DFT + U and hybrid functional approach) is necessary to have a good agreement with experimental values, in contrast to the mean-field treatment in standard xc approximations (such as LDA or GGA-PBE). We acknowledge support from Samsung Research Funding Center of Samsung Electronics (SRFC-MA1501-03).

Granzyme M and K release in human experimental endotoxemia.

PubMed

Wensink, Annette C; Wiewel, Maryse A; Jongeneel, Lieneke H; Boes, Marianne; van der Poll, Tom; Hack, C Erik; Bovenschen, Niels

2016-07-01

Granzymes are serine proteases involved in killing of tumor cells and virally infected cells. However, granzymes are also upregulated in blood under inflammatory conditions and contribute to cytokine release and processing. Here, we show that granzyme M (GrM) and to a lesser extent GrK are transiently elevated in the circulation following LPS administration in humans. GrM is released upon stimulation of whole blood with LPS or the gram-negative bacteria Escherichia coli BL21, Pseudomonas aeruginosa, and Neisseria meningitidis. GrK is only released upon stimulation with P. aeruginosa. Thus, GrM and GrK are differentially released in response to LPS and gram-negative bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial.

PubMed

Lee, Bonsan Bonne; Toh, Swee-Ling; Ryan, Suzanne; Simpson, Judy M; Clezy, Kate; Bossa, Laetitia; Rice, Scott A; Marial, Obaydullah; Weber, Gerard; Kaur, Jasbeer; Boswell-Ruys, Claire; Goodall, Stephen; Middleton, James; Tudehope, Mark; Kotsiou, George

2016-04-16

Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons with SCI. The primary outcome will be analysed using survival analysis of factorial groups, with Cox regression modelling to test the effect of each treatment while allowing for the other, assuming no interaction effect. Hazard ratios and Kaplan-Meier survival curves will be used to summarise results. If these probiotics are shown to be effective in preventing UTI and MRO colonisation, they would be a very attractive alternative for UTI prophylaxis and for combating the increasing rate of antibiotic resistance after SCI. Australian New Zealand Clinical Trials Registry [ ACTRN 12610000512022 ]. Date of registration: 21 June 2010.

Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

PubMed

Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

2017-09-11

In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

Preparation of myeloid derived suppressor cells (MDSC) from naive and pancreatic tumor-bearing mice using flow cytometry and automated magnetic activated cell sorting (AutoMACS).

PubMed

Nelson, Nadine; Szekeres, Karoly; Cooper, Denise; Ghansah, Tomar

2012-06-18

MDSC are a heterogeneous population of immature macrophages, dendritic cells and granulocytes that accumulate in lymphoid organs in pathological conditions including parasitic infection, inflammation, traumatic stress, graft-versus-host disease, diabetes and cancer. In mice, MDSC express Mac-1 (CD11b) and Gr-1 (Ly6G and Ly6C) surface antigens. It is important to note that MDSC are well studied in various tumor-bearing hosts where they are significantly expanded and suppress anti-tumor immune responses compared to naïve counterparts. However, depending on the pathological condition, there are different subpopulations of MDSC with distinct mechanisms and targets of suppression. Therefore, effective methods to isolate viable MDSC populations are important in elucidating their different molecular mechanisms of suppression in vitro and in vivo. Recently, the Ghansah group has reported the expansion of MDSC in a murine pancreatic cancer model. Our tumor-bearing MDSC display a loss of homeostasis and increased suppressive function compared to naïve MDSC. MDSC percentages are significantly less in lymphoid compartments of naïve vs. tumor-bearing mice. This is a major caveat, which often hinders accurate comparative analyses of these MDSC. Therefore, enriching Gr-1(+) leukocytes from naïve mice prior to Fluorescence Activated Cell Sorting (FACS) enhances purity, viability and significantly reduces sort time. However, enrichment of Gr-1(+) leukocytes from tumor-bearing mice is optional as these are in abundance for quick FACS sorting. Therefore, in this protocol, we describe a highly efficient method of immunophenotyping MDSC and enriching Gr-1(+) leukocytes from spleens of naïve mice for sorting MDSC in a timely manner. Immunocompetent C57BL/6 mice are inoculated with murine Panc02 cells subcutaneously whereas naïve mice receive 1XPBS. Approximately 30 days post inoculation; spleens are harvested and processed into single-cell suspensions using a cell dissociation sieve. Splenocytes are then Red Blood Cell (RBC) lysed and an aliquot of these leukocytes are stained using fluorochrome-conjugated antibodies against Mac-1 and Gr-1 to immunophenotype MDSC percentages using Flow Cytometry. In a parallel experiment, whole leukocytes from naïve mice are stained with fluorescent-conjugated Gr-1 antibodies, incubated with PE-MicroBeads and positively selected using an automated Magnetic Activated Cell Sorting (autoMACS) Pro Separator. Next, an aliquot of Gr-1(+) leukocytes are stained with Mac-1 antibodies to identify the increase in MDSC percentages using Flow Cytometry. Now, these Gr1(+) enriched leukocytes are ready for FACS sorting of MDSC to be used in comparative analyses (naïve vs. tumor- bearing) in in vivo and in vitro assays.

Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies

PubMed Central

Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

2017-01-01

Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples. PMID:29312638

Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies.

PubMed

Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

2017-12-12

Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples.

A sugar gustatory receptor identified from the foregut of cotton bollworm Helicoverpa armigera.

PubMed

Xu, Wei; Zhang, Hui-Jie; Anderson, Alisha

2012-12-01

Helicoverpa armigera (Hübner) is one of the most polyphagous and cosmopolitan pest species, the larvae of which feed on numerous important crops. The gustatory system is critical in guiding insect feeding behavior. Here, we identified a gustatory receptor from H. armigera, HaGR9, which shows high levels of identity to DmGR43a from Drosophila melanogaster and BmGR9 from Bombyx mori. Reverse transcriptase PCR (RT-PCR) revealed HaGR9 is highly expressed in larval foregut, with little or no expression in other chemosensory tissues. Membrane topology studies indicated that, like two previously studied B. mori GRs, BmGR8 and BmGR53, HaGR9 has an inverted topology relative to G protein-coupled receptors (GPCRs), an intracellular N-terminus and an extracellular C-terminus. Calcium imaging studies confirmed HaGR9 is a sugar receptor showing dose-dependent responses to D-galactose, D-maltose, and D-fructose. This highly-expressed foregut-specific gustatory receptor may contribute to the regulation of larval feeding behavior.

Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription.

PubMed

Stavreva, Diana A; Wiench, Malgorzata; John, Sam; Conway-Campbell, Becky L; McKenna, Mervyn A; Pooley, John R; Johnson, Thomas A; Voss, Ty C; Lightman, Stafford L; Hager, Gordon L

2009-09-01

Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation.

Glyphosate resistance in Ambrosia trifida: Part 1. Novel rapid cell death response to glyphosate.

PubMed

Van Horn, Christopher R; Moretti, Marcelo L; Robertson, Renae R; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Schulz, Burkhard; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Hall, J Christopher; McLean, Michael D; Lawton, Mark B; Sammons, R Douglas; Wang, Dafu; Westra, Philip; Gaines, Todd A

2018-05-01

Glyphosate-resistant (GR) Ambrosia trifida is now present in the midwestern United States and in southwestern Ontario, Canada. Two distinct GR phenotypes are known, including a rapid response (GR RR) phenotype, which exhibits cell death within hours after treatment, and a non-rapid response (GR NRR) phenotype. The mechanisms of resistance in both GR RR and GR NRR remain unknown. Here, we present a description of the RR phenotype and an investigation of target-site mechanisms on multiple A. trifida accessions. Glyphosate resistance was confirmed in several accessions, and whole-plant levels of resistance ranged from 2.3- to 7.5-fold compared with glyphosate-susceptible (GS) accessions. The two GR phenotypes displayed similar levels of resistance, despite having dramatically different phenotypic responses to glyphosate. Glyphosate resistance was not associated with mutations in EPSPS sequence, increased EPSPS copy number, EPSPS quantity, or EPSPS activity. These encompassing results suggest that resistance to glyphosate in these GR RR A. trifida accessions is not conferred by a target-site resistance mechanism. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Graphene transforms wide band gap ZnS to a visible light photocatalyst. The new role of graphene as a macromolecular photosensitizer.

PubMed

Zhang, Yanhui; Zhang, Nan; Tang, Zi-Rong; Xu, Yi-Jun

2012-11-27

We report the assembly of nanosized ZnS particles on the 2D platform of a graphene oxide (GO) sheet by a facile two-step wet chemistry process, during which the reduced graphene oxide (RGO, also called GR) and the intimate interfacial contact between ZnS nanoparticles and the GR sheet are achieved simultaneously. The ZnS-GR nanocomposites exhibit visible light photoactivity toward aerobic selective oxidation of alcohols and epoxidation of alkenes under ambient conditions. In terms of structure-photoactivity correlation analysis, we for the first time propose a new photocatalytic mechanism where the role of GR in the ZnS-GR nanocomposites acts as an organic dye-like macromolecular "photosensitizer" for ZnS instead of an electron reservoir. This novel photocatalytic mechanism is distinctly different from all previous research on GR-semiconductor photocatalysts, for which GR is claimed to behave as an electron reservoir to capture/shuttle the electrons photogenerated from the semiconductor. This new concept of the reaction mechanism in graphene-semiconductor photocatalysts could provide a new train of thought on designing GR-based composite photocatalysts for targeting applications in solar energy conversion, promoting our in-depth thinking on the microscopic charge carrier transfer pathway connected to the interface between the GR and the semiconductor.

Effects of gastrocnemius recession on ankle motion, strength, and functional outcomes: a systematic review and national healthcare database analysis.

PubMed

Gianakos, Arianna; Yasui, Youichi; Murawski, Christopher D; Kennedy, John G

2016-04-01

The purpose of this systematic review was to report the effects of gastrocnemius recession on ankle dorsiflexion range of motion, function, and push-off power. The MEDLINE and EMBASE databases were reviewed with terms "gastrocnemius recession". The inclusion criteria were: (1) clinical studies, (2) published in a peer-reviewed journal within the past 10 years, and (3) published in English. Excluded were: (1) review articles, (2) cadaveric studies, (3) studies including patients under the age of 18 years, (4) studies evaluating a neurologic condition, (5) level of evidence 5, and (6) Quality of Evidence Score <3. Data were then extracted and analysed for trends. The PearlDiver Database was also used to review de-identified patient information retrospectively between 2007 and 2011. Full-text review yielded 23 articles that fit the inclusion criteria. Twenty-one of 23 (91%) and 2/23 (9%) studies were level of evidence 4 and 3, respectively. Twelve of 23 (52%) studies reported follow-up assessment between 12 and 36 months, and no studies reported longer-term follow-up. Twelve of 12 (100%) studies reported improved dorsiflexion range of motion 9/9 (100%) reported improved AOFAS, and 11/11 (100%) reported improved VAS. Five of 23 (22%) studies reported strength in a measured and controlled fashion with variable results, but of these, no study reported a return to normal power. The mean complication rate was 14%. The available evidence supports that GR improves functional outcomes and increases dorsiflexion range of motion. Furthermore, GR affects gait kinematics, which may cause compensatory effects at the knee, ankle, and subtalar joints. Evidence has shown that power does not return to normal levels. Clinicians may utilize these data clinically to determine whether patients may benefit from GR or not. IV.

Increased antidepressant sensitivity after prefrontal cortex glucocorticoid receptor gene deletion in mice.

PubMed

Hussain, Rifat J; Jacobson, Lauren

2015-01-01

Our laboratory has previously shown that antidepressants regulate glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC). To determine if PFC GR are involved in antidepressant effects on behavior or hypothalamic-pituitary-adrenocortical (HPA) axis activity, we treated floxed GR male mice with saline or 15 or 30 mg/kg/d imipramine after PFC injection of adeno-associated virus 2/9 vectors transducing expression of Cre recombinase, to knock-down GR (PFC-GRKD), or green fluorescent protein (PFC-GFP), to serve as a control. The pattern of virally transduced GR deletion, common to all imipramine treatment groups, included the infralimbic, prelimbic, and medial anterior cingulate cortex at its largest extent, but was confined to the prelimbic and anterior cingulate cortex at its smallest extent. PFC GR knock-down increased behavioral sensitivity to imipramine, with imipramine-treated PFC-GRKD but not PFC-GFP mice exhibiting significant decreases in depression-like immobility during forced swim. PFC GR deletion did not alter general locomotor activity. The 30 mg/kg dose of imipramine increased plasma corticosterone levels immediately after a 5-min forced swim, but PFC GR knock-down had no significant effect on plasma corticosterone under these experimental conditions. We conclude that PFC GR knock-down, likely limited to the medial prelimbic and anterior cingulate cortices, can increase behavioral sensitivity to antidepressants. These findings indicate a novel role for PFC GR in influencing antidepressant response. Copyright © 2014 Elsevier Inc. All rights reserved.

Bacillus amyloliquefaciens subsp. plantarum GR53, a potent biocontrol agent resists Rhizoctonia disease on Chinese cabbage through hormonal and antioxidants regulation.

PubMed

Kang, Sang-Mo; Radhakrishnan, Ramalingam; Lee, In-Jung

2015-10-01

The fungus Rhizoctonia solani is one of the causal agents of numerous diseases that affect crop growth and yield. The aim of this present investigation was to identify a biocontrol agent that acts against R. solani and to determine the agent's protective effect through phytohormones and antioxidant regulation in experimentally infected Chinese cabbage plants. Four rhizospheric soil bacterial isolates GR53, GR169, GR786, and GR320 were tested for their antagonistic activity against R. solani. Among these isolates, GR53 significantly suppressed fungal growth. GR53 was identified as Bacillus amyloliquefaciens subsp. plantarum by phylogenetic analysis of the 16S rDNA sequence. The biocontrol activity of B. amyloliquefaciens subsp. plantarum GR53 was tested in Chinese cabbage plants under controlled conditions. Results showed that R. solani inhibited plant growth (length, width, fresh and dry weight of leaves) by reducing chlorophyll and total phenolic content, as well as by increasing the levels of salicylic acid, jasmonic acid, abscisic acid, and DPPH scavenging activity. By regulating the levels of these compounds, the co-inoculation of B. amyloliquefaciens subsp. plantarum GR53 heightened induced systemic resistance in infected Chinese cabbage, effectively mitigating R. solani-induced damaging effects and improving plant growth. The results obtained from this study suggest that B. amyloliquefaciens subsp. plantarum GR53 is an effective biocontrol agent to prevent the damage caused by R. solani in Chinese cabbage plants.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

PubMed

Chauhan, Abhishek; Yadav, Suraj Singh; Dwivedi, Pradeep; Lal, Nand; Usman, Kauser; Khattri, Sanjay

2016-09-01

Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD. © 2016 Wiley Periodicals, Inc.

EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells.

PubMed

Oberoi, Pranav; Jabulowsky, Robert A; Bähr-Mahmud, Hayat; Wels, Winfried S

2013-01-01

Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.

Interfacial Effects on the Thermal and Mechanical Properties of Graphite/Copper Composites. Final Contractor Report Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Devincent, Sandra Marie

1995-01-01

Graphite surfaces are not wet by pure copper. This lack of wetting has been responsible for a debonding phenomenon that has been found in continuous graphite fiber reinforced copper matrix composites subjected to elevated temperatures. By suitably alloying copper, its ability to wet graphite surfaces can be enhanced. Information obtained during sessile drop testing has led to the development of a copper-chromium alloy that suitably wets graphite. Unidirectionally reinforced graphite/copper composites have been fabricated using a pressure infiltration casting procedure. P100 pitch-based fibers have been used to reinforce copper and copper-chromium alloys. X-ray radiography and optical microscopy have been used to assess the fiber distribution in the cast composites. Scanning electron microscopy and Auger electron spectroscopy analyses were conducted to study the distribution and continuity of the chromium carbide reaction phase that forms at the fiber/matrix interface in the alloyed matrix composites. The effects of the chromium in the copper matrix on the mechanical and thermal properties of P100Gr/Cu composites have been evaluated through tensile testing, three-point bend testing, thermal cycling and thermal conductivity calculations. The addition of chromium has resulted in an increased shear modulus and essentially zero thermal expansion in the P100Gr/Cu-xCr composites through enhanced fiber/matrix bonding. The composites have longitudinal tensile strengths in excess of 700 MPa with elastic moduli of 393 GPa. After 100 hr at 760 deg C 84 percent of the as-cast strength is retained in the alloyed matrix composites. The elastic moduli are unchanged by the thermal exposure. It has been found that problems with spreading of the fiber tows strongly affect the long transverse tensile properties and the short transverse thermal conductivity of the P100Gr/Cu-xCr composites. The long transverse tensile strength is limited by rows of touching fibers which are paths of easy crack propagation under low tensile loads. The short transverse thermal conductivity is dictated by the fiber/matrix interface. Conduction across this interface has been estimated to be two orders of magnitude lower than that across the composite. This is due to the mechanical, and not chemical, nature of Gr/Cu bond.

Discrimination between NL1- and NL2-Mediated Nuclear Localization of the Glucocorticoid Receptor

PubMed Central

Savory, Joanne G. A.; Hsu, Brian; Laquian, Ian R.; Giffin, Ward; Reich, Terry; Haché, Robert J. G.; Lefebvre, Yvonne A.

1999-01-01

Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin α. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin α. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1− GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export. PMID:9891038

Growth restriction, leptin, and the programming of adult behavior in mice.

PubMed

Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

2014-12-15

Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, p<0.05), but GR mice exhibited regression in their escape times on days 2 and 3 (56% regressed vs 22% of control saline mice, p<0.05). Compared to controls, GR mice entered the open arms of the elevated plus maze more often and stayed there longer (72+/-10s vs 36+/-5s, p<0.01). Neonatal leptin supplementation normalized the behavior of GR mice across all behavioral assays. In conclusion, GR alters the social interactions, learning and activity of mice, and supplementation with the neurotrophic hormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets

PubMed Central

SUN, Qinwei; LI, Xi; JIA, Yimin; PAN, Shifeng; LI, Runsheng; YANG, Xiaojing; ZHAO, Ruqian

2016-01-01

Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression. PMID:26875838

Three-dimensional fusion of spaceborne and ground radar reflectivity data using a neural network-based approach

NASA Astrophysics Data System (ADS)

Kou, Leilei; Wang, Zhuihui; Xu, Fen

2018-03-01

The spaceborne precipitation radar onboard the Tropical Rainfall Measuring Mission satellite (TRMM PR) can provide good measurement of the vertical structure of reflectivity, while ground radar (GR) has a relatively high horizontal resolution and greater sensitivity. Fusion of TRMM PR and GR reflectivity data may maximize the advantages from both instruments. In this paper, TRMM PR and GR reflectivity data are fused using a neural network (NN)-based approach. The main steps included are: quality control of TRMM PR and GR reflectivity data; spatiotemporal matchup; GR calibration bias correction; conversion of TRMM PR data from Ku to S band; fusion of TRMM PR and GR reflectivity data with an NN method; interpolation of reflectivity data that are below PR's sensitivity; blind areas compensation with a distance weighting-based merging approach; combination of three types of data: data with the NN method, data below PR's sensitivity and data within compensated blind areas. During the NN fusion step, the TRMM PR data are taken as targets of the training NNs, and gridded GR data after horizontal downsampling at different heights are used as the input. The trained NNs are then used to obtain 3D high-resolution reflectivity from the original GR gridded data. After 3D fusion of the TRMM PR and GR reflectivity data, a more complete and finer-scale 3D radar reflectivity dataset incorporating characteristics from both the TRMM PR and GR observations can be obtained. The fused reflectivity data are evaluated based on a convective precipitation event through comparison with the high resolution TRMM PR and GR data with an interpolation algorithm.

Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

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

Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

1987-10-06

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H/sub 2/O and D/sub 2/O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/submore » 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). (/sup 125/I)hCG was bound to MLTC-1 cells under conditions that allow (37/sup 0/C) or prevent (0/sup 0/C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. (/sup 125/I)DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR.« less

Younger Elementary Students Waste More School Lunch Foods than Older Elementary Students

PubMed Central

Niaki, Shahrbanou F.; Moore, Carolyn E.; Chen, Tzu-An

2016-01-01

Background Children may not receive the nutritional benefits from school lunch meals if they do not eat the foods served. Objective This study investigated whether there were differences in school lunch foods consumed and wasted by grade level of elementary school students. Design In this cross-sectional study, anonymous meal observations were conducted after students selected their reimbursable school lunch meals in the cafeteria lunch line. The amount of foods selected and consumed was recorded using the quarter waste method and food waste was calculated using the information recorded. Participants/setting During the spring of 2013, eight elementary schools (50% low income) enrolling children in kindergarten through grade 5 in one school district in the Houston, Texas area were selected by the Child Nutrition Director. Main outcome measures The amount of kilocalories (kcal) and foods consumed and the percentage wasted were assessed. Statistical analyses performed Analysis of Covariance (ANCOVA) and post hoc analysis were used to examine food consumption and plate waste by grade level [kindergarten and grade 1 (K-Gr1), grade 2 and 3 (Gr2-3) and grade four and five (Gr4-5)], controlling for student sex and school level free/reduced priced meal eligibility (FRP). Results There were 568 nonrandom lunch meal observations of students included in the analyses. Approximately 48% of the observations were from boys; 50% were from low income schools, and were evenly divided by grade. In general, students in K-Gr1 consumed fewer kcal than both Gr2-3 and Gr4-5 students, and Gr2-3 students consumed significantly fewer kcal than Gr4-5 students. K-Gr1 students also consumed less and wasted more total and red-orange vegetables, total/whole/refined grains, and total protein foods than the older students. Gr2-3 students wasted more calories and total grains than Gr4-5 students. K-Gr1 wasted more fruit than Gr2-3 students. Conclusions Overall, younger students in elementary schools (K-Gr1) consumed less of the foods they selected for their lunch meals, and wasted more than older elementary school students. Future studies should investigate why younger children wasted more food and potential strategies to reduce food waste by younger students. PMID:27637576

The statistical mechanics of relativistic orbits around a massive black hole

NASA Astrophysics Data System (ADS)

Bar-Or, Ben; Alexander, Tal

2014-12-01

Stars around a massive black hole (MBH) move on nearly fixed Keplerian orbits, in a centrally-dominated potential. The random fluctuations of the discrete stellar background cause small potential perturbations, which accelerate the evolution of orbital angular momentum by resonant relaxation. This drives many phenomena near MBHs, such as extreme mass-ratio gravitational wave inspirals, the warping of accretion disks, and the formation of exotic stellar populations. We present here a formal statistical mechanics framework to analyze such systems, where the background potential is described as a correlated Gaussian noise. We derive the leading order, phase-averaged 3D stochastic Hamiltonian equations of motion, for evolving the orbital elements of a test star, and obtain the effective Fokker-Planck equation for a general correlated Gaussian noise, for evolving the stellar distribution function. We show that the evolution of angular momentum depends critically on the temporal smoothness of the background potential fluctuations. Smooth noise has a maximal variability frequency {{ν }max }. We show that in the presence of such noise, the evolution of the normalized angular momentum j=\\sqrt{1-{{e}2}} of a relativistic test star, undergoing Schwarzschild (in-plane) general relativistic precession with frequency {{ν }GR}/{{j}2}, is exponentially suppressed for j\\lt {{j}b}, where {{ν }GR}/jb2˜ {{ν }max }, due to the adiabatic invariance of the precession against the slowly varying random background torques. This results in an effective Schwarzschild precession-induced barrier in angular momentum. When jb is large enough, this barrier can have significant dynamical implications for processes near the MBH.

Testing gravity using large-scale redshift-space distortions

NASA Astrophysics Data System (ADS)

Raccanelli, Alvise; Bertacca, Daniele; Pietrobon, Davide; Schmidt, Fabian; Samushia, Lado; Bartolo, Nicola; Doré, Olivier; Matarrese, Sabino; Percival, Will J.

2013-11-01

We use luminous red galaxies from the Sloan Digital Sky Survey (SDSS) II to test the cosmological structure growth in two alternatives to the standard Λ cold dark matter (ΛCDM)+general relativity (GR) cosmological model. We compare observed three-dimensional clustering in SDSS Data Release 7 (DR7) with theoretical predictions for the standard vanilla ΛCDM+GR model, unified dark matter (UDM) cosmologies and the normal branch Dvali-Gabadadze-Porrati (nDGP). In computing the expected correlations in UDM cosmologies, we derive a parametrized formula for the growth factor in these models. For our analysis we apply the methodology tested in Raccanelli et al. and use the measurements of Samushia et al. that account for survey geometry, non-linear and wide-angle effects and the distribution of pair orientation. We show that the estimate of the growth rate is potentially degenerate with wide-angle effects, meaning that extremely accurate measurements of the growth rate on large scales will need to take such effects into account. We use measurements of the zeroth and second-order moments of the correlation function from SDSS DR7 data and the Large Suite of Dark Matter Simulations (LasDamas), and perform a likelihood analysis to constrain the parameters of the models. Using information on the clustering up to rmax = 120 h-1 Mpc, and after marginalizing over the bias, we find, for UDM models, a speed of sound c∞ ≤ 6.1e-4, and, for the nDGP model, a cross-over scale rc ≥ 340 Mpc, at 95 per cent confidence level.

EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE

EPA Science Inventory

EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE. D.K. Tarka1,2 , G.R. Klinefelter2, J.C. Rockett2, J.D. Suarez2, N.L. Roberts2 and J.M. Rogers1,2. 1 University of North Carol...

Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.

PubMed

Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi

2012-10-01

Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

PubMed

Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

2013-08-01

Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

PubMed

Ellenbroek, Johanne H; Töns, Hendrica A; de Graaf, Natascha; Loomans, Cindy J; Engelse, Marten A; Vrolijk, Hans; Voshol, Peter J; Rabelink, Ton J; Carlotti, Françoise; de Koning, Eelco J

2013-01-01

Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice. C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice. SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation. HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

PubMed

Martínez-Levy, G A; Rocha, L; Rodríguez-Pineda, F; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Briones-Velasco, M; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

2018-05-01

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Pushing the Boundaries of Technology, Education, and Design.

ERIC Educational Resources Information Center

Schneider, Jay W.

2000-01-01

Examines Sinclair Community College's (Dayton, OH) development of their 75,000 sq.ft. Center for Interactive Learning where the limits of technology in education can be experimented with, explored, and tested. Design planning, building function, design features, and furniture and finishes are discussed. (GR)

From Where You Sit.

ERIC Educational Resources Information Center

Kennedy, Mike

2001-01-01

Explains how furniture selection for residence halls depends on the space available, the function it is intended to serve, and the types of students who live there. Discusses the creation of a home-like atmosphere, including instituting regulations that let students supply some of their own furniture. (GR)

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

PubMed

Badano, Luigi P; Miglioranza, Marcelo H; Edvardsen, Thor; Colafranceschi, Alexandre Siciliano; Muraru, Denisa; Bacal, Fernando; Nieman, Koen; Zoppellaro, Giacomo; Marcondes Braga, Fabiana G; Binder, Thomas; Habib, Gilbert; Lancellotti, Patrizio

2015-09-01

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Urinary functional outcomes and toxicity five years after proton therapy for low- and intermediate-risk prostate cancer: Results of two prospective trials

PubMed Central

2013-01-01

Background. To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT. Material and methods. Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78–82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively. Results. Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15–25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months. Conclusion. Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15–25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15–25). PMID:23477359

Pilot evaluation of four experimental conditioning treatments to improve the bond strength between resin cement and Y-TZP ceramic.

PubMed

Monaco, Carlo; Cardelli, Paolo; Scotti, Roberto; Valandro, Luiz Felipe

2011-02-01

This study evaluated the bond strength between resin cement and Y-TZP ceramic (Yttrium-stabilized Tetragonal Zirconia Polycrystalline) submitted to different surface conditionings. Fifty Y-TZP ceramic discs (Ø= 10 mm) were allocated into five groups: Gr1 (control)-no conditioning; Gr2-tribochemical silica coating (30-μm SiO(2)) before sintering; Gr3-air abrasion with 50-μm Al(2)O(3) before sintering; Gr4-air abrasion with 110-μ Al(2)O(3) before sintering; Gr5 - air abrasion with 50-μm Al(2)O(3) after sintering. After specimen preparation, cylinders of composite resin were prepared and immediately cemented onto the ceramic. A shear test was performed. One-way ANOVA indicated a statistically significant difference among the groups (p= 0.0019). The mean shear bond strengths (MPa) were: Gr1 = 4.7 ± 0.8,(b) Gr2 = 4.6 ± 0.9,(b) Gr3 = 6.4 ± 1.0,(a) Gr4 = 6.5 ± 1.8,(a) Gr5 = 6 ± 1.3(ab) (same superscript letter indicates statistical similarity). Adhesive fracture between the ceramic and resin cement was the most common failure. No complete cohesive fracture at the ceramic or composite cylinders was noted. Within the limitations of this study, additional surface treatment with air abrasion before and after sintering provided a significant increase in bond strength. Tribochemical silica coating before sintering was not effective as a surface treatment. © 2011 by The American College of Prosthodontists.

Structure and Dynamic Properties of a Glucocorticoid Receptor-Induced Chromatin Transition

PubMed Central

Fletcher, Terace M.; Ryu, Byung-Woo; Baumann, Christopher T.; Warren, Barbour S.; Fragoso, Gilberto; John, Sam; Hager, Gordon L.

2000-01-01

Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633–3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a “hit-and-run” mechanism for GR action in living cells (J. G. McNally, W. G. Müller, D. Walker, and G. L. Hager, Science 287:1262–1264, 2000). PMID:10938123

Separation of an associated 90K heat shock protein from the glucocorticoid receptor complex

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

Miller-Diener, A.; Kirsch, T.; Grove, B.

1986-05-01

A 90K heat shock protein(HSP), observed to copurify with the glucocorticoid receptor(GR), can be separated from the complex by 2 methods, allowing investigation of the role of HSP on kinase activity that was previously reported to be inherent to purified activated GR. Na/sub 2/MoO/sub 4/ stabilized unactivated rat hepatic GR complexes have been purified to >10,000-fold using a purification scheme that involves batchwise treatment of cytosol with phosphocellulose/DNAcellulose, elution from an affinity resin, gel filtration and ion exchange chromatography. Samples were subjected to 10-20% gradient SDS-PAGE. Proteins were transferred to nitrocellulose and blotted against monoclonal antibodies to GR(3A6), HSP ormore » nonspecific IgM/G. Immunoblots indicated that HSP was separated from unactivated GR complexes at the affinity step prior to elution of GR with active steroid. GR eluted from the resin with /sup 3/H Triamcinolone acetonide or /sup 3/H Dexamethasone mesylate had an apparent M/sub r/ = 94-96,000 for the steroid binding subunit and is recognized by 3A6. Purification of GR minus the affinity step resulted in copurification of HSP throughout the procedure. However, after Sephadex G75 filtration and subsequent incubation at 25/sup 0/C, 30 min., HSP was separated from activated (DNA binding) GR on DEAE cellulose-52. HSP did not enhance or inhibit /sup 32/P incorporation of the 94K steroid binding subunit nor did it affect phosphorylation of histones by GR.« less

Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

PubMed

Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

2014-08-01

To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P<.001) and 61 (73%) of 84 non-muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P<.001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P=.025), progression of MI tumors (P=.082), and cancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

J-R fracture characteristics of ferritic steels for RPVs and RCS piping of nuclear power plants

NASA Astrophysics Data System (ADS)

Yoon, Ji-Hyun; Lee, Bong-Sang; Hong, Jun-Hwa

2001-10-01

J-R fracture resistance tests have been performed on 3 heats of SA508-Gr.3 nuclear reactor pressure vessel (RPV) steel as well as 2 heats of SA516-Gr.70 and a heat of SA508-Gr.1a steels for nuclear reactor coolant system (RCS) piping. For the latter two steels, dynamic in addition to static J-R fracture resistances were investigated. From the test results of the SA508-Gr.3 steels, the J-R fracture resistance was superior in the following order: Si-killing steel, modified VCD steel and VCD steel. Microstructural analyses were carried out to correlate J-R fracture resistances with microstructural characteristics. According to the test results for SA508-Gr.1a and SA516-Gr.70 steels, all of the tested steels showed steep drops in fracture resistance at certain temperature and loading rate combinations. One heat of SA516-Gr.70 steel was very sensitive to dynamic strain aging and its fracture resistance was significantly low. It was concluded that microstructural and chemical factors affect the J-R fracture and DSA characteristics of SA516-Gr.70 steels.

Challenges in graphene integration for high-frequency electronics

NASA Astrophysics Data System (ADS)

Giannazzo, F.; Fisichella, G.; Greco, G.; Roccaforte, F.

2016-06-01

This paper provides an overview of the state-of-the-art research on graphene (Gr) for high-frequency (RF) devices. After discussing current limitations of lateral Gr RF transistors, novel vertical devices concepts such as the Gr Base Hot Electron Transistor (GBHET) will be introduced and the main challenges in Gr integration within these architectures will be discussed. In particular, a GBHET device based on Gr/AlGaN/GaN heterostructure will be considered. An approach to the fabrication of this heterostructure by transfer of CVD grown Gr on copper to the AlGaN surface will be presented. The morphological and electrical properties of this system have been investigated at nanoscale by atomic force microscopy (AFM) and conductive atomic force microscopy (CAFM). In particular, local current-voltage measurements by the CAFM probe revealed the formation of a Schottky contact with low barrier height (˜0.41 eV) and excellent lateral uniformity between Gr and AlGaN. Basing on the electrical parameters extracted from this characterization, the theoretical performances of a GBHET formed by a metal/Al2O3/Gr/AlGaN/GaN stack have been evaluated.

Glyphosate Can Decrease Germination of Glyphosate-Resistant Soybeans.

PubMed

Gomes, Marcelo Pedrosa; Bicalho, Elisa Monteze; Smedbol, Élise; Cruz, Fernanda Vieira da Silva; Lucotte, Marc; Garcia, Queila Souza

2017-03-22

We investigated the effects of different concentrations of glyphosate acid and one of its formulations (Roundup) on seed germination of two glyphosate-resistant (GR) and one non-GR variety of soybean. As expected, the herbicide affected the shikimate pathway in non-GR seeds but not in GR seeds. We observed that glyphosate can disturb the mitochondrial electron transport chain, leading to H 2 O 2 accumulation in soybean seeds, which was, in turn, related to lower seed germination. In addition, GR seeds showed increased activity of antioxidant systems when compared to non-GR seeds, making them less vulnerable to oxidative stress induced by glyphosate. The differences in the responses of GR varieties to glyphosate exposure corresponded to their differences in enzymatic activity related to H 2 O 2 scavenging and mitochondrial complex III (the proposed site of ROS induction by glyphosate). Our results showed that glyphosate ought to be used carefully as a pre-emergence herbicide in soybean field crop systems because this practice may reduce seed germination.

Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

PubMed

Horwell, C J; Baxter, P J; Hillman, S E; Calkins, J A; Damby, D E; Delmelle, P; Donaldson, K; Dunster, C; Fubini, B; Kelly, F J; Le Blond, J S; Livi, K J T; Murphy, F; Nattrass, C; Sweeney, S; Tetley, T D; Thordarson, T; Tomatis, M

2013-11-01

The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples, despite substantial differences in the sample mineralogy and eruptive styles. The value of the pro-inflammatory profiles in differentiating the potential respiratory health hazard of volcanic ashes remains uncertain in a protocol designed to inform public health risk assessment, and further research on their role in volcanic crises is warranted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Disparity in Democracies: A Comparative Case Study of Mali and Niger

DTIC Science & Technology

2010-12-01

thought he was. In the spirit of cooperation, Ousmane issued an emotional appeal to the "every patriot,.. .all the Niger political class...even voted on.127 In 1993-1994, eleven Islamic organizations thwarted a government condom distribution campaign aimed at both contraception and AIDS...GR-EN.pdf (accessed October 18, 2010). 123 Radio France Internationale, "Islamic groups attempt to sabotage contraceptive campaign," November 18

Interphase Thermomechanical Reliability and Optimization for High-Performance Ti Metal Laminates

DTIC Science & Technology

2011-12-19

Thermomechanical Reliability and Optimization for High-Performance Ti FA9550-08-l-0015 Metal Laminates Sb. GRANT NUMBER Program Manager: Dr Joycelyn Harrison...OSR-VA-TR-2012-0202 12. DISTRIBUTION/AVAILABILITY STATEMENT A 13. SUPPLEMENTARY NOTES 14. ABSTRACT Hybrid laminated composites such as titanium...graphite (TiGr) laminates are an emerging class of structural materials with the potential to enable a new generation of efficient, high-performance

GR718- Radiation-Tolerant 18x SpaceWire Router

NASA Astrophysics Data System (ADS)

Ekergaren, Jonas; Habinc, Sandi; Johansson, Fredrik; Sturesson, Fredrik; Simlastik, Martin; Hernandez, Francisco; Redant, Steven; Stinkens, Kurt; Thys, Geert; Das Arul Mahesh, Jagadeesa; Suess, Martin

2015-09-01

GR718 is a radiation tolerant 18 port standalone SpaceWire router component that has been developed by Cobham Gaisler together with IMEC (BE), in an activity initiated by the European Space Agency under ESTEC contract 4000105402/12/NL/Cbi. Out of the 18 SpaceWire ports, 16 use on-chip LVDS transceivers, and two use LVTTL signaling. Included also is the mandatory configuration port, as well as an internal port for system level testing. All ports are capable of operating in 200 Mbit/s. UART and JTAG interfaces, that gives access to the on-chip AMBA AHB bus, are provided for configuration and debugging. SPI and GPIO interfaces are accessible through the configuration port, which allows SPI devices to be accessed and general purpose signaling to be performed through RMAP commands. In addition to the mandatory features in the current ECSS SpaceWire standard, GR718 supports group adaptive routing for path addresses, and packet distribution. It also includes support for the incoming SpaceWire standard revision 1 (ECSS-E-ST-50-12C Rev.1), the SpaceWire-D protocol, and the SpaceWire Plug-and-Play protocol currently being developed for ECSS. The technology used is UMC 180 nm, using the DARE library from IMEC, and the package is a 256 pin CQFP. A development board for evaluation and software development has been manufactured as well.

Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in Gossypium raimondii

PubMed Central

He, Qiuling; Jones, Don C.; Li, Wei; Xie, Fuliang; Ma, Jun; Sun, Runrun; Wang, Qinglian; Zhu, Shuijin; Zhang, Baohong

2016-01-01

The R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement. PMID:27009386

Evaluation of a Proposed Biodegradable 188Re Source for Brachytherapy Application

PubMed Central

Khorshidi, Abdollah; Ahmadinejad, Marjan; Hamed Hosseini, S.

2015-01-01

Abstract This study aimed to evaluate dosimetric characteristics based on Monte Carlo (MC) simulations for a proposed beta emitter bioglass 188Re seed for internal radiotherapy applications. The bioactive glass seed has been developed using the sol-gel technique. The simulations were performed for the seed using MC radiation transport code to investigate the dosimetric factors recommended by the AAPM Task Group 60 (TG-60). Dose distributions due to the beta and photon radiation were predicted at different radial distances surrounding the source. The dose rate in water at the reference point was calculated to be 7.43 ± 0.5 cGy/h/μCi. The dosimetric factors consisting of the reference point dose rate, D(r0,θ0), the radial dose function, g(r), the 2-dimensional anisotropy function, F(r,θ), the 1-dimensional anisotropy function, φan(r), and the R90 quantity were estimated and compared with several available beta-emitting sources. The element 188Re incorporated in bioactive glasses produced by the sol-gel technique provides a suitable solution for producing new materials for seed implants applied to brachytherapy applications in prostate and liver cancers treatment. Dose distribution of 188Re seed was greater isotropic than other commercially attainable encapsulated seeds, since it has no end weld to attenuate radiation. The beta radiation-emitting 188Re source provides high doses of local radiation to the tumor tissue and the short range of the beta particles limit damage to the adjacent normal tissue. PMID:26181543

Comfort with Computers in the Library.

ERIC Educational Resources Information Center

Agati, Joseph

2002-01-01

Sets forth a list of do's and don't's when integrating aesthetics, functionality, and technology into college library computer workstation furniture. The article discusses workstation access for both portable computer users and for staff, whose needs involve desktop computers that are possibly networked with printers and other peripherals. (GR)

A Study on Gröbner Basis with Inexact Input

NASA Astrophysics Data System (ADS)

Nagasaka, Kosaku

Gröbner basis is one of the most important tools in recent symbolic algebraic computations. However, computing a Gröbner basis for the given polynomial ideal is not easy and it is not numerically stable if polynomials have inexact coefficients. In this paper, we study what we should get for computing a Gröbner basis with inexact coefficients and introduce a naive method to compute a Gröbner basis by reduced row echelon form, for the ideal generated by the given polynomial set having a priori errors on their coefficients.

Low Phase Noise Fiber Optics Links for Space Applications

DTIC Science & Technology

2005-07-13

photo- oscillateur intégré pour 17 dB de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 18 dB de pertes optiques Liaison...active à 874,2 MHz avec photo- oscillateur intégré pour 20 dB de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 23 dB...de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 25 dB de pertes optiques Liaison active à 874,2 MHz avec photo

Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

PubMed

Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

2010-09-01

Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

Medical History in the Hellenic Journal of Nuclear Medicine.

PubMed

Otte, Andreas

2017-01-01

The Hellenic Journal of Nuclear Medicine is about to celebrate its 20th anniversary end of 2017. On board of the editorial team since 2003, this journal has influenced me like a good friend over the many past years. From time to time, the journal has published interesting and valuable historical notes. They show that nuclear medicine has a history and that medicine is its basis. They also teach us today, and some of the ancient perspectives and approaches are still valid. The reader of HJNM may be interested in these historical contributions, as they are timeless. Therefore, it was our idea to summarize these in the following pages. Where there is a link to the free article, this is noted. Upon opening all articles, you will find out that these are a book or so of its own. In thanks to the editor-in-chief of the Journal for his continuing support on the historical section. Below we refer to the historical papers of the Journal: History of Nuclear Medicine. Nuclear Medicine and History of Science and Philosophy: Atomic Theory of the Matter. G.N. Sfakianakis, 2001; 4(3); 155-60. Editorial. Pioneers of nuclear medicine, Madame Curie. P.C. Grammaticos. 2004; 7(1); 29-30. http://nuclmed.web.auth.gr/ magazine/eng/jan04/editorial.htm Editor's note. Hippocrates' Oath. The editor. 2004; 7(1); 31. Editorial. Useful known and unknown views of the father of modern medicine, Hippocrates and his teacher Democritus. P. Grammaticos, A. Diamantis. 2008; 11(1): 2-4. http://nuclmed.web.auth.gr/magazine/eng/jan08/2.pdf Special Article. The contribution of Maria Sklodowska-Curie and Pierre Curie to Nuclear and Medical Physics. A hundred and ten years after the discovery of radium. A. Diamantis, E. Magiorkinis, 2008; 11(1): 33-8. http://nuclmed.web.auth.gr/magazine/ eng/jan08/33.pdf Brief Historical Review. Lymphatic system and lymphoscintigraphy. P. Valsamaki. 2009; 12(1): 87-89. http://nuclmed.web. auth.gr/magazine/eng/jan09/89.pdf (In Greek) Historical Review. The philosophic and biological views of the "atomic" philosophers, Leucippus and Democritus. E. Magiorkinis. A. Beloukas, A. Diamantis. 2010; 13(2): 111-117. http://nuclmed.web.auth.gr/magazine/eng/may10/9.pdf Correspondence. Neuroimaging in mild traumatic brain injury and M. Ravel's injury. A. Otte. 2012; 15(1): 76. http://nuclmed. web.auth.gr/magazine/eng/jan12/3.pdf Selected Brief Contributions. The "atomic theory" of Leucippus, and its impact on medicine before Hippocrates. G. Tsoucalas, K. Laios et al. 2013; 16(1): 68-9. http://nuclmed.web.auth.gr/magazine/eng/jan13/72.pdf Selected Brief Contributions. Computed tomography alone reveals the secrets of ancient mummies in medical archaeology. A. Otte, T. Thieme et al. 2013; 16(2): 148-9. http://nuclmed.web.auth.gr/magazine/eng/may13/70.pdf Editorial. The timeless influence of Hippocratic ideas on diet, salicylates and personalized medicine. T.C. Karagiannis. 2014; 17(1): 2-6. http://nuclmed.web.auth.gr/magazine/eng/jan14/1.pdf Historical Article. The physician who first applied radiotherapy, Victor Despeignes, on 1896. M. Sgantzos, G. Tsoucalas et al. 2014; 17(1): 45-6. http://nuclmed.web.auth.gr/magazine/eng/jan14/11.pdf Original Articles. Medical practice applied in the ancient Asclepeion in Kos island. M. Mironidou-Tzouveleki, P.M. Tzitzis. 2014; 17(3): 167-70. http://www.nuclmed.web.auth.gr/magazine/eng/sept14/3.pdf Special Historical Article. How a tertiary medical nuclear medicine department at the Himalayan area in India can be established and function in an exemplary manner. Basic rules revisited. V.K. Dhingra, S. Saini et al. 2015; 18(3): 252-6. http:// nuclmed.web.auth.gr/magazine/eng/sept15/13.pdf Historical and Commentary Note. Johann Sebastian Bach's "Goldberg variations" to treat insomnia from renal lithiasis pain. Sleep research in Nuclear Medicine. A. Otte. 2016; 19(1): 13-4. http://nuclmed.web.auth.gr/magazine/eng/jan16/06.pdf Historical Review. The first medical ethics and deontology in Europe as derived from Greek mythology. M.K. Konstantinidou. 2016; 19(2): 155-8.http://nuclmed.web.auth.gr/magazine/eng/may16/11.pdf Historical-Technical Article. The beginning of using X-rays and the evolution of equipment for the treatment of ocular cancer. K. Laios, M. Zozoglou. 2017; 20(1): Ahead of print. And hopefully many more to follow!

[125I]-GR231118: a high affinity radioligand to investigate neuropeptide Y Y1 and Y4 receptors

PubMed Central

Dumont, Yvan; Quirion, Rémi

2000-01-01

GR231118 (also known as 1229U91 and GW1229), a purported Y1 antagonist and Y4 agonist was radiolabelled using the chloramine T method. [125I]-GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h. Saturation binding experiments showed that [125I]-GR231118 binds with very high affinity (Kd of 0.09–0.24 nM) in transfected HEK293 cells with the rat Y1 and Y4 receptor cDNA and in rat brain membrane homogenates. No specific binding sites could be detected in HEK293 cells transfected with the rat Y2 or Y5 receptor cDNA demonstrating the absence of significant affinity of GR231118 for these two receptor classes. Competition binding experiments revealed that specific [125I]-GR231118 binding in rat brain homogenates is most similar to that observed in HEK293 cells transfected with the rat Y1, but not rat Y4, receptor cDNA. Autoradiographic studies demonstrated that [125I]-GR231118 binding sites were fully inhibited by the Y1 antagonist BIBO3304 in most areas of the rat brain. Interestingly, high percentage of [125I]-GR231118/BIBO3304-insensitive binding sites were detected in few areas. These [125I]-GR231118/BIBO3304-insensitive binding sites likely represent labelling to the Y4 receptor subtype. In summary, [125I]-GR231118 is a new radiolabelled probe to investigate the Y1 and Y4 receptors; its major advantage being its high affinity. Using highly selective Y1 antagonists such as BIBO3304 or BIBP3226 it is possible to block the binding of [125I]-GR231118 to the Y1 receptor allowing for the characterization and visualization of the purported Y4 subtype. PMID:10694200

Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs.

PubMed

Musiolik, Judith; van Caster, Patrick; Skyschally, Andreas; Boengler, Kerstin; Gres, Petra; Schulz, Rainer; Heusch, Gerd

2010-01-01

Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK). Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = F(i)+e(-(0.1)(t)((min)-3)).(F(b)-F(i)); F(b), coronary inflow at baseline; F(i), coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80-85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3-AKT and MEK1/2-ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 +/- 2% (mean +/- SEM) of the area at risk with IFR and 29 +/- 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 +/- 4% of the area at risk; BL-GR: 42 +/- 5%; P < 0.05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.