Enzymatic preparation of. cap alpha. - and. beta. -deuterated or tritiated amino acids with l-methionine. gamma. -lyase

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

Esaki, N.; Sawada, S.; Tanaka, H.

L-Methionine ..gamma..-lyase catalyzes the exchange of ..cap alpha..- and ..beta..-hydrogens of L-methionine and S-methyl-L-cysteine with deuterium or tritium of solvents. The rate of ..cap alpha..-hydrogen exchange with deuterium was about 40 times faster than that of the elimination reactions. The deuterium and tritium were exchanged also with the ..cap alpha..- and ..beta..-hydrogens of the straight-chain amino acids which do not undergo the elimination: L-alanine, L-..cap alpha..-aminobutyrate, L-norvaline, and L-norleucine. No exchange occurs for the D-isomers, acidic L-amino acids, basic L-amino acids, and branched-chain L-amino acids, although ..cap alpha..-hydrogen of glycine, L-trypotophan, and L-phenylalanine is exchanged slowly. These enzymatic hydrogen-exchange reactionsmore » facilitate specific labeling of the L-amino acids with deuterium and tritium.« less

Purification and characterization of the glycoprotein hormone. cap alpha. -subunit-like material secreted by HeLa cells

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

Cox, G.S.; Rimerman, R.A.

1988-08-23

The protein secreted by HeLa cells that cross-reacts with antiserum developed against the ..cap alpha..-subunit of human chorionic gonadotropin (hCG) has been purified approximately 30,000-fold from concentrated culture medium by organic solvent fractionation followed by ion exchange, gel filtration, and lectin affinity chromatography. The final preparation had a specific activity (by RIA) of 6.8 x 10/sup 5/ ng of ..cap alpha../mg of protein and appeared homogeneous by electrophoresis on reducing/denaturing polyacrylamide gels (SDS-PAGE). Amino acid analysis indicated that HeLa-..cap alpha.. had a composition very similar to that of the urinary hCG ..cap alpha..-subunit. However, comparison of hCG-..cap alpha.. and HeLa-..capmore » alpha.. demonstrated that the tumor-associated subunit was not identical with its normal counterpart. The purified tumor protein had an apparent molecular weight greater than that of the urinary ..cap alpha..-subunit when analyzed by SDS-PAGE, and this difference was even greater when a partially purified preparation was examined by an immunoblot technique (Western). Isoelectric focusing of the HeLa and hCG subunits demonstrated that the tumor protein had a lower pI. Immunoprecipitation and electrophoresis of ..cap alpha..-subunit from HeLa cultures labeled with (/sup 3/H)fucose indicated that the tumor subunit was fucosylated, whereas analysis of hCG-..cap alpha.. hydrosylates by HPLC confirmed previous reports that the placental subunit does not contain fucose. The results indicate that, regardless of whether or not a single ..cap alpha..-subunit gene is being expressed in both normal and neoplastic tissues, posttranslational modifications lead to a highly altered subunit in the tumor. The differences observed may be useful in diagnosing neoplastic vs hyperplastic conditions and may lend insight into the mechanism of ectopic hormone production by tumors.« less

Velocity space instabilities of alpha particles in tokamak reactors

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

Sigmar, D.J.

1979-01-01

In this lecture on high frequency instability due to isotropic hollow alpha velocity distributions it was first shown that such distributions can actually arise under thermonuclear conditions in a tokamak reactor, particularly for the case of imperfect alpha particle confinement. The toroidal geometry (i.e., the poloidal variation of the alpha gyrofrequency) then leads to linear instability of the compressional Alfven wave ..omega.. = C/sub A/k/sub perpendicular/ with k/sub parallel/ congruent to O, k/sub perpendicular/ rho/sub ..cap alpha../ greater than or equal to 1, v/sub ..cap alpha../ > C/sub A/, at the low harmonics ..omega.. congruent to n ..omega../sub c..cap alpha../.more » Thus the free energy of the inverted alpha distribution is accessible and produces anomalously rapid diffusion of F/sub ..cap alpha../(v/sub perpendicular/). (MOW)« less

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

Popp, R.A.; Marsh, C.L.; Skow, L.C.

Hemoglobins of mouse embryos at 11.5 through 16.5 days of gestation were separated by electrophoresis on cellulose acetate and quantitated by a scanning densitometer to study the effects of two radiation-induced mutations on the expression of embryonic hemoglobin genes in mice. Normal mice produce three kinds of embryonic hemoglobins. In heterozygous ..cap alpha..-thalassemic embryos, expression of EI (x/sub 2/y/sub 2/) and EII (..cap alpha../sub 2/y/sub 2/) is deficient because the x- and ..cap alpha..-globin genes of one of the allelic pairs of Hba on chromosome 11 was deleted or otherwise inactivated by X irradiation. Simultaneous inactivation of the x- andmore » ..cap alpha..-globin genes indicates that these genes must be closely linked. Reduced x- and ..cap alpha..-chain synthesis results in an excess of y chains that associate as homotetramers. This unique y/sub 4/ hemoglobin also appears in ..beta..-duplication embryos where excess y chains are produced by the presence of three rather than two functional alleles of y- and ..beta..-globin genes. In double heterozygotes, which have a single functional allele of x- and ..cap alpha..-globin genes and three functional alleles of y- and ..beta..-globin genes, synthesis of ..cap alpha.. and non-..cap alpha.. chains is severely imbalanced and half of the total hemoglobin is y/sub 4/. Mouse y/sub 4/ has a high affinity for oxygen, P/sub 50/ of less than 10 mm Hg, but it lacks cooperativity so is inefficient for oxygen transport. The death of double heterozygotes in late fetal or neonatal life may be in large part to oxygen deprivation to the tissues.« less

Two subunits of the 55 K porcine zona pellucida glycoprotein family are immunologically distinct

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

Subramanian, M.G.; Yurewicz, E.C.; Sacco, A.G.

1986-03-01

The 55K glycoprotein family (ZP3) of the porcine zona pellucida is comprised of two subunits of 46 K and 45 K which can be resolved by endo-..beta..-galactosidase digestion of ZP3 followed by reversed phase HPLC on Vydac C4 resin. Gel electrophoresis revealed that the 46 K component (EBDG..cap alpha..) is approx. 95% pure and the 45 K component (EBGD..beta..) is 100% pure. In the present study, these two subunits were evaluated immunologically by RIA. Under similar reaction protocols (chloramine-T iodination procedure) comparable specific activities were obtained for EBGD..cap alpha.. (33.06 +/- 7.5 ..mu..ci/..mu..gm), EBGD..beta.. (30.45 +/- 1.6) and ZP3 (26.3more » +/- 1.3). Antibody (Ab) titration studies revealed that EBGD..cap alpha.. and ..beta.. are potent immunogens and /sup 125/I-EBGD..cap alpha.. showed minimal cross reactivity to EBGD..beta..-Ab (8% bound at 1:500 dilution), whereas, /sup 125/I-EBGD..beta.. showed a greater degree of cross reactivity to EBGD..cap alpha..-Ab (23% bound at 1:500 dilution). Maximum binding for the two labeled antigens against homologous Abs (1:500) was > 60%. Dose response studies revealed that in the /sup 125/I-EBGD..cap alpha.. vs EBGD..cap alpha.. -Ab system, the 50% intercept was 3.25 +/- 0.32 ng for EBGD..cap alpha.. and 472.43 +/- 30.26 ng for EBGD..beta.. (p < 0.01), whereas, in the /sup 125/I-EBGD..beta.. vs EBGD..beta..-Ab system the 50% intercept was 3.51 +/- 0.58 for EBGD..beta.. and 166.77 +/- 49.20 for EBGD..cap alpha.. (p < 0.01). No significant differences were observed in the slopes of the dose response curves. It is concluded that the two subunits of ZP3 possess distinct immunologic characteristics as evaluated by RIA.« less

cap alpha. -D-Mannopyranosylmethyl-P-nitrophenyltriazene effects on the degradation and biosynthesis of N-linked oligosaccharide chains on. cap alpha. /sub 1/-acid glycoprotein by liver cells

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

Docherty, P.A.; Aronson, N.N. Jr.

1986-05-01

The effects of ..cap alpha..-D-mannopyranosylmethyl-p-nitrophenyltriazene (..cap alpha..-ManMNT) on the degradation and processing of oligosaccharide chains on ..cap alpha../sub 1/-acid glycoprotein (AGP) were studied. Addition of the triazene to a perfused liver blocked the complete degradation of endocytosed N-acetyl (/sup 14/C)glucosamine-labeled asialo-AGP and caused the accumulation of Man/sub 2/GlcNAc/sub 1/ fragments in the lysosome-enriched fraction of the liver homogenate. This compound also reduced the reincorporation of lysosomally-derived (/sup 14/C)GlcNAc into newly secreted glycoproteins. Cultured hepatocytes treated with the inhibitor synthesized and secreted fully-glycosylated AGP. However, the N-linked oligosaccharide chains on AGP secreted by the ..cap alpha..-ManMNT-treated hepatocytes remained sensitive to digestionmore » with endoglycosidase H, were resistant to neuraminidase, and consisted of Man/sub 9-7/GlcNAc/sub 2/ structures as analyzed by high resolution Bio-Gel P-4 chromatography. As measured by their resistance to cleavage by endoglycosidase H, the normal processing of all six carbohydrate chains on AGP to the complex form did not completely resume until nearly 24 h after triazene treatment. Since ManMNT is likely to irreversibly inactivate ..cap alpha..-D-mannosidases, the return of AGP to secretory forms with complex chains after 24 h probably resulted from synthesis of new processing enzymes.« less

The X-ray Crystal Structures of Human {alpha}-Phosphomannomutase 1 Reveal the Structural Basis of Congenital Disorder of Glycosylation Type 1a

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

Silvaggi,N.; Zhang, C.; Lu, Z.

2006-01-01

Carbohydrate-deficient glycoprotein syndrome type 1a (CDG-1a) is a congenital disease characterized by severe defects in nervous system development. It is caused by mutations in alpha -phosphomannomutase (of which there are two isozymes, {alpha}-PMM1 and {alpha}-PPM2). Here we report the X-ray crystal structures of human {alpha}-PMM1 in the open conformation, with and without the bound substrate, {alpha}-D-mannose 1-phosphate. {alpha}-PMM1, like most Haloalkanoic Acid Dehalogenase Superfamily (HADSF) members, consists of two domains, the cap and core, which open to bind substrate and then close to provide a solvent exclusive environment for catalysis. The substrate phosphate group is observed at a positively chargedmore » site of the cap domain, rather than at the core domain phosphoryl-transfer site defined by the D19 nucleophile and Mg{sup 2+} cofactor. This suggests that substrate binds first to the cap and then is swept into the active site upon cap closure. The orientation of the acid/base residue D21 suggests that {alpha}-PMM uses a different method of protecting the aspartylphosphate from hydrolysis than the HADSF member {beta}-phosphoglucomutase. It is hypothesized that the electrostatic repulsion of positive charges at the interface of the cap and core domains stabilizes {alpha}-PMM1 in the open conformation, and that the negatively charged substrate binds to the cap, thereby facilitating its closure over the core domain. The two isozymes {alpha}-PMM1 and {alpha}-PMM2 are shown to have a conserved active-site structure and to display similar kinetic properties. Analysis of the known mutation sites in the context of the structures reveals the genotype-phenotype relationship underlying CDG-1a.« less

Genomic organization and sequence of the Gus-s/sup a/ allele of the murine. beta. -glucuronidase gene

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

Funkenstein, B.; Leary, S.L.; Stein, J.C.

1988-03-01

The Gus-s/sup ..cap alpha../ allele of the mouse ..beta..-glucuronidase gene exhibits a high degree of inducibility by androgens due to its linkage with the Gus-r/sup ..cap alpha../ regulatory locus. The authors isolated Gus-s/sup ..cap alpha../ on a 28-kilobase pair fragment of mouse chromosome 5 and found that it contains 12 exons and 11 intervening sequences spanning 14 kilobase pairs of this genomic segment. The mRNA cap site was identified by ribonuclease protection and primer extension analyses which revealed an unusually short 5' noncoding sequence of 12 nucleotides. Proximal regulatory sequences in the 5'-flanking DNA and the complete sequence of themore » Gus-s/sup ..cap alpha../ mRNA transcript were also determined. Comparison of the amino acid sequence determined from the Gus-s/sup ..cap alpha../ nucleotide sequence with that of human ..beta..-glucuronidase indicated that the two human mRNA species differ due to alternate splicing of an exon homologous to exon 6 of the mouse gene.« less

Creatine kinase and alpha-actin mRNA levels decrease in diabetic rat hearts

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

Popovich, B.; Barrieux, A.; Dillmann, W.H.

1987-05-01

Diabetic cardiomyopathy is associated with cardiac atrophy and isoenzyme redistribution. To determine if tissue specific changes occur in mRNAs coding for ..cap alpha..-actin and creatine kinase (CK), they performed RNA blot analysis. Total ventricular RNA from control (C) and 4 wk old diabetic (D) rats were hybridized with /sup 32/P cDNA probes for ..cap alpha..-actin and CK. A tissue independent cDNA probe, CHOA was also used. Signal intensity was quantified by photodensitometry. D CK mRNA was 47 +/- 16% lower in D vs C. Insulin increases CK mRNA by 20% at 1.5 hs, and completely reverses the deficit after 4more » wks. D ..cap alpha..-actin mRNA is 66 +/- 18% lower in D vs C. Insulin normalized ..cap alpha..-actin mRNA by 5 hs. CHOA mRNA is unchanged in D vs C, but D + insulin CHOA mRNA is 30 +/- 2% lower than C. In rats with diabetic cardiomyopathy, muscle specific CK and ..cap alpha..-actin mRNAs are decreased. Insulin treatment reverses these changes.« less

Gamma-resonance investigation of the kinetics of the reduction of (. cap alpha. -benzil dioximato-1)(. cap alpha. -benzil dioximato-2)di(pyridine)iron(III)

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

Turte, K.I.; Bulgak, I.I.; Stukan, R.A.

1986-07-01

(..cap alpha..-Benzil dioximato-1)(..cap alpha..-benzil dioximato-2)di(pyridine)iron(III) in the form of the diacetone solvate (II) is spontaneously converted at room temperature into (..cap alpha..-benzil dioximato-1)(..cap alpha..-benzil dioximato-2)di(pyridine)iron(II) (III). The quantitative composition of a sample containing complexes II and III has been determined as a function of the temperature and the time by gamma-resonance spectroscopy, which made it possible to investigate the kinetics of this reaction. The changes obtained in the percentage of complex II in the sample as a function of time at a given temperature was treated with the use of the Kolmogorov-Erofeev equation for a topochemical reaction of the typemore » A/sub s/ ..-->.. B/sub s/ + C/sub g/. The rate constants of the reaction at various temperatures and the activation energy *E have been determined. In the temperature range from 293 to 304/sup 0/K *E = 25.6 kcal/mole. The possibilities of gamma-resonance spectroscopy in the investigation of topochemical reactions associated with changes in the oxidation state of iron ions have been demonstrated.« less

Reconstitution of high affinity. cap alpha. /sub 2/ adrenergic agonist binding by fusion with a pertussis toxin substrate

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

Kim, M.H.; Neubig, R.R.

1986-03-05

High affinity ..cap alpha../sub 2/ adrenergic agonist binding is thought to occur via a coupling of the ..cap alpha../sub 2/ receptor with N/sub i/, the inhibitory guanyl nucleotide binding protein. Human platelet membranes pretreated at pH 11.5 exhibit a selective inactivation of agonist binding and N/sub i/. To further study the mechanism of agonist binding, alkali treated membranes (ATM) were mixed with membranes pretreated with 10 ..mu..M phenoxybenzamine to block ..cap alpha../sub 2/ receptors (POB-M). The combined membrane pellet was incubated in 50% polyethylene glycol (PEG) to promote membrane-membrane fusion and assayed for binding to the ..cap alpha../sub 2/ agonistmore » (/sup 3/H)UK 14,304 (UK) and the antagonist (/sup 3/H) yohimbine. PEG treatment resulted in a 2-4 fold enhancement of UK binding whereas yohimbine binding was unchanged. No enhancement of UK binding was observed in the absence of PEG treatment. The reconstitution was dependent on the addition of POB-M. They found that a 1:1 ratio of POB-M:ATM was optimal. Reconstituted binding was inhibited by GppNHp. Fusion of rat C6 glioma cell membranes, which do not contain ..cap alpha../sub 2/ receptors, also enhanced agonist binding to ATM. Fusion of C6 membranes from cells treated with pertussis toxin did not enhance (/sup 3/H) UK binding. These data show that a pertussis toxin sensitive membrane component, possibly N/sub i/, can reconstitute high affinity ..cap alpha../sub 2/ agonist binding.« less

Ionization of isocitrate bound to pig hear NADP/sup +/-dependent isocitrate dehydrogenase: /sup 13/C NMR study of substrate binding

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

Ehrlich, R.S.; Colman, R.F.

1987-06-16

Isocitrate and ..cap alpha..-ketoglutarate have been synthesized with carbon-13 enrichment at specific positions. The /sup 13/C NMR spectra of these derivatives were measured as a function of pH. The magnitudes of the changes in chemical shifts with pH for free isocitrate and the magnesium-isocitrate complex suggest that the primary site of ionization at the ..beta..-carboxyl. In the presence of the enzyme NADP/sup +/-dependent isocitrate dehydrogenase and the activating metal magnesium, the carbon-13 resonances of all three carboxyls remain constant from pH 5.5 to pH 7.5. Thus, the carboxyls remain in the ionized form in the enzyme-isocitrate complex. The ..cap alpha..-hydroxylmore » carbon resonance could not be located in the enzyme-isocitrate complex, suggesting immobilization of this group. Magnesium produces a 2 ppm downfield shift of the ..beta..-carboxyl but does not change the resonances of the ..cap alpha..- and ..gamma..-carboxyls. This result is consistent with metal activation of both the dehydrogenation and decarboxylation reactions. The /sup 13/C NMR spectrum of ..cap alpha..-ketoglutarate remains unchanged in the presence of isocitrate dehydrogenase, implying the absence of alterations in geometry in the enzyme-bound form. Formation of the quaternary complex with Mg/sup 2 +/ and NADPH leads to loss of the ..cap alpha..-ketoglutarate resonances and the appearance of new resonances characteristic of ..cap alpha..-hydroxyglutarate. In addition, a broad peak ascribed to the enol form of ..cap alpha..-ketoglutarate is observed. The substantial change in the shift of the ..beta..-carboxyl of isocitrate and the lack of significant shifts in the other carboxyls of isocitrate or ..cap alpha..-ketoglutarate suggest that interaction of the ..beta..-carboxyl with the enzyme contributes to the tighter binding of isocitrate and may be significant for the oxidative decarboxylation function of isocitrate dehydrogenase.« less

Lyman-alpha observations of comet Kohoutek 1973 XII with Copernicus

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

Drake, J.F.; Jenkins, E.B.; Bertaux, J.L.

1976-10-01

Comet Kohoutek 1973 XII was observed with the Princeton telescope-spectrometer on the Copernicus satellite on six occasions over a 1-month period starting on 1974 January 29. Positive detection of the cometary L..cap alpha.. emission profile was obtained on January 29 and February 2. Earlier observations of the geocoronal L..cap alpha.. emission profile allowed an instrumental intensity calibration and confirmation of the computed instrumental profile for an extended source at the L..cap alpha.. wavelength.After allowing for broadening by the instrument, we derived from the width of the L..cap alpha.. emission on January 29 a hydrogen-outflow velocity of 10.6 +- 1.8 kmmore » s/sup -1/. The intensity calibration combined with an appropriate cometary model led to cometary water-production rates with average values of 1.3 +- 0.4 x 10/sup 28/ molecules sr/sup -1/ s/sup -1/ for January 29 and 6.0 +- 2.5 x 10/sup 27/ molecules sr/sup -1/ s/sup -1/ for February 2. Only upper limits were obtained for L..cap alpha.. on and after February 14. Searches for OH and D led to negative results. (AIP)« less

Isolation of human hexosaminidase. cap alpha. cDNA and expression of. cap alpha. chains in E. coli

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

Wiktorowicz, J.E.; Whitman, J.M.

1986-05-01

Pooled antisera against homogeneous, glutaraldehyde cross-linked hexosaminidase (hex) A was adsorbed with E. coli lysate insolubilized on Sepharose 4B. Aliquots of a human liver lambdagtll cDNA library (50,000-100,000 pfu) were plated on E. coli Y1090. Expression of cloned cDNA, after sufficient plaque growth at 42/sup 0/, was accomplished by induction with isopropylthiogalactoside soaked nitrocellulose filters. Identification of hex cDNA clones was performed by incubation of the filters with purified antisera. Protein A labelled with I-125 was used to develop the reactive plaques. Positive plaques, identified by autoradiography, were picked, replated at a lower density, and rescreened. This was repeated severalmore » more times until all plaques yielded positive signals. Identification of the clones as containing ..cap alpha.. or ..beta.. cDNA was accomplished by replating the purified phage and rescreening the plaques with anti-hex B antiserum preadsorbed with E. coli lysate. According to this protocol several hex ..cap alpha.. clones have been identified. While these clones generate ..beta..-galactosidase: hex ..cap alpha.. fusion proteins, these findings suggest that in the future it may be possible to obtain large quantities of unmodified hex ..cap alpha.. and ..beta.. polypeptides from E. coli for the study of the structural and enzymatic properties of these polypeptides and for diagnostic purposes in the GM2 gangliosidoses.« less

Pulse radiolysis and 77 K matrix. gamma. irradiation of dimethyl truxinates and trans-methyl cinnamate in 2-methyltetrahydrofuran

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

Takamuku, S.; Kigawa, H.; Suematsu, H.

1982-05-13

One-electron reduction of dimethyl ..mu..-truxinate (..mu..-DMT), dimethyl ..beta..-truxinate (..beta..-DMT), and dimethyl ..cap alpha..-truxillate (..cap alpha..-DMT) has been investigated by pulse radiolysis and 77 K matrix ..gamma.. irradiation of the 2-methyltetrahydrofuran solutions. Cycloreversion of the radical anions formed by an electron attachment to these cyclobutanes was observed in all cases, even at 77 K. The orientation of the cycloreversion was dependent on the stereochemistry of the cyclobutanes, and the selectivity was reasonably explained by a so-called cis effect; the best possible release of steric hindrance decides the primary step of the reaction. In 77 K matrix ..gamma.. irradiation of ..cap alpha..-DMT,more » an intense IR absorption was found after the photobleaching of trapped electrons with light > 690 nm. In other DMTs, the IR absorption band was not observed while the cycloreversion of DMT by mobile electrons occurred. Thus, the IR band in the case of ..cap alpha..-DMT was assigned to an associated dimer anion due to the interaction between the radical anion and the neutral molecule pair of trans-methyl cinnamate orginally formed by the cycloreversion of ..cap alpha..-DMT. The dimer anion was presumed to be oriented in a head-to-tail structure in a solvent cage on the basis of the original configuration of ..cap alpha..-DMT.« less

Metabolism of 4-chlorobenzotrichloride in rats

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

Quistad, G.B.; Mulholland, K.M.; Skiles, G.

Special analytical methodology was developed for purification of 4-chloro(/sup 14/C)benzotrichloride, which is both volatile and hydrolytically unstable at milligram mass levels. When rats were given a single oral dose of 4-chloro(/sup 14/C)benzotrichloride at 1.5 mg/kg, within 4-6 days 87 and 9% of the applied /sup 14/C were excreted in urine and feces, respectively. The major urinary metabolite was identified as 4-chlorohippuric acid, representing 78% of the applied dose. While about two-thirds of the fecal /sup 14/C residues were unextractable with organic solvents, free 4-chlorobenzoic acid and ..cap alpha..,..cap alpha..,4,4'-tetrachlorostilbene contributed 10 and 8% of the fecal /sup 14/C. The metabolicmore » production of ..cap alpha..,..cap alpha..,4,4'-tetrachlorostilbene appears to occur by a novel metabolic pathway.« less

cap alpha. -Methylglucoside satisfies only Na/sup +/-dependent transport system of intestinal epithelium

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

Kimmich, G.A.; Randles, J.

1981-01-01

The unidirectional influx of ..cap alpha..-methylglucoside (..cap alpha..-MG) by isolated chicken intestinal epithelial cells is 98% inhibited by phlorizin. The remaining 2% of the total influx occurs in the absence of Na/sup +/, is not sensitive to phloretin, and is equal to the diffusional entry rate for 2-deoxyglucose. The glucoside is much more strongly accumulated (75-fold) than 3-O-methylglucose (3-OMG) (10-fold). Inhibitors of the serosal sugar carrier (phloretin, cytochalasin B, theophylline, and flavanoids) do not enhance ..cap alpha..-MG accumulation. It is concluded that the glycoside is not a substrate for the intestinal serosal transport system. Steady-state gradients of the sugar canmore » be represented accurately by a concentrative, phlorizin-sensitive system that is opposed by a diffusional efflux process.« less

Characterization of rat leydig cell gonadotropin receptor structure by affinity cross-linking

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

Zhang, Q.Y.; Hwang, J.; Menon, K.M.J.

1986-05-01

The gonadotropin receptor from rat leydig cell has been characterized with respect to binding kinetics and physiological regulation. The present study was intended to examine the structure of the receptor. Leydig cell suspension was prepared by either collagenase digestion or by mechanical disruption of the testis. The cells were incubated with /sup 125/I-hCG and the unreacted hCG was removed by centrifugation. The /sup 125/I-hCG was then covalently linked to the cell surface receptor using cleavable (dithiobis (succinimidyl propionate)) and non-cleavable (disuccinimidyl suberate) cross-linking reagents. The extracted cross-linked membrane proteins were resolved on SDS-polyacrylamide gels under reducing and non-reducing conditions andmore » subjected to autoradiographic analysis. Under non-reducing conditions, two labeled species with M/sub r/ = 87,000 and 120,000 were detected. However, only one labeled band was detected under reducing conditions with M/sub r/ = 64,000. The binding of /sup 125/I-hCG to the receptor was inhibited by hCG and LH, but not by a number of peptides and proteins. The data suggest that hCG receptor in leydig cell is an oligomeric complex consisting of four subunits, ..cap alpha cap alpha beta gamma... The ..beta.. and ..gamma.. subunits are each linked to an ..cap alpha.. subunit through disulfide linkage and the hormone binds to each ..cap alpha.. subunit. The two dimers formed (..cap alpha beta cap alpha gamma..) are associated by noncovalent interactions.« less

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

Yamashita, T.; Fujino, T.; Masaki, N.

The structural parameters of ..cap alpha..- and ..beta..-CdUO/sub 4/ crystals are determined by x-ray powder diffraction technique. ..cap alpha..-CdUO/sub 4/ is rhombohedral and cell parameters are a = 6.233(3) A and ..cap alpha.. = 36.12(5)/sup 0/. ..beta..-CdUO/sub 4/ crystallizes in a C-centered orthorhombic cell with a = 7.023(4), b = 6.849(3), c = 3.514(2) A. The space groups are R3m for ..cap alpha..-CdUO/sub 4/ and Cmmm for ..beta..-CdUO/sub 4/. ..cap alpha..-CdUO/sub 4/: 1U in (000), 1Cd in (1/2 1/2 1/2), 2O(1) in +-(uuu), 2O(2) in +-(vvv); u = 0.113, v= 0.350, Z = 1. ..beta..-CdUO/sub 4/: 2U in (000; 1/2more » 1/2 0), 2Cd in (1/2 0 1/2; 0 1/2 1/2), 40(1) in (0, +-y, 0; 1/2, 1/2 +-y, 0), 4O(2) in (+-x, 0, 1/2; 1/2 +-x, 1/2, 1/2); x = 0.159, y = 0.278, Z = 2. ..beta..-CdUO/sub 4/ contains collinear uranyl UO/sub 2//sup 2 +/ groups with a U-O(1) distance of 1.91 A, located either along or parallel to the c axis whereas the U-O(1) bond length in ..cap alpha..-CdUO/sub 4/ is 1.98 A which is longer than the usual uranyl bond length.« less

Variability of Lyman-alpha emission from Jupiter

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

Cochran, W.D.; Barker, E.S.

1979-12-01

The Jovian L..cap alpha.. emission line was reobserved in 1978 March using the high-resolution spectrometer of the Copernicus satellite. An intensity of 8.3 +- 2.9 kilorayleighs was measured. This value represents a significant increase in intensity over previous (1976) Copernicus observations, but is lower than the recent (1979) values obtained by Voyager 1 and IUE. The increase in intensity has been accompanied by a significant increase in line width givin strong support to the theory that the emission results from resonant scattering of the solar L..cap alpha.. line by H atoms in the upper Jovian atmosphere. The strength of Jovianmore » L..cap alpha.. emission correlates well with the level of solar activity. The solar extreme ultraviolet radiation varies with the solar cycle. This radiation causes the dissociation of H/sub 2/ and CH/sub 4/ into H atoms in the Jovian atmosphere. Therefore, in times of high solar activity, the H column density will increase, causing the observed stronger Jovian L..cap alpha.. emission.« less

A remarkable member of the polyoxometalates: the eight-nickel-capped alpha-keggin polyoxoazonickelate.

PubMed

Dong, Lanjun; Huang, Rudan; Wei, Yongge; Chu, Wei

2009-08-17

The eight-nickel-capped polyoxoazonickelate, [Ni(20)(OH)(24)(MMT)(12)(SO(4))](NO(3))(2).6H(2)O (1; MMT = 2-mercapto-5-methyl-1,3,4-thiadiazole), has been synthesized, which has an alpha-Keggin structure with eight nickel caps. In this structure, the polyatom is the late transition metal Ni(II); the central heteroatom is S, and the organic terminal ligand becomes the primary part of the Keggin structure. This is a Keplerate-type cluster, which shows a central Ni(II)(12) cuboctahedron formed by the 12 Ni(II) centers of the classical alpha-Keggin core and a Ni(II)(8) hexahedron formed by the eight nickel caps.

Glucocorticoids inhibit coordinated translation of. cap alpha. - and. beta. -globin mRNAs in Friend erythroleukemia cells

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

Papaconstantinou, J.; Stewart, J.A.; Rabek, J.P.

The dimethylsulfoxide (Me/sub 2/SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10/sup -5/ to 10/sup -8/ M inhibits by 90-30% and fluocinolone acetonide at concentrations of 10/sup -8/ to 10/sup -11/ M shows a greater than 90% inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the ..cap alpha..- and ..beta..-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and thatmore » the expression of these, in addition to ..cap alpha..- and ..beta..-globin, is affected by glucocorticoids. It is concluded that, although the translation of ..cap alpha..- and ..beta..-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of ..cap alpha..- and ..beta..-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.« less

Characterization of the primary interaction between the mating pheromone, alpha-factor, and its receptor in Saccharomyces cerevisiae

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

Raths, S.K.

1987-01-01

Alpha-factor is a peptide of thirteen amino acids which is required for mating between the haploid mating types, a and ..cap alpha.., in Saccharomyces cerevisiae. An analogue of alpha-factor, DHP/sup 8/ DHP/sup 11/ Nle/sup 12/ tridecapeptide, was catalytically reduced in the presence of /sup 3/H gas for production of a radiolabeled pheromone suitable for use in binding studies. Incorporation of tritium resulted in /sup 3/H-alpha-factor with high specific activity, purity, biological activity and long shelf-life. Binding studies revealed that alpha-factor interacts with its receptor via a simple, reversible process which obeys the law of mass action. Association and dissociation kineticsmore » indicate values of 2.92 x 10/sup 6/ M/sup /minus/1/ min/sup -1/ for k/sub 1/ and between 4 and 7 x 10/sup /minus/2/ min/sup /minus/1/ for k/sub /minus/1/. Saturation binding studies reveal an equilibrium dissociation constant equal to 2.32 x 10/sup /minus/8/ M which approximate the kinetically-derived K/sub D/ of 2.12 x 10/sup /minus/8/ M. Scatchard and Hill analyses as well as dissociation behavior in the presence of excess unlabeled ligand indicate alpha-factor interacts with a homogeneous population of binding sites which do not interact and exhibit one affinity for the alpha-factor pheromone.« less

Cross-linking of hCG to luteal receptors

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

Ji, T.H.; Ji, I.

1985-01-01

Photoaffinity labeling of the lutropin/choriogonadotropin (LH/hCG) receptor system on porcine granulosa cells has demonstrated that both the ..cap alpha.. and ..beta.. subunits of hCG directly photoaffinity label the hormone receptor. Three new bands appear on SDS-PAGE as a consequence of photoaffinity labeling by each subunit: the molecular weights of the three bands (106K, 88K, and 83K) produced by the subunit are larger by approximately 10K than those of the three bands (96K, 76K, and 73K) labeled by the ..cap alpha.. subunit. Although it could be a coincidence that the molecular weight of the ..beta.. subunit is approximately 10K larger thanmore » that of the ..cap alpha.. subunit, the similarity in these differences suggests the possibility that both the ..cap alpha.. and ..beta.. subunits have labeled the same polypeptides.« less

Differentiation to adipocytes in accompanied by an increase in the amounts of Gi- and Go-proteins in 3T3-L1 cells

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

Watkins, D.C.; Northup, J.K.; Malbon, C.C.

Treatment of cultures of 3T3-L1 cells with methylisobutyl-xanthine and dexamethasone has been shown to result in accumulation of lipid and conversion to the morphology of adipocytes in more than 90% of the cells. The status of the stimulatory (Gs), inhibitory (Gi) and Go-proteins during the course of 3T3-L1 differentiation was examined. The amount of alpha subunit of Gs (..cap alpha..Gs), assayed by radiolabeling in the presence of cholera toxin and (/sup 32/P)NAD/sup +/, increased upon differentiation as previously described by others. The amounts of ..cap alpha..Gi and ..cap alpha..Go assayed by radiolabeling in the presence of pertussis toxin and (/supmore » 32/P)NAD/sup +/ increased 3-fold upon differentiation. Immunoblots of cell membranes subjected to gel electrophoresis in sodium dodecyl sulfate were probed with two rabbit antisera raised against bovine brain ..cap alpha..Go and with one raised against the..beta..-subunit of the bovine rod-outer-segment G-protein, referred to as transducin. The immunoblotting data confirm the increase upon differentiation of ..cap alpha..Go and also demonstrate an increase in the amount of the ..beta..-subunit. Thus differentiation of 3T3-L1 cells is accompanied by dramatic changes in the complexion of G-proteins in the membranes.« less

cap alpha. /sub 2/-Adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production

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

Jones, S.B.; Toews, M.L.; Turner, J.T.

1987-03-01

Preincubation of HT29 human colonic adenocarcinoma cells with ..cap alpha../sub 2/-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a (/sup 3/H)adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is ..cap alpha../sub 2/-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an ..cap alpha../sub 2/-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (..cap alpha../sub 1/-adrenergic) and sotalol (..beta..-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-timemore » for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of ..cap alpha../sub 2/-adrenergic responses that are not mediated by a decrease in cyclic AMP.« less

Role of a guanine nucleotide-binding protein in. cap alpha. /sub 1/-adrenergic receptor-mediated Ca/sup 2 +/ mobilization in DDT/sub 1/ MF-2 cells

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

Cornett, L.E.; Norris, J.S.

1987-11-01

In this study the mechanisms involved in ..cap alpha../sub 1/-adrenergic receptor-mediated Ca/sup 2 +/ mobilization at the level of the plasma membrane were investigated. Stimulation of /sup 45/Ca/sup 2 +/ efflux from saponin-permeabilized DDT/sub 1/ MF-2 cells was observed with the addition of either the ..cap alpha../sub 1/-adrenergic agonist phenylephrine and guanosine-5'-triphosphate or the nonhydrolyzable guanine nucleotide guanylyl-imidodiphosphate. In the presence of (/sup 32/P) NAD, pertussis toxin was found to catalyze ADP-ribosylation of a M/sub r/ = 40,500 (n = 8) peptide in membranes prepared from DDT/sub 1/, MF-2 cells, possibly the ..cap alpha..-subunit of N/sub i/. However, stimulation ofmore » unidirectional /sup 45/Ca/sup 2 +/ efflux by phenylephrine was not affected by previous treatment of cells with 100 ng/ml pertussis toxin. These data suggest that the putative guanine nucleotide-binding protein which couples the ..cap alpha../sub 1/-adrenergic receptor to Ca/sup 2 +/ mobilization in DDT/sub 1/ MF-2 cells is not a pertussis toxin substrate and may possibly be an additional member of guanine nucleotide binding protein family.« less

E2C mechanism of elimination reactions. IX. Secondary deuterium isotope effects on rates of bimolecular reactions in alicyclic systems

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

Cook, D.

1976-06-11

Secondary ..cap alpha..-deuterium isotope effects on the rates of NBu/sub 4/OAc and NBu/sub 4/Cl promoted bimolecular reactions (E2 and SN2) of cyclohexyl tosylate and cyclohexyl bromide have been studied. The E2 reactions, previously categorized as E2C-like, show ..cap alpha..-deuterium isotope effects in the range 1.14--1.22, while the related SN2 reactions give values in the range 1.05--1.08. The discrepancy in the magnitude of the ..cap alpha..-deuterium isotope effect for the E2 and SN2 processes is consistent with the view that E2C-like reactions use ''looser'' transition states than those used in the concurrent SN2 reactions. While the reported ..cap alpha..-d isotope effectsmore » do not provide positive evidence to support the idea that the base interacts with C/sub ..cap alpha../ in the E2 transition states of the reactions studied, neither do they substantiate claims for dismissal of the concept. A comparison of the secondary ..gamma..-deuterium and ..beta..'-deuterium isotope effects arising in the reaction of cyclohexyl tosylate with NBu/sub 4/OAc in acetone indicates the two isotope effects to be of equivalent magnitude (k/sub ..beta..'-d/k/sub ..gamma..-d/ = 0.98). This observation can only be rationalized for this reaction in terms of a transition state structure in which there is extensive double bond development. It provides compelling evidence against the involvement of any transition state structure which accommodates extensive positive charge development at C/sub ..cap alpha../.« less

Alpha particle effects in burning tokamak plasmas: overview and specific examples

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

Sigmar, D.J.

1986-07-01

Using the total power balance of an ignited tokamak plasma as a guideline, a range of alpha driven effects is surveyed regarding their impact on achieving and maintaining fusion burn. Specific examples of MHD and kinetic modes and multi species transport dynamics are discussed, including the possible interaction of these categories of effects. This power balance approach rather than a straightforward enumeration of possible effects serves to reveal their non-linear dependence and the ensuing fragility of our understanding of the approach to and maintenance of ignition. Specific examples are given of the interaction between ..cap alpha..-power driven sawtoothing and idealmore » MHD stability, and direct ..cap alpha..-effects on MHD modes including kinetic corrections. Anomalous ion heat transport and central impurity peaking mechanisms and anomalous and collisional ..cap alpha..-transport including the ambipolar electric field are discussed.« less

Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

PubMed

Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

2006-10-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.

Highly excited states in /sup 6/Li by the reaction /sup 9/Be(p,. cap alpha. )/sup 6/Li. [Width of 8. 2-MeV level

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

Delbar, T.; Gregoire, G.; Lega, J.

1976-10-01

The spectra from the reaction /sup 9/Be(p, ..cap alpha..)/sup 6/Li induced by 75 and 30 MeV protons were recorded at theta/sub ..cap alpha../ = 20 and 30/sup 0/ in the laboratory frame. The region from 6 to 18 MeV excitation energy of the residual nucleus was carefully studied for possible levels. Evidence for a T = 1 level at E/sub x/ = 8.2 +- 0.2 MeV with a width GAMMA = 2.2 +- 0.2 MeV is reported. No other levels were observed in the present spectra. (AIP)

Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP).

PubMed

Wadsworth, Teri L; Worstell, Teresa R; Greenberg, Norman M; Roselli, Charles E

2007-05-01

Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis. Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha-dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence. Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance. (c) 2007 Wiley-Liss, Inc.

Comparisons of carcinogenicities of nickel compounds in rats

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

Sunderman, F.W. Jr.; Maenza, R.M.

This study demonstrates marked differences in the incidences of sarcomas in Fischer rats within 2 years after a single im injection of 4 insoluble nickel-containing powders amorphous nickel monosulfide (NiS), nickel subsulfide (..cap alpha..Ni/sub 3/S/sub 2/), partially converted nickel-iron sulfide matte, and metallic nickel. The powders (<2 ..mu..m median particle diameters) were administered in penicillin suspension, and each powder was tested at 2 dosages. Whereas ..cap alpha..Ni/sub 3/S/sub 2/ was highly carcinogenic, amorphous NiS did not induce any tumors. The carcinogenic potency of partially converted nickel-iron sulfide matte was less than ..cap alpha..Ni/sub 3/S/sub 2/ but greater than Ni powder.more » No sarcomas occurred at the injection site in two groups of control rats that received im injections of penicillin or Fe powder. The observed differences in carcinogenic potencies of ..cap alpha..Ni/sub 3/S/sub 2/ and amorphous NiS may provide an experimental approach to elucidate the molecular mechanisms of nickel carcinogenesis.« less

Hydrophobic interactions in complexes of antimicrobial peptides with bacterial polysaccharides.

PubMed

Kuo, Hsin H; Chan, Celine; Burrows, Lori L; Deber, Charles M

2007-06-01

Biofilms of Pseudomonas aeruginosa are responsible for chronic lung infections in cystic fibrosis patients, where they are characterized by overproduction of the exopolysaccharide alginate and are recalcitrant to treatment with conventional antibiotics. Cationic antimicrobial peptides (CAPs) are potential alternatives for the treatment of multi-drug-resistant P. aeruginosa. However, alginate in P. aeruginosa biofilms has been proposed to bind these peptides through hydrophobic interactions, consequently reducing their activity [Chan et al., J Biol Chem 2004; 279: 38749-38754]. Here we perform biophysical analyses of the interactions of alginate with a series of novel peptide antibiotics (alpha-CAPs) of prototypic sequence KK-AAAXAAAAAXAAWAAXAAA-KKKK (where X = Phe, Trp or Leu). The hydrophobic interaction interface in alginate was investigated by examining (i) the effects of polysaccharide composition with respect to D-mannuronate and L-guluronate content; (ii) glycan chain length; (iii) alpha-CAP Trp fluorescence; and (iv) 1-anilinonaphthalene-8-sulfonate fluorescence. The results show that, while M and G residues produce equivalent effects, hydrophobic interactions between alginate and alpha-CAPs require a minimal glycan chain length. Peptide interactions with alginate are deduced to be mediated by hydrophobic microdomains comprised of pyranosyl C-H groups that are inducible upon formation of alpha-CAP-alginate complexes due to charge neutralization between the two species.

Dissimilar effects of chronic treatment with aspirin, flubiprofen and indomethacin on renal prostaglandins

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

Quilley, C.P.; McGiff, J.C.; Quilley, J.

Inhibition of prostaglandin (PG) excretion is not sustained during long-term aspirin administration. The authors compared the effects of 9d treatment of SHR rats with aspirin (A), 200 mg/kg/d s.c., flubiprofen (F), 2.5 mg/kg/12h s.c., and indomethacin (I), 2.5 mg/kg/12 s.c. on excretion of radioimmunoassayable PGE/sub 2/ and PGF/sub 2..cap alpha../. Conversion of 1-(/sup 14/C) arachidonic acid (AA) by renal papillae was also examined. In vehicle-treated control rats (C) PGF/sub 2..cap alpha../ excretion varied from 32.2 +/- 6.2 (mean +/- SEM) to 41.6 +.- 7.3 ng/6h, 3-fold higher than that of PGE/sub 2/. Within 6h of administration all 3 drugs reducedmore » excretion of PGF/sub 2..cap alpha../ and PGE/sub 2/ to less than 20% and 35% of C rats. Although urinary concentrations of PGF/sub 2..cap alpha../ and PGE/sub 2/ in A-treated rats remained depressed, a 2-fold increase in urine volume resulted in excretion rates similar to C rats. In contrast, urine volume in I- and F-treated rats was unaffected while PGF/sub 2..cap alpha../ and PGE/sub 2/ excretion rates in I-treated rats were 50''% of C rats and were also lower than control in F-treated rats. Paradoxically, metabolism of AA to PGs by by renal papillae dissected on day 10, 2-4h after the last drug dose, was markedly inhibited by A (PGF/sub 2..cap alpha../ by 62% and PGE/sub 2/ by 82%), but unaffected by I and F. As the effects of cyclooxygenase inhibitors differ on in vivo and indices of PG production, their intended action should be verified by measuring PG levels in biological fluids.« less

Non-linear vacuum polarization in strong fields

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

Gyulassy, M.

1981-07-01

The Wichmann-Kroll formalism for calculating the vacuum polarization density to first order in ..cap alpha.. but to all orders in Z..cap alpha.. is derived. The most essential quantity is shown to be the electrons Green's function in these calculations. The method of constructing that Green's function in the field of finite radius nuclei is then presented.

Metabolism of. cap alpha. -C/sup 14/-histidine in the intact rat. II. Radioactive excretion products in urine

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

Wolf, G.; Wu, P.H.L.; Heck, W.W.

1956-09-01

The normal metabolic pathways in the intact rat was investigated via the radioactive urinary excretion products following administration of a physiological dose of a radioactive compound such as ..cap alpha..-C/sup 14/-DL-histidine. The major metabolites, except one, excreted in the urine 5 hours after administration of ..cap alpha..-C/sup 14/-DL-histidine were isolated and identified. Glutamic acid and urocanic acids had simlar and low activities, whereas carboxyl-labeled imidazoacetic acid was found to be the principal metabolite with a high level of activity. It was concluded that the main end-product of the catabolism of DL-histidine is imidazoleacetic acid probably formed through imidazolepyruvic acid.

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

Weinstein, L.; Droegemueller, W.; Cornette, J.

A single intra-amniotic injection of (15S)-15 methyl prostaglandin F/sub 2/..cap alpha.. (THAM) was used to induce second trimester abortion in five patients. Serial levels of (15S)-15 methyl prostaglandin F/sub 2/..cap alpha.. were subsequently measured in amniotic fluid and plasma by radioimmunoassay. The slow removal of this drug from the amniotic fluid was documented. Plasma levels of (15S)-15 methyl prostaglandin F/sub 2/..cap alpha.. increased fourfold to sevenfold after clinical rupture of the membranes in three patients, supporting the fact that prostaglandins are well absorbed from the vagina. Because this analogue of prostaglandin can cause marked peripheral bronchoconstriction when administered systemically, itmore » is best to avoid its use in patients with a history of asthma.« less

Self-modulating pressure gauge

DOEpatents

Edwards, D. Jr.; Lanni, C.P.

1979-08-07

An ion gauge is disclosed having a reduced x-ray limit and means for measuring that limit. The gauge comprises an ion gauge of the Bayard-Alpert type having a short collector and having means for varying the grid-collector voltage. The x-ray limit (i.e. the collector current resulting from x-rays striking the collector) may then be determined by the formula: I/sub x/ = ..cap alpha..I/sub l/ - I/sub h//..cap alpha.. - l where: I/sub x/ = x-ray limit, I/sub l/ and I/sub h/ = the collector current at the lower and higher grid voltage respectively; and, ..cap alpha.. = the ratio of the collector current due to positive ions at the higher voltage to that at the lower voltage.

A new genetic factor for root gravitropism in rice (Oryza sativa L.).

PubMed

Shi, Jiang-hua; Hao, Xi; Wu, Zhong-chang; Wu, Ping

2009-10-01

Root gravitropism is one of the important factors to determine root architecture. To understand the mechanism underlying root gravitropism, we isolated a rice (Xiushui63) mutant defective in root gravitropism, designated as gls1. Vertical sections of root caps revealed that gls1 mutant displayed normal distribution of amyloplast in the columella cells compared with the wild type. The gls1 mutant was less sensitive to 2,4-dichlorophenoxyacetic acid (2,4-D) and alpha-naphthaleneacetic acid (NAA) than the wild type. Genetic analysis indicated that the phenotype of gls1 mutant was caused by a single recessive mutation, which is mapped in a 255-kb region between RM16253 and CAPS1 on the short arm of chromosome 4.

Internode length in Pisum. Gene na may block gibberellin synthesis between ent-7. cap alpha. -hydroxykaurenoic acid and biggerellin A/sub 12/-aldehyde. [Pisum sativum

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

Ingram, T.J.; Reid, J.B.

1987-04-01

The elongation response of the gibberellin (GA) deficient genotypes na, ls, and lh of peas (Pisum sativum L.) to a range of GA-precursors was examined. Plants possessing gene na did not respond to precursors in the GA biosynthetic pathway prior to GA/sub 12/-aldehyde. In contrast, plants possessing lh and ls responded as well as wild-type plants (dwarfed with AMO-1618) to these compounds. The results suggest that GA biosynthesis is blocked prior to ent-kaurene in the lh and ls mutants and between ent-7..cap alpha..-hydroxykaurenoic acid and GA/sub 12/-aldehyde in the na mutant. Feeds of ent(/sup 3/H)kaurenoic acid and (/sup 2/H)GA/sub 12/-aldehydemore » to a range of genotypes supported the above conclusions. The na line WL1766 was shown by gas chromatography-mass spectrometry (GC-MS) to metabolize(/sup 2/H)GA/sub 12/-aldehyde to a number of (/sup 2/H)C/sub 19/-GAs including GA/sub 1/. However, there was no indication in na genotypes for the metabolism of ent-(/sup 3/H)kaurenoic acid to these GAs. In contrast, the expanding shoot tissue of all Na genotypes examined metabolized ent-(/sup 3/H)kaurenoic acid to radioactive compounds that co-chromatographed with GA/sub 1/, GA/sub 8/, GA/sub 20/, and GA/sub 29/. However, insufficient material was present for unequivocal identification of the metabolites. The radioactive profiles from HPLC of extracts of the node treated with ent-(/sup 3/H)kaurenoic acid were similar for both Na and na plants and contained ent-16..cap alpha..,17-dihydroxykaurenoic acid and ent-6..cap alpha..,7..cap alpha..,16..beta..,17-tetrahydroxykaurenoic acid (both characterized by GC-MS), suggesting that the metabolites arose from side branches of the main GA-biosynthetic pathway. Thus, both Na and na plants appear capable of ent-7..cap alpha..-hydroxylation.« less

Copernicus observations of Betelgeuse and Antares

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

Bernat, A.P.; Lambert, D.L.

1975-01-01

Copernicus observations of the M-supergiants, ..cap alpha.. Ori and ..cap alpha.. Sco, are presented. The Mg II H and K resonance lines are strongly in emission in both stars. The K line is highly asymmetric in both stars but the H line is symmetric. Upper limits for several other resonance lines are given for ..cap alpha.. Ori. The possibility is explored that the K line asymmetry is caused by overlying resonance lines of Mn I and Fe I formed in the cool circumstellar gas shells around these stars. Observations of the Mn I 4030--4033 A lines are used to showmore » that circumstellar shell absorption is too weak to explain the asymmetry. It is suggested that the absorption occurs in a cool turbulent region between the base of the circumstellar shell and the top of the chromosphere. (auth)« less

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

Walker, T.E.; Han, C.H.; Kollman, V.H.

/sup 13/C NMR of isotopically enriched metabolites has been used to study the metabolism of Microbacterium ammoniaphilum, a bacterium which excretes large quantities of L-glutamic acid into the medium. Biosynthesis from 90% (1-/sup 13/C) glucose results in relatively high specificity of the label, with (2,4-/sup 13/C/sub 2/) glutamate as the major product. The predominant biosynthetic pathway for synthesis of glutamate from glucose was determined to be the Embden Meyerhof glycolytic pathway followed by P-enolpyruvate carboxylase and the first third of the Krebs cycle. Different metabolic pathways are associated with different correlations in the enrichment of the carbons, reflected in themore » spectrum as different /sup 13/C-/sup 13/C scalar multiplet intensities. Hence, intensity and /sup 13/C-/sup 13/C multiplet analysis allows quantitation of the pathways involved. Although blockage of the Krebs cycle at the ..cap alpha..-ketoglutarate dehydrogenase step is the basis for the accumulation of glutamate, significant Krebs cycle activity was found in glucose grown cells, and extensive Krebs cycle activity in cells metabolizing (1-/sup 13/C) acetate. In addition to the observation of the expected metabolites, the disaccharide ..cap alpha..,..cap alpha..-trehalose and ..cap alpha..,..beta..-glucosylamine were identified from the /sup 13/C NMR spectra.« less

DEAD ZONE IN THE POLAR-CAP ACCELERATOR OF PULSARS

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

Chen, Alexander Y.; Beloborodov, Andrei M.

We study plasma flows above pulsar polar caps using time-dependent simulations of plasma particles in the self-consistent electric field. The flow behavior is controlled by the dimensionless parameter {alpha} = j/c{rho}{sub GJ}, where j is the electric current density and {rho}{sub GJ} is the Goldreich-Julian charge density. The region of the polar cap where 0 < {alpha} < 1 is a {sup d}ead zone{sup -}in this zone, particle acceleration is inefficient and pair creation is not expected even for young, rapidly rotating pulsars. Pulsars with polar caps near the rotation axis are predicted to have a hollow-cone structure of radiomore » emission, as the dead zone occupies the central part of the polar cap. Our results apply to charge-separated flows of electrons (j < 0) or ions (j > 0). In the latter case, we consider the possibility of a mixed flow consisting of different ion species, and observe the development of two-stream instability. The dead zone at the polar cap is essential for the development of an outer gap near the null surface {rho}{sub GJ} = 0.« less

Breakup processes in heavy-ion induced reactions

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

Udagawa, T.; Tamura, T.; Shimoda, T.

1979-11-01

Cross sections for breakup of /sup 20/Ne into /sup 16/O and ..cap alpha.. during scattering from /sup 40/Ca were calculated in terms of the distorted-wave Born approximation. The inclusive /sup 16/O cross section observed in the /sup 40/Ca(/sup 20/Ne,/sup 16/O) reaction was then found to be fitted very well by the sum of this breakup contribution and that of the ..cap alpha..-transfer reaction calculated in our previous work.

Dielectronic satellite spectra of hydrogen-like titanium (Ti XXII)

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

Bitter, M.; von Goeler, S.; Cohen, S.

High resolution spectra of the Ly ..cap alpha../sub 1/ and Ly ..cap alpha../sub 2/ lines of hydrogenlike titanium, TiXXII, and the associated dielectronic satellites which are due to transitions 1snl-2pnl with n greater than or equal to 2, have been observed from tokamak discharges with auxiliary ion cyclotron heating (ICRH) with central electron temperatures of 2 keV and central electron densities of 8 x 10/sup 13/ cm/sup -3/ on the Princeton Large Torus (PLT). The data have been used for a detailed comparison with theoretical predictions based on the Z - expansion method and Hartree - Fock calculations. The resultsmore » obtained with the Z - expansion method are in excellent agreement with the observed spectral data except for minor discrepancies between the theoretical and experimental wavelengths of 0.0003 A for the n = 2 satellites and of 0.0001 A for the separation of the Ly ..cap alpha../sub 1/ and Ly ..cap alpha../sub 2/ lines. Very good agreement with the experimental data is also obtained for the results from the Hartree - Fock calculations though somewhat larger discrepancies (approx. = 0.0009 A) exist between experimental and theoretical wavelengths which are systematically too small. The observed spectra are used for diagnosis of the central ion and electron temperatures of the PLT discharges and for a measurement of the dielectronic recombination rate coefficient of TiXXII.« less

Anisotropy of the Fermi surface, Fermi velocity, many-body enhancement, and superconducting energy gap in Nb

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

Crabtree, G.W.; Dye, D.H.; Karim, D.P.

1987-02-01

The detailed angular dependence of the Fermi radius k/sub F/, the Fermi velocity v/sub F/(k), the many-body enhancement factor lambda(k), and the superconducting energy gap ..delta..(k), for electrons on the Fermi surface of Nb are derived with use of the de Haas--van Alphen (dHvA) data of Karim, Ketterson, and Crabtree (J. Low Temp. Phys. 30, 389 (1978)), a Korringa-Kohn-Rostoker parametrization scheme, and an empirically adjusted band-structure calculation of Koelling. The parametrization is a nonrelativistic five-parameter fit allowing for cubic rather than spherical symmetry inside the muffin-tin spheres. The parametrized Fermi surface gives a detailed interpretation of the previously unexplained kappa,more » ..cap alpha..', and ..cap alpha..'' orbits in the dHvA data. Comparison of the parametrized Fermi velocities with those of the empirically adjusted band calculation allow the anisotropic many-body enhancement factor lambda(k) to be determined. Theoretical calculations of the electron-phonon interaction based on the tight-binding model agree with our derived values of lambda(k) much better than those based on the rigid-muffin-tin approximation. The anisotropy in the superconducting energy gap ..delta..(k) is estimated from our results for lambda(k), assuming weak anisotropy.« less

Isolation of tungsten and tantalum isotopes without supports from. cap alpha. -particle-irradiated hafnium targets

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

Gasita, S.M.; Iota, B.Z.; Malachkov, A.G.

1985-11-01

An extraction procedure has been developed for successive isolation of tungsten (/sup 178/W and /sup 181/W) and tantalum (/sup 179/Ta and /sup 182/Ta) isotopes without supports from ..cap alpha..particle-irradiated hafnium targets. The target, irradiated on a cyclotron, is dissolved in hydrofluoric acid. Tantalum isotopes are extracted with tributyl phosphate (TBP) from 1-5 M HF and are then reextracted with a 1:1 ammonia solution, and hydrofluoric acid is removed by heating. Tungsten isotopes are extracted with a chloroform solution or N-benzoyl-N-phenylhydroxylamine (BPHA) from 11-12 M H/sub 2/SO/sub 4/ or ..cap alpha..-benzoin oxime from 4.5-5.5 M H/sub 2/SO/sub 4/ and are thenmore » reextracted with a l:l ammonia solution. The yield of tungsten isotopes is not less than 95%, and the content of radioactive impurities of other isotopes is not more than 0.1%.« less

Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

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

Graves, P.E.; Kaminsky, L.S.; Halpert, J.

Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effectmore » of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.« less

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

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

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with initiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1..mu..m. Abrahamson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will probably affect the ..beta.. component. 23 references, 5 figures, 2 tables.« less

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

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

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberrration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with intiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1 ..mu..m. Abrahmson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will primarily affect the ..beta.. component, resulting in low assessments of interaction site diameters.« less

Exact near-onset analysis of the spin-density-wave instability in ferromagnetic superconductors: The linearly polarized state

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

Hu, C.

1984-09-01

Using an approach similar to Abvikosov's theory of the vortex state near H/sub c/2, we have performed an exact, near-onset analysis of a spin-density-wave instability leading to the ''linearly polarized state'' of Greenside et al. in ferromagnetic superconductors. The approach is based on a generalized Ginzburg-Landau theory for such materials, as formulated by Blount and Varma. Two models have been considered. In the (..cap alpha..,..beta..) model, where the bulk magnetic energy is taken to be (1/2)..cap alpha../sub m/M/sup 2/+(1/4)..beta../sub m/M/sup 4/, we find the transition to be second order, and obtain explicit formulas for various physical quantities to leading ordermore » in the deviation from onset. We have also rigorously analyzed the most favored spatial structure just below onset, among all possibilities allowed by the instability, and have concluded that a plane-wave-like structure is favored in a physical limit considered. In the (..cap alpha..,..gamma..) model, where the bulk magnetic energy is taken to be (1/2)..cap alpha../sub m/M/sup 2/+(1/6)..gamma../sub m/M/sup 6/ as is supported by recent experiments for ErRh/sub 4/B/sub 4/, we find the transition to be first order. This approach is then confined to an unphysical branch, which does not permit us to calculate various physical quantities on the physical branch.« less

Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels

PubMed Central

Nguyen, Huy Q.; Nye, Jonathan; Buster, Daniel W.; Klebba, Joseph E.; Rogers, Gregory C.; Bosco, Giovanni

2015-01-01

The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein. PMID:25723539

Cross sections and differential spectra for reactions of 2-20 MeV neutrons of /sup 27/Al

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

Blann, M.; Komoto, T.T.

1988-01-01

This report summarizes product yields, secondary n,p and ..cap alpha.. spectra, and ..gamma..-ray spectra calculated for incident neutrons of 2-20 MeV on /sup 27/Al targets. Results are all from the code ALICE, using the version ALISO which does weighting of results for targets which are a mix of isotopes. Where natural isotopic targets are involved, yields and n,p,..cap alpha.. spectra will be reported weighted over isotopic yields. Gamma-ray spectra, however, will be reported for the most abundant isotope.

Separation of anionic oligosaccharides by high-performance liquid chromatography

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

Green, E.D.; Baenziger, J.U.

1986-10-01

The authors have developed methods for rapid fractionation of anionic oligosaccharides containing sulfate and/or sialic acid moieties by high-performance liquid chromatography (HPLC). Ion-exchange HPLC on amine-bearing columns (Micropak AX-10 and AX-5) at pH 4.0 is utilized to separate anionic oligosaccharides bearing zero, one, two, three, or four charges, independent of the identity of the anionic moieties (sulfate and/or sialic acid). Ion-exchange HPLC at pH 1.7 allows separation of neutral, mono-, di-, and tetrasialylated, monosulfated, and disulfated oligosaccharides. Oligosaccharides containing three sialic acid residues and those bearing one each of sulfate and sialic acid, however, coelute at pH 1.7. Since themore » latter two oligosaccharide species separate at pH 4.0, analysis at pH 4.0 followed by analysis at pH 1.7 can be utilized to completely fractionate complex mixtures of sulfated and sialylated oligosaccharides. Ion-suppression amine adsorption HPLC has previously been shown to separate anionic oligosaccharides on the basis of net carbohydrate content (size). In this study they demonstrate the utility of ion-suppression amine adsorption HPLC for resolving sialylated oligosaccharide isomers which differ only in the linkages of sialic acid residues (..cap alpha..2,3 vs ..cap alpha..2,6) and/or location of ..cap alpha..2,3- and ..cap alpha..2,6-linked sialic acid moieties on the peripheral branches of oligosaccharides. These two methods can be used in tandem to separate oligosaccharides, both analytically and preparatively, based on their number, types, and linkages of anionic moieties.« less

Tubulin chaperone E binds microtubules and proteasomes and protects against misfolded protein stress.

PubMed

Voloshin, Olga; Gocheva, Yana; Gutnick, Marina; Movshovich, Natalia; Bakhrat, Anya; Baranes-Bachar, Keren; Bar-Zvi, Dudy; Parvari, Ruti; Gheber, Larisa; Raveh, Dina

2010-06-01

Mutation of tubulin chaperone E (TBCE) underlies hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome with defective microtubule (MT) cytoskeleton. TBCE/yeast Pac2 comprises CAP-Gly, LRR (leucine-rich region), and UbL (ubiquitin-like) domains. TBCE folds alpha-tubulin and promotes alpha/beta dimerization. We show that Pac2 functions in MT dynamics: the CAP-Gly domain binds alpha-tubulin and MTs, and functions in suppression of benomyl sensitivity of pac2Delta mutants. Pac2 binds proteasomes: the LRR binds Rpn1, and the UbL binds Rpn10; the latter interaction mediates Pac2 turnover. The UbL also binds the Skp1-Cdc53-F-box (SCF) ubiquitin ligase complex; these competing interactions for the UbL may impact on MT dynamics. pac2Delta mutants are sensitive to misfolded protein stress. This is suppressed by ectopic PAC2 with both the CAP-Gly and UbL domains being essential. We propose a novel role for Pac2 in the misfolded protein stress response based on its ability to interact with both the MT cytoskeleton and the proteasomes.

Prevalence of. cap alpha. /sub 1/-antitrypsin heterozygotes (Pi MZ) in patients with obstructive pulmonary disease

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

Shigeoka, J.W.; Hall, W.J.; Hyde, R.W.

1976-01-01

An increased incidence of intermediate deficiency of serum ..cap alpha../sub 1/-antitrypsin resulting from Pi phenotype MZ has been reported in patients with chronic obstructive pulmonary disease (COPD) by some laboratories but not confirmed by others. Prevalence of Pi MZ was determined in patients with COPD among 502 subjects referred to a pulmonary function testing laboratory in a region with low concentrations of air pollutants. Control prevalences were obtained from 930 randomly selected subjects in the same community as well as from patients without COPD referred to the laboratory. Depending on criteria used to define COPD, 155 to 306 subjects hadmore » COPD. Pi MZ prevalence in subjects with COPD varied from 1.5 to 4 times the prevalence in the community control group and in the patients without COPD. This difference approached significance or was significant. Because Pi MZ was present in only 3.5 to 4.5% of patients with COPD, Pi MZ is not a major factor in the etiology of COPD in this community. The higher incidence of Pi MZ in patients with COPD reported by other investigators may be explained by small sample size, bias in selection of study or control population groups, or the development of COPD from interaction between Pi MZ and air pollutants or other factors not present in this community.« less

Individual neurophysiological profile in external effects investigation

NASA Astrophysics Data System (ADS)

Schastlivtseva, Daria; Tatiana Kotrovskaya, D..

Cortex biopotentials are the significant elements in human psychophysiological individuality. Considered that cortical biopotentials are diverse and individually stable, therefore there is the existence of certain dependence between the basic properties of higher nervous activity and cerebral bioelectric activity. The main purpose of the study was to reveal the individual neurophysiological profile and CNS initial functional state manifestation in human electroencephalogram (EEG) under effect of inert gases (argon, xenon, helium), hypoxia, pressure changes (0.02 and 0.2 MPa). We obtained 5-minute eyes closed background EEG on 19 scalp positions using Ag/AgCl electrodes mounted in an electrode cap. All EEG signals were re-referenced to average earlobes; Fast Furies Transformation analysis was used to calculate the relative power spectrum of delta-, theta-, alpha- and beta frequency band in artifact-free EEG. The study involved 26 healthy men who provided written informed consent, aged 20 to 35 years. Data obtained depend as individual EEG type and initial central nervous functional state as intensity, duration and mix of factors. Pronounced alpha rhythm in the raw EEG correlated with their adaptive capacity under studied factor exposure. Representation change and zonal distribution perversion of EEG alpha rhythm were accompanied by emotional instability, increased anxiety and difficulty adapting subjects. High power factor or combination factor with psychological and emotional or physical exertion minimizes individual EEG pattern.

Calculated half-lives and kinetic energies for spontaneous emission of heavy ions from nuclei

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

Poenaru, D.N.; Greiner, W.; Depta, K.

The most probable decays by spontaneous emission of heavy ions are listed for nuclides with Z = 47--106 and total half-lives>1 ..mu..sec. Partial half-lives, branching ratios relative to ..cap alpha.. decay, kinetic energies, and Q values are estimated by using the analytical superasymmetric fission model, a semiempirical formula for those ..cap alpha..-decay lifetimes which have not been measured, and the new Wapstra--Audi mass tables. Numerous ''stable'' nuclides with Z>40 are found to be metastable with respect to the new decay modes. The current experimental status is briefly reviewed.

Algal succession and chronosequences on abandoned mine spoils

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

Shubert, L.E.; Starks, T.L.

1978-06-01

Soils were collected from spoil material aged 0 to 45 years. The soils were analyzed for the presence of algal species, chlorophyll ..cap alpha.., major cations, anions and trace elements. There was a gradual increase in the number of algal species and chlorophyll ..cap alpha.. from 1 year old spoils to adjacent unmined natural sites. A total of 41 algal species were identified from all sites. Several species were only found at the unmined sites and they may represent a stable algal community. Results of a statistical analysis on the litho- and chronosequence of the soils will be discussed.

Multiconfiguration resonating-group theory of the seven-nucleon system with realistic cluster wave functions

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

Fujiwara, Y.; Tang, Y.C.

1985-02-01

The properties of the seven-nucleon system are examined with a multiconfiguration and multi- channel resonating-group calculation. The cluster internal functions employed explain the charge-form-factor data over a wide range of q/sup 2/ and satisfy the variational stability condition quite well. The model space used is spanned by /sup 3/H+..cap alpha.., n+ /sup 6/Li, n+ /sup 6/Li(, and d+ /sup 5/He cluster configurations. The result shows that the specific distortion of the /sup 3/H+..cap alpha.. system is quite significant. With our multiconfiguration calculation, the ground-state energy is improved by more than 1 MeV. The calculated level spectrum agrees well with themore » level spectrum empirically determined. The energy positions of both natural-parity and unnatural-parity levels are reasonably explained. In addition, we find that, because of centrifugal-barrier effects, the aligned configuration generally makes the most sig- nificant contribution. The characteristics of nucleon-exchange terms are also briefly examined. Here it is found that, at sufficiently high energies where sharp resonance levels do not exist, the essential properties of these terms can already be learned by performing relatively simple single-configuration calculations.« less

Comment on radiative magnetic energy shifts in hydrogen

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

Calmet, J.; Grotch, H.; Owen, D.A.

It is shown that the magnetic radiative energy shift derived from the relativistic-Lamb-shift expression of Erickson and Yennie reduces in the nonrelativistic limit to a formula given by Grotch and Hegstrom, which was derived starting from the nonrelativistic theory. This clears up a discrepancy between those two approaches. The corresponding correction to the g factor, which exists only for states with l not = 0, is estimated to be -0.24 ..cap alpha../sup 3/ for the 2P state of hydrogen.

Biosynthesis of ketomycin. (II) biomimetic model for beta-lactamase catalysis: host-guest interactions in cyclodextrin-penicillin inclusion complex

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

Mak, H.W.

The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine derived from shikimic acid are not intermediates in the biosynthesis. Degradation of ketomycin derived from (1,6-/sup 14/C)shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexane ring of ketomycin. The resistance of pathogenic bacteria to the action of ..beta..-lactam antibiotics is mainly ascribed to their ability to produce ..beta..-lactamase to cleave the ..beta..-lactam ring. It is essential to understandmore » the molecular nature of ..beta..-lactamase-penicillin recognition for designing and formulating more effective ..beta..-lactam antibiotics. A biomimetic study of ..beta..-lactamase is therefore initiated. To meet the requirements of hydrophobic and serine protease characteristics of ..beta..-lactamase, ..cap alpha..-cyclodextrin is chosen as a biomimetic model for ..beta..-lactamase. The structural specificity and the chemical dynamics of ..cap alpha..-cyclodextrin-phenoxymethyl penicillin inclusion complex in solid state and in solution have been determined by IR and NMR spectroscopy. The spectral results strongly indicate that the phenyl portion of the phenoxymethyl penicillin forms a stable inclusion complex with the hydrophobic cavity of ..cap alpha..-cyclodextrin in solution as well as in the solid state. Kinetic studies followed by /sup 1/HNMR and HPLC analyses under alkaline condition have shown that the ..cap alpha..-cyclodextrin mimics the catalytic function of serine of ..beta..-lactamase in the stereospecific hydrolysis of the ..beta..-lactam ring of phenoxymethyl penicillin.« less

[Factorial Structure of the Cardiff Anomalous Perceptions Scale (CAPS) in a Colombian Population Sample].

PubMed

Tamayo-Agudelo, William; Jaén-Moreno, María José; Luque-Luque, Rogelio

2015-01-01

The continuum hypothesis of psychosis assumes that hallucinations are not exclusive of psychotic disorders. A number of psychometric tests have been developed to assess psychosis using a dimensional model. To determine the factorial structure of the Cardiff Anomalous Perceptions Scale (CAPS) for the Colombian population, and to contrast the fit of two factor models previously reported in the literature by conducting a confirmatory factor analysis (CFA). This was a cross-sectional study in which 207 subjects from the general population were assessed using the Cardiff Anomalous Perceptions Scale. A two-factor structure with acceptable ordinal alpha coefficients (α=.88 and α=.87) was found. One factor gathered items related to multimodal perceptual alterations, and a second factor grouped items related with experiences linked to the temporal lobe. The analysis of the first factor indicated that it was dependent on cultural issues for the interpretation of sensations. The second factor appeared almost unchanged on diverse populations, suggesting its transcultural character. When comparing the models proposed by Bell et al. and Jaen-Moreno et al. using the data obtained from the sample, the confirmatory factor analysis conducted indicated inadequate goodness-of-fit indexes (χ(2)). However, some incremental goodness-of-fit indexes (normalized χ(2) [RMSEA]) were acceptable. The Jaén-Moreno et al. model showed the best fit to the data collected from the Colombian sample. The factorial structure of CAPS for the Colombian population appears to be sensitive to cultural issues, especially when describing anomalous sensorial experiences. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Treatment of catastrophic antiphospholipid syndrome with defibrotide, a proposed vascular endothelial cell modulator.

PubMed

Burcoglu-O'Ral, Arsinur; Erkan, Doruk; Asherson, Ronald

2002-09-01

To define at the molecular level the vascular endothelial cell (VEC) injury characteristics of catastrophic antiphospholipid syndrome (CAPS) and to report successful therapeutic use of a VEC modulator, defibrotide. We describe a 55-year-old man with primary APS with an intractable prothrombotic state (CAPS) resistant to combined therapy with heparin, warfarin, aspirin, and dipyridamole. Treatment with defibrotide was conducted in the context of an investigational phase II protocol where the dose was regulated and individualized by disease/patient-specific molecular and clinical markers. The patient entered complete remission with defibrotide treatment. During treatment, dose dependent pharmacological actions of defibrotide and key stress markers for VEC injury were identified. Evidence of defibrotide's polypharmacology included downregulation of cytokines, notably tumor necrosis factor-alpha, as the earliest effect, cellular differentiation of VEC, possibly with direct regulatory effect over cellular genes, and the reversal of platelet consumption and prothrombotic state. Von Willebrand antigen levels were used as the sole marker to guide therapy. This case demonstrates effective remission of CAPS with defibrotide treatment. In contrast to theories that CAPS is triggered by ischemic and thrombotic tissue damage, these data present VEC injury as the primary and representative lesion of CAPS. The pathogenesis may involve concurrent impairment of different VEC functions. Achieving remission may require a polypharmacologic approach, represented here by use of defibrotide.

[Cytokine changes in community-acquired pneumonia in elderly and intervention of traditional Chinese medicine].

PubMed

Ye, Shanghe; Gong, Guolang; Zheng, Haiwen; Hu, Guohua; Xia, Tao

2010-06-01

To make a study of the cytokine changes in community-acquired pneumonia (CAP) in the elderly and the intervention of traditional Chinese medicine that can clear away the lung-heat and dissipate blood stasis (Qingfeihuayu soup). The 82 cases with CAP in the elderly were divided at random into two treatment group and control group. Based on heteropathy, the treatment group was given Qingfeihuayu soup two times a day. The control group was given Rocephin 2 g once daily for 7 days. The clinical effect and the changes in TNF-alpha, IL-6 and IL-10 were observed before and after the treatment. A healthy group was also set up. Before treatment, IL-6 and TNF-alpha in both groups were higher than the healthy group (P < 0.01) and IL-10 lower than the healthy group (P < 0.01). After treatment, IL-6 and TNF-alpha in both groups decreased (P < 0.01) while IL-10 in treatment group increased. There existed a great difference compared with the control group (P < 0.01). The total effective rate in the treatment group is 92.50% while the control group is 85.71%. thus have a great difference (P < 0.05). During the process of the development of CAP in the elderly, there existed the phenomenon of the excessive release of TNF-alpha, IL-6 and the too much inhibition of IL-10. The unbalance of TNF-alpha, IL-6, IL-10 can be a monitoring index reflecting the severity of the disease. The Chinese medicine Qingfeihuayu soup has obviously have regulating and clinical effect.

Results from the Crystal Ball at DORIS II

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

Gaiser, J.E.

1983-10-01

Results are presented from studies of the inclusive photon spectra in hadronic decays of the UPSILON' and UPSILON and the exclusive channel UPSILON' ..-->.. ..gamma gamma..UPSILON ..-->.. ..cap alpha cap alpha..l/sup +/l/sup -/, by the Crystal Ball detector at DORIS II. We measure two signals in the UPSILON' ..-->.. ..gamma.. + anything inclusive channel at E(..gamma..) == 108.3 +- 0.9 +- 3.0 MeV and at E(..gamma..) == 127.5 +- 1.2 +- 4.0 MeV. Branching ratios obtained for these signals are: BR(UPSILON' ..-->.. ..gamma..(108) + anything) == (6.3 +- 1.3 +- 1.4)% BR(UPSILON' ..-->.. ..gamma..(128) + anything) == (6.0 +- 1.3more » +- 1.4)%.« less

MFTF-. cap alpha. + T progress report

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

Nelson, W.D.

1985-04-01

Early in FY 1983, several upgrades of the Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) were proposed to the fusion community. The one most favorably received was designated MFTF-..cap alpha..+T. The engineering design of this device, guided by LLNL, has been a principal activity of the Fusion Engineering Design Center during FY 1983. This interim progress report represents a snapshot of the device design, which was begun in FY 1983 and will continue for several years. The report is organized as a complete design description. Because it is an interim report, some parts are incomplete; theymore » will be supplied as the design study proceeds. As described in this report, MFTF-..cap alpha..+T uses existing facilities, many MFTF-B components, and a number of innovations to improve on the physics parameters of MFTF-B. It burns deuterium-tritium and has a central-cell Q of 2, a wall loading GAMMA/sub n/ of 2 MW/m/sup 2/ (with a central-cell insert module), and an availability of 10%. The machine is fully shielded, allows hands-on maintenance of components outside the vacuum vessel 24 h after shutdown, and has provisions for repair of all operating components.« less

Cold Atmospheric Plasma (CAP) Changes Gene Expression of Key Molecules of the Wound Healing Machinery and Improves Wound Healing In Vitro and In Vivo

PubMed Central

Arndt, Stephanie; Unger, Petra; Wacker, Eva; Shimizu, Tetsuji; Heinlin, Julia; Li, Yang-Fang; Thomas, Hubertus M.; Morfill, Gregor E.; Zimmermann, Julia L.

2013-01-01

Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated. PMID:24265766

Muscarinic cholinergic and alpha/sub 1/ adrenergic receptors in murine atria: phosphatidylinositol breakdown and receptor interaction

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

Scherer, R.W.

Upon stimulation of muscarinic cholinergic receptors, there is a decrease in the force of contraction rate of firing in heart, while stimulation of ..cap alpha.. adrenergic receptors causes an increase in the force of contraction with no change in the heart rate. Yet both receptors stimulate the breakdown of phosphatidylinositol (PI). Therefore, the breakdown of PI was examined to determine how the process differed between the two receptor systems. Murine atria, prelabelled with (/sup 3/H)inositol, were stimulated with the muscarinic cholinergic agonists, carbamylcholine (CARB), and oxotremorine (OXO); and with the ..cap alpha.. adrenergic agonists, norepinephrine (NE) and phenylephrine (PE); eithermore » singly or in combination. Breakdown of PI was assessed by measurement of individual inositol phosphates by anion exchange chromatography. Binding of CARB to atrial muscarinic receptors was measured by competition with (/sup 3/H)quinuclidinyl benzilate.« less

Structural and biological characterization of a capsular polysaccharide produced by Staphylococcus haemolyticus.

PubMed

Flahaut, Sigrid; Vinogradov, Evgeny; Kelley, Kathryn A; Brennan, Shannon; Hiramatsu, Keiichi; Lee, Jean C

2008-03-01

The DNA sequence of the genome of Staphylococcus haemolyticus JCSC1435 revealed a putative capsule operon composed of 13 genes in tandem. The first seven genes (capABCDEFG(Sh)) showed > or = 57% similarity with the Staphylococcus aureus cap5 or cap8 locus. However, the capHIJKLM(Sh) genes are unique to S. haemolyticus and include genes encoding a putative flippase, an aminotransferase, two glycosyltransferases, and a transcriptional regulator. Capsule-like material was readily apparent by immunoelectron microscopy on bacteria harvested in the postexponential phase of growth. Electron micrographs of a JCSC1435 mutant with a deleted cap region lacked the capsule-like material. Both strains produced small amounts of surface-associated material that reacted with antibodies to polyglutamic acid. S. haemolyticus cap genes were amplified from four of seven clinical isolates of S. haemolyticus from humans, and three of these strains produced a serologically cross-reactive capsular polysaccharide. In vitro assays demonstrated that the acapsular mutant strain showed greater biofilm formation but was more susceptible to complement-mediated opsonophagocytic killing than the parent strain. Structural characterization of capsule purified from S. haemolyticus strain JCSC1435 showed a trisaccharide repeating unit: -3-alpha-L-FucNAc-3-(2-NAc-4-N-Asp-2,4,6-trideoxy-beta-D-Glc)-4-alpha-D-GlcNAc-. This structure is unique among staphylococcal polysaccharides in that its composition includes a trideoxy sugar residue with aspartic acid as an N-acyl substituent.

Absolute configuration of a chiral CHD group via neutron diffraction: confirmation of the absolute stereochemistry of the enzymatic formation of malic acid

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

Bau, R.; Brewer, I.; Chiang, M.Y.

Neutron diffraction has been used to monitor the absolute stereochemistry of an enzymatic reaction. (-)(2S)malic-3-d acid was prepared by the action of fumarase on fumaric acid in D/sub 2/O. After a large number of cations were screened, it was found that (+)(R)..cap alpha..-phenylethylamine forms the large crystals necessary for a neutron diffraction analysis. The subsequent structure determination showed that (+)(R)..cap alpha..-phenylethylammonium (-)(2S)malate-3-d has an absolute configuration of R at the CHD site. This result confirms the absolute stereochemistry of fumarate-to-malate transformation as catalyzed by the enzyme fumarase.

Role of carotenoids in the phototropic response of corn seedings

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

Vierstra, R.D.; Poff, K.L.

1981-10-01

The herbicide 4 chloro-5-(methylamino)-2-..cap alpha..,..cap alpha..,..cap alpha..,-trifluoro-m-tolyl)-3(2H)- pyridazinone (SAN 9789), which blocks the synthesis in higher plants of colored carotenoids but not of flavins, was used to examine the involvement of carotenoids in corn seeding phototropism. It was concluded that ''bulk'' carotenoids are not the photoreceptor pigment based on the results that increasing concentrations of SAN 9789 (up to 100 micromolar) did not alter the phototropic sensitivity to 380 nanometers light (using geotropism as a control) and did not increase the threshold intensities of fluence response curves for both 380 and 450 nanometers light even though carotenoid content was reducedmore » to 1 to 2% of normal. SAN 9789 treatment, however, did reduce seedling sensitivity toward 450 nanometers light indicating that carotenoids are involved in phototropism. Carotenoids, which are located mainly in the primary leaves, may act in phototropism as an internal screen, enhancing the light intensity gradient across the seedling and thus contributing to the ability of the seedling to perceive light direction. These results, indicate that the action spectra for phototropic responses can be significantly affected by the absorbance of screening pigments in vivo thus altering its shape from the in vitro absorption spectrum of the photoreceptor pigment.« less

Secondary. cap alpha. -deuterium kinetic isotope effects in solvolyses of ferrocenylmethyl acetate and benzoate in ethanol

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

Sutic, D.; Asperger, S.; Borcic, S.

1982-12-17

Secondary ..cap alpha..-deuterium kinetic isotope effects (KIE) in solvolyses of ferrocenyldideuteriomethyl acetate and benzoate were determined in 96% (v/v) ethanol, at 25/sup 0/C, as k/sub H//k/sub D/ = 1.24 and 1.26, respectively. The KIEs were also determined in the presence of 0.1 mol dm/sup -3/ lithium perchlorate: the k/sub H//k/ sub D/ values were 1.23 and 1.22 for acetate and benzoate complexes, respectively. The maximum KIE for the C-O bond cleavage of a primary substrate is as large as, or larger than, that of secondary derivatives, which is estimated to be 1.23 per deuterium. The measured KIE of about 12%more » per D therefore represents a strongly reduced effect relative to its maximum. The solvolyses exhibit ''a special salt effect''. This effect indicates the presence of solvent-separated ion pairs and the return to tight pairs. As the maximum KIE is expected in solvolyses involving transformation of one type of ion pair into another, the strongly reduced ..cap alpha..-D KIE supports the structure involving direct participation of electrons that in the ground state are localized at the iron atom. The alkyl-oxygen cleavage is accompanied by 10-15% acyl-oxygen cleavage.« less

Hydrogen transport and hydrogen embrittlement in stainless steels

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

Perng, T.P.

1985-01-01

In order to understand the kinetics of gaseous hydrogen-induced slow crack growth (SCG) in metastable austenitic stainless steels, hydrogen permeation and/or cracking velocity were measured and compared for three types of stainless steels. These included austenitic, ferritic, and duplex (..gamma../..cap alpha..) alloys. Deformation in AISI 301 resulted in various amounts of ..cap alpha..' martensite, which enhanced the effective hydrogen diffusivity and permeability. No phase transformation was observed in deformed AISI 310. The effective hydrogen diffusivity in this alloy was slightly reduced after plastic deformation, presumably by dislocation trapping. In either the dynamic or static tensile test, AISI 301 exhibited themore » greatest hydrogen embrittlement and therefore the highest SCG velocity among all the alloys tested in this work. The SCG velocity was believed to be controlled by the rate of accumulation of hydrogen in the embrittlement region ahead of the crack tip and therefore could be explained with the hydrogen transport parameters measured from the permeation experiments. The relatively high SCG velocity in AISI 301 was probably due to the fast transport of hydrogen through the primarily stress-induced ..cap alpha..' phase around the crack. No SCG was observed in AISI 310. The presence of H/sub 2/O vapor was found to reduce both the hydrogen permeation and SCG velocity.« less

Vacuum energy density near static distorted black holes

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

Frolov, V.P.; Sanchez, N.

1986-03-15

We investigate the contribution of massless fields of spins 0, 1/2, and 1 to the vacuum polarization near the event horizon of static Ricci-flat space-times. We do not assume any particular spatial symmetry. Within the Page-Brown ''ansatz'' we calculate /sup ren/ and /sup ren/ near static distorted black holes, for both the Hartle-Hawking (Vertical Bar>/sub H/) and Boulware (Vertical Bar>/sub B/) vacua. Using Israel's description of static space-times, we express these quantities in an invariant geometric way. We obtain that /sub H//sup ren/ and /sub H//sup ren/ near the horizon depend only on the two-dimensional geometry of the horizon surface.more » We find /sub H//sup ren/ = (1/48..pi../sup 2/ )K/sub 0/, /sub H//sup ren/ = (7..cap alpha..+12..beta.. )K/sub 0/ /sup 2/-..cap alpha../sup(/sup 2/)..delta..K/sub 0/. $K sub 0: is the Gaussian curvature of the horizon, and ..cap alpha.. and ..beta.. are numerical coefficients depending on the spin of a field. The term in /sup(/sup 2/)..delta..K/sub 0/ is characteristic of the distortion of the black hole. When the event horizon is not distorted, K/sub 0/ is a constant and this term disappears.« less

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

Calva-Tellez, E.; Yennie, D.R.

The Coulomb corrections of relative order Z..cap alpha.. to inelastic electron and muon scattering are examined. Although individual terms are large, the net result is too small to be experimentally significant.

Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation

PubMed Central

Tomlinson, Gareth H.; Miles, Katherine; Smith, Richard W. P.; Rossi, Adriano G.; Hiemstra, Pieter S.; van ’t Wout, Emily F. A.; Dean, Jonathan L. E.; Gray, Nicola K.; Lu, Wuyuan; Gray, Mohini

2016-01-01

Neutrophils are the first and most numerous cells to arrive at the site of an inflammatory insult and are among the first to die. We previously reported that alpha defensins, released from apoptotic human neutrophils, augmented the antimicrobial capacity of macrophages while also inhibiting the biosynthesis of proinflammatory cytokines. In vivo, alpha defensin administration protected mice from inflammation, induced by thioglychollate-induced peritonitis or following infection with Salmonella enterica serovar Typhimurium. We have now dissected the antiinflammatory mechanism of action of the most abundant neutrophil alpha defensin, Human Neutrophil Peptide 1 (HNP1). Herein we show that HNP1 enters macrophages and inhibits protein translation without inducing the unfolded-protein response or affecting mRNA stability. In a cell-free in vitro translation system, HNP1 powerfully inhibited both cap-dependent and cap-independent mRNA translation while maintaining mRNA polysomal association. This is, to our knowledge, the first demonstration of a peptide released from one cell type (neutrophils) directly regulating mRNA translation in another (macrophages). By preventing protein translation, HNP1 functions as a “molecular brake” on macrophage-driven inflammation, ensuring both pathogen clearance and the resolution of inflammation with minimal bystander tissue damage. PMID:27044108

Assessment of posttraumatic stress disorder in Cambodian refugees using the Clinician-Administered PTSD Scale: psychometric properties and symptom severity.

PubMed

Hinton, Devon E; Chhean, Dara; Pich, Vuth; Pollack, M H; Orr, Scott P; Pitman, Roger K

2006-06-01

Posttraumatic stress disorder (PTSD) symptoms were assessed by using the Clinician-Administered PTSD Scale (CAPS) in a consecutive sample of Cambodian refugees attending a psychiatric clinic in the United States. Psychometric properties of the translated CAPS and severity of PTSD-related symptoms were examined. The CAPS demonstrated adequate psychometric properties, including coefficient alpha (.92) and item-total correlations (.48-.85). Of the sample 56% (101/179) met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for current PTSD. Those patients who met criteria for current PTSD had significantly higher CAPS total scores (M = 65.3, SD = 18.1) than those who did not meet the criteria (M = 13.9, SD = 16.7).

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

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

Matzuk, M.M.; Krieger, M.; Corless, C.L.

1987-09-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common ..cap alpha.. subunit but differ in their hormone-specific ..beta..-subunits. The ..beta.. subunit of hCG (hCG..beta..) is unique among the ..beta.. subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCG..beta.. gene alone or together with the hCG..cap alpha.. gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results revealmore » that hCG..beta.. can be secreted normally in the absence of its O-linked oligosaccharides. hCG..beta.. devoid of O-linked carbohydrate can also combine efficiently with hCG..cap alpha.. and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCG..beta.. O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG.« less

Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio

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

Janssens, P.A.; Lowrey, P.

1987-04-01

Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC/sub 50/s of 100, 100, and 500 nM, respectively. These actions were blocked by the ..beta..-adrenergic antagonist, propranolol, but not by the ..cap alpha..-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10/sup -6/ M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10/sup -5/ M isotocin and slightly decreased by 10/sup -6/ M angiotensin II. (/sup 125/I)-iodocyanopindolol (ICP), amore » ..beta..-adrenergic ligand, bound to isolated carp liver membranes with a K/sub D/ of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with K/sub D/s of 100 nM, 2, 20, 20, 60, and 200 ..mu..M, respectively. The ..cap alpha..-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via ..beta..-adrenergic receptors in carp liver and that ..cap alpha..-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis.« less

Hydrogen and deuterium in the local interstellar medium

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

Murthy, J.N.

1987-01-01

This work reports on the results of a series of IUE observations of interstellar HI and DI Ly..cap alpha.. absorption against the chromospheric Ly..cap alpha.. emission of the nearby late-type stars ..cap alpha.. Cen B(1.3 pc), epsilon Eri (3.3 pc), Procyon (3.5 pc), Altair (5.1 pc), Capella (13.2 pc), and HR 1099 (33 pc). The density, velocity dispersion, and bulk velocity of the neutral hydrogen along the line of sight to each of these stars was derived. Lower limits were placed on the deuterium-to-hydrogen (D/H) ratio towards the same stars. These IUE results are generally consistent with previous observations ofmore » the same stars with the Copernicus satellite showing that this modeling procedure is independent of stellar variations over a period of several years. The HI absorption profile towards Altair shows a broad saturated core and steep line wings, consistent with a multicomponent interstellar medium in that direction. The bulk velocities towards the other stars are consistent with a bulk flow from the approximate direction of the galactic center but do show local variations from a uniform flow, possibly indicating a complicated velocity structure even in the solar neighborhood. Interstellar deuterium is detected towards every star except Altair and the derived values for the D/H ratio are consistent with those previously found with Copernicus.« less

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

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

Green, E.D.; Baenziger, J.U.

1988-01-05

The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunitsmore » with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.« less

Expanded turn conformations: characterization and sequence-structure correspondence in alpha-turns with implications in helix folding.

PubMed

Dasgupta, Bhaskar; Pal, Lipika; Basu, Gautam; Chakrabarti, Pinak

2004-05-01

Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding. Copyright 2004 Wiley-Liss, Inc.

A capacitive, biocompatible and adhesive electrode for long-term and cap-free monitoring of EEG signals.

PubMed

Lee, Seung Min; Kim, Jeong Hun; Byeon, Hang Jin; Choi, Yoon Young; Park, Kwang Suk; Lee, Sang-Hoon

2013-06-01

Long-term electroencephalogram (EEG) monitoring broadens EEG applications to various areas, but it requires cap-free recording of EEG signals. Our objective here is to develop a capacitive, small-sized, adhesive and biocompatible electrode for the cap-free and long-term EEG monitoring. We have developed an electrode made of polydimethylsiloxane (PDMS) and adhesive PDMS for EEG monitoring. This electrode can be attached to a hairy scalp and be completely hidden by the hair. We tested its electrical and mechanical (adhesive) properties by measuring voltage gain to frequency and adhesive force using 30 repeat cycles of the attachment and detachment test. Electrode performance on EEG was evaluated by alpha rhythm detection and measuring steady state visually evoked potential and N100 auditory evoked potential. We observed the successful recording of alpha rhythm and evoked signals to diverse stimuli with high signal quality. The biocompatibility of the electrode was verified and a survey found that the electrode was comfortable and convenient to wear. These results indicate that the proposed EEG electrode is suitable and convenient for long term EEG monitoring.

Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity.

PubMed

Hoffman, Hal M; Wolfe, Frederick; Belomestnov, Pavel; Mellis, Scott J

2008-09-01

Development of an instrument for characterization of symptom patterns and severity in patients with cryopyrin-associated periodic syndromes (CAPS). Two generations of daily health assessment forms (DHAFs) were evaluated in this study. The first-generation DHAF queried 11 symptoms. Analyses of results obtained with that instrument identified five symptoms included in a revised second-generation DHAF that was tested for internal consistency and test-retest reliability. This DHAF was also assessed during the initial portion of a phase 3 clinical study of CAPS treatment. Forty-eight CAPS patients provided data for the first-generation DHAFs. Five symptoms (rash, fever, joint pain, eye redness/pain, and fatigue) were included in the revised second-generation DHAF. Symptom severity was highly variable during all study phases with as many as 89% of patients reporting at least one symptom flare, and percentages of days with flares reaching 58% during evaluation of the second-generation instrument. Mean composite key symptom scores (KSSs) computed during evaluation of the second-generation DHAF correlated well with Physician's Global Assessment of Disease Activity (r=0.91, p<0.0001) and patient reports of limitations of daily activities (r=0.68, p<0.0001). Test-retest reliability and Cronbach's alpha's were high (0.93 and 0.94, respectively) for the second-generation DHAF. Further evaluation of this DHAF during a baseline period and placebo treatment in a phase 3 clinical study of CAPS patients indicated strong correlations between baseline KSS and Physician's Global Assessment of Disease Activity. Cronbach's alpha's at baseline and test-retest reliability were also high. Potentially important study limitations include small sample size, the lack of a standard tool for CAPS symptom assessment against which to validate the DHAF, and no assessment of the instrument's responsivity to CAPS therapy. The DHAF is a new instrument that may be useful for capturing symptom patterns and severity in CAPS patients and monitoring responses to therapies for these conditions.

Validation of the French version of the Child Post-Traumatic Stress Reaction Index: psychometric properties in French speaking school-aged children.

PubMed

Olliac, Bertrand; Birmes, Philippe; Bui, Eric; Allenou, Charlotte; Brunet, Alain; Claudet, Isabelle; Sales de Gauzy, Jérôme; Grandjean, Hélène; Raynaud, Jean-Philippe

2014-01-01

Although the reliable and valid Child Post-Traumatic Stress Reaction Index (CPTS-RI) is a widely used measure of posttraumatic stress disorder (PTSD) symptoms in children, it has not been validated in French-speaking populations. The present study aims to assess the psychometric properties of the CPTS-RI in three samples of French-speaking school-children. Data was obtained from three samples. Sample 1 was composed of 106 children (mean (SD) age = 11.7(0.7), 50% females) victims of an industrial disaster. Sample 2 was composed of 50 children (mean (SD) age = 10.8(2.6), 44% females) who had received an orthopaedic surgical procedure after an accident. Sample 3 was composed of 106 children (mean (SD) age = 11.7(2.2), 44% females) admitted to an emergency department after a road traffic accident. We tested internal consistency using Cronbach's alpha. We examined test-retest reliability using intraclass correlation coefficient. In order to assess the convergent validity of the French version of the CPTS-RI and the Clinician Administered PTS Scale-Child and Adolescent (CAPS-CA), spearman-correlation coefficient was computed. To verify the validity of the cut-off scores, a ROC curve was constructed which evaluated the sensitivity and specificity of each score compared to the diagnosis with the CAPS-CA. We also used principal components analysis with varimax rotation to study the structure of the French version of the CPTS-RI. Cronbach's alpha coefficient was 0.87 for the French version of the CPTS-RI. Two-week test-retest intraclass correlation coefficient (n = 30) was 0.67. The French version of the CPTS-RI was well correlated with the CAPS-CA (r = 0.76, p < 0.001). Taking the CAPS-CA as the diagnostic reference, with a diagnostic cut-off of >24 for the CPTS-RI, the sensitivity and specificities were 100% and 62.6%, respectively. The French version of the CPTS-RI demonstrated a three-factor structure. The CPTS-RI is reliable and valid in French-speaking children.

Preparation of alpha-cyclodextrin-terminated polyrotaxane consisting of beta-cyclodextrins and pluronic as a building block of a biodegradable network.

PubMed

Ooya, Tooru; Ito, Akihiro; Yui, Nobuhiko

2005-05-23

A beta-CD-based biodegradable polyrotaxane was prepared by capping both terminals of polypseudorotaxane consisting of hydrazide-terminated PEG-block-PPG-block-PEG (Pluronic P-105) and beta-CD-succinates with mono-aldehyde alpha-CDs. By decreasing pH, the fluorescent intensity of TNS was increased with time, indicating cleavage of the terminal hydrazone bonds followed by beta-CD-succinate release. The terminal alpha-CD moieties of the polyrotaxane are useful for self-assembled formation with some guest molecules. [Diagram: see text

Solubilization of cyclohexane in aqueous solutions of sodium. cap alpha. -alkyl alkanoates

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

Sagitani, H.; Suzuki, T.; Nagai, M.

1982-01-01

The effect of branched alkyl chain length and the position of the COONa group on the solubilizing power of n-alkane sodium carboxylates was studied. The lipophilic property and the amount of solubilized cyclohexane increased with the branched chain length of branched soaps, and with the change of the position of the -COONa group from 3 to 7 in the alkyl chain of pentadecane -3, -5, and -7 sodium carboxylates. Alpha-branched soaps having proper branched alkyl chains were better solubilizers for cyclohexane than straight chain compounds. The amount of cyclohexane solublized by C/sub 10/ H/sub 21/ CH(C/sub 6/H/sub 13/) COONa wasmore » about three times greater than the amount solubilized by C/sub 17/ H/sub 35/ COONa. There was a marked increase in the solubilization of cyclohexane replacing ..cap alpha..-branched fatty acid soaps with optimum amount of cosurfactants such as C/sub 8/H/sub 17/ (OCH/sub 2/CH/sub 2/)/sub 2/OH. Namely, solubilization increased markedly at the optimum hydrophile-lipophile balance of mixed surfactant. 21 references.« less

Inhibition of radioemesis by disruption of catecholamines in dogs

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

Luthra, Y.K.; Mattsson, J.L.; Yochmowitz, M.G.

1981-03-01

Dogs were treated 30 min to 1 h before x irradiation with ..cap alpha..-methyl-p-tyrosine or 6-hydroxydopamine. A third group of dogs was given a known antiradioemetic drug, haloperidol to verify the sensitivity of the procedure. Irradiated but untreated controls were also used. Light methoxyflurane anesthesia was used for restraint during the exposure. Exposure dose was 800 rad kerma delivered at 50 rad/min to a 10 x 10-cm area covering the abdominal area from xiphoid to pubis. Haloperidol and 6-hydroxydopamine significantly reduced the number of emetic episodes and delayed the onset time to the first episode, ..cap alpha..-Methyl-p-tyrosine caused no significantmore » changes. The effectiveness of 6-hydroxydopamine indicates that catecholaminergic neurons are involved in radioemesis, whereas haloperidol and phenothiazine-derivative tranquilizers inhibit radiomesis by blocking catecholamine receptor neurons.« less

ADP-ribosylation of membrane components by pertussis and cholera toxin

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

Ribeiro-Neto, F.A.P.; Mattera, F.; Hildebrandt, J.D.

1985-01-01

Pertussis and cholera toxins are important tools to investigate functional and structural aspects of the stimulatory (N/sub s/) and inhibitory (N/sub i/) regulatory components of adenylyl cyclase. Cholera toxin acts on N/sub s/ by ADP-ribosylating its ..cap alpha../sub s/ subunit; pertussis toxin acts on N/sub i/ by ADP-ribosylating its ..cap alpha..; subunit. By using (/sup 32/P)NAD/sup +/ and determining the transfer of its (/sup 32/P)ADP-ribose moiety to membrane components, it is possible to obtain information on N/sub s/ and N/sub i/. A set of protocols is presented that can be used to study simultaneously and comparatively the susceptibility of N/submore » s/ and N/sub i/ to be ADP-ribosylated by cholera and pertussis toxin.« less

/sup 45/Ca efflux for myometrial cells: comparison of the effects of prostaglandin F/sub 2/. cap alpha. (PGF/sub 2/), oxytocin (OT) and arachidonate (A)

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

Katona, G.; Molnar, M.; Toth, M.

1986-03-01

The aim of this study was to measure PGF/sub 2..cap alpha../-induced Ca/sup 2 +/ release from uterine cells and to compare this to the actions of OT and A. Smooth muscle cells isolated from the uterus (shell gland) of laying hens were cultured for 7 days in M199 plus 10% fetal calf serum. The cells were treated with digitonin (20..mu..M) and preloaded with /sup 45/Ca for 40 min. Addition of PGF/sub 2..cap alpha../ caused a biphasic /sup 45/Ca-efflux. There was a small but significant /sup 45/Ca-release within 30 sec (rapid phase) followed by a larger one within 7 min (slowmore » phase). In comparison, both OT and A stimulated /sup 45/Ca efflux during a single, slow phase. The maximal effect of A was observed at < 7 min, whereas that of OT was slower, peaking after 7 min. Mepacrin, an inhibitor of A release, attenuated the action of OT without having any effect on A promoted /sup 45/Ca-efflux. Indomethacin, an inhibitor of PG synthase, failed to suppress the Ca-releasing effect of A suggesting the A itself or a lipoxygenase product may have been responsible for the observed effects. Moreover, these results provide suggestive evidence that A release is an important step in the action of various uterotonic agents converging on the mobilization of intracellular Ca.« less

Congenital Muscle Disease Study of Patient and Family Reported Medical Information

ClinicalTrials.gov

2017-05-05

Congenital Muscular Dystrophy (Including Unspecified/Undiagnosed); Dystroglycanopathy; Congenital Fiber Type Disproportion; Rigid Spine Muscular Dystrophy; Congenital Myopathy (Including Unspecified/Undiagnosed); Collagen VI CMD (Ullrich CMD, Intermediate, Bethlem Myopathy); Laminin Alpha 2 Related Congenital Muscular Dystrophy; LAMA2-CMD/Merosin Deficient/MDC1A; Walker-Warburg Syndrome; Muscle-Eye-Brain Disease; Fukuyama/Fukutin Related Muscular Dystrophy; Integrin Alpha 7 Deficiency; Integrin Alpha 9 Deficiency; LMNA-CMD/Lamin A/C/Laminopathy; SEPN1-Related Myopathy; Bethlem Myopathy; Actin Aggregation Myopathy; Cap Disease; Central Core Disease; Centronuclear Myopathy; Core Rod Myopathy; Hyaline Body Myopathy; Multiminicore Myopathy; Myotubular Myopathy; Nemaline Myopathy; Tubular Aggregate Myopathy; Zebra Body Myopathy; Reducing Body Myopathy; Spheroid Body Myopathy; LGMD1B (LMNA); LGMD1E (DES); LGMD2G (TCAP); LGMD2H (TRIM32); LGMD2I (FKRP); LGMD2J (TTN); LGMD2K (POMT1); LGMD2M (FKTN); LGMD2N (POMT2); LGMD2O (POMGnT1); LGMD2P (DAG1); LGMD2Q (PLEC1); LGMD2R (DES); LGMD2S (TRAPPC11); LGMD2T (GMPPB); LGMD2U (ISPD); LGMD2V (GAA); Ullrich Congenital Muscular Dystrophy; Titinopathy; Choline Kinase B Receptor; Emery-Dreifuss Muscular Dystrophy; RYR1 Related Myopathy; SYNE1/Nesprin Related Muscular Dystrophy; Telethonin Related Muscular Dystrophy (TCAP/Titin-Cap); Congenital Myasthenic Syndrome; Escobar Syndrome; Myofibrillar Myopathy; Malignant Hyperthermia; Alpha-Dystroglycan Related Muscular Dystrophy (DAG1, DPM1, DPM2, DPM3, FKRP, FKTN); Alpha-Dystroglycan Related Muscular Dystrophy (GAA, ISPD, LARGE, POMT1, POMT2, POMGnT1); Alpha-Dystroglycan Related Muscular Dystrophy (Unspecified/Undiagnosed/Other)

The relationship between red meat allergy and sensitization to gelatin and galactose-alpha-1,3-galactose

PubMed Central

Mullins, Raymond James; James, Hayley; Platts-Mills, Thomas A.E.; Commins, Scott

2012-01-01

Background We have observed patients clinically allergic to red meat and meat-derived gelatin. Objective We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and alpha-Gal. Methods Adult patients evaluated 1997-2011 for suspected allergy/anaphylaxis to medication, insect venom or food were skin tested with gelatin colloid. In vitro (ImmunoCap) testing was undertaken where possible. Results Positive gelatin tests were observed in 40/1335 individuals; 30/40 patients with red meat allergy (12 also clinically allergic to gelatin); 2/2 with gelatin colloid anaphylaxis; 4/172 with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02 to 0.4g); 4/368 with drug allergy. Testing was negative in all patients with venom allergy (n=241), non-meat food allergy (n=222), and miscellaneous disorders (n=290). ImmunoCap was positive to alpha-Gal in 20/24 meat allergics and in 20/22 with positive gelatin skin tests. The results of gelatin skin testing and anti-alpha-Gal IgE were strongly correlated (r=0.46; P<0.01). Alpha-Gal was detected in bovine gelatin colloids at concentrations of ~ 0.44 to 0.52ug/gm gelatin by inhibition radioimmunoassay. Conclusion Most patients allergic to red meat were sensitized to gelatin and a subset was clinically allergic to both. The detection of alpha-Gal in gelatin and correlation between the results of alpha-Gal and gelatin testing raises the possibility that alpha-Gal IgE may be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, alpha-Gal and gelatin (with or without clinical reactivity) remains uncertain. PMID:22480538

Crystal structure of Bacillus anthracis transpeptidase enzyme CapD.

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

Wu, R.; Richter, S.; Zhang, R.

2009-09-04

Bacillus anthracis elaborates a poly-{gamma}-d-glutamic acid capsule that protects bacilli from phagocytic killing during infection. The enzyme CapD generates amide bonds with peptidoglycan cross-bridges to anchor capsular material within the cell wall envelope of B. anthracis. The capsular biosynthetic pathway is essential for virulence during anthrax infections and can be targeted for anti-infective inhibition with small molecules. Here, we present the crystal structures of the {gamma}-glutamyltranspeptidase CapD with and without {alpha}-l-Glu-l-Glu dipeptide, a non-hydrolyzable analog of poly-{gamma}-d-glutamic acid, in the active site. Purified CapD displays transpeptidation activity in vitro, and its structure reveals an active site broadly accessible for poly-{gamma}-glutamatemore » binding and processing. Using structural and biochemical information, we derive a mechanistic model for CapD catalysis whereby Pro{sup 427}, Gly{sup 428}, and Gly{sup 429} activate the catalytic residue of the enzyme, Thr{sup 352}, and stabilize an oxyanion hole via main chain amide hydrogen bonds.« less

Professions and Working Conditions Associated With Community-Acquired Pneumonia.

PubMed

Almirall, Jordi; Serra-Prat, Mateu; Bolíbar, Ignasi; Palomera, Elisabet; Roig, Jordi; Boixeda, Ramon; Bartolomé, Maria; de la Torre, Mari; Parra, Olga; Torres, Antoni

2015-12-01

Community-acquired pneumonia (CAP) is not considered a professional disease, and the effect of different occupations and working conditions on susceptibility to CAP is unknown. The aim of this study is to determine whether different jobs and certain working conditions are risk factors for CAP. Over a 1-year period, all radiologically confirmed cases of CAP (n=1,336) and age- and sex-matched controls (n=1,326) were enrolled in a population-based case-control study. A questionnaire on CAP risk factors, including work-related questions, was administered to all participants during an in-person interview. The bivariate analysis showed that office work is a protective factor against CAP, while building work, contact with dust and sudden changes of temperature in the workplace were risk factors for CAP. The occupational factor disappeared when the multivariate analysis was adjusted for working conditions. Contact with dust (previous month) and sudden changes of temperature (previous 3 months) were risk factors for CAP, irrespective of the number of years spent working in these conditions, suggesting reversibility. Some recent working conditions such as exposure to dust and sudden changes of temperature in the workplace are risk factors for CAP. Both factors are reversible and preventable. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Alterations in the function of circulating mononuclear cells derived from patients with Crohn’s disease treated with mastic

PubMed Central

Kaliora, Andriana C; Stathopoulou, Maria G; Triantafillidis, John K; Dedoussis, George VZ; Andrikopoulos, Nikolaos K

2007-01-01

AIM: To assess the effects of mastic administration on cytokine production of circulating mononuclear cells of patients with active Crohn's disease (CD). METHODS: The study was conducted in patients with established mildly to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Recruited to a 4 wk treatment with mastic caps (6 caps/d,0.37 g/cap) were 10 patients and 8 controls, all of who successfully completed the protocol. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), macrophage migration inhibitory factor (MIF) and intracellular antioxidant glutathione (GSH) were evaluated in peripheral blood mononuclear cells (PBMC) before and after treatment. RESULTS: Treating CD patients with mastic resulted in the reduction of TNF-α secretion (2.1 ± 0.9 ng/mL vs 0.5 ± 0.4 ng/mL, P = 0.028). MIF release was significantly increased (1.2 ± 0.4 ng/mL vs 2.5 ± 0.7 ng/mL, P = 0.026) meaning that random migration and chemotaxis of monocytes/macrophages was inhibited. No significant changes were observed in IL-6, MCP-1 and GSH concentrations. CONCLUSION: This study shows that mastic acts as an immunomodulator on PBMC, acting as a TNF-α inhibitor and a MIF stimulator. Although further double-blind, placebo-controlled studies in a large number of patients is required to clarify the role of this natural product, this finding provides strong evidence that mastic might be an important regulator of immunity in CD. PMID:18023095

Effects of growth retardants and fumigations with ozone and sulfur dioxide on growth and flowering of Euphorbia pulcherrima Willd

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

Cathey, H.M.; Heggestad, H.E.

1973-01-01

Eight cultivars of poinsettia, Euphorbia pulcherrima Willd., were evaluated for sensitivity to ..cap alpha..-cyclopropyl-..cap alpha.. (4-methoxyphenyl)-5-pyrimidine methanol (ancymidol) and protection from ozone and sulfur dioxide injury afforded by applications of ancymidol and (2-chloroethyl) trimethyl ammonium chloride (chlormequat). Foliar sprays of ancymidol were at least 80 to 500 times and the soil drench 1000 times more active than chlormequat in retarding stem elongation. The diam of the bracts was reduced, but branching increased more on plants treated with ancymidol than on untreated plants. The cv. Annette Hegg (AH) was more sensitive to ozone fumigations than was Eckespoint C-1' (C-1). Sulfur dioxidemore » also caused more injury to AH than to C-1. Ancymidol and chlormequat reduced visible injury induced by ozone and sulfur dioxide.« less

Copernicus observational searches for OH and H/sub 2/O in diffuse clouds

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

Smith, W.H.; Snow, T.P. Jr.

1979-03-01

An intensive search for OH and H/sub 2/O in the directions of sigma Sco, ..cap alpha.. Cam, and omicron Per was undertaken with the Copernicus satellite. Multiple scans were carried out over the wavelength region for the expected absorption features due to the OH D--X and H/sub 2/O C--X transitions. The feature due to OH was possibly detected toward sigma Sco, and only an upper limit can be given toward ..cap alpha.. Cam. H/sub 2/O was not detected in any of the stars at the signal level accumulated. The OH abundance toward sigma Sco and the respective lower limits formore » the OH/H/sub 2/O ratios are discussed with regard to the extant models for the steady-state abundances of OH and H/sub 2/O, and shown not to be inconsistent with ion-molecule schemes.« less

Tumor initiating activities of various derivatives of benz(a)anthracene and 7, 12-dimethyl-benz(a)anthracene in mouse skin

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

Slaga, T.J.; Gleason, G.L.; DiGiovanni, J.

Current information indicates that polycyclic aromatic hydrocarbons (PAH) exert their toxic, mutagenic, and carcinogenic activities after they have been metabolically activated by target cells to reactive epoxides. The results obtained from IN VIVO and IN VITRO binding, mutagenicity, metabolism, and carcinogenicity studies have led to the conclusion that BP-7, 8-diol is a proximate carcinogenic metabolite of BP, and the BP-diol-epoxide is an ultimate carcinogenic metabolite of BP. Recent results concerning the strong carcinogenicity of BP-7..beta.., 8..cap alpha..-diol-9..cap alpha..,10..cap alpha..-epoxide in newborn mice and in mouse skin strongly indicate that it is the ultimate carcinogenic metabolite of BP. Since diol-epoxides maymore » be responsible for the carcinogenicity of PAH other than BP, diols and diol-epoxides as well as other derivatives of PAH were tested for skin tumor-initiation in a two-stage system of tumorigenesis. In addition, since activation of methylated PAH may involve the side-chain methyl group, the skin tumor-initiating activity of various side-chain derivatives of methylated PA were determined. In this report, the skin tumor initiation of various derivatives of a nonmethylated PAH, BA as well as a methylated PAH, DMBA are compared. The data suggest that bay region diol-epoxides may be important in BA and DMBA carcinogenicity in mice which is supportive of the theory proposed by Jerina and co-workers which predicts that diol-epoxides in the bay region are the major determinants of PAH carcinogenicity.« less

Assignments of /sup 1/H nuclear magnetic resonances of the cystyl, asparaginyl, and aromatic residues of arginine vasopressin in D/sub 2/O. A comparison with lysine vasopressin and oxytocin in terms of solution conformation

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

Wyssbrod, H.R.; Fischman, A.J.; Live, D.H.

1979-07-18

The resonances of the C/sup ..cap alpha../ and C/sup ..beta../ protons of the cystyl, asparaginyl, and aromatic residues of (8-arginine)vasopressin (AVP) in D/sub 2/O at pD 3.8 and 20/sup 0/C were assigned in a rigorous manner by the use of isotopic isomers of AVP that contain specific replacements of protons by deuterons and by comparison of /sup 1/H NMR characteristics of AVP to those of (8-lysine)vasopressin (LVP) and oxytocin (OT). Although there is extensive overlap of resonances of C/sup ..beta../ protons even at 360 MHz, all of the chemical shifts of these protons and most of the couplings between themmore » and their vicinal C/sup ..cap alpha../ protons could be determined, at least to a first approximation. It was concluded that the cyclic moieties (residues 1-6) of AVP, LVP, and OT possess essentially the same overall backbone conformation, and that the side-chain conformation - or rotamer populations - about the C/sup ..cap alpha../-C/sup ..beta../ bonds of the cystyl residue (positions 1 and 6), the tyrosyl residue (position 2), and the asparaginyl residue (position 5) are similar. This study indicates that selective replacements of C/sup ..beta../ protons by deuterons are necessary to improve the accuracy of coupling constants extracted from 360-MHz spectra of a AVP for use in conformational analysis.« less

Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism.

PubMed

Zimmermann, E; Wassmer, S; Steudle, V

1996-01-01

Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis.

PubMed

Salnikow, Konstantin; Davidson, Todd; Zhang, Qunwei; Chen, Lung Chi; Su, Weichen; Costa, Max

2003-07-01

Nickel is a potent environmental pollutant in industrial countries. Because nickel compounds are carcinogenic, exposure to nickel represents a serious hazard to human health. The understanding of how nickel exerts its toxic and carcinogenic effects at a molecular level may be important in risk assessment, as well as in the treatment and prevention of occupational diseases. Previously, using human and rodent cells in vitro, we showed that hypoxia-inducible signaling pathway was activated by carcinogenic nickel compounds. Acute exposure to nickel resulted in the accumulation of hypoxia-inducible transcription factor (HIF)-1, which strongly activated hypoxia-inducible genes, including the recently discovered tumor marker NDRG1 (Cap43). To further identify HIF-1-dependent nickel-inducible genes and to understand the role of the HIF-dependent signaling pathway in nickel-induced transformation, we used the Affymetrix GeneChip to compare the gene expression profiles in wild-type cells or in cells from HIF-1 alpha knockout mouse embryos exposed to nickel chloride. As expected, when we examined 12,000 genes for expression changes, we found that genes coding for glycolytic enzymes and glucose transporters, known to be regulated by HIF-1 transcription factor, were induced by nickel only in HIF-1 alpha-proficient cells. In addition, we found a number of other hypoxia-inducible genes up-regulated by nickel in a HIF-dependent manner including BCL-2-binding protein Nip3, EGLN1, hypoxia-inducible gene 1 (HIG1), and prolyl 4-hydroxylase. Additionally, we found a number of genes induced by nickel in a HIF-independent manner, suggesting that Ni activated other signaling pathways besides HIF-1. Finally, we found that in HIF-1 alpha knockout cells, nickel strongly induced the expression of the whole group of genes that were not expressed in the presence of HIF-1. Because the majority of modulated genes were induced or suppressed by nickel in a HIF-1-dependent manner, we elucidated the role of HIF-1 transcription factor in cell transformation. In HIF-1 alpha-proficient cells, nickel exposure increased soft agar growth, whereas it decreased soft agar growth in HIF-1 alpha-deficient cells. We hypothesize that the induction of HIF-1 transcription factor by nickel may be important during the nickel-induced carcinogenic process.

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

PubMed Central

Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J

2000-01-01

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. PMID:11133399

Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model.

PubMed

Koopman, F A; Vosters, J L; Roescher, N; Broekstra, N; Tak, P P; Vervoordeldonk, M J

2015-10-01

Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's syndrome and type 1 diabetes. The alpha-7 nicotinic acetylcholine receptor (α7nAChR) was stimulated with AR-R17779 or nicotine in NOD mice. In a second study, unilateral cervical vagotomy was performed. α7nAChR expression, focus scores, and salivary flow were evaluated in salivary glands (SG) and insulitis score in the pancreas. Cytokines were measured in serum and SG. α7nAChR was expressed on myoepithelial cells in SG. Monocyte chemotactic protein-1 levels were reduced in SG after AR-R17779 treatment and tumor necrosis factor production was increased in the SG of the vagotomy group compared to controls. Focus score and salivary flow were unaffected. NOD mice developed diabetes more rapidly after vagotomy, but at completion of the study there were no statistically significant differences in number of mice that developed diabetes or in insulitis scores. Intervention of the CAP in NOD mice leads to minimal changes in inflammatory cytokines, but did not affect overall inflammation and function of SG or development of diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alpha-catenin-dependent recruitment of the centrosomal protein CAP350 to adherens junctions allows epithelial cells to acquire a columnar shape.

PubMed

Gavilan, Maria P; Arjona, Marina; Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R; Bornens, Michel; Rios, Rosa M

2015-03-01

Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis.

Alpha-catenin-Dependent Recruitment of the Centrosomal Protein CAP350 to Adherens Junctions Allows Epithelial Cells to Acquire a Columnar Shape

PubMed Central

Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R.; Bornens, Michel; Rios, Rosa M.

2015-01-01

Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis. PMID:25764135

Magnesium Induced Nucleophile Activation in the Guanylyltransferase mRNA Capping Enzyme

PubMed Central

Swift, Robert V.; Ong, Chau D.; Amaro, Rommie E.

2012-01-01

The messenger RNA guanylyltransferase, or mRNA capping enzyme, co-transcriptionally caps the 5′-end of nascent mRNA with GMP during the second in a set of three enzymatic reactions that result in the formation of an N7-methyl guanosine cap during mRNA maturation. The mRNA capping enzyme is characterized, in part, by a conserved lysine nucleophile that attacks the alpha-phosphorous atom of GTP, forming a lysine-GMP intermediate. Experiments have firmly established that magnesium is required for efficient intermediate formation, but have provided little insight into the requirement’s molecular origins. Using empirical and thermodynamic integration pKa estimates, along with conventional MD simulations, we show that magnesium binding likely activates the lysine nucleophile by increasing its acidity and by biasing the deprotonated nucleophile into conformations conducive to intermediate formation. These results provide additional functional understanding of an important enzyme in the mRNA transcript life cycle and allow functional analogies to be drawn that affect our understanding of the metal dependence of related superfamily members. PMID:23205906

Risk Factors for Drug-Resistant Cap in Immunocompetent Patients.

PubMed

Arancibia, Francisco; Ruiz, Mauricio

2017-03-01

The increase in drug-resistant community-acquired pneumonia (CAP) is an important problem all over the world. This article explores the current state of antimicrobial resistance of different bacteria that cause CAP and also assesses risk factors to identify those pathogens. In the last two decades, it has been documented that there is a significant increase in drug-resistant Streptococcus pneumoniae and other bacteria causing CAP. The most important risk factors are overuse of antibiotics, prior hospitalization, and lung comorbidities. The direct consequences can be severe, including prolonged stays in hospital, increased costs, and morbi-mortality. However, drug-resistant CAP declined after the introduction of the pneumococcal conjugate vaccine. This review found an increase in resistance to the antibiotics used in CAP, and the risk factor can be used for identifying patients with drug-resistant CAP and initiate appropriate treatment. Judicious use of antibiotics and the development of effective new vaccines are needed.

Clinical audit project in undergraduate medical education curriculum: an assessment validation study

PubMed Central

Steketee, Carole; Mak, Donna

2016-01-01

Objectives To evaluate the merit of the Clinical Audit Project (CAP) in an assessment program for undergraduate medical education using a systematic assessment validation framework. Methods A cross-sectional assessment validation study at one medical school in Western Australia, with retrospective qualitative analysis of the design, development, implementation and outcomes of the CAP, and quantitative analysis of assessment data from four cohorts of medical students (2011- 2014). Results The CAP is fit for purpose with clear external and internal alignment to expected medical graduate outcomes.  Substantive validity in students’ and examiners’ response processes is ensured through relevant methodological and cognitive processes. Multiple validity features are built-in to the design, planning and implementation process of the CAP.  There is evidence of high internal consistency reliability of CAP scores (Cronbach’s alpha > 0.8) and inter-examiner consistency reliability (intra-class correlation>0.7). Aggregation of CAP scores is psychometrically sound, with high internal consistency indicating one common underlying construct.  Significant but moderate correlations between CAP scores and scores from other assessment modalities indicate validity of extrapolation and alignment between the CAP and the overall target outcomes of medical graduates.  Standard setting, score equating and fair decision rules justify consequential validity of CAP scores interpretation and use. Conclusions This study provides evidence demonstrating that the CAP is a meaningful and valid component in the assessment program. This systematic framework of validation can be adopted for all levels of assessment in medical education, from individual assessment modality, to the validation of an assessment program as a whole.  PMID:27716612

Clinical audit project in undergraduate medical education curriculum: an assessment validation study.

PubMed

Tor, Elina; Steketee, Carole; Mak, Donna

2016-09-24

To evaluate the merit of the Clinical Audit Project (CAP) in an assessment program for undergraduate medical education using a systematic assessment validation framework. A cross-sectional assessment validation study at one medical school in Western Australia, with retrospective qualitative analysis of the design, development, implementation and outcomes of the CAP, and quantitative analysis of assessment data from four cohorts of medical students (2011- 2014). The CAP is fit for purpose with clear external and internal alignment to expected medical graduate outcomes.  Substantive validity in students' and examiners' response processes is ensured through relevant methodological and cognitive processes. Multiple validity features are built-in to the design, planning and implementation process of the CAP.  There is evidence of high internal consistency reliability of CAP scores (Cronbach's alpha > 0.8) and inter-examiner consistency reliability (intra-class correlation>0.7). Aggregation of CAP scores is psychometrically sound, with high internal consistency indicating one common underlying construct.  Significant but moderate correlations between CAP scores and scores from other assessment modalities indicate validity of extrapolation and alignment between the CAP and the overall target outcomes of medical graduates.  Standard setting, score equating and fair decision rules justify consequential validity of CAP scores interpretation and use. This study provides evidence demonstrating that the CAP is a meaningful and valid component in the assessment program. This systematic framework of validation can be adopted for all levels of assessment in medical education, from individual assessment modality, to the validation of an assessment program as a whole.

Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

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

Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

1988-07-12

The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no suchmore » effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.« less

Host-pathogen interactions. XXIX. Oligogalacturonides released from sodium polypectate by endopolygalacturonic acid lyase are elicitors of phytoalexins in soybean. [Glycine max L

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

Davis, K.R.; Darvill, A.G.; Albersheim, P.

1986-02-01

Recent studies have demonstrated that an apparently homogeneous preparation of an ..cap alpha..-1,4-D-endopolygalacturonic acid lyase (EC 4.2,2.2) isolated from the phytopathogenic bacterium Erwinia carotovora induced phytoalexin accumulation in cotyledons of soybean (Glycine max (L.) Merr. cv Wayne) and that this pectin-degrading enzyme released heat-stable elicitors of phytoalexins from soybean cell walls, citrus pectin, and sodium polypectate. The present paper reports the purification, by anion-exchange chromatography on QAE-Sephadex columns followed by gel-permeation chromatography on a Bio-Gel P-6 column, of the two fractions with highest specific elicitor activity present in a crude elicitor-preparation obtained by lyase treatment of sodium polypectate. Structural analysismore » of the fraction with highest specific elicitor activity indicated that the major, if not only, component was a decasaccharide of ..cap alpha..-1,4-D-galactosyluronic acid that contained the expected product of lyase cleavage, 4-deoxy-..beta..-L-5-threo-hexopyranos-4-enyluronic acid (4,5-unsaturated galactosyluronic acid), at the nonreducing terminus. This modified decagalacturonide fraction exhibited half-maximum and maximum elicitor activity at 1 microgram/cotyledon (6 micromolar) and 5 micrograms/cotyledon (32 micromolar) galactosyluronic acid equivalents, respectively. Reducing 90 to 95% of the carboxyl groups of the galactosyluronic acid residues abolished the elicitor activity of the decagalacturonide fraction. The second most elicitor-active fraction contained mostly undeca-..cap alpha..-1,4-D-galactosyluronic acid that contained 4,5-unsaturated galactosyluronic acid at the nonreducing termini. This fraction exhibited half-maximum and maximum elicitor activity at approximately 3 micrograms/cotyledon (17 micromolar) and 6 micrograms/cotyledon (34 micromolar) galactosyluronic acid equivalents, respectively.« less

Inhibition of metabolism and DNA binding of polycyclic aromatic hydrocarbons (PAHs) by plant phenols in epidermis of SENCAR mice

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

Das, M.; Bik, D.P.; Bickers, D.R.

1986-03-05

Naturally occurring plant phenols such as tannic acid (TA), quercetin (QT), myricetin (MY) and anthraflavic acid (AA) have been shown to inhibit the mutagenicity of several bay-region diolepoxides of PAHs. Since skin is a target for PAH carcinogenesis, they investigated the effect of these plant phenols on epidermal aryl hydrocarbon hydroxylase (AHH) activity and the binding of PAHs to DNA in SENCAR mice. Each of the plant phenols tested was found to be an in vitro and in vivo inhibitor of epidermal AHH activity with I/sub 50/ values ranging from 4.4 x 10/sup -5/ - 12.4 x 10/sup -5/M inmore » control and 3-methylcholanthrene (MCA) pretreated skin. On an equimolar basis TA was the most potent inhibitor with a Ki of 81 ..mu..M. Incubation of TA, QT, MY and AA with epidermal microsomes resulted in varying degrees of inhibition of enzyme mediated covalent binding of benzo(a)pyrene (BP) to calf thymus DNA. TA (25 ..mu..M) showed maximum inhibition (64%). A single topical application (12 ..mu..mol) of TA, QT, MY and AA resulted in significant decrease in the binding of BP, BP-7,8-diol and 7,12-dimethylbenz(a)anthracene to epidermal DNA. The formation of (+)-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydro-BP-deoxyguanine adduct in epidermis was significantly reduced (62-86%) following topical application of the plant phenols. Their results suggest that some of these plant phenols have substantial though variable potential to modify the risk of PAHs induced skin carcinogenicity.« less

Bonding in the first-row diatomic molecules within the local spin-density approximation

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

Painter, G.S.; Averill, F.W.

1982-08-15

The Hohenberg-Kohn-Sham density-functional equations in the local spin-density approximation (LSDA) have been solved with essentially no loss of accuracy for dimers of the first row of the Periodic Table with the use of a fully-self-consistent spin-polarized Gaussian-orbital approach. Spectroscopic constants (binding energies, equilibrium separations, and ground-state vibrational frequencies) have been derived from the calculated potential-energy curves. Intercomparison of results obtained using the exchange-correlation functionals of Slater (scaled exchange or X..cap alpha..), Gunnarsson and Lundqvist (GL), and Vosko, Wilk, and Nusair (VWN) permits assessment of the relative merits of each and serves to identify general shortcomings in the LSDA. Basic trendsmore » are similar for each functional, but the treatment of the spin dependence of the exchange-correlation energy in the GL and VWN functionals yields a variation of the binding energy across the series which is more systematic than that in the X..cap alpha.. approximation. Agreement between the present results and those of Dunlap, Connolly, and Sabin in the X..cap alpha.., approximation confirms the accuracy of the variational charge-density-fit procedure used in the latter work. The refinements in correlation treatment within the VWN functional are reflected in improvements in binding energies which are only slight for most dimers in the series. This behavior is attributed to the error remaining in the exchange channel within the LSDA and demonstrates the necessity for self-interaction corrections for more accurate binding-energy determinations. Within the current LSDA, absolute accuracies of the VWN functional for the first-row dimers are within 2.3 eV for binding energies, 0.07 a.u. for bond lengths, and approx.200 cm/sup -1/ for vibrational frequencies.« less

ESR study of electron reactions with esters and triglycerides

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

Sevilla, M.D.; Morehouse, K.M.; Swarts, S.

1981-04-02

Reactions which occurred after electron attachment at 77K to a number of small carboxylic acid esters and triglycerides in an aqueous glass are reported. Most ester anions are found to decay on warming to form alkyl radicals by ..beta.. scission: RC(O/sup -/)OR' ..-->.. RCO/sub 2//sup -/ + R'.. The alkyl radical (R'.) produced by annealing is found to abstract hydrogen from the parent ester at an ..cap alpha..-carbon site, R'.+ R''CH/sub 2/CO/sub 2/R' ..-->.. R''CHCO/sub 2/R', or in the case of ethyl formate from the formate hydrogen, CH/sub 3/CH/sub 2/.+ HCO/sub 2/C/sub 2/H/sub 5/ ..-->.. C/sub 2/H/sub 6/ +.CO/sub 2/C/submore » 2/H/sub 5/. Results found for the methyl formate anion suggest hydrogen abstraction by the anion itself may compete with alkyl radical formation. The anion of the triglyceride triacetin is found to undergo an analogous mechanism to the ester anions producing the propane diol diester radical, .CH/sub 2/CH(Ac)CH/sub 2/(Ac), Ac = acetate. This species subsequently abstracts hydrogen from the parent compound to produce the ..cap alpha..-carbon radical, .CH/sub 2/CO/sub 2/R. Results found after annealing the tripropionin radical anion give evidence for abstraction from the ..cap alpha.. carbon in the propionate side groups producing CH/sub 3/CHCO/sub 2/R. Studies of a ..gamma..-irradiated ester (ethyl myristate) and two triglycerides (tripalmitin and tristearin) yield results which suggest that the mechanism of ester anion decay found in aqueous glasses applies to ..gamma..-irradiated neat long-chain esters and triglycerides. Results found in this work are compared to the results of product analysis.« less

Structural elucidation of the Brucella melitensis M antigen by high-resolution NMR at 500 MHz

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

Bundle, D.R.; Cherwonogrodzky, J.W.; Perry, M.B.

The Brucella M antigen from the species type strain Brucella melitensis 16M has been identified as a component of the cell wall lipopolysaccharide (LPS). O polysaccharide liberated from this LPS by mild acid hydrolysis exhibited M activity in serological tests and was shown to be a homopolymer of 4-formamido-4,6-dideoxy-..cap alpha..-D-mannopyranosyl residues arranged in an oligosaccharide repeating unit as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the native lipopolysaccharide. Structural analysis of the O polysaccharide by NMR methods was difficult due to apparent microheterogeneity of the repeating unit, which was in fact caused by the presence of rotational isomers ofmore » the N-formyl moiety. This problem was resolved by chemical modification of the polysaccharide to its amino and N-acetyl derivatives, the 500-MHz /sup 1/H and 125-MHz /sup 13/C NMR spectra of which could be analyzed in terms of a unique structure through application of pH-dependent ..beta..-shifts and two-dimensional techniques that included COSY, relayed COSY, and NOESY experiments together with heteronuclear C/H shift correlation spectroscopy. On the basis of these experiments and supported by methylation and periodate oxidation data, the structure of the M polysaccharide was determined as a linear polymer of unbranched pentasaccharide repeating units consisting of four 1,2-linked and one 1,3-lined 4,6-dideoxy-4-formamido-..cap alpha..-D-mannopyranosyl residues. The marked structural similarity of the M antigen and the A antigen, which is known to be a 1,2-linked homopolysaccharide of 4,6-dideoxy-4-formamido-..cap alpha..-D-mannopyranosyl units, accounts for cross-serological reactions of the two and the long-standing confusion surrounding the nature of their antigenic determinants.« less

Community–Academic Partnership Participation

PubMed Central

Drahota, Amy; Spurgeon, Emily

2015-01-01

Community–academic partnerships (CAPs) improve the research process, outcomes, and yield benefits for the community and researchers. This exploratory study examined factors important in community stakeholders’ decision to participate in CAPs. Autism spectrum disorder (ASD) community stakeholders, previously contacted to participate in a CAP (n = 18), completed the 15-item Decision to Participate Questionnaire (DPQ). The DPQ assessed reasons for participating or declining participation in the ASD CAP. CAP participants rated networking with other providers, fit of collaboration with agency philosophy, and opportunity for future training/consultations as factors more important in their decision to participate in the ASD CAP than nonparticipants. Nonparticipants reported the number of requests to participate in research as more important in their decision to decline participation than participants. Findings reveal important factors in community stakeholders’ decision to participate in CAPs that may provide guidance on increasing community engagement in CAPs and help close the science-to-service gap. PMID:25976376

Increased helix and protein stability through the introduction of a new tertiary hydrogen bond.

PubMed

Peterson, R W; Nicholson, E M; Thapar, R; Klevit, R E; Scholtz, J M

1999-03-12

In an effort to quantify the importance of hydrogen bonding and alpha-helix formation to protein stability, a capping box motif was introduced into the small phosphocarrier protein HPr. Previous studies had confirmed that Ser46, at the N-cap position of the short helix-B in HPr, serves as an N-cap in solution. Thus, only a single-site mutation was required to produce a canonical S-X-X-E capping box: Lys49 at the N3 position was substituted with a glutamic acid residue. Thermal and chemical denaturation studies on the resulting K49E HPr show that the designed variant is approximately 2 kcal mol-1 more stable than the wild-type protein. However, NMR studies indicate that the side-chain of Glu49 does not participate in the expected capping H-bond interaction, but instead forms a new tertiary H-bond that links helix-B to the four-stranded beta-sheet of HPr. Here, we demonstrate that a strategy in which new non-native H-bonds are introduced can generate proteins with increased stability. We discuss why the original capping box design failed, and compare the energetic consequences of the new tertiary side-chain to main-chain H-bond with a local (helix-capping) side-chain to main-chain H-bond on the protein's global stability. Copyright 1999 Academic Press.

Supramolecular Inclusion in Cyclodextrins: A Pictorial Spectroscopic Demonstration

ERIC Educational Resources Information Center

Haldar, Basudeb; Mallick, Arabinda; Chattopadhyay, Nitin

2008-01-01

A spectroscopic experiment is presented that reveals that the hydrophobically end-modified water-soluble polymeric fluorophore, pyrene end-capped poly(ethylene oxide) (PYPY), interacts differently with [alpha], [beta], and [gamma]-cyclodextrins (CD) to form supramolecular inclusion complexes. The emission spectrum of PYPY in aqueous solution shows…

SU-E-T-59: Calculations of Collimator Scatter Factors (Sc) with and Without Custom-Made Build-Up Caps for CyberKnife

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

Wokoma, S; Yoon, J; Jung, J

2014-06-01

Purpose: To investigate the impact of custom-made build-up caps for a diode detector in robotic radiosurgery radiation fields with variable collimator (IRIS) for collimator scatter factor (Sc) calculation. Methods: An acrylic cap was custom-made to fit our SFD (IBA Dosimetry, Germany) diode detector. The cap has thickness of 5 cm, corresponding to a depth beyond electron contamination. IAEA phase space data was used for beam modeling and DOSRZnrc code was used to model the detector. The detector was positioned at 80 cm source-to-detector distance. Calculations were performed with the SFD, with and without the build-up cap, for clinical IRIS settingsmore » ranging from 7.5 to 60 mm. Results: The collimator scatter factors were calculated with and without 5 cm build-up cap. They were agreed within 3% difference except 15 mm cone. The Sc factor for 15 mm cone without buildup was 13.2% lower than that with buildup. Conclusion: Sc data is a critical component in advanced algorithms for treatment planning in order to calculate the dose accurately. After incorporating build-up cap, we discovered differences of up to 13.2 % in Sc factors in the SFD detector, when compared against in-air measurements without build-up caps.« less

Elastic and inelastic scattering of alpha particles from /sup 40,44/Ca over a broad range of energies and angles

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

Delbar, T.; Gregoire, G.; Paic, G.

1978-09-01

Angular distributions for ..cap alpha.. particle elastic scattering by /sup 40,44/Ca and excitation of the 3.73 MeV 3/sup -/ collective state of /sup 40/Ca were measured for incident energies ranging from 40 to 62 MeV. An extensive optical model analysis of these elastic scattering cross sections and other available data, using squared Woods-Saxon form factors, results in potentials with fixed geometry for both real and imaginary parts and depths with smooth energy behavior over a broad incident energy range. These results are discussed in the frame of the semi-classical approximation developed by Brink and Takigawa. The sensitiveness of the calculatedmore » elastic scattering cross sections to the real part of the potentials as a function of the projectile-target distance has been investigated by means of a notch test. Distorted-wave Born-approximtion calculations for the excitation of the 3.73 MeV 3/sup -/ state of /sup 40/Ca are presented.« less

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes.

PubMed

Wiersma, Anje C; Leegwater, Peter Aj; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

2007-10-19

Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

Function of the two Xenopus smad4s in early frog development.

PubMed

Chang, Chenbei; Brivanlou, Ali H; Harland, Richard M

2006-10-13

Signals from the transforming growth factor beta family members are transmitted in the cell through specific receptor-activated Smads and a common partner Smad4. Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal and neural induction. To further understand the functions of the Smad4s in early frog development, we analyzed their activities in detail. We report that Smad10 is a mutant form of Smad4beta that harbors a missense mutation of a conserved arginine to histidine in the MH1 domain. The mutation results in enhanced association of Smad10 with the nuclear transcription corepressor Ski and leads to its neural inducing activity through inhibition of bone morphogenetic protein (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta was required for both activin- and BMP-mediated mesodermal induction in animal caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was involved directly in neural induction. Expression of Smad4beta-MO in early frog embryos resulted in reduction of mesodermal markers and defects in axial structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha, is expressed at high levels maternally and during early gastrulation, our data suggest that although Smad4alpha and Smad4beta may have similar activities, they are differentially utilized during frog embryogenesis, with only Smad4beta being essential for mesoderm induction.

Disc valve for sampling erosive process streams

DOEpatents

Mrochek, J.E.; Dinsmore, S.R.; Chandler, E.W.

1984-08-16

This is a patent for a disc-type, four-port sampling valve for service with erosive high temperature process streams. Inserts and liners of ..cap alpha..-silicon carbide respectively, in the faceplates and in the sampling cavities, limit erosion while providing lubricity for a smooth and precise operation. 1 fig.

The Effect of an Offset Polar Cap Dipolar Magnetic Field on the Modeling of the Vela Pulsar's Gamma-Ray Light Curves

NASA Technical Reports Server (NTRS)

Barnard, M.; Venter, C.; Harding, A. K.

2016-01-01

We performed geometric pulsar light curve modeling using static, retarded vacuum, and offset polar cap (PC) dipole B-fields (the latter is characterized by a parameter epsilon), in conjunction with standard two-pole caustic (TPC) and outer gap (OG) emission geometries. The offset-PC dipole B-field mimics deviations from the static dipole (which corresponds to epsilon equals 0). In addition to constant-emissivity geometric models, we also considered a slot gap (SG) E-field associated with the offset-PC dipole B-field and found that its inclusion leads to qualitatively different light curves. Solving the particle transport equation shows that the particle energy only becomes large enough to yield significant curvature radiation at large altitudes above the stellar surface, given this relatively low E-field. Therefore, particles do not always attain the radiation-reaction limit. Our overall optimal light curve fit is for the retarded vacuum dipole field and OG model, at an inclination angle alpha equals 78 plus or minus 1 degree and observer angle zeta equals 69 plus 2 degrees or minus 1 degree. For this B-field, the TPC model is statistically disfavored compared to the OG model. For the static dipole field, neither model is significantly preferred. We found that smaller values of epsilon are favored for the offset-PC dipole field when assuming constant emissivity, and larger epsilon values favored for variable emissivity, but not significantly so. When multiplying the SG E-field by a factor of 100, we found improved light curve fits, with alpha and zeta being closer to best fits from independent studies, as well as curvature radiation reaction at lower altitudes.

The rebirth of the cervical cap.

PubMed

Cappiello, J D; Grainger-Harrison, M

1981-01-01

In an effort to dispel myths surrounding the cervical cap, the historical and political factors affecting the cap's use in the U.S. are described. Clinical aspects of cap fitting are also included. The cervical cap has found only limited acceptance in the U.S. Skepticisms on the part of physicians may be the result of 2 factors: confusion of the cervical cap with intracervical devices used for artificial insemination and confusion with stem pessaries; and the lack of clinical research and statistical evaluation of efficacy rates. The latter factor prompted Tietze et al. to conduct the only U.S. statistical study of the cap in 1953. Of the 143 women studied, the pregnancy rate was 7.6/100 years of use. Of the 28 unplanned pregnancies, 6 were related to faulty technique or omission of a spermicide and 10 were instances of admittedly irregular use. When these failures are omitted, the theoretical effectiveness rate is about 98%. Some practitioners are concerned about an increased incidence of cervical erosion with cap use. Possibly currently conducted studies will show that cap and spermicide users have a lower incidence of cervical erosion than women using no contraceptive method. Study findings suggest that the cervical cap may afford protection without any spermicidal supplement, but the use of spermicides continues to be recommended to clients. Advantages of the cervical cap include the following: it can be left in place longer than a diaphragm without additional applications of spermicide in the vagina; and the insertion of the cap is unrelated to the time of intercourse. Despite research on toleration of the cap for 3 weeks at a time, it is recommended that the cap be worn for only a few days at a time. At this time there are no manufacturers of cervical caps for contraceptive use in the U.S. The cap is now being imported from England and it costs $6.00. A factor that has made the cap unpopular with many physicians is the lengthy time required for fitting. An assessment guide that physicians can use to incorporate cervical caps in their practice is included. The guide covers medical/gynecological history; informed consent; pelvic examinations; assessment; fitting the cap; and instructing the client. Instructions for client use are also outlined.

Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study

PubMed Central

Millett, Elizabeth R C; De Stavola, Bianca L; Smeeth, Liam; Thomas, Sara L

2015-01-01

Objectives To determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time. Design Cohort study. Setting Primary and secondary care in England. Population 39 211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥65 and had at least 1 CAP episode between April 1998 and March 2011. Main outcome measures The association between hospitalisation within 28 days of CAP diagnosis (a ‘post-CAP’ hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period. Results 14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998–2000) to 86% (2009–2010). Duration of hospitalisation and 28-day mortality decreased over the study period. Conclusions The risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and patient behaviour. PMID:26631055

Importance of the lid and cap domains for the catalytic activity of gastric lipases.

PubMed

Miled, N; Bussetta, C; De caro, A; Rivière, M; Berti, L; Canaan, S

2003-09-01

Human gastric lipase (HGL) is an enzyme secreted by the stomach, which is stable and active despite the highly acidic environment. It has been clearly established that this enzyme is responsible for 30% of the fat digestion processes occurring in human. This globular protein belongs to the alpha/beta hydrolase fold family and its catalytic serine is deeply buried under a domain called the extrusion domain, which is composed of a 'cap' domain and a segment consisting of 58 residues, which can be defined as a lid. The exact roles played by the cap and the lid domains during the catalytic step have not yet been elucidated. We have recently solved the crystal structure of the open form of the dog gastric lipase in complex with a covalent inhibitor. The detergent molecule and the inhibitor were mimicking a triglyceride substrate that would interact with residues belonging to both the cap and the lid domains. In this study, we have investigated the role of the cap and the lid domains, using site-directed mutagenesis procedures. We have produced truncated mutants lacking the lid and the cap. After expressing these mutants and purifying them, their activity was found to have decreased drastically in comparison with the wild type HGL. The lid and the cap domains play an important role in the catalytic reaction mechanism. Based on these results and the structural data (open form of DGL), we have pointed out the cap and the lid residues involved in the binding with the lipidic substrate.

Laser surface treatment for porous and textured Ca-P bio-ceramic coating on Ti-6Al-4V.

PubMed

Paital, Sameer R; Dahotre, Narendra B

2007-12-01

In the present paper the feasibility of depositing a porous calcium phosphate (CaP) bio-ceramic coating using a continuous wave Nd:YAG laser on a Ti-6Al-4V substrate has been demonstrated. The advantages offered by such porous bio-ceramic coating are its inertness combined with the mechanical stability of the highly convoluted interface that develops when bone grows into the pores of ceramic. The formation of different phases with varying laser fluences is studied using x-ray diffraction (XRD). A quantitative estimation of the crystallite size and relative amounts of Ti and other predominant phases such as TiO(2) and alpha-tricalcium phosphate (alpha-TCP) were obtained. An increase in the crystallite size with increasing laser fluence is observed for all the above three phases. It is observed that TiO(2) is the predominant phase for all laser fluences and there is an increase in the alpha-TCP phase with increasing laser fluence. Surface porosity measurements indicated a decreasing trend with increasing laser fluence. Microhardness measurements in the cross section of samples showed a maximum hardness within the coating. The bioactivity of the coatings was further demonstrated by the formation of an apatite-like layer on the surface of the sample after being immersed in a simulated biofluid.

Yang-Lee zeros, Julia sets, and their singularity spectra

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

Hu, B.; Lin, B.

1989-05-01

We have studied the global scaling properties of the Julia sets of the Yang-Lee zeros of the s-state Potts model on the diamond hierarchical lattice. The singularity spectrum f(..cap alpha..) and the generalized dimension D/sub q/ are calculated for different s values. General observations are made on their variations.

N-(/sup 11/C)-methyl-p-substituted phentermine analogs as potential brain blood flow agents for positron tomography

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

Kizuka, H.; Elmaleh, D.R.; Boudreaux, G.J.

The addition of a methyl group to the ..cap alpha..-position of amphetamine increases both the lipophilicity of the agent and its resistance to metabolism by monoamine oxidase. In addition, since tritium substituted phenteramine analog studies suggested that the p-halo phentermines had a greater concentration in the brain and prolonged retention time, the authors evaluated the biological behavior of positron labeled ..cap alpha..-methylamphetamine (phenteramine) in rats, dogs and monkeys. The N-(/sup 11/C) methyl analogs of p-chloro (I) and p-fluoro (II) phentermines were prepared by methylation of their primary amines using /sup 11/Ch/sub 3/I. Biodistribution studies in rats shows brain uptake ismore » in the range of 1% dose/gr at 5 and 15 min for both agents. The activity in blood and eyes is low. Sequential images of the dogs' brain over 1 hour revealed a clearance of <15%. Images of the monkey brain were also obtained using a MGH positron camera PCR-I.« less

Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

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

Faraci, W.S.; Walsh, C.T.

1988-05-03

Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substratemore » PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.« less

Mobilization of tissue cadmium in mice and calves and reversal of cadmium induced tissue damage in calves by zinc

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

Reddy, C.S.; Mohammad, F.K.; Ganjam, V.K.

1987-08-01

Earlier studies demonstrated that simultaneous dietary Zn supplementation to calves fed Cd, significantly decreased the accumulation of Cd in liver, kidney and muscle. However, studies are lacking in evaluating the effectiveness of zinc in reducing Cd-burden in animals with pre-existing tissue Cd-load, a situation encountered in chronic Cd intoxication. This study examined the effects of oral Zn (AnO) on tissue Cd levels in mice. N-acetylcysteine (NAC) and sodium sulfate (SS) were also used to evaluate the effects of providing organic and inorganic sources of sulfur on tissue Cd levels. Following demonstration of reduced Cd levels in tissues of mice receivingmore » antidotal Zn, subsequent investigation was aimed at studying the reversal of Cd-induced changes by Zn. The authors also examined whether Cd-induced reduction in epididymal 5 ..cap alpha..-reductase activity could explain previously reported low levels of circulating dihydrotestosterone (DHT) following Cd treatment. The ability of Zn to reverse the inhibition of 5 ..cap alpha..-reductase activity by Cd was also examined.« less

Study on great northern beans (Phaseolus vulgaris): effect of drum drying process on bean flour properties and effect on gamma radiation on bean starch properties

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

Rayas-Solis, P.

Great Northern bean (Phaseolus vulgaris L.) drum dried flours at native pH of 6.54, pH 6 and 7 showed reduced activities of trypsin inhibitor, ..cap alpha..-amylase inhibitor, hemagglutinating titer, and nitrogen solubility. Electrophoretic analyses showed a slight modification of the native bean proteins, and the presence of at least four trypsin inhibitors. The study of the effect of 2.5-20 kGy irradiation doses on Great Northern beans showed essentially no modification of the electrophoretic mobility of the storage proteins or the trypsin inhibitors. Nitrogen solubility and hemagglutinating activity were essentially unchanged. With the 20 kGy dose, decrease in ..cap alpha..-amylase inhibitormore » activity, decrease reactive/available lysine content, and decrease cooking time of the irradiated beans after 11 months of storage were observed. Taste panel results indicated that the control and 20 kGy irradiated bean were significantly different at 5% level. At 20 kGy dose, the beans developed a partially water soluble brown color.« less

Mutations in a gene encoding the. cap alpha. subunit of a Saccharomyces cerevisiae G protein indicate a role in mating pheromone signaling

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

Jahng, K.Y.; Ferguson, J.; Reed, S.I.

1988-06-01

Mutations which allowed conjugation by Saccharomyces cerevisiae cells lacking a mating pheromone receptor gene were selected. One of the genes defined by such mutations was isolated from a yeast genomic library by complementation of a temperature-sensitive mutation and is identically to the gene GPA1 (also known as SCG1), recently shown to be highly homologous to gene encoding the ..cap alpha.. subunits of mammalian G proteins. Physiological analysis of temperature-sensitive gpal mutations suggests that the encoded G protein is involved in signaling in response to mating pheromones. Mutational disruption of G-protein activity causes cell-cycle arrest in G/sub 1/, deposition of mating-specificmore » cell surface aggultinins, and induction of pheromone-specific mRNa, all of which are responses to pheromone in wild-type cells. In addition, mutants can conjugate without the benefit of mating pheromone or pheromone receptor. A model is presented where the activated G protein has a negative impact on a constitutive signal which normally keeps the pheromone response repressed.« less

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

Downes, R.A.

Galactic plane ultraviolet-excess (uv-excess) objects covering about 1000 square degrees of sky were surveyed. Photographic plates were obtained with both uv and blue filters, to select the uv-excess candidates, which were then observed spectroscopically to determine their classification. Most of the objects selected were nearby early-type stars with low interstellar reddening; however, a collection of hot white dwarfs, subdwarf O (sdO) stars, subdwarf B (sdB) stars, and cataclysmic variables was also found. Photoelectric photometry was obtained for these stars and a statistical analysis was performed to determine the space densities and scale heights for the four classes of objects. Severalmore » interesting objects (or class of objects) were discovered, and data for some of these stars are presented. Among the peculiar objects found are an emission-line white dwarf similar to the pulsating PG 1159 stars, a Population II Wolf-Rayet star, a previously catalogued object with a strong Fe II emission-line spectrum, and a new class of object, resembling the sdB stars, that shows variable strength H..cap alpha.. absorption, with the H..cap alpha.. line sometimes completely filled in.« less

Nucleotide sequence of the gene encoding the nitrogenase iron protein of Thiobacillus ferrooxidans

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

Pretorius, I.M.; Rawlings, D.E.; O'Neill, E.G.

1987-01-01

The DNA sequence was determined for the cloned Thiobacillus ferrooxidans nifH and part of the nifD genes. The DNA chains were radiolabeled with (..cap alpha..-/sup 32/P)dCTP (3000 Ci/mmol) or (..cap alpha..-/sup 35/S)dCTP (400 Ci/mmol). A putative T. ferrooxidans nifH promoter was identified whose sequences showed perfect consensus with those of the Klebsiella pneumoniae nif promoter. Two putative consensus upstream activator sequences were also identified. The amino acid sequence was deduced from the DNA sequence. In a comparison of nifH DNA sequences from T. ferrooxidans and eight other nitrogen-fixing microbes, a Rhizobium sp. isolated from Parasponia andersonii showed the greatest homologymore » (74%) and Clostridium pasteurianum (nifH1) showed the least homology (54%). In the comparison of the amino acid sequences of the Fe proteins, the Rhizobium sp. and Rhizobium japonicum showed the greatest homology (both 86%) and C. pasteurianum (nifH1 gene product) demonstrated the least homology (56%) to the T. ferrooxidans Fe protein.« less

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

Nomura, S.; Enna, S.J.

Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar inmore » the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.« less

Direct /sup 125/I-radioligand assays for serum progesterone compared with assays involving extraction of serum

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

Ratcliffe, W.A.; Corrie, J.E.T.; Dalziel, A.H.

1982-06-01

Two direct radioimmunoassays for progesterone in 50 ..mu..L of unextracted serum or plasma with assays involving extraction of serum were compared. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11..cap alpha..-hemisuccinyl conjugate and the radioligand /sup 125/I-labeled progesterone 11..cap alpha..-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r > 0.96)more » with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. We conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum.« less

Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review

PubMed Central

Bose, Susmita; Tarafder, Solaiman

2012-01-01

Calcium phosphates (CaPs) are the most widely used bone substitutes in bone tissue engineering due to their compositional similarities to bone mineral and excellent biocompatibility. In recent years, CaPs, especially hydroxyapatite and tricalcium phosphate, have attracted significant interest in simultaneous use as bone substitute and drug delivery vehicle, adding a new dimension to their application. CaPs are more biocompatible than many other ceramic and inorganic nanoparticles. Their biocompatibility and variable stoichiometry, thus surface charge density, functionality, and dissolution properties, make them suitable for both drug and growth factor delivery. CaP matrices and scaffolds have been reported to act as delivery vehicles for growth factors and drugs in bone tissue engineering. Local drug delivery in musculoskeletal disorder treatments can address some of the critical issues more effectively and efficiently than the systemic delivery. CaPs are used as coatings on metallic implants, CaP cements, and custom designed scaffolds to treat musculoskeletal disorders. This review highlights some of the current drug and growth factor delivery approaches and critical issues using CaP particles, coatings, cements, and scaffolds towards orthopedic and dental applications. PMID:22127225

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

Hall, J.; Richard, P.; Gray, T.J.

The systematics of single and double K-shell-vacancy production in titanium has been investigated in the limit of zero target thickness (approx.1 ..mu..g/cm/sup 2/) for incident C, N, O, F, Mg, Al, Si, S, and Cl ions over a maximum energy range of 0.5 to 6.5 MeV/amu. This corresponds to collision systems with 0.27< or =Z/sub 1//Z/sub 2/< or =0.77 and 0.24< or =v/sub 1//vK< or =0.85, where v/sub 1/ is the projectile nuclear velocity and vK is the mean velocity of an electron in the target K shell. The present work is divided into four major sections. (1) Single K-shell-vacancymore » production has been investigated by measuring K..cap alpha.. and K..beta.. p satellite x-ray-production cross sections for projectiles incident with no K-shell vacancies. For incident ions with Z/sub 1/> or =9, the contribution due to electron-transfer processes from the target K shell to outer shells of the projectile has also been noted. (2) Single K-shell--to--K-shell electron-transfer cross sections have been obtained indirectly by the measuring of the enhancement in the Ti K x-ray production cross section for bare incident projectiles over ions incident with no initial K-shell vacancies. (3) Double K-vacancy production has been investigated by measuring the K..cap alpha.. hypersatellite intensity in ratio to the total K..cap alpha.. intensity. (4) Double K-shell--to--K-shell electron-transfer cross sections have been obtained indirectly with the use of a procedure similar to that used for single K to K transfer. The measured cross sections have been compared to theoretical models for direct Coulomb ionization and inner-shell electron transfer and have been used to investigate the relative importance of these mechanisms for K-vacancy production in heavy-ion--atom collisions.« less

Absolute configurations of organometallic compounds. III. Structure and absolute configuration of the square-pyramidal complex ((+)/sub 579/-(C/sub 5/H/sub 5/)Mo(CO)/sub 2/(NN*))PF/sub 6/(NN* = Schiff base derived from pyridine-2-carbaldehyde and (S)-(-)-. cap alpha. -phenylethylamine)

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

Bernal, I.; LaPlaca, S.J.; Korp, J.

The structure of (+)/sub 579/-(eta/sup 5/-C/sub 5/H/sub 5/Mo(CO)/sub 2/(NN*))PF/sub 6/ with NN* = the Schiff base derived from pyridine-2-carbaldehyde and (S)-(--)-..cap alpha..-phenylethylamine was determined using standard single-crystal x-ray diffraction methods. The absolute configuration was determined by refinement of the data using the anomalous scattering contributions of Mo and P to a final R(F) = 0.056 for 2634 independent reflections having I greater than 3 sigma (I). The substance crystallizes in the space group P2/sub 1/2/sub 1/2/sub 1/ with unit cell dimensions of a = 12.249 (4), b = 9.236 (3), and c = 20.692 (9) A and Z = 4more » molecules/unit cell. The square-pyramidal coordination of the Mo atom is defined by two carbonyl carbons and two Schiff base nitrogens occupying the four basal plane sites and the five carbons of the eta/sup 5/-C/sub 5/H/sub 5/ ligand in the axial position. The Mo--ligand distances and the bond lengths and angles within the ligands are normal and compare closely with those of recent structure determinations of comparable precision. The Mo atom is 0.95 A above the plane formed by the four basal plane ligands. The conformation of the (S)-..cap alpha..-phenylethyl group with respect to the ligand plane, defined by the pyridine ring, the imine system, and the Mo atom, is discussed. The configuration at the metal atom in the (+)/sub 579/ isomer is specified as (S). The PF/sub 6//sup -/ anion executes large amplitude torsional motion in the lattice, as is commonly the case for this anion when not hydrogen bonded.« less

Biochemistry of snake venom neurotoxins and their application to the study of synapse. [Neurotoxins isolated from venom of the Formosan banded krait

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

Hanley, M.R.

1978-11-01

The crude venom of the Formosan banded krait, Bungarus multicinctus, was separated into eleven lethal protein fractions. Nine fractions were purified to final homogeneous toxins, designated ..cap alpha..-bungarotoxin, ..beta..-bungarotoxin, and toxins 7, 8, 9A, 11, 12, 13, and 14. Three of the toxins, ..cap alpha..-bungarotoxin, 7, and 8, were identified as post-synaptic curarimimetic neurotoxins. The remaining toxins were identified as pre-synaptic neurotoxins. ..cap alpha..-Bungarotoxin, toxin 7, and toxin 8 are all highly stable basic polypeptides of approx. 8000 daltons molecular weight. The pre-synaptic toxins fell into two structural groups: toxin 9A and 14 which were single basic chains of approx.more » 14,000 daltons, and ..beta..-bungarotoxin, and toxins 11 thru 13 which were composed of two chains of approx. 8000 and approx. 13,000 daltons covalently linked by disulfides. All the pre-synaptic neurotoxins were shown to have intrinsic calcium-dependent phospholipase A activities. Under certain conditions, intact synaptic membranes were hydrolyzed more rapidly than protein-free extracted synaptic-lipid liposomes which, in turn, were hydrolyzed more rapidly than any other tested liposomes. It was speculated that cell-surface arrays of phosphatidyl serine/glycolipids created high affinity target sites for ..beta..-bungarotoxin. Single-chain toxins were found to be qualitatively different from the two-chain toxins in their ability to block the functioning of acetylcholine receptors, and were quantitatively different in their enzymatic and membrane disruptive activities. ..beta..-Bungarotoxin was shown to be an extremely potent neuronal lesioning agent. There was no apparent selectivity for cholinergic over non-cholinergic neurons, nor for nerve terminals over cell bodies. It was suggested that ..beta..-bungarotoxin can be considered a useful new histological tool, which may exhibit some regional selectivity.« less

Light-Curve Modelling Constraints on the Obliquities and Aspect Angles of the Young Fermi Pulsars

NASA Technical Reports Server (NTRS)

Pierbattista, M.; Harding, A. K.; Grenier, I. A.; Johnson, T. J.; Caraveo, P. A.; Kerr, M.; Gonthier, P. L.

2015-01-01

In more than four years of observation the Large Area Telescope on board the Fermi satellite has identified pulsed gamma-ray emission from more than 80 young or middle-aged pulsars, in most cases providing light curves with high statistics. Fitting the observed profiles with geometrical models can provide estimates of the magnetic obliquity alpha and of the line of sight angle zeta, yielding estimates of the radiation beaming factor and radiated luminosity. Using different gamma-ray emission geometries (Polar Cap, Slot Gap, Outer Gap, One Pole Caustic) and core plus cone geometries for the radio emission, we fit gamma-ray light curves for 76 young or middle-aged pulsars and we jointly fit their gamma-ray plus radio light curves when possible. We find that a joint radio plus gamma-ray fit strategy is important to obtain (alpha, zeta) estimates that can explain simultaneously detectable radio and gamma-ray emission: when the radio emission is available, the inclusion of the radio light curve in the fit leads to important changes in the (alpha, gamma) solutions. The most pronounced changes are observed for Outer Gap and One Pole Caustic models for which the gamma-ray only fit leads to underestimated alpha or zeta when the solution is found to the left or to the right of the main alpha-zeta plane diagonal respectively. The intermediate-to-high altitude magnetosphere models, Slot Gap, Outer Gap, and One pole Caustic, are favored in explaining the observations. We find no apparent evolution of a on a time scale of 106 years. For all emission geometries our derived gamma-ray beaming factors are generally less than one and do not significantly evolve with the spin-down power. A more pronounced beaming factor vs. spin-down power correlation is observed for Slot Gap model and radio-quiet pulsars and for the Outer Gap model and radio-loud pulsars. The beaming factor distributions exhibit a large dispersion that is less pronounced for the Slot Gap case and that decreases from radio-quiet to radio-loud solutions. For all models, the correlation between gamma-ray luminosity and spin-down power is consistent with a square root dependence. The gamma-ray luminosities obtained by using the beaming factors estimated in the framework of each model do not exceed the spin-down power. This suggests that assuming a beaming factor of one for all objects, as done in other studies, likely overestimates the real values. The data show a relation between the pulsar spectral characteristics and the width of the accelerator gap. The relation obtained in the case of the Slot Gap model is consistent with the theoretical prediction.

Risk factors for community-acquired pneumonia in adults in Europe: a literature review

PubMed Central

Torres, Antoni; Peetermans, Willy E; Viegi, Giovanni; Blasi, Francesco

2013-01-01

Background Community-acquired pneumonia (CAP) causes considerable morbidity and mortality in adults, particularly in the elderly. Methods Structured searches of PubMed were conducted to identify up-to-date information on the incidence of CAP in adults in Europe, as well as data on lifestyle and medical risk factors for CAP. Results The overall annual incidence of CAP in adults ranged between 1.07 to 1.2 per 1000 person-years and 1.54 to 1.7 per 1000 population and increased with age (14 per 1000 person-years in adults aged ≥65 years). Incidence was also higher in men than in women and in patients with chronic respiratory disease or HIV infection. Lifestyle factors associated with an increased risk of CAP included smoking, alcohol abuse, being underweight, having regular contact with children and poor dental hygiene. The presence of comorbid conditions, including chronic respiratory and cardiovascular diseases, cerebrovascular disease, Parkinson's disease, epilepsy, dementia, dysphagia, HIV or chronic renal or liver disease all increased the risk of CAP by twofold to fourfold. Conclusion A range of lifestyle factors and underlying medical conditions are associated with an increased risk of CAP in European adults. Understanding of the types of individual at greatest risk of CAP can help to ensure that interventions to reduce the risk of infection and burden of disease are targeted appropriately. PMID:24130229

Time-resolved spectroscopy of dye-labeled photoactive yellow protein suggests a pathway of light-induced structural changes in the N-terminal cap.

PubMed

Hoersch, Daniel; Otto, Harald; Cusanovich, Michael A; Heyn, Maarten P

2009-07-14

The photoreceptor PYP responds to light activation with global conformational changes. These changes are mainly located in the N-terminal cap of the protein, which is approximately 20 A away from the chromophore binding pocket and separated from it by the central beta-sheet. The question of the propagation of the structural change across the central beta-sheet is of general interest for the superfamily of PAS domain proteins, for which PYP is the structural prototype. Here we measured the kinetics of the structural changes in the N-terminal cap by transient absorption spectroscopy on the ns to second timescale. For this purpose the cysteine mutants A5C and N13C were prepared and labeled with thiol reactive 5-iodoacetamidofluorescein (IAF). A5 is located close to the N-terminus, while N13 is part of helix alpha1 near the functionally important salt bridge E12-K110 between the N-terminal cap and the central anti-parallel beta-sheet. The absorption spectrum of the dye is sensitive to its environment, and serves as a sensor for conformational changes near the labeling site. In both labeled mutants light activation results in a transient red-shift of the fluorescein absorption spectrum. To correlate the conformational changes with the photocycle intermediates of the protein, we compared the kinetics of the transient absorption signal of the dye with that of the p-hydroxycinnamoyl chromophore. While the structural change near A5 is synchronized with the rise of the I(2) intermediate, which is formed in approximately 200 mus, the change near N13 is delayed and rises with the next intermediate I(2)', which forms in approximately 2 ms. This indicates that different parts of the N-terminal cap respond to light activation with different kinetics. For the signaling pathway of photoactive yellow protein we propose a model in which the structural signal propagates from the chromophore binding pocket across the central beta-sheet via the N-terminal region to helix alpha1, resulting in a large change in the protein conformation.

L-selectin-carbohydrate interactions: relevant modifications of the Lewis x trisaccharide.

PubMed

Sanders, W J; Katsumoto, T R; Bertozzi, C R; Rosen, S D; Kiessling, L L

1996-11-26

Protein-carbohydrate interactions are known to mediate cell-cell recognition and adhesion events. Specifically, three carbohydrate binding proteins termed selectins (E-, P-, and L-selectin) have been shown to be essential for leukocyte rolling along the vascular endothelium, the first step in the recruitment of leukocytes from the blood into inflammatory sites or into secondary lymphoid organs. Although this phenomenon is well-established, little is known about the molecular-level interactions on which it depends. All three selectins recognize sulfated and sialylated derivatives of the Lewis x [Le(x):Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and Lewis a [Le(a): Gal beta 1-->3(Fuc alpha 1-->4)GlcNAc] trisaccharide cores with affinities in the millimolar range, and it is believed that variants of these structures are the carbohydrate determinants of selectin recognition. Recently it was shown that the mucin GlyCAM-1, a secreted physiological ligand for L-selectin, is capped with sulfated derivatives of sialyl Lewis x [sLe(x): Sia alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and that sulfation is required for the high-affinity interaction between GlyCAM-1 and L-selectin. To elucidate the important sites of sulfation on Le(x) with respect to L-selectin recognition, we have synthesized six sulfated Le(x) analogs and determined their abilities to block binding of a recombinant L-selectin-Ig chimera to immobilized GlyCAM-1. Our results suggest that 6-sulfo sLe(x) binds to L-selectin with higher affinity than does sLe(x) or 6'-sulfo sLe(x) and that sulfation of sLe(x) capping groups on GlyCAM-1 at the 6-position is important for L-selectin recognition.

Capsaicinoids improve consequences of physical activity.

PubMed

Sahin, Kazim; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Erten, Fusun; Juturu, Vijaya

2018-01-01

The purpose of this study was to investigate the effects of capsaicinoids (CAPs) on lipid metabolism, inflammation, antioxidant status and the changes in gene products involved in these metabolic functions in exercised rats. A total of 28 male Wistar albino rats were randomly divided into four groups (n = 7) (i) No exercise and no CAPs, (ii) No exercise + CAPs (iii) Regular exercise, (iv) Regular exercise + CAPs. Rats were administered as 0.2 mg capsaicinoids from 10 mg/kg BW/day Capsimax ® daily for 8 weeks. A significant decrease in lactate and malondialdehyde (MDA) levels and increase in activities of antioxidant enzymes were observed in the combination of regular exercise and CAPs group ( P < 0.0001). Regular exercise + CAPs treated rats had greater nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) levels in muscle than regular exercise and no exercise rats ( P < 0.001). Nevertheless, regular exercise + CAPs treated had lower nuclear factor kappa B (NF-κB) and IL-10 levels in muscle than regular exercise and control rats ( P < 0.001). Muscle sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptors (LXR), ATP citrate lyase (ACLY) and fatty acid synthase (FAS) levels in the regular exercise + CAPs group were lower than all groups ( P < 0.05). However, muscle PPAR-γ level was higher in the regular exercise and CAPs alone than the no exercise rats. These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats.

Mo(CO)/sub 6/-promoted reductive cleavage of the carbon-sulfur bond

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

Luh, T.Y.; Wong, C.S.

1985-12-13

In order to study the reductive cleavage of carbon-sulfur bonds by Mo(CO/sub 6/, various organosulfur compounds are reacted with Mo(CO)/sub 6/ in THF. Results of these experiments demonstrate that benzylic-, aryl-, or ..cap alpha..-acyl-activated carbon-sulfur bonds are reduced by treatment with Mo(CO)/sub 6/. 1 table.

EPA'S FIELD DEMONSTRATION OF INNOVATIVE CAPPING TECHNOLOGIES FOR THE RISK MANAGEMENT OF CONTAMINATED SEDIMENTS

EPA Science Inventory

Research on capping technologies is directed at assessing the effectiveness of innovative capping materials, factors that control contaminant release at the sediment-water interface, installation of cap, resuspension mechanism, and gas ebullition. U.S. EPA's Land Remediation and ...

Alpha3, a transposable element that promotes host sexual reproduction.

PubMed

Barsoum, Emad; Martinez, Paula; Aström, Stefan U

2010-01-01

Theoretical models predict that selfish DNA elements require host sex to persist in a population. Therefore, a transposon that induces sex would strongly favor its own spread. We demonstrate that a protein homologous to transposases, called alpha3, was essential for mating type switch in Kluyveromyces lactis. Mutational analysis showed that amino acids conserved among transposases were essential for its function. During switching, sequences in the 5' and 3' flanking regions of the alpha3 gene were joined, forming a DNA circle, showing that alpha3 mobilized from the genome. The sequences encompassing the alpha3 gene circle junctions in the mating type alpha (MATalpha) locus were essential for switching from MATalpha to MATa, suggesting that alpha3 mobilization was a coupled event. Switching also required a DNA-binding protein, Mating type switch 1 (Mts1), whose binding sites in MATalpha were important. Expression of Mts1 was repressed in MATa/MATalpha diploids and by nutrients, limiting switching to haploids in low-nutrient conditions. A hairpin-capped DNA double-strand break (DSB) was observed in the MATa locus in mre11 mutant strains, indicating that mating type switch was induced by MAT-specific DSBs. This study provides empirical evidence for selfish DNA promoting host sexual reproduction by mediating mating type switch.

Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape.

PubMed

Patterson, Miranda J; McKenzie, Christopher G; Smith, Deborah A; da Silva Dantas, Alessandra; Sherston, Sam; Veal, Elizabeth A; Morgan, Brian A; MacCallum, Donna M; Erwig, Lars-Peter; Quinn, Janet

2013-12-20

As Candida albicans is the major fungal pathogen of humans, there is an urgent need to understand how this pathogen evades toxic reactive oxygen species (ROS) generated by the host immune system. A key regulator of antioxidant gene expression, and thus ROS resistance, in C. albicans is the AP-1-like transcription factor Cap1. Despite this, little is known regarding the intracellular signaling mechanisms that underlie the oxidation and activation of Cap1. Therefore, the aims of this study were; (i) to identify the regulatory proteins that govern Cap1 oxidation, and (ii) to investigate the importance of Cap1 oxidation in C. albicans pathogenesis. In response to hydrogen peroxide (H2O2), but not glutathione-depleting/modifying oxidants, Cap1 oxidation, nuclear accumulation, phosphorylation, and Cap1-dependent gene expression, is mediated by a glutathione peroxidase-like enzyme, which we name Gpx3, and an orthologue of the Saccharomyces cerevisiae Yap1 binding protein, Ybp1. In addition, Ybp1 also functions to stabilise Cap1 and this novel function is conserved in S. cerevisiae. C. albicans cells lacking Cap1, Ybp1, or Gpx3, are unable to filament and thus, escape from murine macrophages after phagocytosis, and also display defective virulence in the Galleria mellonella infection model. Ybp1 is required to promote the stability of fungal AP-1-like transcription factors, and Ybp1 and Gpx3 mediated Cap1-dependent oxidative stress responses are essential for the effective killing of macrophages by C. albicans. Activation of Cap1, specifically by H2O2, is a prerequisite for the subsequent filamentation and escape of this fungal pathogen from the macrophage.

Comment on de-averaged back-angle heavy-ion elastic scattering excitation functions

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

Hussein, M.S.; Canto, L.F.; Donangelo, R.

1984-06-01

It is suggested that the de-averaged 180/sup 0/ excitation function of /sup 16/O+ /sup 28/Si, recently considered by Frahn and Kaufmann, is strongly model dependent. Within a multistep ..cap alpha..-transfer description of the back-angle anomaly, we obtain a de-averaged 180/sup 0/ excitation function that exhibits a more regular gross structure.

Doppler-broadening measurements of x-ray lines for determination of the ion temperature in tokamak plasmas

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

Bitter, M.; von Goeler, S.; Horton, R.

1979-01-29

Ion-temperature results are deduced from Doppler-broadening measurements of the K..cap alpha.. (1s-2p) resonance line emitted from heliumlike iron impurity ions in the hot central core of PLT (Princeton Large Torus) tokamak discharges. The measurements were performed using a high-resolution Bragg-crystal spectrometer with a multiwire proportional counter.

Structural phase transitions in GaAs to 108 GPa

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

Weir, S.T.; Vohra, Y.K.; Vanderborgh, C.A.

1989-01-15

The III-V compound GaAs was studied using energy-dispersive x-ray diffraction with a synchro- tron source up to a pressure of 108 GPa. When the pressure was increased to 16.6 GPa, the GaAs sample transformed from the zinc-blende structure to an orthorhombic structure (GaAs(II)), space group Pmm2, consisting of a primitive orthorhombic lattice with a basis of (0,0,0) and (0,(1/2,..cap alpha..), where ..cap alpha.. = 0.35. Upon a further increase of pressure to 24 +- 1 GPa, GaAs(II) transformed to another orthorhombic structure (GaAs(III)), space group Imm2, consisting of a body-centered orthorhombic lattice with a basis of (0,0,0) and (0, (1/2,..delta..),more » where ..delta.. is 0.425 at 28.1 GPa. With increasing pressure, ..delta.. approached (1/2 and the GaAs(III) structure gradually assumed the symmetry of the simple hexagonal structure. The transition to the simple hexagonal structure (GaAs(IV)) was completed in the vicinity of 60--80 GPa. The structure remains simple hexagonal up to at least 108 GPa, the highest pressure reached in this study.« less

Use of antibodies specific to defined regions of scorpion. cap alpha. -toxin to study its interaction with its receptor site on the sodium channel

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

Ayeb, M.E.; Bahraoui, E.M.; Granier, C.

1986-10-21

Five antibody populations selected by immunoaffinity chromatography for the specificity toward various regions of toxin II of the scorpion Androctonus australis Hector were used to probe the interaction of this protein with its receptor site on the sodium channel. These studies indicate that two antigenic sites, one located around the disulfide bridge 12-63 and one encompassing residues 50-59, are involved in the molecular mechanisms of toxicity neutralization. Fab fragments specific to the region around disulfide bridge 12-63 inhibit binding of the /sup 125/I-labeled toxin to its receptor site. Also, these two antigenic regions are inaccessible to the antibodies when themore » toxin is bound to its receptor site. In contrast, the two other antigenic sites encompassing the only ..cap alpha..-helix region (residues 23-32) and a ..beta..-turn structure (residues 32-35) are accessible to the respective antibodies when the toxin is bound to its receptor. Together, these data support the recent proposal that a region made of residues that are conserved in the scorpion toxin family is involved in the binding of the toxin to the receptor.« less

Survey of the (. cap alpha. ,/sup 2/He) reaction on 1p- and 2s1d-shell nuclei

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

Jahn, R.; Stahel, D.P.; Wozniak, G.J.

A /sup 2/He detection system has been developed and used to investigate the (..cap alpha..,/sup 2/He) reaction at bombarding energies of 55 and 65 MeV on targets of /sup 12/C, /sup 13/C, /sup 14/N, /sup 15/N, /sup 16/O, /sup 18/O, /sup 20/Ne, /sup 22/Ne, /sup 24/Mg, /sup 26/Mg, /sup 28/Si, /sup 29/Si, /sup 32/S, /sup 36/Ar, /sup 38/Ar, and /sup 40/Ca. Preferential population of two-neutron states with dominant (d/sub 5/2/)/sup 2//sub 4/, (d/sub 3/2/f/sub 7/2/)/sub 5/, and (f/sub 7/2/)/sup 2//sub 6/ character was observed. A linear A dependence of the binding energies of the J/sup ..pi../ = 5/sup -/ andmore » 6/sup +/ states was obtained. This systematic behavior is well described by the Bansal-French model, using the parameters a = - 0.30 MeV and b = 2.6 MeV. Simple shell-model calculations for the 2n configurations are in good agreement with the experimental data.« less

Effects of capsaicin in the motor nerve.

PubMed

Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Preparation and characterization of highly water-soluble magnetic Fe3O4 nanoparticles via surface double-layered self-assembly method of sodium alpha-olefin sulfonate

NASA Astrophysics Data System (ADS)

Li, Honghong; Qin, Li; Feng, Ying; Hu, Lihua; Zhou, Chunhua

2015-06-01

A kind of double-layered self-assembly sodium alpha-olefin sulfonate (AOS) capped Fe3O4 magnetic nanoparticles (Fe3O4-AOS-MN) with highly water-solubility was prepared by a wet co-precipitation method with a pH of 4.8. The resulting Fe3O4-AOS-MN could be dispersed into water to form stable magnetic fluid without other treatments. The result of X-ray diffraction (XRD) indicated that the Fe3O4-AOS-MN maintained original crystalline structure and exhibited a diameter of about 7.5 nm. The iron oxide phase of nanoparticles determined by Raman spectroscopy is Fe3O4. Transmission electron microscopy (TEM) analysis confirmed that the Fe3O4-AOS-MN with spherical morphology were uniformly dispersed in water. FT-IR spectroscopy (FT-IR) and thermo-gravimetric analysis (TGA) verified the successful preparation of Fe3O4-AOS-MN capped with double-layered self-assembled AOS. The corresponding capacities of monolayer chemical absorption and the second-layer self-assembly absorption were respectively 4.07 and 14.71 wt% of Fe3O4-MN, which were much lower than those of other surfactants. Vibrating sample magnetometer (VSM) test result showed Fe3O4-AOS-MN possessed superparamagnetic behavior with the saturation magnetization value of about 44.45 emu/g. The blocking temperature TB of Fe3O4-AOS-MN capped with double-layered AOS is 170 K.

Direct assays of radiation-induced DNA base lesions in mammalian cells: Technical progress report, July 1, 1986--December 1, 1988

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

Wheeler, K.T. Jr.

1988-01-01

Our cesium irradiator was installed in April 1987 and has the capability of irradiating DNA solutions, cells and animals at dose rates from >60 Gy/min to <10/sup /minus/2/ Gy/min. By early summer all of the dosimetry and set-ups were established to perform this research. In may 1987, Dr. Krystyna Lesiak left to return to the National Institutes of Health. However, she has remained a collaborator over the past 1/1/2/ years. She has synthesized a large lot of ..cap alpha..-deoxyadenosine, isolated a large batch of both the R and S isomer of cyclodeoxyadenosine and has capped the ..cap alpha..-deoxyadenonsine for usemore » in a DNA synthesizer that uses phosphoramidite chemistry. In November 1987, Dr. Andrzej Surowiec joined our unit as a Visiting Research Assistant Professor. Dr. Surowiec has a MS degree in electrical engineering and did his Ph.D. in Biophysics studying the conductivity of DNA in dilute solution. He has been performing the helix-coil transition experiments. In November 1987, Dr. Steven Swarts also joined our unit as a Postdoctoral Fellow. He received his Ph.D. from Oakland University under Dr. Michael Sevilla with whom we have a collaboration studying the induction of base damage in hydrated DNA. Dr. Swarts has a strong background in spectroscopy and, therefore, was a key individual for determination of the limitations of the HPLC assays and the establishment of a GC/MS capability equivalent to Dr. M. Dizdaroglu at the National Bureau of Standards. 9 refs., 1 tab.« less

Hydrothermal synthesis of alpha- and beta-HgS nanostructures

NASA Astrophysics Data System (ADS)

Galain, Isabel; María, Pérez Barthaburu; Ivana, Aguiar; Laura, Fornaro

2017-01-01

We synthesized HgS nanostructures by the hydrothermal method in order to use them as electron acceptors in hybrid organic-inorganic solar cells. We employed different mercury sources (HgO and Hg(CH3COO)2) and polyvinylpyrrolidone (PVP) or hexadecanethiol (HDT) as stabilizing/capping agent for controlling size, crystallinity, morphology and stability of the obtained nanostructures. We also used thiourea as sulfur source, and a temperature of 180 °C during 6 h. Synthesized nanostructures were characterized by powder X-Ray Diffraction, Diffuse Reflectance Infrared Fourier Transform and Transmission Electron Microscopy. When PVP acts as stabilizing agent, the mercury source has influence on the size -but not in morphology- of the beta-HgS obtained nansostructures. HDT has control over nanostructures' size and depending on the relation Hg:HDT, we obtained a mixture of alpha and beta HgS which can be advantageous in the application in solar cells, due their absorption in different spectral regions. The smallest nanostructures obtained have a mean diameter of 20 nm when using HDT as capping agent. Also, we deposited the aforementioned nanostructures onto flat glass substrates by the spin coating technique as a first approach of an active layer of a solar cell. The depositions were characterized by atomic force microscopy. We obtained smaller particle deposition and higher particle density -but a lower area coverage (5%) - in samples with HDT as capping agent. This work presents promising results on nanostructures for future application on hybrid solar cells. Further efforts will be focused on the deposition of organic-inorganic layers.

Hydrogen peroxide yields mechanistic insights into human mRNA capping enzyme function

PubMed Central

Mullen, Nicholas J.

2017-01-01

Capping of nascent RNA polymerase II (Pol II) transcripts is required for gene expression and the first two steps are catalyzed by separate 5′ triphosphatase and guanylyltransferase activities of the human capping enzyme (HCE). The cap is added co-transcriptionally, but how the two activities are coordinated is unclear. Our previous in vitro work has suggested that an unidentified factor modulates the minimum length at which nascent transcripts can be capped. Using the same well-established in vitro system with hydrogen peroxide as a capping inhibitor, we show that this unidentified factor targets the guanylyltransferase activity of HCE. We also uncover the mechanism of HCE inhibition by hydrogen peroxide, and by using mass spectrometry demonstrate that the active site cysteine residue of the HCE triphosphatase domain becomes oxidized. Using recombinant proteins for the two separated HCE domains, we provide evidence that the triphosphatase normally acts on transcripts shorter than can be acted upon by the guanylyltransferase. Our further characterization of the capping reaction dependence on transcript length and its interaction with the unidentified modulator of capping raises the interesting possibility that the capping reaction could be regulated. PMID:29028835

Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD

DTIC Science & Technology

2012-08-01

SUPPLEMENTARY NOTES 14. ABSTRACT We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder...compounds to therapeutically target eIF4E-eIF4G interactions and eIF4A for treating patients with ASD. 15. SUBJECT TERMS autism spectrum...Introduction We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder (ASD). To test this

Community-acquired pneumonia in patients with and without chronic obstructive pulmonary disease.

PubMed

Molinos, L; Clemente, M G; Miranda, B; Alvarez, C; del Busto, B; Cocina, B R; Alvarez, F; Gorostidi, J; Orejas, C

2009-06-01

The purpose of this study was to analyse the possible differences, especially those regarding mortality, between patients hospitalized for community-acquired pneumonia (CAP) with and without chronic obstructive pulmonary disease (COPD), and the risk factors related to mortality in the COPD group. 710 patients with CAP were included in a prospective multicenter observational study. 244 of the patients had COPD confirmed by spirometry. COPD was associated with mortality in patients with CAP (OR=2.62 CI: 1.08-6.39). Patients with COPD and CAP had a significantly higher 30-day mortality rate as compared to patients without COPD. Multivariate analysis showed that PaO(2)< or =60 mmHg (OR=7.95; 95% CI: 3.40-27.5), PaCO(2)> or =45 mmHg (OR=4.6; CI: 2.3-15.1); respiratory rate > or =30/min (OR=12.25; CI: 3.45-35.57), pleural effusion (OR=8.6; 95% CI: 2.01-24.7), septic shock (OR=12.6; 95% CI: 3.4-45.66) and renal failure (OR=13.4; 95% CI: 3.2-37.8) were significantly related to mortality. Purulent sputum and fever were considered as protective factors. COPD was an independent risk factor for mortality in patients with CAP. Hypoxemia and hypercapnia are associated with mortality in patients with CAP with and without COPD. Chronic obstructive pulmonary disease and PaCO(2) value could be useful prognostic factors and should be incorporated in risk stratification in patients with CAP.

Polariton effects in naphthalene crystals

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

Robinette, Susan Louise

1977-10-01

The experimental verification of the two-step nature of energy dissipation of photon energy by a crystal is the subject of this dissertation. The ..cap alpha..(O,O) Davydov component of the lowest energy singlet transition in pure strain-free napthalene single crystals is shown to exhibit an increase in absorption with increasing temperature, due to an increase in polariton damping via polariton-phonon scattering processes. (GHT)

EFFECT OF POLONIUM /cap alpha/ RADIATION ON GELATINE (in French)

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

Ader, M.

1962-08-01

When a nuclear plate, which has been exposed to radiation, developed, and dried, is exposed to a Po source, no effect can be detected by either the eye or the microscope. However if the plate is placed in distilled water, the emulsion thickness of the irradiated region is reduced by approximately 20 mu . A ridge'' separates this region from the nonirradiated region. The ridge contains piles of silver grains, very deformed traces of the old radiation, and some gelatin fragments. It appears that the alpha particles penetrating the gelatine transforms this gelatin, reversible protein, into a substance soluble'' inmore » distilled water or entrained by the distilled water. (J.S.R.)« less

Severe community-acquired pneumonia. Risk factors and follow-up epidemiology.

PubMed

Ruiz, M; Ewig, S; Torres, A; Arancibia, F; Marco, F; Mensa, J; Sanchez, M; Martinez, J A

1999-09-01

The aim of the study was to determine risk factors for severe community-acquired pneumonia (CAP) as well as to compare microbial patterns of severe CAP to a previous study from our respiratory intensive care unit (ICU) originating from 1984 to 1987. Patients admitted to the ICU according to clinical judgment were defined as having severe CAP. For the study of risk factors, a hospital-based case-control design was used, matching each patient with severe CAP to a patient hospitalized with CAP but not requiring ICU admission. Microbial investigation included noninvasive and invasive techniques. Overall, 89 patients with severe CAP were successfully matched to a control patient. The presence of an alcohol ingestion of >/= 80 g/d (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.4 to 10.6, p = 0.008) was found to be an independent risk factor for severe CAP and prior ambulatory antimicrobial treatment (OR 0.37, 95% CI 0.17 to 0.79, p = 0.009) to be protective. Streptococcus pneumoniae (24%) continued to be the most frequent pathogen; however, 48% of strains were drug-resistant. "Atypical" bacterial pathogens were significantly more common (17% versus 6%, p = 0.006) and Legionella spp. less common (2% versus 14%, p = 0.004) than in our previous study, whereas gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa continued to represent important pathogens (6% and 5%, respectively). Our findings provide additional evidence for the importance of the initiation of early empiric antimicrobial treatment for a favorable outcome of CAP. Variations of microbial patterns are only in part due to different epidemiological settings. Therefore, initial empiric antimicrobial treatment will also have to take into account local trends of changing microbial patterns.

Management of community-acquired pneumonia in older adults

PubMed Central

Simonetti, Antonella F.; Viasus, Diego; Garcia-Vidal, Carolina

2014-01-01

Community-acquired pneumonia (CAP) is an increasing problem among the elderly. Multiple factors related to ageing, such as comorbidities, nutritional status and swallowing dysfunction have been implicated in the increased incidence of CAP in the older population. Moreover, mortality in patients with CAP rises dramatically with increasing age. Streptococcus pneumoniae is still the most common pathogen among the elderly, although CAP may also be caused by drug-resistant microorganisms and aspiration pneumonia. Furthermore, in the elderly CAP has a different clinical presentation, often lacking the typical acute symptoms observed in younger adults, due to the lower local and systemic inflammatory response. Several independent prognostic factors for mortality in the elderly have been identified, including factors related to pneumonia severity, inadequate response to infection, and low functional status. CAP scores and biomarkers have lower prognostic value in the elderly, and so there is a need to find new scales or to set new cut-off points for current scores in this population. Adherence to the current guidelines for CAP has a significant beneficial impact on clinical outcomes in elderly patients. Particular attention should also be paid to nutritional status, fluid administration, functional status, and comorbidity stabilizing therapy in this group of frail patients. This article presents an up-to-date review of the main aspects of CAP in elderly patients, including epidemiology, causative organisms, clinical features, and prognosis, and assesses key points for best practices for the management of the disease. PMID:25165554

Long noncoding RNA BDNF-AS is associated with clinical outcomes and has functional role in human prostate cancer.

PubMed

Li, Wensheng; Dou, Zhongling; We, Shuguang; Zhu, Zhiyi; Pan, Dong; Jia, Zhaohui; Liu, Hui; Wang, Xiaobin; Yu, Guoqiang

2018-06-01

The underlying molecular mechanisms of prostate cancer (CaP) are largely unknown. We investigated the expression, prognostic value and functional role of long non-coding RNA (lncRNA) brain-derived neurotrophin factor antisense (BDNF-AS) in CaP. Clinical tumor samples were excised from patients with CaP. Their endogenous BDNF-AS expression levels were evaluated by qRT-PCR. Correlations between CaP patients' endogenous BDNF-AS expression and their clinicopathological factors, overall survival were statistically analyzed. BDNF-AS expression levels were also probed in immortal CaP cell lines. In LNCaP and PC-3 cells, BDNF-AS was ectopically overexpressed through lentiviral transduction. The functions of BDNF-AS upregulation on CaP cell development were evaluated both in vitro and in vivo. BDNF-AS was downregulated in human CaP tumors. Low BDNF-AS expression was correlated with CaP patients' poor prognosis and shorter overall survival. BDNF-AS was also found to be lowly expressed in CaP cell lines. In LNCaP and PC-3 cells, lentivirus-driven BDNF-AS overexpression exerted significantly tumor-suppressing effects on hindering cancer cell proliferation and invasion in vitro, and explant growth in vivo. Downregulated BDNF-AS in CaP patients could be a potential prognostic biomarker for predicating poor prognosis and survival. Upregulating BDNF-AS may be a novel molecular intervening target for CaP treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

PubMed

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Comparison of U.S. Environmental Protection Agency’s CAP88 PC versions 3.0 and 4.0

DOE PAGES

Jannik, Tim; Farfan, Eduardo B.; Dixon, Ken; ...

2015-08-01

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within itsmore » corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes EPA made in the external ground shine calculations.« less

Determination of molybdenum in sea and estuarine water with BETA-naphthoin oxime and neutron activation

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

Kuathilake, A.I.; Chatt, A.

1980-05-01

An analytical method has been developed for the determination of submicrogram quantities of molybdenum in sea and esturaine water. The method consists of preconcentration of molybdenum with BETA-naphthoin oxime followed by the determination of the element employing neutron activation analysis. Various factors that can influence yield and selectivity of the preconcentration process have been investigated in detail. A comparison study between ..cap alpha..-benzoin oxime and BETA-naphthoin oxime in preconcentrating molybdenum has been carried out using a standard steel sample. The method has been applied to determine molybdenum content of sea and estuarine water. A detection limit of 0.32 ..mu..g Momore » L/sup -1/ seawater has been acheived. The precision and accuracy of the method have been evaluated using an intercomparison fresh water and a biological standard reference material. 1 figure, 9 tables.« less

Elastic and inelastic scattering of alpha particles on /sup 5/8Ni and /sup 6/0Ni in a broad range of energy and angle

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

Budzanowski, A.; Dabrowski, H.; Freindl, L.

1978-03-01

The differential cross sections for ..cap alpha.. particles elastically and inelastically scattered from /sup 5/8Ni (at 29, 34, 38, and 58 MeV) and elastically scattered from /sup 6/0Ni (at 29 and 34 MeV), are measured together with excitation functions in the 25--38 MeV region at 178.5/sup 0/ lab. These data together with the data of 26.5, 32.3, 104, and 139 MEV for /sup 5/8Ni and 32.3 and 104 MeV for /sup 6/0Ni from other sources were analyzed using an optical model with volume and surface absorptions and the Saxon-Woods square form factors. The analysis yielded energy dependent depths of bothmore » real and imaginary parts of the potential and constant geometric parameters. The analytical expressions for depths of the real and both absorption potentials are obtained. The coupled channel calculations using the above optical potential were performed for the first excited state of /sup 5/8Ni. Both elastic scattering data and coupling with the first excited state of /sup 5/8Ni are well reproduced using the above potential in the wide scattering energy range.« less

The uteroglobin fold.

PubMed

Callebaut, I; Poupon, A; Bally, R; Demaret, J P; Housset, D; Delettré, J; Hossenlopp, P; Mornon, J P

2000-01-01

Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small- to medium-sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the alpha/beta hydrolase family, making it a well-suited "geode" structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity.

Impact evaluation of environmental factors on respiratory function of asthma patients living in urban territory.

PubMed

Veremchuk, Lyudmila V; Tsarouhas, Konstantinos; Vitkina, Tatyana I; Mineeva, Elena E; Gvozdenko, Tatyana A; Antonyuk, Marina V; Rakitskii, Valeri N; Sidletskaya, Karolina A; Tsatsakis, Aristidis M; Golokhvast, Kirill S

2018-04-01

Environmental pollution, local climatic conditions and their association with the prevalence and exacerbation of asthma are topics of intense current medical investigation. Air pollution in the area of Vladivostock was estimated both by the index of emission volumes of "air gaseous components" (nitrogen oxide and nitrogen dioxide, formaldehyde, hydrogen sulfide, carbon monoxide) in urban atmosphere and by mass spectrometric analysis of precipitates in snow samples. A total of 172 local asthma patients (101 controlled-asthma patients-CAP and 71 non-controlled asthma patients - nCAP) were evaluated with the use of spirometry and body plethysmography. Airway obstruction reversibility was evaluated with the use of an inhaled bronchodilator. Using discriminant analysis the association of environmental parameters with clinical indices of asthma patients is explored and thresholds of impact are established. CAP presented high sensitivity to large-size suspended air particles and to several of the studied climatic parameters. Discriminant analysis showed high values of Wilks' lambda index (α = 0.69-0.81), which implies limited influence of environmental factors on the respiratory parameters of CAP. nCAP were more sensitive and susceptible to the majority of the environmental factors studied, including air suspended toxic metals particles (Cr, Zn and Ni). Air suspended particles showed higher tendency for pathogenicity in nCAP population than in the CAP, with a wider range of particle sizes being involved. Dust fractions ranging from 0 to 1 μm and from 50 to 100 μm were additionally implicated compared to CAP group. Considerably lowest thresholds levels of impact are calculated for nCAP. Copyright © 2017. Published by Elsevier Ltd.

Time variations of magnetospheric intensities of outer zone protons, alpha particles and ions (Z greater than or equal to 2). Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Randall, B. A.

1973-01-01

A comprehensive study of the temporal behavior of trapped protons, alpha particles and ions (Z 2) in outer zone of the earth's magnetosphere has been made. These observations were made by the Injun V satellite during the first 21 months of operation, August 1968 to May 1970. Rapid increases in the observed number of particles followed by slower exponential decay characterize the data. Comparisons are made with the temporal behavior of interplanetary particles of the same energy observed by Explorer 35. Increases in the trapped fluxes generally correspond to enhanced interplanetary activity. The energy spectra of protons and alpha particles at L = 3 have similar shapes when compared on an energy per charge basis while the respective polar cap spectra have similar shape on an energy per nucleon basis. Apparent inward trans-L motion of energetic protons is observed. These particles are diffused inward by a process involving fluctuating electric fields. The loss of trapped low altitude protons, alpha particles and ions (Z 2) is controlled by coulombic energy loss in the atmosphere.

Community‐Academic Partnerships: A Systematic Review of the State of the Literature and Recommendations for Future Research

PubMed Central

MEZA, ROSEMARY D.; BRIKHO, BRIGITTE; NAAF, MEGHAN; ESTABILLO, JASPER A.; GOMEZ, EMILY D.; VEJNOSKA, SARAH F.; DUFEK, SARAH; STAHMER, AUBYN C.; AARONS, GREGORY A.

2016-01-01

Policy Points: Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research, to provide firsthand knowledge and insight.Based on our systematic review of major literature databases, we recommend using a single term, community‐academic partnership (CAP), and a conceptual definition to unite multiple research disciplines and strengthen the field.Interpersonal and operational factors that facilitate or hinder the collaborative process have been consistently identified, including “trust among partners” and “respect among partners” (facilitating interpersonal factors) and “excessive time commitment” (hindering operational factor).Once CAP processes and characteristics are better understood, the effectiveness of collaborative partner involvement can be tested. Context Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research. Community stakeholders can provide firsthand knowledge and insight, thereby increasing research relevance and feasibility. Despite the greater emphasis and use of community‐academic partnerships (CAP) across multiple disciplines, definitions of partnerships and methodologies vary greatly, and no systematic reviews consolidating this literature have been published. The purpose of this article, then, is to facilitate the continued growth of this field by examining the characteristics of CAPs and the current state of the science, identifying the facilitating and hindering influences on the collaborative process, and developing a common term and conceptual definition for use across disciplines. Methods Our systematic search of 6 major literature databases generated 1,332 unique articles, 50 of which met our criteria for inclusion and provided data on 54 unique CAPs. We then analyzed studies to describe CAP characteristics and to identify the terms and methods used, as well as the common influences on the CAP process and distal outcomes. Findings CAP research spans disciplines, involves a variety of community stakeholders, and focuses on a large range of study topics. CAP research articles, however, rarely report characteristics such as membership numbers or duration. Most studies involved case studies using qualitative methods to collect data on the collaborative process. Although various terms were used to describe collaborative partnerships, few studies provided conceptual definitions. Twenty‐three facilitating and hindering factors influencing the CAP collaboration process emerged from the literature. Outcomes from the CAPs most often included developing or refining tangible products. Conclusions Based on our systematic review, we recommend using a single term, community‐academic partnership, as well as a conceptual definition to unite multiple research disciplines. In addition, CAP characteristics and methods should be reported more systematically to advance the field (eg, to develop CAP evaluation tools). We have identified the most common influences that facilitate and hinder CAPs, which in turn should guide their development and sustainment. PMID:26994713

Negative interference by rheumatoid factor in alpha-fetoprotein chemiluminescent microparticle immunoassay.

PubMed

Wang, Hui; Bi, Xiaohui; Xu, Lei; Li, Yirong

2017-01-01

Background Rheumatoid factor causes positive interference in multiple immunoassays. Recently, negative interference has also been found in immunoassays in the presence of rheumatoid factor. The chemiluminescent microparticle immunoassay is widely used to determine serum alpha-fetoprotein. However, it is not clear whether the presence of rheumatoid factor in the serum causes interference in the chemiluminescent microparticle immunoassay of alpha-fetoprotein. Methods Serum alpha-fetoprotein was determined using the ARCHITECT alpha-fetoprotein assay. The estimation of alpha-fetoprotein recovery was carried out in samples prepared by diluting high-concentration alpha-fetoprotein serum with rheumatoid factor-positive or rheumatoid factor-negative serum. Paramagnetic microparticles coated with hepatitis B surface antigen-anti-HBs complexes were used to remove rheumatoid factor from the serum. Results The average recovery of alpha-fetoprotein was 88.4% and 93.8% in the rheumatoid factor-positive and rheumatoid factor-negative serum samples, respectively. The recovery of alpha-fetoprotein was significantly lower in the rheumatoid factor-positive serum samples than in the rheumatoid factor-negative serum samples. In two of five rheumatoid factor-positive samples, a large difference was found (9.8%) between the average alpha-fetoprotein recoveries in the serially diluted and initial recoveries. Fourteen rheumatoid factor-positive serum samples were pretreated with hepatitis B surface antigen-anti-HBs complex-coated paramagnetic microparticles. The alpha-fetoprotein concentrations measured in the pretreated samples increased significantly. Conclusions It was concluded that the alpha-fetoprotein chemiluminescent microparticle immunoassay is susceptible to interference by rheumatoid factor, leading to significantly lower results. Eliminating the incidence of negative interference from rheumatoid factor should be an important goal for immunoassay providers. In the meantime, laboratorians must remain alert to the negative interference by rheumatoid factor, and in some cases, pretreat rheumatoid factor-positive samples with blocking or absorbing reagents.

Age and seasonal differences in the synthesis and metabolism of testosterone by testicular tissue and pineal HIOMT activity of Uinta ground squirrels (Spermophilus armatus)

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

Ellis, L.C.; Balph, D.F.

Male Uinta ground squirrels (Spermophilus armatus) were sacrificed from a free-living population during the breeding season, which immediately followed emergence from hibernation; after the reproductive season; and just prior to aestivation/hibernation. HIOMT activity of the pineal gland was assayed and related to the ability of the gonads to synthesize and metabolize testosterone. Older squirrels had higher HIOMT activity than did the younger animals. The activity of this enzyme was lowest in squirrels during the breeding season. HIOMT activity increased after the breeding season to its highest level just before the squirrels enter aestivation/hibernation. At this time, testicular weight increased concomitantmore » with an apparent increase in HIOMT activity. Testicular size and weight were largest at the time of emergence of the animals from hibernation. Androgen synthesis was also greatest during the breeding season. As would be expected, both decreased rapidly thereafter. The testes formed little 17..cap alpha..,20..cap alpha..-dihydroxyprogesterone during or after the breeding season, contrary to what has been reported for rats and house sparrows. The older squirrels demonstrated a greater capacity for testosterone metabolism during the breeding season than did the younger animals.« less

Fluorescence alteration of MPA capped CdSe quantum dots by spontaneous biomarker protein adsorption.

PubMed

Rowley, Amber; Parks, Tegan; Parks, Kaden; Medley, Kyle; Cordner, Alex; Yu, Ming

2018-05-23

Quantum dots (QDs) have significant potentials in biomedical applications of bioimaging and biosensing. Spontaneous adsorption of proteins on QDs surface is a common phenomenon, which occurred to serum proteins in biological samples, and has been observed to enhance QDs fluorescence. In this study, fluorescence alteration of 3-mercaptopropionic acid (MPA) capped CdSe quantum dots by four individual biomarker proteins was investigated. By monitoring the fluorescence emission of QDs, the biomarker protein adsorbed spontaneously on QDs surface was recognized and quantified. When alpha fetoprotein (AFP) or heat shock protein 90 alpha (HSP90α) were present, the QDs became brighter. The presence of cytochrome C (CytoC) or lysozyme (Lyz) made the QDs dimmer first, and then brighter. Within 5 min response time all four biomarker proteins were detected individually with the estimated detection limit in the range of 1-10 ng/mL and good linear dynamic ranges. The results suggested that the fluorescence of QDs was responsive to not only serum proteins but also biomarker proteins. The fluorescence response was able to correlate quantitatively with the amount of biomarker proteins in relatively low concentrations. These results provide more information to understand QDs and support their applications in biomedical fields. Copyright © 2018. Published by Elsevier Inc.

Role of calcium in the constriction of isolated cerebral arteries

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

Wendling, W.W.

1987-01-01

Calcium entry blockers (CEB) have been used in the experimental treatment or prevention of many cerebrovascular disorders including stroke, post-ischemic hypoperfusion after cardiac arrest, cerebral vasospasm after subarachnoid hemorrhage, and migraine headache. However, the mechanism of action of these drugs on the cerebral circulation is poorly understood. This study examined the effects of calcium antagonists, Ca/sup 2 +/-deficient solutions, and vasocostrictors on cerebrovascular tone and /sup 45/Ca fluxes, to determine the role of calcium in cerebral arterial constriction. A Scatchard plot of /sup 45/Ca binding to BMCA showed that Ca/sup 2 +/ was bound at either low or high affinitymore » binding sties. The four vasoconstrictors (potassium, serotonin, PGF/sub 2 ..cap alpha../, or SQ-26,655) each increased low affinity /sup 45/Ca uptake into BMCA. The results demonstrate that: (1) Potassium and serotonin constrict BMCA mainly by promoting Ca/sup 2 +/ influx through CEB-sensitive channels; (2) PGF/sub 2 ..cap alpha../ and SQ-26,655 constrict BMCA in part by promoting Ca/sup 2 +/ influx through CEB-sensitive channels, and in part by releasing Ca/sup 2 +/ from depletable internal stores; (3) The major action of CEB on BMCA is to block vasoconstrictor-induced Ca/sup 2 +/ uptake through both potential-operated (K/sup +/-stimulated) and receptor-operated channels.« less

Neutral amino acid transport across brain microvessel endothelial cell monolayers

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

Audus, K.L.; Borchardt, R.T.

1986-03-01

Brain microvessel endothelial cells (BMEC) which form the blood-brain barrier (BBB) possess an amino acid carrier specific for large neutral amino acids (LNAA). The carrier is important for facilitating the delivery of nutrient LNAA's and centrally acting drugs that are LNAA's, to the brain. Bovine BMEC's were isolated and grown up to complete monolayers on regenerated cellulose-membranes in primary culture. To study the transendothelial transport of leucine, the monolayers were placed in a side-by-side diffusion cell, and transport across the monolayers followed with (/sup 3/H)-leucine. The transendothelial transport of leucine in this in vitro model was determined to be bidirectional,more » and time-, temperature-, and concentration-dependent. The transport of leucine was saturable and the apparent K/sub m/ and V/sub max/, 0.18 mM and 6.3 nmol/mg/min, respectively. Other LNAA's, including the centrally acting drugs, ..cap alpha..-methyldopa, L-DOPA, ..cap alpha..-methyl-tyrosine, and baclofen, inhibited leucine transport. The leucine carrier was also found to be stereospecific and not sensitive to inhibitors of active transport. These results are consistent with previous in vitro and in vivo studies. Primary cultures of BMEC's appear to be a potentially important tool for investigating at the cellular level, the transport mechanisms of the BBB.« less

Imidazoline ring cleavage in 1,3,6,10-tetraazatetracyclo-(7. 3. 1. 0/sup 2,7/. 0/sup 6,13/)trideca-4,11-dienes, leading to the formation of diquinoxalino(1,2-. cap alpha. :2',3'-d)pyrrole derivatives

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

Charushin, V.N.; Petrova, G.M.; Aleksandrov, G.G.

1987-10-01

Dibenzo(d,k)-1,3,6,10-tetraazatetracyclo(7.3.1.0/sup 2,7/.0/sup 6,13/) trideca-4,11-dienes undergo addition reactions at the C/sub (2)/ carbon atom with alcohols and thiols, accompanied by cleavage of the C-N bond of the imidazoline ring, to generate diquinoxalino(1,2-..cap alpha..:2',3'-d)pyrrole derivatives. /sup 1/H NMR spectra were recorded on Perkin-Elmer R 12B (60 MHz) and Bruker WH-90 spectrometer for CDCl/sub 3/ solutions at 40/sup 0/C and with TMS as internal standard. /sup 13/C NMR spectra were obtained on a Bruker WH-90 (22.62 MHz) spectrometer. /sup 13/C chemical shifts were measured relative to solvent signals (deltaCDCl/sub 3/ 77.0 ppm). /sup 13/C NMR spectra of compounds IIa and g were takenmore » using full spin-spin carbon-proton decoupling. In order to measure SSCC the spectrum was recorded both with proton coupling and also with selective decoupling of individual protons and their attached /sup 13/C carbon nuclei.« less

Characterization of HeLa 5'-nucleotidase: a stable plasma membrane marker

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

Brake, E.T.; Will, P.C.; Cook, J.S.

1977-11-22

The enzyme 5'-nucleotidase, assayed as 5'-AMPase, has been extensively characterized and established as a stable, quantitative plasma membrane marker in HeLa S3 cells. The 5'-AMPase has a K/sub m/ of 7.0 ..mu..m. There are activity optima at pH7 and 10; the latter is Mg/sup 2 +/-dependent. The membrane preparations have a small amount of acid phosphatase activity that is distinct from 5'-AMPase activity but no alkaline phosphatase. ADP, ATP and ..cap alpha.., ..beta..-methylene adenosine-5'-diphosphate are strongly inhibitory. Mg/sup 2 +/, Ca/sup 2 +/, or Co/sup 2 +/ do not affect the pH 7.0 activity; Mn/sup 2 +/ activates slightly, whereasmore » Zn/sup 2 +/, Cu/sup 2 +/, and Ni/sup 2 +/ are inhibitory. EDTA slowly inactivates, but removal of the EDTA without the addition of divalent cations restores activity. The inactivation is also substantially reversed by Co/sup 2 +/ or Mn/sup 2 +/. ConA strongly inhibits, and ..cap alpha..-methyl-D-mannoside or glucose relieves the inhibition, indicating that the 5'-AMPase is a glycoprotein. Histidine is also inhibitory. Ouabain, phloretin, cytochalasin B, cysteine, phenylalanine, N-ethylmaleimide, and iodoacetic acid are without effect.« less

Polyamidoamine dendrimers-capped carbon dots/Au nanocrystal nanocomposites and its application for electrochemical immunosensor.

PubMed

Gao, Qi; Han, Jingman; Ma, Zhanfang

2013-11-15

In this work, polyamidoamine dendrimers capped-carbon dots (PAMAM-CDs) were fabricated by one-step microwave assisted pyrolysis of citric acid (CA) and PAMAM, where the formation of CDs and the surface passivation were accomplished simultaneously. The obtained graphitic PAMAM-CDs, with abundant amine groups, were employed as reducing and capping agents for the formation of PAMAM-CDs/Au nanocrystal nanocomposites. The resulting nanocomposites exhibited excellent conductivity, stability and biocompatibility on the surface of electrode and were designed as an immobilized matrix for sensitive immunosensing of alpha-fetoprotein (AFP). The proposed immunosensor showed a wide linear detection range from 100 fg mL(-1) to 100 ng mL(-1). The detection limit for AFP was 0.025 pg mL(-1). Importantly, the immunosensor was evaluated for the analysis of clinical serum samples, obtaining a good correlation with enzyme-linked immunosorbent assay (ELISA). The results indicated that the immunosensor provided a possible application for the detection of AFP in clinical diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Validity of the posttraumatic stress disorders (PTSD) checklist in pregnant women.

PubMed

Gelaye, Bizu; Zheng, Yinnan; Medina-Mora, Maria Elena; Rondon, Marta B; Sánchez, Sixto E; Williams, Michelle A

2017-05-12

The PTSD Checklist-civilian (PCL-C) is one of the most commonly used self-report measures of PTSD symptoms, however, little is known about its validity when used in pregnancy. This study aims to evaluate the reliability and validity of the PCL-C as a screen for detecting PTSD symptoms among pregnant women. A total of 3372 pregnant women who attended their first prenatal care visit in Lima, Peru participated in the study. We assessed the reliability of the PCL-C items using Cronbach's alpha. Criterion validity and performance characteristics of PCL-C were assessed against an independent, blinded Clinician-Administered PTSD Scale (CAPS) interview using measures of sensitivity, specificity and receiver operating characteristics (ROC) curves. We tested construct validity using exploratory and confirmatory factor analytic approaches. The reliability of the PCL-C was excellent (Cronbach's alpha =0.90). ROC analysis showed that a cut-off score of 26 offered optimal discriminatory power, with a sensitivity of 0.86 (95% CI: 0.78-0.92) and a specificity of 0.63 (95% CI: 0.62-0.65). The area under the ROC curve was 0.75 (95% CI: 0.71-0.78). A three-factor solution was extracted using exploratory factor analysis and was further complemented with three other models using confirmatory factor analysis (CFA). In a CFA, a three-factor model based on DSM-IV symptom structure had reasonable fit statistics with comparative fit index of 0.86 and root mean square error of approximation of 0.09. The Spanish-language version of the PCL-C may be used as a screening tool for pregnant women. The PCL-C has good reliability, criterion validity and factorial validity. The optimal cut-off score obtained by maximizing the sensitivity and specificity should be considered cautiously; women who screened positive may require further investigation to confirm PTSD diagnosis.

Observations of the boundary layer, cloud, and aerosol variability in the southeast Pacific near-coastal marine stratocumulus during VOCALS-REx

NASA Astrophysics Data System (ADS)

Zheng, X.; Albrecht, B.; Jonsson, H. H.; Khelif, D.; Feingold, G.; Minnis, P.; Ayers, K.; Chuang, P.; Donaher, S.; Rossiter, D.; Ghate, V.; Ruiz-Plancarte, J.; Sun-Mack, S.

2011-09-01

Aircraft observations made off the coast of northern Chile in the Southeastern Pacific (20° S, 72° W; named Point Alpha) from 16 October to 13 November 2008 during the VAMOS Ocean-Cloud- Atmosphere-Land Study-Regional Experiment (VOCALS-REx), combined with meteorological reanalysis, satellite measurements, and radiosonde data, are used to investigate the boundary layer (BL) and aerosol-cloud-drizzle variations in this region. On days without predominately synoptic and meso-scale influences, the BL at Point Alpha was typical of a non-drizzling stratocumulus-topped BL. Entrainment rates calculated from the near cloud-top fluxes and turbulence in the BL at Point Alpha appeared to be weaker than those in the BL over the open ocean west of Point Alpha and the BL near the coast of the northeast Pacific. The cloud liquid water path (LWP) varied between 15 g m-2 and 160 g m-2. The BL had a depth of 1140 ± 120 m, was generally well-mixed and capped by a sharp inversion without predominately synoptic and meso-scale influences. The wind direction generally switched from southerly within the BL to northerly above the inversion. On days when a synoptic system and related mesoscale costal circulations affected conditions at Point Alpha (29 October-4 November), a moist layer above the inversion moved over Point Alpha, and the total-water mixing ratio above the inversion was larger than that within the BL. The accumulation mode aerosol varied from 250 to 700 cm-3 within the BL, and CCN at 0.2 % supersaturation within the BL ranged between 150 and 550 cm-3. The main aerosol source at Point Alpha was horizontal advection within the BL from south. The average cloud droplet number concentration ranged between 80 and 400 cm-3. While the mean LWP retrieved from GOES was in good agreement with the in situ measurements, the GOES-derived cloud droplet effective radius tended to be larger than that from the aircraft in situ observations near cloud top. The aerosol and cloud LWP relationship reveals that during the typical well-mixed BL days the cloud LWP increased with the CCN concentrations. On the other hand, meteorological factors and the decoupling processes have large influences on the cloud LWP variation as well.

[Comparison of expression of transforming growth factor-β1 in rat dental pulp during direct pulp capping with 2 capping agents].

PubMed

Zhang, Xiao-fang; Yao, Ya-peng; Kang, Hong-ying; Dong, Pei

2014-04-01

To examine and compare the expression of transforming growth factor-β1(TGF-β1) in rat dental pulp after direct pulp capping with calcium hydroxide (CH) and mineral trioxide aggregate (MTA). The model of direct dental pulp capping after first molars was established in 28 female Wistar rats with CH and MTA. The rats were sacrificed 1, 3, 5, 7, 14,21 and 28 days after direct pulp capping. TGF-β1 expression in pulp tissues were measured with immunohistochemical staining. The data was analyzed by Dunnett t test and paired t test with SPSS 13.0 software package. The results showed that no TGF-β1 expression was detected in the control group. After direct pulp capping with MTA, TGF-β1 expression gradually increased and reached peak expression on 5 day. TGF-β1 expression gradually decreased afterwards and reached normal on 21 day after direct pulp. TGF-β1 was mainly expressed in neutrophils, odontoblasts cells, vascular endothelial cells and fibroblasts. The expression of TGF-β1 was significantly different between 2 capping agents 1, 3, 5, 7, 14 days after direct pulp capping (P<0.05). The results suggest that TGF-β1 expression increases at first and then decreases after direct pulp capping. The type of capping agents has an impact on the expression of TGF-β1 after direct pulp capping. MTA enhances more TGFβ-1 expression than CH 1, 3, 5, 7 and 14 days after direct pulp capping. Supported by Science and Technology Plan Project of Liaoning Province (2009225001-2).

Questionnaire based assessment of patients' acceptability of leukocytapheresis for the treatment of inflammatory bowel disease.

PubMed

Nagase, Kazuko; Fukuanga, Ken; Yokoyama, Yoko; Kamikozuru, Koji; Miwa, Hiroto; Nakamura, Shiro

2013-10-01

The aim of the present study was to assess patients' acceptance of therapeutic leukocytapheresis known as cytapheresis (CAP) for the treatment of an active flare of inflammatory bowel disease (IBD). A questionnaire was sent to 155 IBD patients who had been treated with CAP for an active flare of IBD at the IBD center of Hyogo College of Medicine between January 2009 and July 2012. In the questionnaire, patients were asked to evaluate CAP including efficacy, safety, unfavorable features and their willingness to be retreated with CAP for a subsequent IBD flare-up. Seventy-eight percent (112 of 155 patients) including 86 with ulcerative colitis and 26 with Crohn's disease completed the questionnaire. The need for coming to hospital for CAP, needle pain during blood access, sparing time for CAP process were scored by 57%, 58%, and 58.9% of the patients, respectively as unfavorable. Patients highly favored the safety of CAP, the sum of very and relatively favorable was 89%, higher than for efficacy (68%). Seventy-two percent of patients favored retreatment with CAP. In binary logistic regression analysis, the levels of satisfaction for efficacy (P < 0.001), and inconvenience for CAP treatment time (P < 0.001) were highly significant factors for patients' willingness to be retreated. Bearing in mind that CAP is a non-pharmacologic treatment intervention, our analyses indicated that IBD patients favored high efficacy, as well as comfort of CAP or maintaining their normal social activity even during an active phase of the disease. Patient's acceptability for CAP appeared to be determined by the balance of these factors. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

Tumor necrosis factor-{alpha} enhances IL-15-induced natural killer cell differentiation

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

Lee, Jiwon; Lee, Suk Hyung; Korea University of Science and Technology, Yusong, Daejeon 305-333

2009-09-04

The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-{alpha} (TNF-{alpha}) is a positive regulator of NK cell differentiation. TNF-{alpha} augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-{alpha} alone also induced NK cell maturation as well as IL-15. TNF-{alpha} also increased IFN-{gamma} production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-{alpha} and IL-15. In addition, TNF-{alpha} increased nuclear factor-kappamore » B (NF-{kappa}B) activity in NK cells and inhibition of NF-{kappa}B impeded TNF-{alpha}-enhanced NK cell maturation. Overall, these data suggest that TNF-{alpha} significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-{kappa}B activity.« less

Introduction of potential helix-capping residues into an engineered helical protein.

PubMed

Parker, M H; Hefford, M A

1998-08-01

MB-1 is an engineered protein that was designed to incorporate high percentages of four amino acid residues and to fold into a four-alpha-helix bundle motif. Mutations were made in the putative loop I and III regions of this protein with the aim of increasing the stability of the helix ends. Four variants, MB-3, MB-5, MB-11 and MB-13, have replacements intended to promote formation of an 'N-capping box'. The loop I and III sequences of MB-3 (both GDLST) and MB-11 (GGDST) were designed to cause alphaL C-terminal 'capping' motifs to form in helices I and III. MB-5 has a sequence, GPDST, that places proline in a favourable position for forming beta-turns, whereas MB-13 (GLDST) has the potential to form Schellman C-capping motifs. Size-exclusion chromatography suggested that MB-1, MB-3, MB-5, MB-11 and MB-13 all form dimers, or possibly trimers. Free energies for the unfolding of each of these variants were determined by urea denaturation, with the loss of secondary structure followed by CD spectroscopy. Assuming an equilibrium between folded dimer and unfolded monomer, MB-13 had the highest apparent stability (40.5 kJ/mol, with +/-2.5 kJ/mol 95% confidence limits), followed by MB-11 (39.3+/-5.9 kJ/mol), MB-3 (36.4+/-1.7 kJ/mol), MB-5 (34.7+/-2.1 kJ/mol) and MB-1 (29.3+/-1.3 kJ/mol); the same relative stabilities of the variants were found when a folded trimer to unfolded monomer model was used to calculate stabilities. All of the variants were relatively unstable for dimeric proteins, but were significantly more stable than MB-1. These findings suggest that it might be possible to increase the stability of a protein for which the three-dimensional structure is unknown by placing amino acid residues in positions that have the potential to form helix- and turn-stabilizing motifs.

Eukaryotic Translation Initiation Factor 4E Availability Controls the Switch between Cap-Dependent and Internal Ribosomal Entry Site-Mediated Translation†

PubMed Central

Svitkin, Yuri V.; Herdy, Barbara; Costa-Mattioli, Mauro; Gingras, Anne-Claude; Raught, Brian; Sonenberg, Nahum

2005-01-01

Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5′ end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation initiation bypasses the requirement for the cap and eIF4E and occurs on viral and cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we demonstrate that eIF4E availability plays a critical role in the switch from cap-dependent to IRES-mediated translation in picornavirus-infected cells. When both capped and IRES-containing mRNAs are present (as in intact cells or in vitro translation extracts), a decrease in the amount of eIF4E associated with the eIF4F complex elicits a striking increase in IRES-mediated viral mRNA translation. This effect is not observed in translation extracts depleted of capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for translation. These data explain numerous reported observations where viral mRNAs are preferentially translated during infection. PMID:16287867

Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation.

PubMed

Svitkin, Yuri V; Herdy, Barbara; Costa-Mattioli, Mauro; Gingras, Anne-Claude; Raught, Brian; Sonenberg, Nahum

2005-12-01

Translation of m7G-capped cellular mRNAs is initiated by recruitment of ribosomes to the 5' end of mRNAs via eukaryotic translation initiation factor 4F (eIF4F), a heterotrimeric complex comprised of a cap-binding subunit (eIF4E) and an RNA helicase (eIF4A) bridged by a scaffolding molecule (eIF4G). Internal translation initiation bypasses the requirement for the cap and eIF4E and occurs on viral and cellular mRNAs containing internal ribosomal entry sites (IRESs). Here we demonstrate that eIF4E availability plays a critical role in the switch from cap-dependent to IRES-mediated translation in picornavirus-infected cells. When both capped and IRES-containing mRNAs are present (as in intact cells or in vitro translation extracts), a decrease in the amount of eIF4E associated with the eIF4F complex elicits a striking increase in IRES-mediated viral mRNA translation. This effect is not observed in translation extracts depleted of capped mRNAs, indicating that capped mRNAs compete with IRES-containing mRNAs for translation. These data explain numerous reported observations where viral mRNAs are preferentially translated during infection.

All-night EEG power spectral analysis of the cyclic alternating pattern components in young adult subjects.

PubMed

Ferri, Raffaele; Bruni, Oliviero; Miano, Silvia; Plazzi, Giuseppe; Terzano, Mario G

2005-10-01

To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP), taking into account the ongoing EEG background and the nonCAP (NCAP) periods in the whole night polysomnographic recordings of normal young adults. Sixteen normal healthy subjects were included in this study. Each subject underwent one polysomnographic night recording; sleep stages were scored following standard criteria. Subsequently, each CAP A phase was detected in all recordings, during NREM sleep, and classified into 3 subtypes (A1, A2, and A3). The same channel used for the detection of CAP A phases (C3/A2 or C4/A1) was subdivided into 2-s mini-epochs. For each mini-epoch, the corresponding CAP condition was determined and power spectra calculated in the frequency range 0.5-25 Hz. Average spectra were obtained for each CAP condition, separately in sleep stage 2 and SWS, for each subject. Finally, the first 6h of sleep were subdivided into 4 periods of 90 min each and the same spectral analysis was performed for each period. During sleep stage 2, CAP A subtypes differed from NCAP periods for all frequency bins between 0.5 and 25 Hz; this difference was most evident for the lowest frequencies. The B phase following A1 subtypes had a power spectrum significantly higher than that of NCAP, for frequencies between 1 and 11 Hz. The B phase after A2 only differed from NCAP for a small but significant reduction in the sigma band power; this was evident also after A3 subtypes. During SWS, we found similar results. The comparison between the different CAP subtypes also disclosed significant differences related to the stage in which they occurred. Finally, a significant effect of the different sleep periods was found on the different CAP subtypes during sleep stage 2 and on NCAP in both sleep stage 2 and SWS. CAP subtypes are characterized by clearly different spectra and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This finding underlines a probable different functional meaning of the same CAP subtype during different sleep stages. We also found 3 clear peaks of difference between CAP subtypes and NCAP in the delta, alpha, and beta frequency ranges which might indicate the presence of 3 frequency components characterizing CAP subtypes, in different proportion in each of them. The B component of CAP differs from NCAP because of a decrease in power in the sigma frequency range. This study shows that A components of CAP might correspond to periods in which the very-slow delta activity of sleep groups a range of different EEG activities, including the sigma and beta bands, while the B phase of CAP might correspond to a period in which this activity is quiescent or inhibited.

In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis.

PubMed

Feliciani, C; Toto, P; Amerio, P; Pour, S M; Coscione, G; Shivji, G; Wang, B; Sauder, D N

2000-01-01

Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1alpha and tumor necrosis factor-alpha, in lesional and perilesional areas. Results were confirmed by reverse transcriptase-polymerase chain reaction, demonstrating overexpression of both cytokines in vivo. To study the role of these cytokines in the pathogenesis of pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that pemphigus vulgaris IgG induced interleukin-1alpha and tumor necrosis factor-alpha mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1alpha and tumor necrosis factor-alpha in keratinocytes cultures. A combination of anti-interleukin-1alpha and anti-tumor necrosis factor-alpha antibodies inhibited in vitro pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-alpha in pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE-/-, interleukin-1beta-/-) and tumor necrosis factor-alpha receptor deficient mice (TNFR1R2-/-). Both groups demonstrated a decreased susceptibility to the passive transfer of pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-alpha in the pathogenesis of pemphigus vulgaris.

Comparative Effectiveness of a Convection-Type and Radiation-Type Cooling Cap on a Turbosupercharger

DTIC Science & Technology

1946-06-01

i176014333182-— IWTICNAIIADVISORY (x14MmTm 3’023AERONNJTICS TECHNICAL NOTE NO. 1082 C(MPARATJNE EET’ACTIVENESSOF A COHV3CTION-TYI?EAND A RADIA’EEON...Electric Company that the radiation cap has a lesser cooling effect than the N4CA TN NO. 1082 ● convection cap, other factors influence the selection of...For the convection-type cap, slots were cut h 3 , b NACA TN No. 1082 the bottom of the radiation-type cap, as indicated in figure 3, and the cooling

Prevalence and predictive factors of moderate/severe liver steatosis in chronic hepatitis C (CHC) infected patients evaluated with Controlled Attenuation Parameter (CAP).

PubMed

Cardoso, Ana Carolina; Perez, Renata M; de Figueiredo-Mendes, Claudio; Carvalho Leite, Nathalie; Coelho, Henrique Sergio Moraes; Villela-Nogueira, Cristiane A

2018-05-16

A novel controlled attenuation parameter (CAP) using FibroScan ® has been developed for assessment of liver steatosis. The aim was to evaluate the frequency and associated factors for moderate/severe steatosis evaluated by CAP in CHC patients submitted to transient elastography (TE) by FibroScan ® . CHC patients underwent TE with CAP evaluation. The classification of steatosis was defined as: CAP < 222 dB/m = S0; CAP ≥ 222 dB/m and <233dB /m = S1; ≥233 dB/m <290dB/m = S2 and >= 290 dB/m = S3. The prevalence of moderate/severe steatosis (CAP ≥ S2) and the related independent factors were identified by a logistic regression analysis. A significance level of 5% was adopted. 1104 CHC patients, 85% genotype-1 were included (mean age 55 ± 11 yrs; 46% male, mean BMI 25 ± 4 Kg/m 2 ). Systemic arterial hypertension and type 2 diabetes mellitus prevalences were 39% and 17% respectively. Liver stiffness measurement ≥ 9.5 kPa was observed in 39% of patients and steatosis was identified in 50% (S1 = 7%, S2 = 28% and S3 = 15%). The variables independently associated with moderate/severe steatosis were: male gender (OR=1.35; p=0.037; 95% CI:1.01 - 1.81); systemic arterial hypertension (OR=1.57; p=0.002; 95% CI:1.17 - 2.10) and BMI (OR=1.17; p <0.01;95% CI: 1.12 - 1.22). In conclusion, when CAP was adopted as a tool to detect steatosis, genotype 1 CHC patients presented a high prevalence of moderate/advanced steatosis. In these patients, liver steatosis was associated mostly to metabolic factors (arterial hypertension and high BMI). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Controversies in diagnosis and management of community-acquired pneumonia.

PubMed

Sparham, Sarah; Charles, Patrick Gp

2017-04-17

Community-acquired pneumonia (CAP) is a common condition; however, it appears to be overdiagnosed. Diagnosing CAP too frequently may be adding to the problems of overuse of antibiotics, such as bacterial resistance in the community and greater costs and complications in individuals. Data support that most patients with non-severe CAP can be treated for 3-5 days; however, most patients with CAP are receiving much longer courses of therapy. Macrolides such as azithromycin have the potential to prolong the QT interval, although large population studies show that this does not appear to result in excess cardiac mortality. CAP is associated with an increase in a variety of cardiac complications, most notably infarctions and worsening cardiac failure, so clinicians should be vigilant for signs and symptoms of these complications, particularly in patients with a history of ischaemic cardiac disease or the presence of cardiac risk factors. Cardiac risk factors should be assessed and managed in patients with CAP over 40 years of age, although there are yet to be data to show that this approach reduces deaths. Corticosteroids may have a slight effect on reducing deaths in patients with severe CAP, but this must be balanced against the significant potential for side effects.

Child psychiatry: what are we teaching medical students?

PubMed

Dingle, Arden D

2010-01-01

The author describes child and adolescent psychiatry (CAP) undergraduate teaching in American and Canadian medical schools. A survey asking for information on CAP teaching, student interest in CAP, and opinions about the CAP importance was sent to the medical student psychiatry director at 142 accredited medical schools in the United States and Canada. The results were summarized and various factors considered relevant to CAP student interest were analyzed statistically. Approximately 81% of the schools returned surveys. Most teach required CAP didactics in the preclinical and clinical years. Almost 63% of the schools have CAP clinical rotations; most are not required. Twenty-three percent of all medical students have a clinical CAP experience during their psychiatry clerkship. The majority of schools have CAP electives, and approximately 4.8% of students participate. Child and adolescent psychiatry leadership, early exposure to CAP, and CAP clinical experiences were related to student CAP interest, but these relationships were not statistically significant. The time allotted to teaching CAP in the undergraduate medical curriculum is minimal, consistent with previous survey results. Most schools require didactic instruction averaging about 12 hours and offer elective clinical opportunities. The survey findings should help direct future planning to improve CAP medical student education.

Mechanism of the lysosomal membrane enzyme acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase

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

Bame, K.J.

1986-01-01

Acetyl-CoA:..cap alpha..-glucosaminide N-acetyltransferase is a lysosomal membrane enzyme, deficient in the genetic disease Sanfilippo C syndrome. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal ..cap alpha..-glucosamine residues of heparan sulfate within the organelle. The reaction mechanism was examined using high purified lysosomal membranes from rat liver and human fibroblasts. The N-acetyltransferase reaction is optimal above pH 5.5 and a 2-3 fold stimulation of activity is observed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicate that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. The bindingmore » of acetyl-CoA to the enzyme is measured by exchange label from (/sup 3/H)CoA to acetyl-CoA, and is optimal at pH's above 7.0. The acetyl-enzyme intermediate is formed by incubating membranes with (/sup 3/H)acetyl-CoA. The acetyl group can be transferred to glucosamine, forming (/sup 3/H)N-acetylglucosamine; the transfer is optimal between pH 4 and 5. Lysosomal membranes from Sanfilippo C fibroblasts confirm that these half reactions carried out by the N-acetyltransferase. The enzyme is inactivated by N-bromosuccinimide and diethylpyrocarbonate, indicating that a histidine is involved in the reaction. These results suggest that the histidine residue is at the active site of the enzyme. The properties of the N-acetyltransferase in the membrane, the characterization of the enzyme kinetics, the chemistry of a histidine mediated acetylation and the pH difference across the lysosomal membrane all support a transmembrane acetylation mechanism.« less

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

Hawkins, C.A.

Tests of QED to order ..cap alpha../sup 4/ performed with the ASP detector at PEP are presented. Measurements have been made of exclusive e/sup +/e/sup -/e/sup +/e/sup -/, e/sup +/e/sup -/..gamma gamma.. and ..gamma gamma gamma gamma.. final states with all particles above 50 milliradians with respect to the e/sup +/e/sup -/ beam line. These measurements represent a significant increase in statistics over previous measurements. All measurements agree well with theoretical predictions. 5 refs., 1 tab.

Binding Linkage in a Telomere DNA–Protein Complex at the Ends of Oxytricha nova Chromosomes

PubMed Central

Buczek, Pawel; Orr, Rochelle S.; Pyper, Sean R.; Shum, Mili; Ota, Emily Kimmel Irene; Gerum, Shawn E.; Horvath, Martin P.

2005-01-01

Alpha and beta protein subunits of the telomere end binding protein from Oxytricha nova (OnTEBP) combine with telomere single strand DNA to form a protective cap at the ends of chromosomes. We tested how protein–protein interactions seen in the co-crystal structure relate to DNA binding through use of fusion proteins engineered as different combinations of domains and subunits derived from OnTEBP. Joining alpha and beta resulted in a protein that bound single strand telomere DNA with high affinity (KD-DNA=1.4 nM). Another fusion protein, constructed without the C-terminal protein–protein interaction domain of alpha, bound DNA with 200-fold diminished affinity (KD-DNA=290 nM) even though the DNA-binding domains of alpha and beta were joined through a peptide linker. Adding back the alpha C-terminal domain as a separate protein restored high-affinity DNA binding. The binding behaviors of these fusion proteins and the native protein subunits are consistent with cooperative linkage between protein-association and DNA-binding equilibria. Linking DNA–protein stability to protein–protein contacts at a remote site may provide a trigger point for DNA–protein disassembly during telomere replication when the single strand telomere DNA must exchange between a very stable OnTEBP complex and telomerase. PMID:15967465

Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam

PubMed Central

Panchal, Trupti; Chen, Xi; Poon, James; Kouptsova, Jane

2017-01-01

Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2–3 germline stem cells. In particular, we focused on the question of how cap cells form. Cap cells express Tj and are considered the key component of a mature germline stem cell niche. We conclude that Tj controls the specification of cap cells, as the complete loss of Tj function caused the development of additional terminal filament cells at the expense of cap cells, and terminal filament cells developed cap cell characteristics when induced to express Tj. Further, we propose that Tj controls the morphogenetic behavior of cap cells as they adopted the shape and spatial organization of terminal filament cells but otherwise appeared to retain their fate when Tj expression was only partially reduced. Our data indicate that Tj contributes to the establishment of germline stem cells by promoting the cap cell fate, and controls the stem cell-carrying capacity of the niche by regulating niche architecture. Analysis of the interactions between Tj and the Notch (N) pathway indicates that Tj and N have distinct functions in the cap cell specification program. We propose that formation of cap cells depends on the combined activities of Tj and the N pathway, with Tj promoting the cap cell fate by blocking the terminal filament cell fate, and N supporting cap cells by preventing the escort cell fate and/or controlling the number of cap cell precursors. PMID:28542174

Community-acquired pneumonia due to gram-negative bacteria and pseudomonas aeruginosa: incidence, risk, and prognosis.

PubMed

Arancibia, Francisco; Bauer, Torsten T; Ewig, Santiago; Mensa, Josep; Gonzalez, Julia; Niederman, Michael S; Torres, Antoni

2002-09-09

Initial empirical antimicrobial treatment of patients with community-acquired pneumonia (CAP) is based on expected microbial patterns. We determined the incidence of, prognosis of, and risk factors for CAP due to gram-negative bacteria (GNB), including Pseudomonas aeruginosa. Consecutive patients with CAP hospitalized in our 1000-bed tertiary care university teaching hospital were studied prospectively. Independent risk factors for CAP due to GNB and for death were identified by means of stepwise logistic regression analysis. From January 1, 1997, until December 31, 1998, 559 hospitalized patients with CAP were included. Sixty patients (11%) had CAP due to GNB, including P aeruginosa in 39 (65%). Probable aspiration (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.02-5.2; P =.04), previous hospital admission (OR, 3.5; 95% CI, 1.7-7.1; P<.001), previous antimicrobial treatment (OR, 1.9; 95% CI, 1.01-3.7; P =.049), and the presence of pulmonary comorbidity (OR, 2.8; 95% CI, 1.5-5.5; P =.02) were independent predictors of GNB. In a subgroup analysis of P aeruginosa pneumonia, pulmonary comorbidity (OR, 5.8; 95% CI, 2.2-15.3; P<.001) and previous hospital admission (OR, 3.8; 95% CI, 1.8-8.3; P =.02) were predictive. Infection with GNB was independently associated with death (relative risk, 3.4; 95% CI, 1.6-7.4; P =.002). In our setting, in every tenth patient with CAP, an etiology due to GNB has to be considered. Patients with probable aspiration, previous hospitalization or antimicrobial treatment, and pulmonary comorbidity are especially prone to GNB. These pathogens are also an independent risk factor for death in patients with CAP.

Continuous antibiotic prophylaxis reduces the risk of febrile UTI in children with asymptomatic antenatal hydronephrosis with either ureteral dilation, high-grade vesicoureteral reflux, or ureterovesical junction obstruction.

PubMed

Herz, Daniel; Merguerian, Paul; McQuiston, Leslie

2014-08-01

The efficacy and utility of continuous antibiotic prophylaxis (CAP) in children with congenital antenatal hydronephrosis (ANH) is uncertain. The literature has both supportive and contradictory evidence. The growing trend not to place children with ANH on CAP has created varied clinical practice based on anecdotal individual case characteristics. Our goal was to compare individual infant characteristics between those children who were maintained on CAP to those that were not to try to determine predisposing risk factors to febrile. All electronic medical records (EMRs) of children referred to our institution for congenital ANH over a period from 2001 to 2011 were examined. We excluded those referred for urinary tract infection (UTI) who had a history of congenital ANH. We also excluded those with incomplete records, or follow-up less than 2 years. Children were divided into two groups: those maintained on CAP (YCAP) and those not maintained on CAP (NCAP). Our primary endpoint was febrile UTI. Follow-up was at least 24 months. Demographic, perinatal and postnatal clinical data were recorded. Statistical analysis was performed using STATA Version 11.1. Of the 405 children fitting inclusion criteria, 278 (68.6%) children were maintained on CAP and 127 (31.4%) were not on CAP. The incidence of prematurity, oligohydramnios, perinatal respiratory complications, use of perinatal antibiotics, circumcision status, renal anomalies, associated medical diagnoses, and low birth weight did not differ between the two groups. Overall the incidence of febrile UTI during the follow-up period was 22.2%. The incidence of febrile UTI between the YCAP and NCAP groups was significant (YCAP = 7.9% and NCAP 18.7%, p = 0.021). Multivariate logistic regression using CAP as the dichotomous dependent variable revealed that ureteral dilation, high-grade vesicoureteral reflux (VUR), and ureterovesical junction (UVJ) obstruction were independent risk factors for febrile UTI. More specifically, children with ureteral dilation >11 mm NOT maintained on CAP had a 5.54 (OR = 5.54; CI = 3.15-7.42, p = 0.001) fold increased risk of febrile UTI compared to those maintained on CAP. The presence of ureteral dilation, high grade VUR, and UVJ obstruction were independent risk factors for development of UTI in children with congenital ANH. Therefore CAP may have a significant role in reducing the risk of febrile UTI in children with ANH with those identifiable risk factors, but otherwise seems unnecessary. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Generation of human induced pluripotent stem cells using non-synthetic mRNA.

PubMed

Rohani, L; Fabian, C; Holland, H; Naaldijk, Y; Dressel, R; Löffler-Wirth, H; Binder, H; Arnold, A; Stolzing, A

2016-05-01

Here we describe some of the crucial steps to generate induced pluripotent stem cells (iPSCs) using mRNA transfection. Our approach uses a V. virus-derived capping enzyme instead of a cap-analog, ensuring 100% proper cap orientation for in vitro transcribed mRNA. V. virus' 2'-O-Methyltransferase enzyme creates a cap1 structure found in higher eukaryotes and has higher translation efficiency compared to other methods. Use of the polymeric transfection reagent polyethylenimine proved superior to other transfection methods. The mRNA created via this method did not trigger an intracellular immune response via human IFN-gamma (hIFN-γ) or alpha (hIFN-α) release, thus circumventing the use of suppressors. Resulting mRNA and protein were expressed at high levels for over 48h, thus obviating daily transfections. Using this method, we demonstrated swift activation of pluripotency associated genes in human fibroblasts. Low oxygen conditions further facilitated colony formation. Differentiation into different germ layers was confirmed via teratoma assay. Reprogramming with non-synthetic mRNA holds great promise for safe generation of iPSCs of human origin. Using the protocols described herein we hope to make this method more accessible to other groups as a fast, inexpensive, and non-viral reprogramming approach. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Comparison of U.S. Environmental Protection Agency's CAP88 PC Versions 3.0 and 4.0.

PubMed

Jannik, Tim; Farfan, Eduardo B; Dixon, Ken; Newton, Joseph; Sailors, Christopher; Johnson, Levi; Moore, Kelsey; Stahman, Richard

2015-08-01

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (U.S. EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with U.S. EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within its corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective dose. A detailed summary for select radionuclides of concern at the Savannah River Site (60Co, 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes U.S. EPA made in the external ground shine calculations.

Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

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

Patterson, Edward I.; EH Graham Centre for Agricultural Innovation; Dombrovski, Andrew K.

2013-09-06

Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediatemore » nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.« less

Quantitative analysis of sleep EEG microstructure in the time-frequency domain.

PubMed

De Carli, Fabrizio; Nobili, Lino; Beelke, Manolo; Watanabe, Tsuyoshi; Smerieri, Arianna; Parrino, Liborio; Terzano, Mario Giovanni; Ferrillo, Franco

2004-06-30

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to each event, corresponding to background activity, pre-arousal period and arousal. The study was supplemented by the analysis of time-frequency distribution of EEG within each subtype of phase A in the CAP. The arousals were characterized by the increase of alpha and beta power with regard to background. Within NREM sleep most of the arousals were preceded by a transient increase of delta power. The time-frequency evolution of the phase A of the CAP sequence showed a strong prevalence of delta activity during the whole A1, but high amplitude delta waves were found also in the first 2/3 s of A2 and A3, followed by desynchronization. Our results underline the strict relationship between the ASDA arousals, and the subtype A2 and A3 within the CAP: in both the association between a short sequence of transient slow waves and the successive increase of frequency and decrease of amplitude characterizes the arousal response.

Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

PubMed

Bahia, Malkeet S; Silakari, Om

2010-05-01

Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

Clinical presentation and diagnostic workup for community-acquired pneumonia: the Gulf Corporation Council CAP Working Group consensus statement.

PubMed

Memish, Z A; Arabi, Y M; Ahmed, Q A; Al Jahdali, H; Shibl, A M; Niederman, M S

2007-10-01

Community-acquired pneumonia (CAP) is diagnosed on the basis of a suggestive history and compatible physical findings and new infiltrates on a chest radiograph. No criteria or combination of criteria based on history and physical examination have been found to be gold standard. With the rise in elderly Gulf Cooperation Council (GCC) residents, CAP is likely to present with non-classical manifestations such as somnolence, new anorexia, and confusion and carries a worse outcome than CAP in their younger counterparts. Tuberculosis should be considered in the differential diagnosis of unresolving CAP in the GCC region. Diagnostic work up depends on severity of CAP, clinical course and underlying risk factors.

Bronchoalveolar carcinoma (adenocarcinoma) mimicking recurrent bacterial community-acquired pneumonia (CAP).

PubMed

Cunha, Burke A; Syed, Uzma; Mikail, Nardeen

2012-01-01

Depending on the community-acquired pneumonia (CAP) pathogen, host factors, and immune status, CAPs resolve on chest x-rays at different rates. CAPs that resolve more slowly than expected, or not at all, are termed "slowly or non-resolving CAPs." In contrast, recurrent CAPs may be due to host defense defects (eg, multiple myelomas) or post-obstructive bronchogenic carcinomas. There are a variety of noninfectious disorders that may mimic CAPs on chest x-ray: alveolar hemorrhage, pulmonary drug reactions, radiation pneumonitis, Wegener's granulomatosis, bronchiolitis obliterans organizing pneumonia, bronchogenic carcinomas, and lymphomas. Noninfectious mimics of recurrent CAPs include congestive heart failure, pulmonary emboli, infarctions, sarcoidosis, and systemic lupus erythematosus pneumonitis. We present the case of a middle-aged man who presented with recurrent right middle lobe and right lower lobe CAPs. Diagnostic bronchoscopy showed no bronchial obstruction, but open lung biopsy showed bronchoalveolar carcinoma (well-differentiated adenocarcinoma). Bronchoalveolar carcinomas presenting as post-obstructive or recurrent CAPs are rare because the spread is along tissue planes and not endobronchially. The case described demonstrates a rare cause of bronchogenic carcinoma mimicking recurrent CAP. Copyright © 2012 Elsevier Inc. All rights reserved.

Investigations of vegetation and soils information contained in LANDSAT Thematic Mapper and Multispectral Scanner data

NASA Technical Reports Server (NTRS)

Crist, E. P.; Laurin, R.; Colwell, J. E.; Kauth, R. J.

1984-01-01

An extension of the TM tasseled cap transformation to reflectance factor data is presented, and the basic concepts underlying the tasseled cap transformations are described. The ratio of TM bands 5 and 7, and TM tasseled cap wetness, are both shown to offer promise of direct detection of available soil moisture. Some effects of organic matter and other soil characteristics or constituents on TM tasseled cap spectral response are also considered.

The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

PubMed

Mathaes, Roman; Mahler, Hanns-Christian; Buettiker, Jean-Pierre; Roehl, Holger; Lam, Philippe; Brown, Helen; Luemkemann, Joerg; Adler, Michael; Huwyler, Joerg; Streubel, Alexander; Mohl, Silke

2016-02-01

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process. Copyright © 2015 Elsevier B.V. All rights reserved.

Resident CAPS on dense-core vesicles docks and primes vesicles for fusion

PubMed Central

Kabachinski, Greg; Kielar-Grevstad, D. Michelle; Zhang, Xingmin; James, Declan J.; Martin, Thomas F. J.

2016-01-01

The Ca2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells requires a priming step during which SNARE protein complexes assemble. CAPS (aka CADPS) is one of several factors required for vesicle priming; however, the localization and dynamics of CAPS at sites of exocytosis in live neuroendocrine cells has not been determined. We imaged CAPS before, during, and after single-vesicle fusion events in PC12 cells by TIRF micro­scopy. In addition to being a resident on cytoplasmic dense-core vesicles, CAPS was present in clusters of approximately nine molecules near the plasma membrane that corresponded to docked/tethered vesicles. CAPS accompanied vesicles to the plasma membrane and was present at all vesicle exocytic events. The knockdown of CAPS by shRNA eliminated the VAMP-2–dependent docking and evoked exocytosis of fusion-competent vesicles. A CAPS(ΔC135) protein that does not localize to vesicles failed to rescue vesicle docking and evoked exocytosis in CAPS-depleted cells, showing that CAPS residence on vesicles is essential. Our results indicate that dense-core vesicles carry CAPS to sites of exocytosis, where CAPS promotes vesicle docking and fusion competence, probably by initiating SNARE complex assembly. PMID:26700319

Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China.

PubMed

Liu, Ya-Fen; Gao, Yan; Chen, Mei-Fang; Cao, Bin; Yang, Xiao-Hua; Wei, Lai

2013-07-09

Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.

Passive radon/thoron personal dosimeter using an electrostatic collector and a diffused-junction detector

NASA Astrophysics Data System (ADS)

Bigu, J.; Raz, R.

1985-01-01

A solid-state alpha dosimeter has been designed and tested suitable for personal and environmental radon/thoron monitoring. The dosimeter basically consists of an electrostatic collector and an alpha-particle counting system with spectroscopy capabilities. The sensitive volume (˜20 cm3) of the electrostatic collector consists of a cylindrically shaped metal wire screen and a diffused-junction silicon alpha-detector covered with a thin aluminized Mylar sheet. A dc voltage (˜500 V) is applied between the wire screen and the Mylar sheet, with the latter held at negative potential relative to the former. Data can be retrieved during or after sampling by means of a microcomputer (Epson HX20) via a RS-232 communication interface unit. The dosimeter has been calibrated in a large (26 m3) radon/thoron test facility. A linear relationship was found between the dosimeter's alpha-count and both radon gas concentration and radon daughter working level. The dosimeter is mounted on top of an ordinary miner's cap lamp battery and is ideally suited for personal monitoring in underground uranium mines and other working areas. The dosimeter presented here is a considerably improved version of an earlier prototype.

Aging and behavior of functional TiO2 nanoparticles in aqueous environment.

PubMed

Lu, Huiting; Dong, Haifeng; Fan, Wenhong; Zuo, Jinxing; Li, Xiaomin

2017-03-05

Nanoparticles are usually functionalized with various surface capping moieties in practical applications. Understand the behavior and fate of them is critical to evaluate or even predict their risk to environment. However, little attention has been denoted on this issue until now. Using three commercial TiO 2 nanoparticles with different capping moieties, their aging procedures and corresponding change as well as their byproducts were systematically studied. Comprehensive microscopic and spectrometric measurements demonstrated a capping agent-dependent with the aging procedure. All the aging agents exhibited sharp change in morphologies compared to the fresh counterparts. The degraded degree and surface properties including surface charge and hydrophobicity of the functional TiO 2 nanoparticles were varied depended on the capping moieties. Furthermore, the behaviors of these byproducts in various background media had also been investigated. Contrastively, environment factors such as pH, electrolyte valence, and humic acid regardless of capping moieties govern the behavior of these byproducts, despite of the capping moieties slightly affect the point of zero charge. This study highlights the influence of the capping moieties and environmental factors to the transformation progress of functional nanomaterials in environment exposure, which contributes to design and assess the environmental risk of other analogous functional nanoparticles in practical application. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of type I sensitization to alpha-gal in forest service employees and hunters.

PubMed

Fischer, J; Lupberger, E; Hebsaker, J; Blumenstock, G; Aichinger, E; Yazdi, A S; Reick, D; Oehme, R; Biedermann, T

2017-10-01

The production of IgE molecules specific to the carbohydrate galactose-α-1,3-galactose (alpha-gal) is known to induce delayed anaphylaxis against mammalian meat. Tick bites constitute the primary sensitization source, as ticks transfer alpha-gal in their saliva to a host during a bite. The reported prevalence of alpha-gal-specific IgE (alpha-gal-sIgE) positivity varies between different populations from diverse geographic regions. To investigate the prevalence of alpha-gal-sIgE positivity in a population of forest service employees who are highly exposed to ticks in comparison with a residential population and a historic sample. A cross-sectional study evaluating 300 forest service employees and hunters from southwest Germany was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. The prevalence of alpha-gal-sIgE-positive individuals was compared with a matched cohort composed of a residential population and blood samples from forest service employees collected 15 years ago. In the study population, the prevalence of alpha-gal-sIgE-positive (≥0.10 kU A /L) individuals was 35.0%, whereas the prevalence of individuals with alpha-gal-sIgE levels ≥0.35 kU A /L was 19.3%. Alpha-gal-sIgE positivity was associated with total IgE levels and recent tick bites. Mammalian meat-induced delayed anaphylaxis was found in 8.6% of the participants with alpha-gal-sIgE levels ≥0.35 kU A /L. For forest service employees and hunters, the odds ratio for alpha-gal-sIgE positivity was 2.48 compared to the residential population. The prevalence of alpha-gal-sIgE positivity in the current and historic cohort was comparable. Forest service employees and hunters compose a population with a high prevalence of alpha-gal-sIgE positivity and carry a considerable risk of red meat allergy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Updated greenhouse gas and criteria air pollutant emission factors and their probability distribution functions for electricity generating units

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

Cai, H.; Wang, M.; Elgowainy, A.

Greenhouse gas (CO{sub 2}, CH{sub 4} and N{sub 2}O, hereinafter GHG) and criteria air pollutant (CO, NO{sub x}, VOC, PM{sub 10}, PM{sub 2.5} and SO{sub x}, hereinafter CAP) emission factors for various types of power plants burning various fuels with different technologies are important upstream parameters for estimating life-cycle emissions associated with alternative vehicle/fuel systems in the transportation sector, especially electric vehicles. The emission factors are typically expressed in grams of GHG or CAP per kWh of electricity generated by a specific power generation technology. This document describes our approach for updating and expanding GHG and CAP emission factors inmore » the GREET (Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation) model developed at Argonne National Laboratory (see Wang 1999 and the GREET website at http://greet.es.anl.gov/main) for various power generation technologies. These GHG and CAP emissions are used to estimate the impact of electricity use by stationary and transportation applications on their fuel-cycle emissions. The electricity generation mixes and the fuel shares attributable to various combustion technologies at the national, regional and state levels are also updated in this document. The energy conversion efficiencies of electric generating units (EGUs) by fuel type and combustion technology are calculated on the basis of the lower heating values of each fuel, to be consistent with the basis used in GREET for transportation fuels. On the basis of the updated GHG and CAP emission factors and energy efficiencies of EGUs, the probability distribution functions (PDFs), which are functions that describe the relative likelihood for the emission factors and energy efficiencies as random variables to take on a given value by the integral of their own probability distributions, are updated using best-fit statistical curves to characterize the uncertainties associated with GHG and CAP emissions in life-cycle modeling with GREET.« less

Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.

PubMed

Ribeiro, Maisa; Teixeira, Sarah R; Azevedo, Monarko N; Fraga, Ailton C; Gontijo, Antônio Pm; Vêncio, Eneida F

2017-04-01

To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

Revealing the X-Ray Emission Processes of Old Rotation-Powered Pulsars: XMM-Newton Observations of PSR B0950+08, PSR B0823+26 and PSR J2043+2740

NASA Technical Reports Server (NTRS)

Becker, Werner; Weisskopf, Martin C.; Tenant, Allyn F.; Jessmer, Axel; Zhang, Shiang N.

2004-01-01

We have completed part of a program to study the X-ray emission properties of old rotation-powered pulsars with XMM-Newton in order to probe and identify the origin of their X radiation. The X-ray emission from these old pulsars is largely dominated by non-thermal processes. None of the observed spectra required adding a thermal component consisting of either a hot polar cap or surface cooling emission to model the data. The energy spectrum of PSR B0950+08 is best described by a single power law of photon-index alpha = 1.93(sup +0.14)(sub -0.12). Three-sigma temperature upper limits for possible contributions from a heated polar cap or the whole neutron star surface are T(sup infinity)(sub pc) < 0.87 x 10(exp 6) K and T(sup infinity)(sub s) < 0.48 x 10(exp 6) K, respectively. We also find that the X-ray emission from PSR B0950+08 is pulsed with two peaks per rotation period. The phase separation between the two X-ray peaks is approx. 144 deg (maximum to maximum) which is similar to the pulse peak separation observed in the radio band at 1.4 GHz. The fraction of X-ray pulsed photons is approx. 30%. A phase resolved spectral analysis confirms the nonthermal nature of the pulsed emission and finds power law slopes of alpha = 2.4(sup +0.52)(sub -0.42) and alpha = 1.93(sup +0.29)(sub -0.24) for the pulse peaks P1 and P2, respectively. The spectral emission properties observed for PSR B0823+26 are similar to those of PSR B0950+08. Its energy spectrum is very well described by a single power law with photon-index alpha = 2.5(sup +0.52)(sub -0.24. Three-sigma temperature upper limits for thermal contributions from a hot polar cap or from the entire neutron star surface are T(sup infinity)(sub pc) < 1.17 x 10(exp 6) K and T(sup infinity)(sub s) < 0.5 x 10(exp 6) K, respectively. There is evidence for pulsed X-ray emission at the - 97% confidence level with a pulsed fraction of 49 +/- 22%. For PSR 52043+2740 we report the first detection of X-ray emission. A power law spectrum, or a combination of a thermal and a power law spectrum all yield acceptable descriptions of its X-ray spectrum. No X-ray pulses are detected from PSR J2043+2740 but the sensitivity is low - the 2-sigma pulsed fraction upper limit is 57% assuming a sinusoidal pulse profile.

DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

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

Kuzuhara, T.; Suganuma, M.; Oka, K.

2007-11-03

Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggestsmore » a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.« less

Link between microstability and macrostability of plasmas

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

Litwin, C.

A mechanism linking high-frequency microinstabilities and the low-frequencymacrostability is proposed. The coupling is provided by the time-averagedforce, ponderomotive force, of unstable high-frequency waves. Two specificexamples of this phenomenon are discussed. It is shown that an..cap alpha..-particle loss-cone instability stabilizes the flute mode of anignited, axisymmetric mirror plasma. In tokamaks, the ion-whistler instability,driven by an anisotropic population of energetic particles, stabilizes theinternal kink mode for JET range of parameters.

Coupling ligand recognition to protein folding in an engineered variant of rabbit ileal lipid binding protein.

PubMed

Kouvatsos, Nikolaos; Meldrum, Jill K; Searle, Mark S; Thomas, Neil R

2006-11-28

We have engineered a variant of the beta-clam shell protein ILBP which lacks the alpha-helical motif that caps the central binding cavity; the mutant protein is sufficiently destabilised that it is unfolded under physiological conditions, however, it unexpectedly binds its natural bile acid substrates with high affinity forming a native-like beta-sheet rich structure and demonstrating strong thermodynamic coupling between ligand binding and protein folding.

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

Anderson, W.F.; Martinell, J.; Whitney, J.B. III

The group of diseases called the thalassemias is the largest single-gene health problem in the world according the World Health Organization. The thalassemias are lethal hereditary anemias in which the infants cannot make their own blood. Three mouse mutants are shown to be models of the human disease ..cap alpha..-thalassemia. However, since an additional gene is affected, these mutants represent a particularly severe condition in which death occurs in the homozygous embryo even before globin genes are activated. Phenotypic and genotypic characteristics are described. (ACR)

In-vivo measurement of lithium in the brain and other organs

DOEpatents

Vartsky, D.; Wielopolski, L.; LoMonte, A.F.; Ellis, K.J.; Cohn, S.H.

1983-08-26

An in-vivo method of measurement of the amount of lithium present in tissue and organs of breathing animals is described. The basis for the technique is the lithium-1 neutron interaction - /sup 6/Li(n,..cap alpha..)T. The lithium is irradiated with thermal neutrons to produce tritium atoms. The tritium diffuses into the tissues and is exhaled. By measuring the amount of tritium exhaled, the lithium concentration in the irradiated zone is determined.

Investigations in the ionosphere on Kosmos 378. VII. Simultaneous ground-based and satellite measurements of the parameters of the high latitude ionosphere

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

Afonin, V.V.; Gdalevich, G.L.; Gubskii, V.F.

1975-01-01

The parameters of the high-latitude ionospheric plasma at night were measured simultaneously in the winter of 1970 by Kosmos 378 and by the ground-based observatory at Noril'sk. A comparison of ground-based and satellite measurements showed good agreement of n/sub e/ when the Chapman approximation for the ..cap alpha..-layer and Jacchia's 1971 model of the upper atmosphere are used.

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

Akhtar, R.A.; Abdel-Latif, A.A.

Muscarinic cholinergic and ..cap alpha../sub 1/-adrenergic agonists provoke hydrolysis of PIP/sub 2/ into diacylglycerol (DG) and inositol trisphosphate (IP/sub 3/) in a wide variety of tissue. Recently, IP/sub 3/ has been shown to mobilize Ca/sup 2 +/ from ER in several permeabilized tissue preparations. Although rabbit cornea is enriched in ACh and NE, the physiological function of these neurotransmitters is unclear. The present studies were initiated to determine the effects of cholinergic and adrenergic agonists on PIP/sub 2/ turnover in the cornea. Addition of ACh or NE (50 ..mu..M each) to the /sup 32/P-labeled corneas for 10 min decreased themore » radioactivity in PIP/sub 2/ by 33 and 36%, and increased the radioactivity in phosphatidic acid by 72 and 52%, respectively. When the corneas were labeled with myo-(/sup 3/H)inositol, ACh and NE increased the accumulation of IP/sub 3/ by 92 and 48%, respectively. The effects of ACh and NE on phospholipid labeling and IP/sub 3/ accumulation were specifically inhibited by atropine (10 ..mu..M) and prazosin (10 ..mu..M), respectively. The data suggest the presence of muscarinic cholinergic and ..cap alpha../sub 1/-adrenergic receptors in the rabbit cornea. Furthermore, activation of these receptors leads to cleavage of PIP/sub 2/ into DG and IP/sub 3/ which may function as second messengers in this tissue.« less

ROAM mutations causing increased expression of yeast genes: their activation by signals directed toward conjugation functions and their formation by insertion of tyl repetitive elements

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

Errede, B.; Cardillo, T.S.; Wever, G.

1980-01-01

Mechanisms available to eukaryotic organisms for the coordinate regulation of gene expression are being examined by genetic and biochemical characterization of an unusual mutation, CYC7-H2, which causes overproduction of iso-2-cytochrome c in the yeast Saccharomyces cerevisiae. The CYC7-H2 mutation causes approximately a twenty fold overproduction of iso-2-cytochrome c in haploid strains but only a one to four fold overproduction in MATa/MAT..cap alpha.. diploid strains. This regulation of overproduction has been characterized as a response to signals controlling conjugation in yeast. The CYC7-H2 mutation is closely related to other regulatory mutations occurring at the cargA, cargB and DUR1,2 loci which aremore » the structural genes for arginase, ornithine transaminase and urea amidolyase, respectively. Similar to the CYC7-H2 mutation, the mutations designated cargA/sup +/O/sup h/, cargB/sup +/O/sup h/ and durO/sup h/ cause constitutive production of their respective gene products at much lower levels in MATa/MAT..cap alpha.. diploid strains than in the corresponding haploid strains. Observations characterizing the regulation of overproduction in the CYC7-H2 mutant are presented with the additional and parallel observations for the O/sup h/ mutants.« less

Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

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

Werb, Z.; Aggeler, J.

1978-04-01

We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continuedmore » presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.« less

CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions.

PubMed

James, Declan J; Kowalchyk, Judith; Daily, Neil; Petrie, Matt; Martin, Thomas F J

2009-10-13

Ca(2+)-dependent activator protein for secretion (CAPS) is an essential factor for regulated vesicle exocytosis that functions in priming reactions before Ca(2+)-triggered fusion of vesicles with the plasma membrane. However, the precise events that CAPS regulates to promote vesicle fusion are unclear. In the current work, we reconstituted CAPS function in a SNARE-dependent liposome fusion assay using VAMP2-containing donor and syntaxin-1/SNAP-25-containing acceptor liposomes. The CAPS stimulation of fusion required PI(4,5)P(2) in acceptor liposomes and was independent of Ca(2+), but Ca(2+) dependence was restored by inclusion of synaptotagmin. CAPS stimulated trans-SNARE complex formation concomitant with the stimulation of full membrane fusion at physiological SNARE densities. CAPS bound syntaxin-1, and CAPS truncations that competitively inhibited syntaxin-1 binding also inhibited CAPS-dependent fusion. The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane.

New serum biomarkers for prostate cancer diagnosis

PubMed Central

Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

2014-01-01

Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

Inhibitory spectrum of alpha 2-plasmin inhibitor.

PubMed Central

Saito, H; Goldsmith, G H; Moroi, M; Aoki, N

1979-01-01

alpha 2-Plasmin inhibitor (alpha 2PI) has been recently characterized as a fast-reacting inhibitor of plasmin in human plasma and appears to play an important role in the regulation of fibrinolysis in vivo. We have studied the effect of purified alpha 2PI upon various proteases participating in human blood coagulation and kinin generation. At physiological concentration (50 microgram/ml), alpha 2PI inhibited the clot-promoting and prekallikrein-activating activity of Hageman factor fragments, the amidolytic, kininogenase, and clot-promoting activities of plasma kallikrein, and the clot-promoting properties of activated plasma thromboplastin antecedent (PTA, Factor XIa) and thrombin. alpha 2PI had minimal inhibitory effect on surface-bound activated PTA and activated Stuart factor (Factor Xa). alpha 2PI did not inhibit the activity of activated Christmas factor (Factor IXa) or urinary kallikrein. Heparin (1.5-2.0 units/ml) did not enhance the inhibitory function of alpha 2PI. These results suggest that, like other plasma protease inhibitors, alpha 2PI possesses a broad in vitro spectrum of inhibitory properties. PMID:156364

Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids.

PubMed

Annavarapu, Srinivas; Nanda, Vikas

2009-09-22

Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Propensities for amino acids to occur in contiguous alpha(L) helices correlate with published thermodynamic scales for incorporation of D-amino acids into alpha(R) helices. Two backbone rules for terminating a left-handed helix are found: an alpha(R) conformation is disfavored at the amino terminus, and a beta(R) conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to alpha(L) helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. By examining left-handed alpha-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed alpha-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds.

Fluorescence microscopic analysis of antifungal effects of cold atmospheric pressure plasma in Saccharomyces cerevisiae.

PubMed

Itooka, Koki; Takahashi, Kazuo; Izawa, Shingo

2016-11-01

Cold atmospheric pressure plasma (CAP) has potential to be utilized as an alternative method for sterilization in food industries without thermal damage or toxic residues. In contrast to the bactericidal effects of CAP, information regarding the efficacy of CAP against eukaryotic microorganisms is very limited. Therefore, herein we investigated the effects of CAP on the budding yeast Saccharomyces cerevisiae, with a focus on the cellular response to CAP. The CAP treatment caused oxidative stress responses including the nuclear accumulation of the oxidative stress responsive transcription factor Yap1, mitochondrial fragmentation, and enhanced intracellular oxidation. Yeast cells also induced the expression of heat shock protein (HSP) genes and formation of Hsp104 aggregates when treated with CAP, suggesting that CAP denatures proteins. As phenomena unique to eukaryotic cells, the formation of cytoplasmic mRNP granules such as processing bodies and stress granules and changes in the intracellular localization of Ire1 were caused by the treatment with CAP, indicating that translational repression and endoplasmic reticulum (ER) stress were induced by the CAP treatment. These results suggest that the fungicidal effects of CAP are attributed to the multiple severe stresses.

Chios mastic treatment of patients with active Crohn’s disease

PubMed Central

Kaliora, Andriana C; Stathopoulou, Maria G; Triantafillidis, John K; Dedoussis, George VZ; Andrikopoulos, Nikolaos K

2007-01-01

AIM: To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn’s disease (CD). METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values ± SE and P < 0.05 was considered to indicate statistical significance. RESULTS: Patients exhibited significant reduction of CDAI (222.9 ± 18.7 vs 136.3 ± 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 ± 9.3 pg/mL vs 7.2 ± 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 ± 13.1 mg/mL vs 19.7 ± 5.5, P = 0.028). TAP was significantly increased (0.15 ± 0.09 vs 0.57 ± 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD. PMID:17278198

Effects of chronic plus acute prolonged stress on measures of coping style, anxiety, and evoked HPA-axis reactivity.

PubMed

Roth, Megan K; Bingham, Brian; Shah, Aparna; Joshi, Ankur; Frazer, Alan; Strong, Randy; Morilak, David A

2012-11-01

Exposure to psychological trauma is the precipitating factor for PTSD. In addition, a history of chronic or traumatic stress exposure is a predisposing risk factor. We have developed a Chronic plus Acute Prolonged Stress (CAPS) treatment for rats that models some of the characteristics of stressful events that can lead to PTSD in humans. We have previously shown that CAPS enhances acute fear responses and impairs extinction of conditioned fear. Further, CAPS reduced the expression of glucocorticoid receptors in the medial prefrontal cortex. In this study we examined the effects of CAPS exposure on behavioral stress coping style, anxiety-like behaviors, and acute stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Male Sprague-Dawley rats were exposed to CAPS treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/day, 14 days) followed on day 15 by a single 1-h session of sequential acute stressors (social defeat, immobilization, swim). After CAPS or control treatment, different groups were tested for shock probe defensive burying, novelty suppressed feeding, or evoked activation of adrenocorticotropic hormone (ACTH) and corticosterone release by an acute immobilization stress. CAPS resulted in a decrease in active burying behavior and an increase in immobility in the shock probe test. Further, CAPS-treated rats displayed increases in the latency to feed in the novelty suppressed feeding test, despite an increase in food intake in the home cage. CAPS treatment also reduced the HPA response to a subsequent acute immobilization stress. These results further validate CAPS treatment as a rat model of relevance to PTSD, and together with results reported previously, suggest that CAPS impairs fear extinction, shifts coping behavior from an active to a more passive strategy, increases anxiety, and alters HPA reactivity, resembling many aspects of human PTSD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Solid Rocket Booster Hydraulic Pump Port Cap Joint Load Testing

NASA Technical Reports Server (NTRS)

Gamwell, W. R.; Murphy, N. C.

2004-01-01

The solid rocket booster uses hydraulic pumps fabricated from cast C355 aluminum alloy, with 17-4 PH stainless steel pump port caps. Corrosion-resistant steel, MS51830 CA204L self-locking screw thread inserts are installed into C355 pump housings, with A286 stainless steel fasteners installed into the insert to secure the pump port cap to the housing. In the past, pump port cap fasteners were installed to a torque of 33 Nm (300 in-lb). However, the structural analyses used a significantly higher nut factor than indicated during tests conducted by Boeing Space Systems. When the torque values were reassessed using Boeing's nut factor, the fastener preload had a factor of safety of less than 1, with potential for overloading the joint. This paper describes how behavior was determined for a preloaded joint with a steel bolt threaded into steel inserts in aluminum parts. Finite element models were compared with test results. For all initial bolt preloads, bolt loads increased as external applied loads increased. For higher initial bolt preloads, less load was transferred into the bolt, due to external applied loading. Lower torque limits were established for pump port cap fasteners and additional limits were placed on insert axial deformation under operating conditions after seating the insert with an initial preload.

Psychometric Properties and Factor Structure of the German Version of the Clinician-Administered PTSD Scale for DSM-5.

PubMed

Müller-Engelmann, Meike; Schnyder, Ulrich; Dittmann, Clara; Priebe, Kathlen; Bohus, Martin; Thome, Janine; Fydrich, Thomas; Pfaltz, Monique C; Steil, Regina

2018-05-01

The Clinician-Administered PTSD Scale (CAPS) is a widely used diagnostic interview for posttraumatic stress disorder (PTSD). Following fundamental modifications in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5), the CAPS had to be revised. This study examined the psychometric properties (internal consistency, interrater reliability, convergent and discriminant validity, and structural validity) of the German version of the CAPS-5 in a trauma-exposed sample ( n = 223 with PTSD; n =51 without PTSD). The results demonstrated high internal consistency (αs = .65-.93) and high interrater reliability (ICCs = .81-.89). With regard to convergent and discriminant validity, we found high correlations between the CAPS severity score and both the Posttraumatic Diagnostic Scale sum score ( r = .87) and the Beck Depression Inventory total score ( r = .72). Regarding the underlying factor structure, the hybrid model demonstrated the best fit, followed by the anhedonia model. However, we encountered some nonpositive estimates for the correlations of the latent variables (factors) for both models. The model with the best fit without methodological problems was the externalizing behaviors model, but the results also supported the DSM-5 model. Overall, the results demonstrate that the German version of the CAPS-5 is a psychometrically sound measure.

Severe community-acquired Enterobacter pneumonia: a plea for greater awareness of the concept of health-care-associated pneumonia

PubMed Central

2011-01-01

Background Patients with Enterobacter community-acquired pneumonia (EnCAP) were admitted to our intensive care unit (ICU). Our primary aim was to describe them as few data are available on EnCAP. A comparison with CAP due to common and typical bacteria was performed. Methods Baseline clinical, biological and radiographic characteristics, criteria for health-care-associated pneumonia (HCAP) were compared between each case of EnCAP and thirty age-matched typical CAP cases. A univariate and multivariate logistic regression analysis was performed to determine factors independently associated with ENCAP. Their outcome was also compared. Results In comparison with CAP due to common bacteria, a lower leukocytosis and constant HCAP criteria were associated with EnCAP. Empiric antibiotic therapy was less effective in EnCAP (20%) than in typical CAP (97%) (p < 0.01). A delay in the initiation of appropriate antibiotic therapy (3.3 ± 1.6 vs. 1.2 ± 0.6 days; p < 0.01) and an increase in duration of mechanical ventilation (8.4 ± 5.2 vs. 4.0 ± 4.3 days; p = 0.01) and ICU stay were observed in EnCAP patients. Conclusions EnCAP is a severe infection which is more consistent with HCAP than with typical CAP. This retrospectively suggests that the application of HCAP guidelines should have improved EnCAP management. PMID:21569334

Tumor necrosis factor-alpha-independent downregulation of hepatic cholesterol 7alpha-hydroxylase gene in mice treated with lead nitrate.

PubMed

Kojima, Misaki; Sekikawa, Kenji; Nemoto, Kiyomitsu; Degawa, Masakuni

2005-10-01

We previously reported that lead nitrate (LN), an inducer of hepatic tumor necrosis factor-alpha (TNF-alpha), downregulated gene expression of cholesterol 7alpha-hydroxylase. Herein, to clarify the role of TNF-alpha in LN-induced downregulation of cholesterol 7alpha-hydroxylase, effects of LN on gene expression of hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) in TNF-alpha-knockout (KO) and TNF-alpha-wild-type (WT) mice were comparatively examined. Gene expression of hepatic Cyp7a1 in both WT and KO mice decreased to less than 5% of the corresponding controls at 6-12 h after treatment with LN (100 mumol/kg body weight, iv). Levels of hepatic TNF-alpha protein in either WT or KO mice were below the detection limit, although expression levels of the TNF-alpha gene markedly increased at 6 h in WT mice by LN treatment, but not in KO mice. In contrast, in both WT and KO mice, levels of hepatic IL-1beta protein, which is known to be a suppressor of the cholesterol 7alpha-hydroxylase gene in hamsters, were significantly increased 3-6 h after LN treatment. Furthermore, LN-induced downregulation of the Cyp7a1 gene did not necessarily result from altered gene expression of hepatic transcription factors, including positive regulators (liver X receptor alpha, retinoid X receptor alpha, fetoprotein transcription factor, and hepatocyte nuclear factor 4alpha) and a negative regulator small heterodimer partner responsible for expression of the Cyp7a1 gene. The present findings indicated that LN-induced downregulation of the Cyp7a1 gene in mice did not necessarily occur through a TNF-alpha-dependent pathway and might occur mainly through an IL-1beta-dependent pathway.

Polar cap models of gamma-ray pulsars: Emision from single poles of nearly aligned rotators

NASA Technical Reports Server (NTRS)

Daugherty, Joseph K.; Harding, Alice K.

1994-01-01

We compare a new Monte Carlo simulation of polar cap models for gamma-ray pulsars with observations of sources detected above 10 MeV by the Compton Observatory (CGRO). We find that for models in which the inclination of the magnetic axis is comparable to the angular radius of the polar cap, the radiation from a single cap may exhibit a pusle with either a single broad peak as in PSR 1706-44 and PSR 1055-52, or a doubly peaked profile comparable to those observed from the Crab, Vela and Geminga pulsars. In general, double pulses are seen by observers whose line of sight penetrates into the cap interior and are due to enhanced emission near the rim. For cascades induced by culvature radiation, increased rim emission occurs even when electrons are accelerated over the entire cap, since electrons from the interior escape along magnetic field lines with less curvature and hence emit less radiation. However, we obtain better fits to the duty cycles of observed profiles if we make the empirical assumption that acceleration occurs only near the rim. In either case, the model energy spectra are consistent with most of the observed sources. The beaming factors expected from nearly aligned rotators, based on standard estimates for the cap radius, imply that their luminosities need not be as large as in the case of orthogonal rotators. However, small beam angles are also a difficutly with this model because they imply low detection probablities. In either case the polar cap radius is a critical factor, and in this context we point out that plasma loading of the field lines should make the caps larger than the usual estimates based on pure dipole fields.

Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus.

PubMed

Del Bufalo, Donatella; Ciuffreda, Ludovica; Trisciuoglio, Daniela; Desideri, Marianna; Cognetti, Francesco; Zupi, Gabriella; Milella, Michele

2006-06-01

Mammalian target of rapamycin (mTOR) is increasingly recognized as a master regulator of fundamental cellular functions, whose deregulation may underlie neoplastic transformation and progression. Hence, mTOR has recently emerged as a promising target for therapeutic anticancer interventions in several human tumors, including breast cancer. Here, we investigated the antiangiogenic potential of temsirolimus (also known as CCI-779), a novel mTOR inhibitor currently in clinical development for the treatment of breast cancer and other solid tumors. Consistent with previous reports, sensitivity to temsirolimus-mediated growth inhibition varied widely among different breast cancer cell lines and was primarily due to inhibition of proliferation with little, if any, effect on apoptosis induction. In the HER-2 gene-amplified breast cancer cell line BT474, temsirolimus inhibited vascular endothelial growth factor (VEGF) production in vitro under both normoxic and hypoxic conditions through inhibition of hypoxia-stimulated hypoxia-inducible factor (HIF)-1alpha expression and transcriptional activation. Interestingly, these effects were also observed in the MDA-MB-231 cell line, independent of its inherent sensitivity to the growth-inhibitory effects of temsirolimus. A central role for mTOR (and the critical regulator of cap-dependent protein translation, eIF4E) in the regulation of VEGF production by BT474 cells was further confirmed using a small interfering RNA approach to silence mTOR and eIF4E protein expression. In addition to its effect on HIF-1alpha-mediated VEGF production, temsirolimus also directly inhibited serum- and/or VEGF-driven endothelial cell proliferation and morphogenesis in vitro and vessel formation in a Matrigel assay in vivo. Overall, these results suggest that antiangiogenic effects may substantially contribute to the antitumor activity observed with temsirolimus in breast cancer.

Child protective services utilization of child abuse pediatricians: A mixed methods study.

PubMed

Girardet, Rebecca; Bolton, Kelly; Hashmi, Syed; Sedlock, Emily; Khatri, Rachna; Lahoti, Nina; Lukefahr, James

2018-02-01

Several children's hospitals and medical schools across Texas have child abuse pediatricians (CAPs) who work closely with child protection workers to help ensure accurate assessments of the likelihood of maltreatment in cases of suspected abuse and neglect. Since the state does not mandate which cases should be referred to a CAP center, we were interested in studying factors that may influence workers' decisions to consult a CAP. We used a mixed methods study design consisting of a focus group followed by a survey. The focus group identified multiple factors that impact workers' decision-making, including several that involve medical providers. Responses from 436 completed surveys were compared to employees' number of years of employment and to the state region in which they worked. Focus group findings and survey responses revealed frustration among many workers when dealing with medical providers, and moderate levels of confidence in workers' abilities to make accurate determinations in cases involving medical information. Workers were more likely to refer cases involving serious physical injury than other types of cases. Among workers who reported prior interactions with a CAP, experiences and attitudes regarding CAPs were typically positive. The survey also revealed significant variability in referral practices by state region. Our results suggest that standard guidelines regarding CAP referrals may help workers who deal with cases involving medical information. Future research and quality improvement efforts to improve transfers of information and to better understand the qualities that CPS workers appreciate in CAP teams should improve CAP-CPS coordination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

PubMed

Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

1999-03-15

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

Prebiotic syntheses of vitamin coenzymes: II. Pantoic acid, pantothenic acid, and the composition of coenzyme A

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

Pantoic acid can by synthesized in good prebiotic yield from isobutyraldehyde or alpha-ketoisovaleric acid + H2CO + HCN. Isobutyraldehyde is the Strecker precursor to valine and alpha-ketoisovaleric acid is the valine transamination product. Mg2+ and Ca2+ as well as several transition metals are catalysts for the alpha-ketoisovaleric acid reaction. Pantothenic acid is produced from pantoyl lactone (easily formed from pantoic acid) and the relatively high concentrations of beta-alanine that would be formed on drying prebiotic amino acid mixtures. There is no selectivity for this reaction over glycine, alanine, or gamma-amino butyric acid. The components of coenzyme A are discussed in terms of ease of prebiotic formation and stability and are shown to be plausible choices, but many other compounds are possible. The gamma-OH of pantoic acid needs to be capped to prevent decomposition of pantothenic acid. These results suggest that coenzyme A function was important in the earliest metabolic pathways and that the coenzyme A precursor contained most of the components of the present coenzyme.

Origin of ice-rafted debris: Pleistocene paleoceanography in the western Arctic Ocean

NASA Astrophysics Data System (ADS)

Bischof, Jens; Clark, David L.; Vincent, Jean-Serge

1996-12-01

The composition of Pleistocene ice-rafted debris (IRD) >250 µm was analyzed quantitatively by grain counting in five sediment cores from the western central Arctic Ocean and compared with the composition of till clasts from NW Canada in order to determine the dropstone origin and to reconstruct the Pleistocene ice driftways and surface currents. The IRD composition alternates repeatedly between carbonate- and quartz-dominated assemblages, along with metamorphic and igneous rocks, clastic rocks, and some chert. The highest quartz content is found on the Alpha Ridge, while carbonate percentages are highest on the Northwind Ridge (NWR) and the Chukchi Cap. The source for the carbonates is the area around Banks and Victoria Islands and parts of northern Canada. Quartz most likely originated from the central Queen Elizabeth Islands. IRD on the southeastern Alpha Ridge is dominated by mafic crystalline rocks from northern Ellesmere Island and northern Greenland. At least six major glacial intervals are identified within the last 1 million years, during which icebergs drifted toward the west in the Beaufort Sea, straight northward in the central Arctic Ocean, and northeastward on the SE Alpha Ridge.

The Nematode Eukaryotic Translation Initiation Factor 4E/G Complex Works with a trans-Spliced Leader Stem-Loop To Enable Efficient Translation of Trimethylguanosine-Capped RNAs ▿ †

PubMed Central

Wallace, Adam; Filbin, Megan E.; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E.

2010-01-01

Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5′ end through the eIF4F initiation complex binding to the 5′ m7G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5′ end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m7G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5′ untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs. PMID:20154140

The nematode eukaryotic translation initiation factor 4E/G complex works with a trans-spliced leader stem-loop to enable efficient translation of trimethylguanosine-capped RNAs.

PubMed

Wallace, Adam; Filbin, Megan E; Veo, Bethany; McFarland, Craig; Stepinski, Janusz; Jankowska-Anyszka, Marzena; Darzynkiewicz, Edward; Davis, Richard E

2010-04-01

Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of TMG-capped mRNAs in nematodes requires the SL sequence. Here we define a core set of nucleotides and a stem-loop within the 22-nucleotide nematode SL that stimulate translation of mRNAs with a TMG cap. The structure and core nucleotides are conserved in other nematode SLs and correspond to regions of SL1 required for early Caenorhabditis elegans development. These SL elements do not facilitate translation of m(7)G-capped RNAs in nematodes or TMG-capped mRNAs in mammalian or plant translation systems. Similar stem-loop structures in phylogenetically diverse SLs are predicted. We show that the nematode eukaryotic translation initiation factor 4E/G (eIF4E/G) complex enables efficient translation of the TMG-SL RNAs in diverse in vitro translation systems. TMG-capped mRNA translation is determined by eIF4E/G interaction with the cap and the SL RNA, although the SL does not increase the affinity of eIF4E/G for capped RNA. These results suggest that the mRNA 5' untranslated region (UTR) can play a positive and novel role in translation initiation through interaction with the eIF4E/G complex in nematodes and raise the issue of whether eIF4E/G-RNA interactions play a role in the translation of other eukaryotic mRNAs.

Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation*

PubMed Central

Timpano, Sara; Uniacke, James

2016-01-01

Translation initiation is a focal point of translational control and requires the binding of eIF4E to the 5′ cap of mRNA. Under conditions of extreme oxygen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap-dependent translation mediated by a homolog of eIF4E, eIF4E2. This homolog forms a complex with the oxygen-regulated hypoxia-inducible factor 2α and can escape translation repression. This complex mediates cap-dependent translation under cell culture conditions of 1% oxygen (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (ambient air). However, emerging evidence suggests that culturing cells in ambient air, or “normoxia,” is far from physiological or “normal.” In fact, oxygen in human tissues ranges from 1–11% or “physioxia.” Here we show that two distinct modes of cap-dependent translation initiation are active during physioxia and act on separate pools of mRNAs. The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polysome association and the status of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxia-inducible factor 2α expression (eIF4E2-dependent). We have identified oxygen conditions where eIF4E is the dominant cap-binding protein (21% normoxia or standard cell culture conditions), where eIF4E2 is the dominant cap-binding protein (1% hypoxia or ischemic diseases and cancerous tumors), and where both cap-binding proteins act simultaneously to initiate the translation of distinct mRNAs (1–11% physioxia or during development and stem cell differentiation). These data suggest that the physioxic proteome is generated by initiating translation of mRNAs via two distinct but complementary cap-binding proteins. PMID:27002144

Polysaccharide from black currant (Ribes nigrum L.) stimulates dendritic cells through TLR4 signaling.

PubMed

Ashigai, Hiroshi; Komano, Yuta; Wang, Guanying; Kawachi, Yasuji; Sunaga, Kazuko; Yamamoto, Reiko; Takata, Ryoji; Miyake, Mika; Yanai, Takaaki

2017-01-01

Black currant ( Ribes nigrum ) has various beneficial properties for human health. In particular, polysaccharide from black currant was found to be an immunostimulating food ingredient and was reported to have antitumor activity in a mouse model. We named it cassis polysaccharide (CAPS). In a previous study, CAPS administration caused tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production in vitro and in vivo , but the immunological mechanism of CAPS was not demonstrated. In this study, we revealed the CAPS immunostimulating mechanism in vitro . First, we found that CAPS activated dendritic cells (DCs). Second, we investigated whether it depends on Toll-like receptor 4 (TLR4) and myeloid differentiation primary response (Myd). We concluded that CAPS stimulates DCs through Myd88 depending TLR4 signaling and activates Th1-type cytokine release.

Tumor necrosis factor-alpha inhibits stem cell factor-induced proliferation of human bone marrow progenitor cells in vitro. Role of p55 and p75 tumor necrosis factor receptors.

PubMed Central

Rusten, L S; Smeland, E B; Jacobsen, F W; Lien, E; Lesslauer, W; Loetscher, H; Dubois, C M; Jacobsen, S E

1994-01-01

Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes with a number of hematopoietic growth factors. However, little is known about growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown to act as a bidirectional regulator of myeloid cell proliferation and differentiation. This study was designed to examine interactions between TNF-alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells. Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF receptor, whereas little or no inhibition was signaled through the p75 TNF receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+ bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event as well. Images PMID:7518828

Regulation of nicotinic acetylcholine receptor phosphorylation in rat myotubes by forskolin and cAMP

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

Miles, K.; Anthony, D.T.; Rubin, L.L.

1987-09-01

The nicotinic acetylcholine receptor (Ac-ChoR) from rat myotubes prelabeled in culture with (/sup 32/P)orthophosphate was isolated by acetylcholine affinity chromatography followed by immunoaffinity chromatography. Under basal conditions, the nicotinic AcChoR was shown to be phosphorylated in situ on the ..beta.. and delta subunits. Regulation of AcChoR phosphorylation by cAMP-dependent protein kinase was explored by the addition of forskolin or cAMP analogues to prelabeled cell cultures. Forskolin, an activator of adenylate cyclase, stimulated the phosphorylation of the delta subunit 20-fold over basal phosphorylation and induced phosphorylation of the ..cap alpha.. subunit. The effect of forskolin was dose dependent with a half-maximalmore » response at 8 ..mu..M in the presence of 35 ..mu..M Ro 20-1724, a phosphodiesterase inhibitor. Stimulation of delta subunit phosphorylation was almost maximal within 5 min, whereas stimulation of ..cap alpha.. subunit phosphorylation was not maximal until 45 min after forskolin treatment. Stimulation of AcChoR phosphorylation by 8-benzylthioadenosine 3',5'-cyclic monophosphate was identical to that obtained by forskolin. Two-dimensional thermolytic phosphopeptide maps of the delta subunit revealed a single major phosphopeptide. These results correlate closely with the observed effects of forskolin on AcChoR desensitization in muscle and suggest that cAMP-dependent phosphorylation of the delta subunit increases the rate of AcChoR desensitization in rat myotubes.« less

Cirrus Airframe Parachute System and Odds of a Fatal Accident in Cirrus Aircraft Crashes.

PubMed

Alaziz, Mustafa; Stolfi, Adrienne; Olson, Dean M

2017-06-01

General aviation (GA) accidents have continued to demonstrate high fatality rates. Recently, ballistic parachute recovery systems (BPRS) have been introduced as a safety feature in some GA aircraft. This study evaluates the effectiveness and associated factors of the Cirrus Airframe Parachute System (CAPS) at reducing the odds of a fatal accident in Cirrus aircraft crashes. Publicly available Cirrus aircraft crash reports were obtained from the National Transportation Safety Board (NTSB) database for the period of January 1, 2001-December 31, 2016. Accident metrics were evaluated through univariate and multivariate analyses regarding odds of a fatal accident and use of the parachute system. Included in the study were 268 accidents. For CAPS nondeployed accidents, 82 of 211 (38.9%) were fatal as compared to 8 of 57 (14.0%) for CAPS deployed accidents. After controlling for all other factors, the adjusted odds ratio for a fatal accident when CAPS was not deployed was 13.1. The substantial increased odds of a fatal accident when CAPS was not deployed demonstrated the effectiveness of CAPS at providing protection of occupants during an accident. Injuries were shifted from fatal to serious or minor with the use of CAPS and postcrash fires were significantly reduced. These results suggest that BPRS could play a significant role in the next major advance in improving GA accident survival.Alaziz M, Stolfi A, Olson DM. Cirrus Airframe Parachute System and odds of a fatal accident in Cirrus aircraft crashes. Aerosp Med Hum Perform. 2017; 88(6):556-564.

Characterization of NLRP3 variants in Japanese cryopyrin-associated periodic syndrome patients.

PubMed

Ohnishi, Hidenori; Teramoto, Takahide; Iwata, Hiroaki; Kato, Zenichiro; Kimura, Takeshi; Kubota, Kazuo; Nishikomori, Ryuta; Kaneko, Hideo; Seishima, Mariko; Kondo, Naomi

2012-04-01

The etiology of cryopyrin-associated periodic syndrome (CAPS) is caused by germline gene mutations in NOD-like receptor family, pryin domain containing 3 (NLRP3)/cold-induced autoinflammatory syndrome 1 (CIAS1). CAPS includes diseases with various severities. The aim of this study was to characterize patients according to the disease severity of CAPS. Five Japanese patients with four kinds of gene variations in NLRP3 were found and diagnosed as CAPS or juvenile idiopathic arthritis. Two mutations in NLRP3, Y563N and E688K, found in CAPS patients exhibit significant positive activities in the nuclear factor-κB reporter gene assay. Increased serum interleukin (IL)-18 levels were only observed in severe cases of CAPS. In mild cases of CAPS, the serum IL-18 levels were not increased, although lipopolysaccharide- or hypothermia-enhanced IL-1β and IL-18 production levels by their peripheral blood mononuclear cells were detectable. This series of case reports suggests that a combination of in vitro assays could be a useful tool for the diagnosis and characterization of the disease severity of CAPS.

Association between cardiovascular risk profiles and the presence and extent of different types of coronary atherosclerotic plaque as detected by multidetector computed tomography.

PubMed

Bamberg, Fabian; Dannemann, Nina; Shapiro, Michael D; Seneviratne, Sujith K; Ferencik, Maros; Butler, Javed; Koenig, Wolfgang; Nasir, Khurram; Cury, Ricardo C; Tawakol, Ahmed; Achenbach, Stephan; Brady, Thomas J; Hoffmann, Udo

2008-03-01

To assess the association between cardiovascular risk factors and extent of noncalcified- (NCAP), mixed- (MCAP), and calcified coronary atherosclerotic plaque (CAP). In this cross-sectional study, we included consecutive subjects who presented with chest pain but had no history of coronary artery disease (CAD) and did not develop acute coronary syndrome. Contrast-enhanced 64-slice coronary MDCT was performed to determine the presence of NCAP, MCAP, and CAP for each coronary segment. Among 195 patients (91 women, mean age: 54.6+/-12.0) exclusively NCAP was detected in 11 patients (5.6%). The extent of NCAP decreased and the extent of MCAP and CAP increased with age (P=0.06, P=0.02, and P=0.13, respectively). Hyperlipidemia and family history of CAD were associated with the extent of NCAP after adjusting for other risk factors (P=0.02 and P=0.04, respectively) or for the extent of MCAP and CAP (P=0.02 and P=0.05, respectively). Our data suggest that only a small proportion of individuals have exclusively NCAP and indicate that the relation of NCAP and CAP changes with age. Among individual risk factors, hyperlipidemia and family history of CAD may be associated with the extent of NCAP. Larger observational trials are necessary to confirm our findings.

Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities.

PubMed

Tan, Shyh-Han; Petrovics, Gyorgy; Srivastava, Shiv

2018-04-22

Prostate cancer (CaP) is the most commonly diagnosed non-cutaneous cancer and the second leading cause of male cancer deaths in the United States. Among African American (AA) men, CaP is the most prevalent malignancy, with disproportionately higher incidence and mortality rates. Even after discounting the influence of socioeconomic factors, the effect of molecular and genetic factors on racial disparity of CaP is evident. Earlier studies on the molecular basis for CaP disparity have focused on the influence of heritable mutations and single-nucleotide polymorphisms (SNPs). Most CaP susceptibility alleles identified based on genome-wide association studies (GWAS) were common, low-penetrance variants. Germline CaP-associated mutations that are highly penetrant, such as those found in HOXB13 and BRCA2 , are usually rare. More recently, genomic studies enabled by Next-Gen Sequencing (NGS) technologies have focused on the identification of somatic mutations that contribute to CaP tumorigenesis. These studies confirmed the high prevalence of ERG gene fusions and PTEN deletions among Caucasian Americans and identified novel somatic alterations in SPOP and FOXA1 genes in early stages of CaP. Individuals with African ancestry and other minorities are often underrepresented in these large-scale genomic studies, which are performed primarily using tumors from men of European ancestry. The insufficient number of specimens from AA men and other minority populations, together with the heterogeneity in the molecular etiology of CaP across populations, challenge the generalizability of findings from these projects. Efforts to close this gap by sequencing larger numbers of tumor specimens from more diverse populations, although still at an early stage, have discovered distinct genomic alterations. These research findings can have a direct impact on the diagnosis of CaP, the stratification of patients for treatment, and can help to address the disparity in incidence and mortality of CaP. This review examines the progress of understanding in CaP genetics and genomics and highlight the need to increase the representation from minority populations.

p130Cas-associated Protein (p140Cap) as a New Tyrosine-phosphorylated Protein Involved in Cell Spreading

PubMed Central

Di Stefano, Paola; Cabodi, Sara; Erba, Elisabetta Boeri; Margaria, Valentina; Bergatto, Elena; Giuffrida, Maria Gabriella; Silengo, Lorenzo; Tarone, Guido; Turco, Emilia; Defilippi, Paola

2004-01-01

Integrin-mediated cell adhesion stimulates a cascade of signaling pathways that control cell proliferation, migration, and survival, mostly through tyrosine phosphorylation of signaling molecules. p130Cas, originally identified as a major substrate of v-Src, is a scaffold molecule that interacts with several proteins and mediates multiple cellular events after cell adhesion and mitogen treatment. Here, we describe a novel p130Cas-associated protein named p140Cap (Cas-associated protein) as a new tyrosine phosphorylated molecule involved in integrin- and epidermal growth factor (EGF)-dependent signaling. By affinity chromatography of human ECV304 cell extracts on a MBP-p130Cas column followed by mass spectrometry matrix-assisted laser desorption ionization/time of flight analysis, we identified p140Cap as a protein migrating at 140 kDa. We detected its expression in human, mouse, and rat cells and in different mouse tissues. Endogenous and transfected p140Cap proteins coimmunoprecipitate with p130Cas in ECV304 and in human embryonic kidney 293 cells and associate with p130Cas through their carboxy-terminal region. By immunofluorescence analysis, we demonstrated that in ECV304 cells plated on fibronectin, the endogenous p140Cap colocalizes with p130Cas in the perinuclear region as well as in lamellipodia. In addition p140Cap codistributes with cortical actin and actin stress fibers but not with focal adhesions. We also show that p140Cap is tyrosine phosphorylated within 15 min of cell adhesion to integrin ligands. p140Cap tyrosine phosphorylation is also induced in response to EGF through an EGF receptor dependent-mechanism. Interestingly expression of p140Cap in NIH3T3 and in ECV304 cells delays the onset of cell spreading in the early phases of cell adhesion to fibronectin. Therefore, p140Cap is a novel protein associated with p130Cas and actin cytoskeletal structures. Its tyrosine phosphorylation by integrin-mediated adhesion and EGF stimulation and its involvement in cell spreading on matrix proteins suggest that p140Cap plays a role in controlling actin cytoskeleton organization in response to adhesive and growth factor signaling. PMID:14657239

Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD

DTIC Science & Technology

2013-08-01

dependent translation is a causative factor in autism spectrum disorder (ASD). To test this hypothesis, we have been studying transgenic mice that...determine whether eIF4E transgenic mice display cellular and molecular abnormalities due to excessive cap-dependent translation. mice. Our studies ...will provide information concerning whether overexpression of eIF4E is a biological risk factor for ASD. Our studies also will provide important

Measuring the environmental awareness of young farmers

NASA Astrophysics Data System (ADS)

Kountios, G.; Ragkos, A.; Padadavid, G.; Hadjimitsis, D.

2017-09-01

Young farmers in Europe, especially the beneficiaries of Common Agricultural Policy (CAP) funding schemes, are considered as the ones who could ensure the sustainability of the European Model of Agriculture. Economic efficiency and competitiveness, aversion of depopulation of rural areas and environmental protection constitute some of the key objectives of the CAP and young farmers are expected to play a role to all of them. This study proposes a way of measuring the potential of young farmers to contribute to the latter objectives of the CAP by estimating their environmental attitudes. Data from a questionnaire survey of 492 Greek young farmers were used to design a latent construct measuring their environmental attitudes. The latent construct was designed by means of an Explanatory Factor Analysis (EFA) using the responses to a set of 12 Likert-scale items. The results the EFA yielded a latent construct with three factors related to "Environmental pollution and policies (EPP)", "Environmental factors and food quality (EFF)" and "Farming practices and the environment". These results were validated through a CFA where 8 items in total were categorized in the three factors (latent variables). The utilization of the latent construct for the effective implementation of CAP measures could ameliorate the relationships of agriculture and environment in general.

Effective control of modified palygorskite to NH4+-N release from sediment.

PubMed

Chen, Lei; Zheng, Tianyuan; Zhang, Junjie; Liu, Jie; Zheng, Xilai

2014-01-01

Sediment capping is an in situ treatment technology that can effectively restrain nutrient and pollutant release from the sediment in lakes and reservoirs. Research on sediment capping has focused on the search for effective, non-polluting and affordable capping materials. The efficiency and mechanism of sediment capping with modified palygorskite in preventing sediment ammonia nitrogen (NH4+-N) release to surface water were investigated through a series of batch and sediment capping experiments. Purified palygorskite and different types of modified palygorskite (i.e. heated, acid-modified and NaCI-modified palygorskite) were used in this investigation. Factors affecting control efficiency, including the temperature, thickness and grain size of the capping layer, were also analysed. The batch tests showed that the adsorption of NH4+-N on modified palygorskite achieved an equilibration in the initial 45 min, and the adsorption isotherm followed the Freundlich equation. Sediment capping experiments showed that compared with non-capped condition, covering the sediment with modified palygorskite and sand both inhibited NH4+-N release to the overlying water. Given its excellent chemical stability and strong adsorption, heated palygorskite, which has a NH4+-N release inhibition ratio of 41.3%, is a more effective sediment capping material compared with sand. The controlling effectiveness of the modified palygorskite increases with thicker capping layer, lower temperature and smaller grain size of the capping material.

Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

NASA Technical Reports Server (NTRS)

Reed, G. L.; Matsueda, G. R.; Haber, E.

1992-01-01

Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

C/EBP beta regulation of the tumor necrosis factor alpha gene.

PubMed Central

Pope, R M; Leutz, A; Ness, S A

1994-01-01

Activated macrophages contribute to chronic inflammation by the secretion of cytokines and proteinases. Tumor necrosis factor alpha (TNF alpha) is particularly important in this process because of its ability to regulate other inflammatory mediators in an autocrine and paracrine fashion. The mechanism(s) responsible for the cell type-specific regulation of TNF alpha is not known. We present data to show that the expression of TNF alpha is regulated by the transcription factor C/EBP beta (NF-IL6). C/EBP beta activated the TNF alpha gene promoter in cotransfection assays and bound to it at a site which failed to bind the closely related protein C/EBP alpha. Finally, a dominant-negative version of C/EBP beta blocked TNF alpha promoter activation in myeloid cells. Our results implicate C/EBP beta as an important regulator of TNF alpha by myelomonocytic cells. Images PMID:7929820

Integrative assessment of brain function in PTSD: brain stability and working memory.

PubMed

Veltmeyer, Melinda D; McFarlane, Alexander C; Bryant, Richard A; Mayo, Therese; Gordon, Evian; Clark, C Richard

2006-03-01

Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

Prostate cancer risk prediction in a urology clinic in Mexico.

PubMed

Liang, Yuanyuan; Messer, Jamie C; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

2013-10-01

To evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score ≥ 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC. Rates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13). Lack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics. Copyright © 2013 Elsevier Inc. All rights reserved.

Bone Factors Regulating the Osteotropism of Metastatic Breast Cancer

DTIC Science & Technology

1999-10-01

C141: NIP3 (NIP3) C04j: rac-alpha serine/threonine kinase (rac-PK-alpha); protein kinase (PKB); c- akt ; aktl C09j: IEX-1L anti-death protein; PRG-l; DIF...fringe Elongation factor 1 alpha-I Transcription Factors GATA 3 Zinc finger GL IC CREB2/ATF4 IN-4-alpha NSEB (YB-i) C-1 Sinl NFkappaB p52 Trmansduction

Identification of the functional domain in the transcription factor RTEF-1 that mediates alpha 1-adrenergic signaling in hypertrophied cardiac myocytes.

PubMed

Ueyama, T; Zhu, C; Valenzuela, Y M; Suzow, J G; Stewart, A F

2000-06-09

Cardiac myocytes respond to alpha(1)-adrenergic receptor stimulation by a progressive hypertrophy accompanied by the activation of many fetal genes, including skeletal muscle alpha-actin. The skeletal muscle alpha-actin gene is activated by signaling through an MCAT element, the binding site of the transcription enhancer factor-1 (TEF-1) family of transcription factors. Previously, we showed that overexpression of the TEF-1-related factor (RTEF-1) increased the alpha(1)-adrenergic response of the skeletal muscle alpha-actin promoter, whereas TEF-1 overexpression did not. Here, we identified the functional domains and specific sequences in RTEF-1 that mediate the alpha(1)-adrenergic response. Chimeric TEF-1 and RTEF-1 expression constructs localized the region responsible for the alpha(1)-adrenergic response to the carboxyl-terminal domain of RTEF-1. Site-directed mutagenesis was used to inactivate eight serine residues of RTEF-1, not present in TEF-1, that are putative targets of alpha(1)-adrenergic-dependent kinases. Mutation of a single serine residue, Ser-322, reduced the alpha(1)-adrenergic activation of RTEF-1 by 70% without affecting protein stability, suggesting that phosphorylation at this serine residue accounts for most of the alpha(1)-adrenergic response. Thus, these results demonstrate that RTEF-1 is a direct target of alpha(1)-adrenergic signaling in hypertrophied cardiac myocytes.

mRNA Cap Methyltransferase, RNMT-RAM, Promotes RNA Pol II-Dependent Transcription.

PubMed

Varshney, Dhaval; Lombardi, Olivia; Schweikert, Gabriele; Dunn, Sianadh; Suska, Olga; Cowling, Victoria H

2018-05-01

mRNA cap addition occurs early during RNA Pol II-dependent transcription, facilitating pre-mRNA processing and translation. We report that the mammalian mRNA cap methyltransferase, RNMT-RAM, promotes RNA Pol II transcription independent of mRNA capping and translation. In cells, sublethal suppression of RNMT-RAM reduces RNA Pol II occupancy, net mRNA synthesis, and pre-mRNA levels. Conversely, expression of RNMT-RAM increases transcription independent of cap methyltransferase activity. In isolated nuclei, recombinant RNMT-RAM stimulates transcriptional output; this requires the RAM RNA binding domain. RNMT-RAM interacts with nascent transcripts along their entire length and with transcription-associated factors including the RNA Pol II subunits SPT4, SPT6, and PAFc. Suppression of RNMT-RAM inhibits transcriptional markers including histone H2BK120 ubiquitination, H3K4 and H3K36 methylation, RNA Pol II CTD S5 and S2 phosphorylation, and PAFc recruitment. These findings suggest that multiple interactions among RNMT-RAM, RNA Pol II factors, and RNA along the transcription unit stimulate transcription. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Influence of rate of force application during compression on tablet capping.

PubMed

Sarkar, Srimanta; Ooi, Shing Ming; Liew, Celine Valeria; Heng, Paul Wan Sia

2015-04-01

Root cause and possible processing remediation of tablet capping were investigated using a specially designed tablet press with an air compensator installed above the precompression roll to limit compression force and allow extended dwell time in the precompression event. Using acetaminophen-starch (77.9:22.1) as a model formulation, tablets were prepared by various combinations of precompression and main compression forces, set precompression thickness, and turret speed. The rate of force application (RFA) was the main factor contributing to the tablet mechanical strength and capping. When target force above the force required for strong interparticulate bond formation, the resultant high RFA contributed to more pronounced air entrapment, uneven force distribution, and consequently, stratified densification in compact together with high viscoelastic recovery. These factors collectively had contributed to the tablet capping. As extended dwell time assisted particle rearrangement and air escape, a denser and more homogenous packing in the die could be achieved. This occurred during the extended dwell time when a low precompression force was applied, followed by application of main compression force for strong interparticulate bond formation that was the most beneficial option to solve capping problem. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Discordance of physician clinical judgment vs. pneumonia severity index (PSI) score to admit patients with low risk community-acquired pneumonia: a prospective multicenter study.

PubMed

Marcos, Pedro J; Restrepo, Marcos I; González-Barcala, Francisco J; Soni, Nilam J; Vidal, Iria; Sanjuàn, Pilar; Llinares, Diego; Ferreira-Gonzalez, Lucía; Rábade, Carlos; Otero-González, Isabel; Marcos, Pedro; Verea-Hernando, Héctor

2017-06-01

The relationship between clinical judgment and the pneumonia severity index (PSI) score in deciding the site of care for patients with community-acquired pneumonia (CAP) has not been well investigated. The objective of the study was to determine the clinical factors that influence decision-making to hospitalize low-risk patients (PSI ≤2) with CAP. An observational, prospective, multicenter study of consecutive CAP patients was performed at five hospitals in Spain. Patients admitted with CAP and a PSI ≤2 were identified. Admitting physicians completed a patient-specific survey to identify the clinical factors influencing the decision to admit a patient. The reason for admission was categorized into 1 of 6 categories. We also assessed whether the reason for admission was associated with poorer clinical outcomes [intensive care unit (ICU) admission, 30-day mortality or readmission]. One hundred and fifty-five hospitalized patients were enrolled. Two or more reasons for admission were seen in 94 patients (60.6%), including abnormal clinical test results (60%), signs of clinical deterioration (43.2%), comorbid conditions (28.4%), psychosocial factors (28.4%), suspected H1N1 pneumonia (20.6%), and recent visit to the emergency department (ED) in the past 2 weeks (7.7%). Signs of clinical deterioration and abnormal clinical test results were associated with poorer clinical outcomes (P<0.005). Low-risk patients with CAP and a PSI ≤2 are admitted to the hospital for multiple reasons. Abnormal clinical test results and signs of clinical deterioration are two specific reasons for admission that are associated with poorer clinical outcomes in low risk CAP patients.

Risk factors for latex allergy in patients with spina bifida and latex sensitization.

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Mezzetti, P; Cianferoni, A; Danti, D A; Mercurella, A; Vierucci, A

1999-05-01

Some subjects with spina bifida (SB) and latex sensitization (cutaneous and/or serum IgE) can have clinical reactions, while others may have no symptoms after the exposure to latex products. This study was carried out to determine the risk factors associated with latex allergy in patients affected with SB and latex sensitization. Fifty-nine consecutive subjects affected with SB, besides answering a questionnaire, underwent a skin-prick test (SPT) to latex and the determination of the specific serum IgE (RAST CAP) to latex. The total serum IgE concentration was determined and SPT to common aero- and food-allergens, skin tests (prick + prick) with fresh foods (kiwi, pear, orange, pineapple, tomato, banana) and RAST CAP to the same foods tested by the prick + prick technique, were also performed. Fifteen out of the 59 subjects (25%) were sensitized to latex according to the presence of IgE to latex detected by SPT (nine patients) and/or RAST CAP (13 patients). Five out of the 15 sensitized patients (33%) suffered from clinical reactions to latex (urticaria, conjunctivitis, angioedema, rhinitis, bronchial asthma) while they were using latex gloves and while inflating latex balloons. In the 15 sensitized patients, the presence of specific latex seric IgE > 3.5 kU/L (>/= class 3), a positive latex SPT, an elevated total serum IgE, and a positive prick + prick and/or a positive RAST CAP to foods, were significant (P < 0.05) risk factors associated with latex symptoms. The other factors tested (age, gender, months of intermittent bladder catheterization, surgical procedures, SPT reactivity and clinical reactions to aero-allergens and food-allergens, skin tests for fresh foods, positive RAST CAP to foods) were not significantly different in symptomatic and asymptomatic patients. Significant risk factors for symptoms to latex in patients with SB and latex sensitization were a presence of specific IgE to latex > 3.5 kU/L, a more frequent positive latex SPT, elevated total IgE, and one or more positive prick + prick and/or RAST CAP to fresh foods.

Experimental demonstration of 24-Gb/s CAP-64QAM radio-over-fiber system over 40-GHz mm-wave fiber-wireless transmission.

PubMed

Zhang, Junwen; Yu, Jianjun; Chi, Nan; Li, Fan; Li, Xinying

2013-11-04

We propose and demonstrate a novel CAP-ROF system based on multi-level carrier-less amplitude and phase modulation (CAP) 64QAM with high spectrum efficiency for mm-wave fiber-wireless transmission. The performance of novel CAP modulation with high order QAM, for the first time, is investigated in the mm-wave fiber-wireless transmission system. One I/Q modulator is used for mm-wave generation and base-band signal modulation based on optical carrier suppression (OCS) and intensity modulation. Finally, we demonstrated a 24-Gb/s CAP-64QAM radio-over-fiber (ROF) system over 40-km stand single-mode-fiber (SMMF) and 1.5-m 38-GHz wireless transmission. The system operation factors are also experimentally investigated.

The catheter hub disinfection cap as esophageal foreign body.

PubMed

Tawfik, Kareem O; Myer, Charles M; Shikary, Tasneem; Goldschneider, Kenneth R

2015-12-01

Disinfection caps are increasingly being used to prevent catheter-associated bloodstream infections. These devices, designed for continuous passive disinfection of catheter hubs, are typically small and often brightly colored. As such, they have the potential to become pediatric airway and esophageal foreign bodies. We report two patients who developed esophageal foreign body following ingestion of disinfection caps. Given the increasing use of these devices, it is imperative that health care providers be aware of this potential iatrogenic problem. We propose that the use of disinfection caps may not be appropriate in pediatric patients with risk factors for foreign body ingestion. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

CAPS and Munc13: CATCHRs that SNARE Vesicles.

PubMed

James, Declan J; Martin, Thomas F J

2013-12-04

CAPS (Calcium-dependent Activator Protein for Secretion, aka CADPS) and Munc13 (Mammalian Unc-13) proteins function to prime vesicles for Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells. CAPS and Munc13 proteins contain conserved C-terminal domains that promote the assembly of SNARE complexes for vesicle priming. Similarities of the C-terminal domains of CAPS/Munc13 proteins with Complex Associated with Tethering Containing Helical Rods domains in multi-subunit tethering complexes (MTCs) have been reported. MTCs coordinate multiple interactions for SNARE complex assembly at constitutive membrane fusion steps. We review aspects of these diverse tethering and priming factors to identify common operating principles.

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-{alpha}-induced vascular endothelial dysfunction

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

Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.

2007-06-01

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-{alpha})-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-{alpha} induces various biological effects on vascular cells, TNF-{alpha} dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-{alpha} concentrations, we adopted the lower TNF-{alpha} (0.2 ng/ml) to rule out the possible involvement of other TNF-{alpha}-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-{alpha}-induced adhesion molecule expression and monocyte-endothelial monolayermore » binding. BSO attenuated the TNF-{alpha}-induced nuclear factor-kappaB (NF-{kappa}B) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-{alpha}. Inhibition of ERK, JNK, or NF-{kappa}B attenuates TNF-{alpha}-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-{alpha} induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-{kappa}B in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-{alpha}. Although AP-1 activation by the lower TNF-{alpha} was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-{alpha}-induced adhesion molecule expression.« less

Induction of Myeloid-Derived Suppressor Cells in Cryopyrin-Associated Periodic Syndromes.

PubMed

Ballbach, Marlene; Hall, Tobias; Brand, Alina; Neri, Davide; Singh, Anurag; Schaefer, Iris; Herrmann, Eva; Hansmann, Sandra; Handgretinger, Rupert; Kuemmerle-Deschner, Jasmin; Hartl, Dominik; Rieber, Nikolaus

2016-01-01

Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations in the NLRP3 gene leading to overproduction of IL-1β and other NLRP3 inflammasome products. Myeloid-derived suppressor cells (MDSCs) represent a novel innate immune cell subset capable of suppressing T-cell responses. As inflammasome products were previously found to induce MDSCs, we hypothesized that NLRP3 inflammasome-dependent factors induce the generation of MDSCs in CAPS. We studied neutrophilic MDSCs, their clinical relevance, and MDSC-inducing factors in a unique cohort of CAPS patients under anti-IL-1 therapy. Despite anti-IL-1 therapy and low clinical disease activity, CAPS patients showed significantly elevated MDSCs compared to healthy controls. MDSCs were functionally competent, as they suppressed polyclonal T-cell proliferation, as well as Th1 and Th17 responses. In addition, MDSCs decreased monocytic IL-1β secretion. Multiplex assays revealed a distinct pattern of MDSC-inducing cytokines, chemokines, and growth factors. Experimental analyses demonstrated that IL-1 cytokine family members and autoinflammation-associated alarmins differentially induced human MDSCs. Increased MDSCs might represent a novel autologous anti-inflammatory mechanism in autoinflammatory conditions and may serve as a future therapeutic target. © 2016 S. Karger AG, Basel.

Occurrence of rhombic prisms in some structures

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

Nyman, H.

1976-02-01

An ideal rhombic prism is defined as two regular trigonal prisms sharing a square face. In terms of such rhombic prisms, the structures of CrB and ..cap alpha..-PdCl/sub 2/, U/sub 3/Si/sub 2/ and Au/sub 3/Zn, and CoCa/sub 3/ and PdS are easily described. A network of rhombic prisms, with cubic symmetry, is also used to describe the structures of CoAs/sub 3/, Sc(OH)/sub 3/, WAl/sub 12/, and NaMn/sub 7/O/sub 12/.

In vitro histamine H/sub 2/-antagonist activity of the novel compound HUK 978

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

Coombes, J.D.; Norris, D.B.; Rising, T.J.

1985-11-04

Histamine stimulated adenylate cyclase from guinea-pig fundic mucosa and /sup 3/H-tiotidine binding in guinea-pig cerebral cortex were used to assess the in-vitro histamine H/sub 2/-activity of the novel H/sub 2/-antagonist HUK 978. The results showed that HUK 978 was a more potent H/sub 2/-antagonist than either cimetidine or ranitidine. HUK 978 was also shown to be devoid of activity at the histamine H-/sub 1/-receptor, the muscarinic receptor and the ..cap alpha.. and ..beta..-adrenergic receptors.

A new mechanism for DNA alterations induced by alpha particles such as those emitted by radon and radon progeny.

PubMed Central

Lehnert, B E; Goodwin, E H

1997-01-01

The mechanism(s) by which alpha (alpha) particles like those emitted from inhaled radon and radon progeny cause their carcinogenic effects in the lung remains unclear. Although direct nuclear traversals by alpha-particles may be involved in mediating these outcomes, increasing evidence indicates that a particles can cause alterations in DNA in the absence of direct hits to cell nuclei. Using the occurrence of excessive sister chromatid exchanges (SCE) as an index of DNA damage in human lung fibroblasts, we investigated the hypothesis that alpha-particles may induce DNA damage through the generation of extracellular factors. We have found that a relatively low dose of alpha-particles can result in the generation of extracellular factors, which, upon transfer to unexposed normal human cells, can cause excessive SCE to an extent equivalent to that observed when the cells are directly irradiated with the same irradiation dose. A short-lived, SCE-inducing factor(s) is generated in alpha-irradiated culture medium containing serum in the absence of cells. A more persistent SCE-inducing factor(s), which can survive freeze-thaw and is heat labile is produced by fibroblasts after exposure to the alpha-particles. These results indicate that the initiating target for alpha-particle-induced genetic changes can be larger than a cell's nucleus or even a whole cell. How transmissible factors like those observed here in vitro may extend to the in vivo condition in the context of a-particle-induced carcinogenesis in the respiratory tract remains to be determined. PMID:9400706

[Cytochemical localization and properties of selected nucleolytic enzymes].

PubMed

Sierakowska, Halina

2015-01-01

In the article there are shortly outlined studies on cytochemical localization of selected nucleolytic enzymes carried out between 1957-1986 by David Shugar and his coworkers. The histochemical localization of several nucleolytic enzymes in animal and plant tissues was determined by synthesis of specific substrates, alpha-naphthyl esters of 5'- and 3'-nucleotides and their derivatives. In rat tissues phosphodiesterase I was localized in the plasma membrane whereas phosphodiesterase II in the lizosomes, reflecting their physiological roles. The localization of pancreatic type ribonuclease in animal tissues was determined, indicating its role in extracellular digestion. Plant nucleotide pyrophosphatase was localized in several tissues, purified to near homogeneity from potato tubers and its properties and substrate specificity were determined. Application of this enzyme for removal of m7GMP from the "cap" of eukaryotic mRNA allowed to elucidate the role of "cap" in mRNA binding to ribosomes in the process of translation. Furthermore, cyclic nucleotide phosphodiesterase was isolated from potato tubers and its physicochemical properties, oligomeric structure and substrate specificity were elucidated.

Optimized Design and Synthesis of Cell Permeable Biarsenical Cyanine Probe for Imaging Tagged Cytosolic Bacterial Proteins

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

Fu, Na; Xiong, Yijia; Squier, Thomas C.

2013-01-21

To optimize cellular delivery and specific labeling of tagged cytosolic proteins by biarsenical fluorescent probes build around a cyanine dye scaffold, we have systematically varied the polarity of the hydrophobic tails (i.e., 4-5 methylene groups appended by a sulfonate or methoxy ester moiety) and arsenic capping reagent (ethanedithiol versus benzenedithiol). Targeted labeling of the cytosolic proteins SlyD and the alpha subunit of RNA polymerase engineered with a tetracysteine tagging sequences demonstrate the utility of the newly synthesized probes for live-cell visualization, albeit with varying efficiencies and background intensities. Optimal routine labeling and visualization is apparent using the ethanedithiol capping reagentmore » with the uncharged methoxy ester functionalized acyl chains. These measurements demonstrate the general utility of this class of photostable and highly fluorescent biarsenical reagents based on the cyanine scaffold for in vivo targeting of tagged cellular proteins for live cell measurements of protein dynamics.« less

Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

PubMed

Aragonès, Gemma; Auguet, Teresa; Guiu-Jurado, Esther; Berlanga, Alba; Curriu, Marta; Martinez, Salomé; Alibalic, Ajla; Aguilar, Carmen; Hernández, Esteban; Camara, María-Luisa; Canela, Núria; Herrero, Pol; Ruyra, Xavier; Martín-Paredero, Vicente; Richart, Cristóbal

2016-03-04

Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance.

Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

PubMed

Lee, Jung-Hwan; Om, Ji-Yeon; Kim, Yong-Hee; Kim, Kwang-Mahn; Choi, Eun-Ha; Kim, Kyoung-Nam

2016-01-01

The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP)-induced radicals on the epidermal growth factor receptor (EGFR), which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

Resident CAPS on dense-core vesicles docks and primes vesicles for fusion.

PubMed

Kabachinski, Greg; Kielar-Grevstad, D Michelle; Zhang, Xingmin; James, Declan J; Martin, Thomas F J

2016-02-15

The Ca(2+)-dependent exocytosis of dense-core vesicles in neuroendocrine cells requires a priming step during which SNARE protein complexes assemble. CAPS (aka CADPS) is one of several factors required for vesicle priming; however, the localization and dynamics of CAPS at sites of exocytosis in live neuroendocrine cells has not been determined. We imaged CAPS before, during, and after single-vesicle fusion events in PC12 cells by TIRF micro-scopy. In addition to being a resident on cytoplasmic dense-core vesicles, CAPS was present in clusters of approximately nine molecules near the plasma membrane that corresponded to docked/tethered vesicles. CAPS accompanied vesicles to the plasma membrane and was present at all vesicle exocytic events. The knockdown of CAPS by shRNA eliminated the VAMP-2-dependent docking and evoked exocytosis of fusion-competent vesicles. A CAPS(ΔC135) protein that does not localize to vesicles failed to rescue vesicle docking and evoked exocytosis in CAPS-depleted cells, showing that CAPS residence on vesicles is essential. Our results indicate that dense-core vesicles carry CAPS to sites of exocytosis, where CAPS promotes vesicle docking and fusion competence, probably by initiating SNARE complex assembly. © 2016 Kabachinski, Kielar-Grevstad, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Communication requirements of sparse Cholesky factorization with nested dissection ordering

NASA Technical Reports Server (NTRS)

Naik, Vijay K.; Patrick, Merrell L.

1989-01-01

Load distribution schemes for minimizing the communication requirements of the Cholesky factorization of dense and sparse, symmetric, positive definite matrices on multiprocessor systems are presented. The total data traffic in factoring an n x n sparse symmetric positive definite matrix representing an n-vertex regular two-dimensional grid graph using n exp alpha, alpha not greater than 1, processors are shown to be O(n exp 1 + alpha/2). It is O(n), when n exp alpha, alpha not smaller than 1, processors are used. Under the conditions of uniform load distribution, these results are shown to be asymptotically optimal.

Transforming growth factor-{alpha} enhances corneal epithelial cell migration by promoting EGFR recycling.

PubMed

McClintock, Jennifer L; Ceresa, Brian P

2010-07-01

PURPOSE. The goal of this study was to determine the molecular mechanism by which transforming growth factor-alpha (TGF-alpha) is a more potent activator of epidermal growth factor receptor (EGFR)-mediated corneal wound healing than epidermal growth factor (EGF). METHODS. Telomerase immortalized human corneal epithelial (hTCEpi) cells and primary human corneal epithelial cells were tested for their ability to migrate in response to EGF and TGF-alpha. In parallel, the endocytic trafficking of the EGFR in response to these same ligands was examined using indirect immunofluorescence, immunoblots, and radioligand binding. RESULTS. TGF-alpha, compared with EGF, is a more potent activator of corneal epithelial cell migration. Although both TGF-alpha and EGF were able to induce EGFR internalization and phosphorylation, only those receptors that were stimulated with EGF progressed to lysosomal degradation. EGFRs stimulated with TGF-alpha recycled back to the plasma membrane, where they could be reactivated with ligand. CONCLUSIONS. This study reveals that EGFR-mediated cell migration is limited by ligand-stimulated downregulation of the EGFR. This limitation can be overcome by treating cells with TGF-alpha because TGF-alpha stimulates EGFR endocytosis, but not degradation. After internalization of the TGF-alpha/EGFR complex, EGFR recycles back to the plasma membrane, where it can be restimulated. This sequence of events provides the receptor multiple opportunities for stimulation. Thus, stimulation with TGF-alpha prolongs EGFR signaling compared with EGF.

Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

PubMed

Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

2017-12-18

Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

Observations of the boundary layer, cloud, and aerosol variability in the southeast Pacific coastal marine stratocumulus during VOCALS-REx

NASA Astrophysics Data System (ADS)

Zheng, X.; Albrecht, B.; Jonsson, H. H.; Khelif, D.; Feingold, G.; Minnis, P.; Ayers, K.; Chuang, P.; Donaher, S.; Rossiter, D.; Ghate, V.; Ruiz-Plancarte, J.; Sun-Mack, S.

2011-05-01

Aircraft observations made off the coast of northern Chile in the Southeastern Pacific (20° S, 72° W; named Point Alpha) from 16 October to 13 November 2008 during the VAMOS Ocean-Cloud-Atmosphere-Land Study-Regional Experiment (VOCALS-REx), combined with meteorological reanalysis, satellite measurements, and radiosonde data, are used to investigate the boundary layer (BL) and aerosol-cloud-drizzle variations in this region. The BL at Point Alpha was typical of a non-drizzling stratocumulus-topped BL on days without predominately synoptic and meso-scale influences. The BL had a depth of 1140 ± 120 m, was well-mixed and capped by a sharp inversion. The wind direction generally switched from southerly within the BL to northerly above the inversion. The cloud liquid water path (LWP) varied between 15 g m-2 and 160 g m-2. From 29 October to 4 November, when a synoptic system affected conditions at Point Alpha, the cloud LWP was higher than on the other days by around 40 g m-2. On 1 and 2 November, a moist layer above the inversion moved over Point Alpha. The total-water specific humidity above the inversion was larger than that within the BL during these days. Entrainment rates (average of 1.5 ± 0.6 mm s-1) calculated from the near cloud-top fluxes and turbulence (vertical velocity variance) in the BL at Point Alpha appeared to be weaker than those in the BL over the open ocean west of Point Alpha and the BL near the coast of the northeast Pacific. The accumulation mode aerosol varied from 250 to 700 cm-3 within the BL, and CCN at 0.2 % supersaturation within the BL ranged between 150 and 550 cm-3. The main aerosol source at Point Alpha was horizontal advection within the BL from south. The average cloud droplet number concentration ranged between 80 and 400 cm-3, which was consistent with the satellite-derived values. The relationship of cloud droplet number concentration and CCN at 0.2 % supersaturation from 18 flights is Nd =4.6 × CCN0.71. While the mean LWP retrieved from GOES was in good agreement with the in situ measurements, the GOES-derived cloud droplet effective radius tended to be larger than that from the aircraft {in situ} observations near cloud top. The aerosol and cloud LWP relationship reveals that during the typical well-mixed BL days the cloud LWP increased with the CCN concentrations. On the other hand, meteorological factors and the decoupling processes have large influences on the cloud LWP variation as well.

Modeling and simulation for the field emission of carbon nanotubes array

NASA Astrophysics Data System (ADS)

Wang, X. Q.; Wang, M.; Ge, H. L.; Chen, Q.; Xu, Y. B.

2005-12-01

To optimize the field emission of the infinite carbon nanotubes (CNTs) array on a planar cathode surface, the numerical simulation for the behavior of field emission with finite difference method was proposed. By solving the Laplace equation with computer, the influence of the intertube distance, the anode-cathode distance and the opened/capped CNT on the field emission of CNTs array were taken into account, and the results could accord well with the experiments. The simulated results proved that the field enhancement factor of individual CNT is largest, but the emission current density is little. Due to the enhanced screening of the electric field, the enhancement factor of CNTs array decreases with decreasing the intertube distance. From the simulation the field emission can be optimized when the intertube distance is close to the tube height. The anode-cathode distance hardly influences the field enhancement factor of CNTs array, but can low the threshold voltage by decreasing the anode-cathode distance. Finally, the distribution of potential of the capped CNTs array and the opened CNTs array was simulated, which the results showed that the distribution of potential can be influenced to some extent by the anode-cathode distance, especially at the apex of the capped CNTs array and the brim of the opened CNTs array. The opened CNTs array has larger field enhancement factor and can emit more current than the capped one.

Permanent renal loss following tumor necrosis factor α antagonists for arthritis.

PubMed

Chen, Tzu-Jen; Yang, Ya-Fei; Huang, Po-Hao; Lin, Hsin-Hung; Huang, Chiu-Ching

2010-06-01

Tumor necrosis factor alpha (TNF-alpha) antagonists are now widely used in the treatment of aggressive rheumatoid arthritis and are generally well tolerated. Although rare, they could induce systemic lupus erythematosus, glomerulonephritis, and antineutrophil cytoplasmic antibody associated systemic vasculitis. Tumor necrosis factor alpha antagonists associated glomerulonephritis usually subsides after discontinuation of the therapy and subsequent initiation of corticosteroids and immunosuppressive agents. Here we describe crescentic glomerulonephritis progression to end-stage renal disease in a patient following two doses of TNF-alpha antagonists for the treatment of reactive arthritis. To our knowledge, dialysis dependent permanent renal loss after TNF-alpha antagonists has not yet been reported. We suggest the renal function should be closely monitored in patients treated with TNF-alpha antagonists by rheumatologists.

Expression of transforming growth factor alpha and epidermal growth factor receptor messenger RNA in neoplastic and nonneoplastic human kidney tissue.

PubMed

Mydlo, J H; Michaeli, J; Cordon-Cardo, C; Goldenberg, A S; Heston, W D; Fair, W R

1989-06-15

Using Northern blot analysis, we have demonstrated that mRNA for transforming growth factor alpha (TGF-alpha) was expressed in five malignant kidney tissue specimens but was not detected in their autologous nonneoplastic homologues. In addition, the expression of epidermal growth factor (EGF) receptor mRNA in these malignant tissues was 2- to 3-fold greater than in nontransformed tissues. In two cases examined using immunohistochemistry, we were able to correlate the increased expression of the mRNA with an increase in protein expression. Since TGF-alpha is known to bind to the EGF receptor, the finding of an increased expression of both TGF-alpha and EGF receptor mRNA in kidney tumor tissue suggests that interaction between TGF-alpha and the EGF receptor may play a role in promoting transformation and/or proliferation of kidney neoplasms, perhaps by an autocrine mechanism.

Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis.

PubMed

Tutau, Federico; Rodríguez-Ortigosa, Carlos; Puche, Juan Enrique; Juanarena, Nerea; Monreal, Iñigo; García Fernández, María; Clavijo, Encarna; Castilla, Alberto; Castilla-Cortázar, Inma

2009-01-01

Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-alpha (IFN-alpha) therapy seems to suppress the progression of hepatic fibrosis. The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-alpha to Wistar rats with CCl(4)-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology. The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection. Both IGF-I and IFN-alpha exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-alpha-therapy did not. The inhibition of TGF-beta expression was only observed by the effect of IFN-alpha-therapy. In addition, only the co-administration of IGF-I and IFN-alpha was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture. The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.

Hypermethylated-capped selenoprotein mRNAs in mammals

PubMed Central

Wurth, Laurence; Gribling-Burrer, Anne-Sophie; Verheggen, Céline; Leichter, Michael; Takeuchi, Akiko; Baudrey, Stéphanie; Martin, Franck; Krol, Alain; Bertrand, Edouard; Allmang, Christine

2014-01-01

Mammalian mRNAs are generated by complex and coordinated biogenesis pathways and acquire 5′-end m7G caps that play fundamental roles in processing and translation. Here we show that several selenoprotein mRNAs are not recognized efficiently by translation initiation factor eIF4E because they bear a hypermethylated cap. This cap modification is acquired via a 5′-end maturation pathway similar to that of the small nucle(ol)ar RNAs (sn- and snoRNAs). Our findings also establish that the trimethylguanosine synthase 1 (Tgs1) interacts with selenoprotein mRNAs for cap hypermethylation and that assembly chaperones and core proteins devoted to sn- and snoRNP maturation contribute to recruiting Tgs1 to selenoprotein mRNPs. We further demonstrate that the hypermethylated-capped selenoprotein mRNAs localize to the cytoplasm, are associated with polysomes and thus translated. Moreover, we found that the activity of Tgs1, but not of eIF4E, is required for the synthesis of the GPx1 selenoprotein in vivo. PMID:25013170

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

PubMed

Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; p< 0.001; random effects: RR=1.90, 95%CI, 0.66-5.44; p=0.233) can significantly increase the risk of lymphoma. Exposition of anti-tumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Measuring Psychological Capital: Construction and Validation of the Compound PsyCap Scale (CPC-12)

PubMed Central

Lorenz, Timo; Beer, Clemens; Pütz, Jan; Heinitz, Kathrin

2016-01-01

With the Psychological Capital Questionnaire (PCQ) being the standard measure to assess psychological capital (PsyCap) in the context of organizations, this paper aims to broaden this domain-specific approach by introducing a measure with universal claim. Two studies were conducted to create and validate a German self-report scale (CPC-12) measuring PsyCap. We performed confirmatory factor analyses and correlations with other positive psychological constructs on the data of two German samples (N1 = 321; N2 = 202). The twelve-item CPC-12 exhibits the anticipated factorial structure with a very good model fit and associations to other constructs concur with previous findings with other measures of PsyCap. PMID:27035437

Oxide and hydrogen capped ultrasmall blue luminescent Si nanoparticles

NASA Astrophysics Data System (ADS)

Belomoin, Gennadiy; Therrien, Joel; Nayfeh, Munir

2000-08-01

We dispersed electrochemical etched silicon into a colloid of ultrasmall ultrabright Si nanoparticles. Direct imaging using transmission electron microscopy shows particles of ˜1 nm in diameter, and infrared and electron photospectroscopy show that they are passivated with hydrogen. Under 350 nm excitation, the luminescence is dominated by an extremely strong blue band at 390 nm. We replace hydrogen by a high-quality ultrathin surface oxide cap by self-limiting oxidation in H2O2. Upon capping, the excitation efficiency drops, but only by a factor of 2, to an efficiency still two-fold larger than that of fluorescein. Although of slightly lower brightness, capped Si particles have superior biocompatability, an important property for biosensing applications.

Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis.

PubMed

Clarke, Murray C H; Figg, Nichola; Maguire, Janet J; Davenport, Anthony P; Goddard, Martin; Littlewood, Trevor D; Bennett, Martin R

2006-09-01

Vascular smooth muscle cell (VSMC) apoptosis occurs in many arterial diseases, including aneurysm formation, angioplasty restenosis and atherosclerosis. Although VSMC apoptosis promotes vessel remodeling, coagulation and inflammation, its precise contribution to these diseases is unknown, given that apoptosis frequently accompanies vessel injury or alterations to flow. To study the direct consequences of VSMC apoptosis, we generated transgenic mice expressing the human diphtheria toxin receptor (hDTR, encoded by HBEGF) from a minimal Tagln (also known as SM22alpha) promoter. Despite apoptosis inducing loss of 50-70% of VSMCs, normal arteries showed no inflammation, reactive proliferation, thrombosis, remodeling or aneurysm formation. In contrast, VSMC apoptosis in atherosclerotic plaques of SM22alpha-hDTR Apoe-/- mice induced marked thinning of fibrous cap, loss of collagen and matrix, accumulation of cell debris and intense intimal inflammation. We conclude that VSMC apoptosis is 'silent' in normal arteries, which have a large capacity to withstand cell loss. In contrast, VSMC apoptosis alone is sufficient to induce features of plaque vulnerability in atherosclerosis. SM22alpha-hDTR Apoe-/- mice may represent an important new model to test agents proposed to stabilize atherosclerotic plaques.

A New Conjugation Method Used for the Development of an Immunoassay for the Detection of Amanitin, a Deadly Mushroom Toxin.

PubMed

Bever, Candace S; Barnych, Bogdan; Hnasko, Robert; Cheng, Luisa W; Stanker, Larry H

2018-06-28

One of the deadliest mushrooms is the death cap mushroom, Amanita phalloides . The most toxic constituent is α-amanitin, a bicyclic octapeptide, which damages the liver and kidneys. To develop a new tool for detecting this toxin, polyclonal antibodies were generated and characterized. Both α- and β-amanitin were coupled to carrier proteins through four different linking chemistries, one of which has never before been described. These conjugates were evaluated for their effectiveness in generating antibodies specific for the free toxin, as well as their utility in formatting heterogeneous assays with high sensitivity. Ultimately, these efforts yielded a newly described conjugation procedure utilizing periodate oxidation followed by reductive amination that successfully resulted in generating sensitive immunoassays (limit of detection (LOD), ~1.0 µg/L). The assays were characterized for their selectivity and were found to equally detect α-, β-, and γ-amanitin, and not cross-react with other toxins tested. Toxin detection in mushrooms was possible using a simple sample preparation method. This enzyme-linked immunosorbent assay (ELISA) is a simple and fast test, and readily detects amatoxins extracted from A. phalloides .

Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the Wild-Type Cytolytic Toxin.

PubMed

Fiaschi, Luigi; Di Palo, Benedetta; Scarselli, Maria; Pozzi, Clarissa; Tomaszewski, Kelly; Galletti, Bruno; Nardi-Dei, Vincenzo; Arcidiacono, Letizia; Mishra, Ravi P N; Mori, Elena; Pallaoro, Michele; Falugi, Fabiana; Torre, Antonina; Fontana, Maria Rita; Soriani, Marco; Bubeck Wardenburg, Juliane; Grandi, Guido; Rappuoli, Rino; Ferlenghi, Ilaria; Bagnoli, Fabio

2016-06-01

Staphylococcus aureus alpha-hemolysin (Hla) assembles into heptameric pores on the host cell membrane, causing lysis, apoptosis, and junction disruption. Herein, we present the design of a newly engineered S. aureus alpha-toxin, HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is able to form heptamers in aqueous solution in the absence of lipophilic substrata, and its structure, obtained by transmission electron microscopy and single-particle reconstruction analysis, resembles the cap of the wild-type cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and to its receptor ADAM10 and to lack hemolytic and cytotoxic activity. Immunological studies using human sera as well as sera from mice convalescent from S. aureus infection suggested that the heptameric conformation of HlaPSGS mimics epitopes exposed by the cytolytic Hla pore during infection. Finally, immunization with this newly engineered Hla generated high protective immunity against staphylococcal infection in mice. Overall, this study provides unprecedented data on the natural immune response against Hla and suggests that the heptameric HlaPSGS is a highly valuable vaccine candidate against S. aureus. Copyright © 2016 Fiaschi et al.

Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the Wild-Type Cytolytic Toxin

PubMed Central

Fiaschi, Luigi; Di Palo, Benedetta; Scarselli, Maria; Pozzi, Clarissa; Tomaszewski, Kelly; Galletti, Bruno; Nardi-Dei, Vincenzo; Arcidiacono, Letizia; Mishra, Ravi P. N.; Mori, Elena; Pallaoro, Michele; Falugi, Fabiana; Torre, Antonina; Fontana, Maria Rita; Soriani, Marco; Bubeck Wardenburg, Juliane; Grandi, Guido; Rappuoli, Rino

2016-01-01

Staphylococcus aureus alpha-hemolysin (Hla) assembles into heptameric pores on the host cell membrane, causing lysis, apoptosis, and junction disruption. Herein, we present the design of a newly engineered S. aureus alpha-toxin, HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is able to form heptamers in aqueous solution in the absence of lipophilic substrata, and its structure, obtained by transmission electron microscopy and single-particle reconstruction analysis, resembles the cap of the wild-type cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and to its receptor ADAM10 and to lack hemolytic and cytotoxic activity. Immunological studies using human sera as well as sera from mice convalescent from S. aureus infection suggested that the heptameric conformation of HlaPSGS mimics epitopes exposed by the cytolytic Hla pore during infection. Finally, immunization with this newly engineered Hla generated high protective immunity against staphylococcal infection in mice. Overall, this study provides unprecedented data on the natural immune response against Hla and suggests that the heptameric HlaPSGS is a highly valuable vaccine candidate against S. aureus. PMID:27030589

A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation

PubMed Central

Shen, Yang; Zeng, Lin; Novosyadlyy, Ruslan; Forest, Amelie; Zhu, Aiping; Korytko, Andrew; Zhang, Haifan; Eastman, Scott W; Topper, Michael; Hindi, Sagit; Covino, Nicole; Persaud, Kris; Kang, Yun; Burtrum, Douglas; Surguladze, David; Prewett, Marie; Chintharlapalli, Sudhakar; Wroblewski, Victor J; Shen, Juqun; Balderes, Paul; Zhu, Zhenping; Snavely, Marshall; Ludwig, Dale L

2015-01-01

Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, have emerged as promising therapeutic alternatives to combinations of individual monoclonal antibodies. Here, we describe the engineering and development of a novel, human bi-functional antibody-receptor domain fusion molecule with ligand capture (bi-AbCap) through the fusion of the domain 2 of human vascular endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against insulin-like growth factor – type I receptor (IGF-IR). The bi-AbCap possesses excellent stability and developability, and is the result of minimal engineering. Beyond potent neutralizing activities against IGF-IR and VEGF, the bi-AbCap is capable of cross-linking VEGF to IGF-IR, leading to co-internalization and degradation of both targets by tumor cells. In multiple mouse xenograft tumor models, the bi-AbCap improves anti-tumor activity over individual monotherapies. More importantly, it exhibits superior inhibition of tumor growth, compared with the combination of anti-IGF-IR and anti-VEGF therapies, via powerful blockade of both direct tumor cell growth and tumor angiogenesis. The unique “capture-for-degradation” mechanism of the bi-AbCap is informative for the design of next-generation bi-functional anti-cancer therapies directed against independent signaling pathways. The bi-AbCap design represents an alternative approach to the creation of dual-targeting antibody fusion molecules by taking advantage of natural receptor-ligand interactions. PMID:26073904

Thalidomide in rat liver cirrhosis: blockade of tumor necrosis factor-alpha via inhibition of degradation of an inhibitor of nuclear factor-kappaB.

PubMed

Paul, Shelley Chireyath; Lv, Peng; Xiao, Yan-Jv; An, Ping; Liu, Shi-Quan; Luo, He-Sheng

2006-01-01

Thalidomide inhibited tumor necrosis factor-alpha (TNF-alpha) effectively in many trials. The aim of this study was to investigate the effect of thalidomide on the expression of nuclear factor-kappaB (NF-kappaB), inhibitor of NF-kappaB (IkappaB) and TNF-alpha in a rat model of liver cirrhosis. Liver cirrhosis was achieved by intraperitoneal injection of carbon tetrachloride thrice weekly, and thalidomide (10 or 100 mg/kg/day) was given daily by intragastric route for 8 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), prealbumin (PA), hyaluronic acid (HA) and laminin (LN), and hydroxyproline (HYP), NF-kappaBp65, alpha-smooth muscle actin (alpha-SMA) protein and TNF-alpha mRNA were studied in the liver, IkappaBalpha and TNF-alpha protein in the cytoplasm and NF-kappaBp65 protein in the nucleus. Compared with nontreated cirrhotic rats, the histopathology of rats given thalidomide (100 mg/kg) was significantly better. Serum ALT, AST, HA and LN and HYP content in the liver were significantly decreased and PA was elevated (p < 0.01) in this group; the expression of TNF-alpha mRNA and protein, NF-kappaBp65 and alpha-SMA were significantly decreased and IkappaBalpha protein was also elevated (p < 0.01). Thalidomide downregulates NF-kappaB-induced TNF-alpha and activates hepatic stellate cells (HSC) via inhibition of IkappaB degradation to prevent liver cirrhosis. Copyright 2006 S. Karger AG, Basel.

Chloro-, methyl-, and (tetrahydroborato)tris((hexamethyldisilyl)amido)thorium(IV) and -uranium(IV). Crystal structure of (tetrahydroborato)tris((hexamethyldisilyl)amido)thorium(IV)

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

Turner, H.W.; Andersen, R.A.; Zalkin, A.

1979-05-01

Reaction of sodium (hexamethyldisilyl)amide with thorium tetrachloride or uranium tetrachloride yields chlorotris-((hexamethyldisilyl)amido)thorium(IV) or -uranium(IV), respectively. The chloroamides of thorium or uranium react with dimethylmagnesium or methyllithium yielding the methyl derivatives MeTh(N(SiMe/sub 3/)/sub 2/)/sub 3/ or MeU(N(SiMe/sub 3/)/sub 2/)/sub 3/, respectively. The chloro compounds yield BH/sub 4/M(N(SiMe/sub 3/)/sub 2/)/sub 3/ upon reaction with lithium tetrahydroborate, where M is thorium or uranium. Infrared spectra of the tetrahydroborate derivatives suggest that BH/sub 4/ is bonded in a tridentate fashion in both compounds, the metal atoms being six-coordinate. Single-crystal X-ray analysis of the thorium borohydride confirms the infrared result. The white BH/sub 4/Th(N(Si(CH/sub 3/))/submore » 2/)/sub 3/ crystals are rhombohedral with cell dimensions a/sub r/ = 11.137 A and ..cap alpha../sub r/ = 113.61/sup 0/; the triply primitive hexagonal cell has a/sub h/ = 18.640 (3) A c/sub h/ = 8.604 (1) A, V = 2489 A/sup 3/, Z = 3, and D/sub x/ = 1.40 g/cm/sup 3/, space group R3m. The structure was refined by full-matrix least squares to a conventional R factor of 0.031 for 1014 data. The Th atom is on a threefold axis 2.32 A from three nitrogen atoms and 2.61 A from the boron atom, a distance which represents a triple bridge bond between Th and B. The three (dimethylsilyl)amide ligands are disordered by a mirror plane parallel to the threefold axis. CH/sub 3/Th(N(Si(CH/sub 3/)/sub 3/)/sub 2/)/sub 3/ is isomorphous with BH/sub 4/Th(N(Si(CH/sub 3/)/sub 3/)/sub 2/)/sub 3/ with cell dimensions a/sub h/ = 18.68 (1) A and c/sub h/ = 8.537 (6) A. The diffraction data yielded integral'' = 12.16 +- 0.33 e for the imaginary scattering term for Th with Cu K..cap alpha.. radiation.« less

[Epidemiology of community-acquired pneumonia].

PubMed

Irizar Aramburu, María Isabel; Arrondo Beguiristain, María Angeles; Insausti Carretero, María Jesus; Mujica Campos, Justo; Etxabarri Perez, Pilar; Ganzarain Gorosabel, Roman

2013-12-01

To determine the incidence rate, hospital admission, their mortality related factors in community-acquired pneumonia (CAP) in adults in Gipuzkoa. Prospective observational multicenter study of patients over 14 years-old with CAP treated by 33 primary care physicians for a year. Confirmation of the radiologist for diagnosis of pneumonia was required. The participating physicians collected the sociodemographic and clinical variables of all patients with CAP seen in the clinic during one year, and followed-up on the 2nd, 10th and 40th day. Same variables were collected from patients who had CAP in the study period and were diagnosed elsewhere. The number of patients over 14 years old with CAP during the study was 406 for a population of 48,905 inhabitants. The incidence of CAP was 8.3 cases per 1000 inhabitants/year, and included 56% males and 44% females. The mean age was 56.2 years. The rate of hospital admission during the study period was 28.6% and was not related to comorbidity or age. The overall mortality rate was 2.7% with a mean age of 83.7 years, and was only related to age. The incidence of CAP was 8.3 cases per 1000 inhabitants per year. Just over one in four CAP required hospitalization and 2.7% of patients with CAP died. Only age was related to mortality. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell.

PubMed

Meng, Wenbo; Li, Xun; Bai, Zhongtian; Li, Yan; Yuan, Jinqiu; Liu, Tao; Yan, Jun; Zhou, Wence; Zhu, Kexiang; Zhang, Hui; Li, Yumin

2014-01-01

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit.

PubMed

Araya, Jun; Cambier, Stephanie; Morris, Alanna; Finkbeiner, Walter; Nishimura, Stephen L

2006-08-01

Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-beta is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, alpha(v)beta(6) and alpha(v)beta(8), are responsible for almost all of the TGF-beta activation in the EMTU. Both alpha(v)beta(8) and alpha(v)beta(6) contribute to fetal tracheal epithelial activation of TGF-beta, whereas only alpha(v)beta(8) contributes to fetal tracheal fibroblast activation of TGF-beta. Interestingly, fetal tracheal epithelial alpha(v)beta(8)-mediated TGF-beta activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in alpha(v)beta(8)-mediated activation of TGF-beta. Autocrine alpha(v)beta(8)-mediated TGF-beta activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-beta within the EMTU.

Identification of the antigenic determinants of factors 8, 9, and 34 of genus Candida.

PubMed

Kobayashi, H; Oyamada, H; Suzuki, A; Shibata, N; Suzuki, S; Okawa, Y

1996-10-21

We investigated the antigenic determinants of factors 8, 9, and 34 of the genus Candida among pathogenic yeasts by enzyme-linked immunosorbent assay (ELISA) using mannans of Saccharomyces cerevisiae wild type and mutant types, mnn 1-mnn 4 and mnn 2. Results of ELISA including antisera against the antigenic factors of genus Candida (Candida Check, latron; FAbs) indicated that these three types of mannan distinctly react with FAbs 34, 8 and 9, respectively. To identify the recognition sites of these FAbs, we compared the ability of various oligosaccharides to inhibit the binding of the mannans to FAbs. The results indicated that FAb 34 preferentially recognizes linear side chains containing a non-reducing terminal alpha-1,3-linked mannose residue, Man(alpha)1 --> 3Man(alpha)1 --> (2Man(alpha)1 --> )n(2Man) (n > or = 0), and that one of the recognition sites of FAb 9 is linear alpha-1,6-linked oligomannosyl series, Man(alpha)1 --> (6Man(alpha)1 --> )n(6Man) (n > or = 2). On the other hand, the recognition site of FAb 8 apparently consisted of two alpha-1,2-linked oligomannosyl side chains and an alpha-1,6-linked mannose residue that originated from the mannan backbone, Man(alpha)1 --> 2Man(alpha)1 --> 2(Man(alpha)1 -->2Man(alpha)1 --> 6)Man.

Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model.

PubMed

Norris, Erin H; Uryu, Kunihiro; Leight, Susan; Giasson, Benoit I; Trojanowski, John Q; Lee, Virginia M-Y

2007-02-01

The factors initiating or contributing to the pathogenesis of Parkinson's disease and related neurodegenerative synucleinopathies are still largely unclear, but environmental factors such as pesticides have been implicated. In this study, A53T mutant human alpha-synuclein transgenic mice (M83), which develop alpha-synuclein neuropathology, were treated with the pesticides paraquat and maneb (either singly or together), and their effects were analyzed. Immunohistochemical and biochemical analyses showed that chronic treatment of M83 transgenic mice with both pesticides (but not with either pesticide alone) drastically increased neuronal alpha-synuclein pathology throughout the central nervous system including the hippocampus, cerebellum, and sensory and auditory cortices. alpha-Synuclein-associated mitochondrial degeneration was observed in M83 but not in wild-type alpha-synuclein transgenic mice. Because alpha-synuclein inclusions accumulated in pesticide-exposed M83 transgenic mice without a motor phenotype, we conclude that alpha-synuclein aggregate formation precedes disease onset. These studies support the notion that environmental factors causing nitrative damage are closely linked to mechanisms underlying the formation of alpha-synuclein pathologies and the onset of Parkinson's-like neurodegeneration.

A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement*

PubMed Central

Chuang, Tzu-Wei; Lee, Kuo-Ming; Lou, Yuan-Chao; Lu, Chia-Chen; Tarn, Woan-Yuh

2016-01-01

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. PMID:26887951

Initial management of pneumonia and sepsis: factors associated with improved outcome.

PubMed

Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J

2012-01-01

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

Dry etching, surface passivation and capping processes for antimonide based photodetectors

NASA Astrophysics Data System (ADS)

Dutta, Partha; Langer, Jeffery; Bhagwat, Vinay; Juneja, Jasbir

2005-05-01

III-V antimonide based devices suffer from leakage currents. Surface passivation and subsequent capping of the surfaces are absolutely essential for any practical applicability of antimonide based devices. The quest for a suitable surface passivation technology is still on. In this paper, we will present some of the promising recent developments in this area based on dry etching of GaSb based homojunction photodiodes structures followed by various passivation and capping schemes. We have developed a damage-free, universal dry etching recipe based on unique ratios of Cl2/BCl3/CH4/Ar/H2 in ECR plasma. This novel dry plasma process etches all III-V compounds at different rates with minimal damage to the side walls. In GaSb based photodiodes, an order of magnitude lower leakage current, improved ideality factor and higher responsivity has been demonstrated using this recipe compared to widely used Cl2/Ar and wet chemical etch recipes. The dynamic zero bias resistance-area product of the Cl2/BCl3/CH4/Ar/H2 etched diodes (830 Ω cm2) is higher than the Cl2/Ar (300 Ω cm2) and wet etched (330 Ω cm2) diodes. Ammonium sulfide has been known to passivate surfaces of III-V compounds. In GaSb photodiodes, the leakage current density reduces by a factor of 3 upon sulfur passivation using ammonium sulfide. However, device performance degrades over a period of time in the absence of any capping or protective layer. Silicon Nitride has been used as a cap layer by various researchers. We have found that by using silicon nitride caps, the devices exhibit higher leakage than unpassivated devices probably due to plasma damage during SiNx deposition. We have experimented with various polymers for capping material. It has been observed that ammonium sulfide passivation when combined with parylene capping layer (150 Å), devices retain their improved performance for over 4 months.

Effect of capping and particle size on Raman laser-induced degradation of {gamma}-Fe{sub 2}O{sub 3} nanoparticles

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

Varadwaj, K.S.K.; Panigrahi, M.K.; Ghose, J.

2004-11-01

Diol capped {gamma}-Fe{sub 2}O{sub 3} nanoparticles are prepared from ferric nitrate by refluxing in 1,4-butanediol (9.5nm) and 1,5-pentanediol (15nm) and uncapped particles are prepared by refluxing in 1,2-propanediol followed by sintering the alkoxide formed. X-ray diffraction (XRD) shows that all the samples have the spinel phase. Raman spectroscopy shows that the samples prepared in 1,4-butanediol and 1,5-pentanediol and 1,2-propanediol (sintered at 573 and 673K) are {gamma}-Fe{sub 2}O{sub 3} and the 773K-sintered sample is Fe{sub 3}O{sub 4}. Raman laser studies carried out at various laser powers show that all the samples undergo laser-induced degradation to {alpha}-Fe{sub 2}O{sub 3} at higher lasermore » power. The capped samples are however, found more stable to degradation than the uncapped samples. The stability of {gamma}-Fe{sub 2}O{sub 3} sample with large particle size (15.4nm) is more than the sample with small particle size (10.2nm). Fe{sub 3}O{sub 4} having a particle size of 48nm is however less stable than the smaller {gamma}-Fe{sub 2}O{sub 3} nanoparticles.« less

Phase field models for heterogeneous nucleation: Application to inoculation in alpha-solidifying Ti-Al-B alloys

NASA Astrophysics Data System (ADS)

Apel, M.; Eiken, J.; Hecht, U.

2014-02-01

This paper aims at briefly reviewing phase field models applied to the simulation of heterogeneous nucleation and subsequent growth, with special emphasis on grain refinement by inoculation. The spherical cap and free growth model (e.g. A.L. Greer, et al., Acta Mater. 48, 2823 (2000)) has proven its applicability for different metallic systems, e.g. Al or Mg based alloys, by computing the grain refinement effect achieved by inoculation of the melt with inert seeding particles. However, recent experiments with peritectic Ti-Al-B alloys revealed that the grain refinement by TiB2 is less effective than predicted by the model. Phase field simulations can be applied to validate the approximations of the spherical cap and free growth model, e.g. by computing explicitly the latent heat release associated with different nucleation and growth scenarios. Here, simulation results for point-shaped nucleation, as well as for partially and completely wetted plate-like seed particles will be discussed with respect to recalescence and impact on grain refinement. It will be shown that particularly for large seeding particles (up to 30 μm), the free growth morphology clearly deviates from the assumed spherical cap and the initial growth - until the free growth barrier is reached - significantly contributes to the latent heat release and determines the recalescence temperature.

Alpha Power Modulates Perception Independently of Endogenous Factors.

PubMed

Brüers, Sasskia; VanRullen, Rufin

2018-01-01

Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF), a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution). Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between alpha power and perception is not a mere consequence of fluctuations in endogenous factors.

Ballistocardiogram Artifact Removal with a Reference Layer and Standard EEG Cap

PubMed Central

Luo, Qingfei; Huang, Xiaoshan; Glover, Gary H.

2014-01-01

Background In simultaneous EEG-fMRI, the EEG recordings are severely contaminated by ballistocardiogram (BCG) artifacts, which are caused by cardiac pulsations. To reconstruct and remove the BCG artifacts, one promising method is to measure the artifacts in the absence of EEG signal by placing a group of electrodes (BCG electrodes) on a conductive layer (reference layer) insulated from the scalp. However, current BCG reference layer (BRL) methods either use a customized EEG cap composed of electrode pairs, or need to construct the custom reference layer through additional model-building experiments for each EEG-fMRI experiment. These requirements have limited the versatility and efficiency of BRL. The aim of this study is to propose a more practical and efficient BRL method and compare its performance with the most popular BCG removal method, the optimal basis sets (OBS) algorithm. New Method By designing the reference layer as a permanent and reusable cap, the new BRL method is able to be used with a standard EEG cap, and no extra experiments and preparations are needed to use the BRL in an EEG-fMRI experiment. Results The BRL method effectively removed the BCG artifacts from both oscillatory and evoked potential scalp recordings and recovered the EEG signal. Comparison with Existing Method Compared to the OBS, this new BRL method improved the contrast-to-noise ratios of the alpha-wave, visual, and auditory evoked potential signals by 101%, 76%, and 75% respectively, employing 160 BCG electrodes. Using only 20 BCG electrodes, the BRL improved the EEG signal by 74%/26%/41% respectively. Conclusion The proposed method can substantially improve the EEG signal quality compared with traditional methods. PMID:24960423

Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model.

PubMed

Wang, Wanjun; Zhou, Ji; Chen, Minjie; Huang, Xingke; Xie, Xiaoyun; Li, Weihua; Cao, Qi; Kan, Haidong; Xu, Yanyi; Ying, Zhekang

2018-04-17

Exposure to ambient fine particulate matter (PM 2.5 ) correlates with abnormal glucose homeostasis, but the underlying biological mechanism has not been fully understood. The gut microbiota is an emerging crucial player in the homeostatic regulation of glucose metabolism. Few studies have investigated its role in the PM 2.5 exposure-induced abnormalities in glucose homeostasis. C57Bl/6J mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) for 12 months using a versatile aerosol concentration enrichment system (VACES) that was modified for long-term whole-body exposures. Their glucose homeostasis and gut microbiota were examined and analysed by correlation and mediation analysis. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) showed that CAP exposure markedly impaired their glucose and insulin tolerance. Faecal microbiota analysis demonstrated that the impairment in glucose homeostasis was coincided with decreased faecal bacterial ACE and Chao-1 estimators (the indexes of community richness), while there was no significant change in all faecal fungal alpha diversity estimators. The Pearson's correlation analyses showed that the bacterial richness estimators were correlated with glucose and insulin tolerance, and the mediation analyses displayed a significant mediation of CAP exposure-induced glucose intolerance by the alteration in the bacterial Chao-1 estimator. LEfSe analyses revealed 24 bacterial and 21 fungal taxa differential between CAP- and FA-exposed animals. Of these, 14 and 20 bacterial taxa were correlated with IPGTT AUC and ITT AUC, respectively, and 5 fungal taxa were correlated with abnormalities in glucose metabolism. Chronic exposure to PM 2.5 causes gut dysbiosis and may subsequently contribute to the development of abnormalities in glucose metabolism.

Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer.

PubMed

Weihrauch, Martin R; Ansén, Sascha; Jurkiewicz, Elke; Geisen, Caroline; Xia, Zhinan; Anderson, Karen S; Gracien, Edith; Schmidt, Manuel; Wittig, Burghardt; Diehl, Volker; Wolf, Juergen; Bohlen, Heribert; Nadler, Lee M

2005-08-15

We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen-derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells. HLA-A2-positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, human T-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-gamma intracellular cytokine assays were done to evaluate CTL reactivity. Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1-specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1-specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen-specific CD8+ cells decreased by an average 14%. The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1-specific T cells were observed in 47% of patients after vaccination.

Factors associated with the pricing of childhood vaccines in the U.S. public sector.

PubMed

Chen, Weiwei; Messonnier, Mark; Zhou, Fangjun

2018-02-01

Vaccine purchase cost has grown substantially over the last few decades. A closer look at vaccine prices reveals that not all vaccines shared the same increasing pattern. Various factors, such as vaccine attributes, competition, and supply shortages, could relate to price changes. In this study, we examined whether a variety of factors influenced the prices of noninfluenza childhood vaccines purchased in the public sector from 1996 to 2014. The association differed among price-capped vaccines and combination vaccines. There was an increasing time trend in real prices for non-price-capped vaccines, which was mostly offset by the effect of market longevity. The effect of competition in lowering prices was more pronounced among non-price-capped vaccines when manufacturer and vaccine component fixed effects were excluded. Supply shortage, manufacturer name change, and number of vaccine doses in series showed no effect. The results may help policy makers better understand price behaviors and make more informed decisions in vaccine planning and financing. Copyright © 2017 John Wiley & Sons, Ltd.

Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells.

PubMed

van de Water, B; Tijdens, I B; Verbrugge, A; Huigsloot, M; Dihal, A A; Stevens, J L; Jaken, S; Mulder, G J

2000-08-18

Decreased phosphorylation of focal adhesion kinase and paxillin is associated with loss of focal adhesions and stress fibers and precedes the onset of apoptosis (van de Water, B., Nagelkerke, J. F., and Stevens, J. L. (1999) J. Biol. Chem. 274, 13328-13337). The cortical actin cytoskeletal network is also lost during apoptosis, yet little is known about the temporal relationship between altered phosphorylation of proteins that are critical in the regulation of this network and their potential cleavage by caspases during apoptosis. Adducins are central in the cortical actin network organization. Cisplatin caused apoptosis of renal proximal tubular epithelial cells, which was associated with the cleavage of alpha-adducin into a 74-kDa fragment; this was blocked by a general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk). Hemagglutinin-tagged human alpha-adducin was cleaved into a similar 74-kDa fragment by caspase-3 in vitro but not by caspase-6 or -7. Asp-Arg-Val-Asp(29)-Glu, Asp-Ile-Val-Asp(208)-Arg, and Asp-Asp-Ser-Asp(633)-Ala were identified as the principal caspase-3 cleavage sites; Asp-Asp-Ser-Asp(633)-Ala was key in the formation of the 74-kDa fragment. Cisplatin also caused an increased phosphorylation of alpha-adducin and gamma-adducin in the MARCKS domain that preceded alpha-adducin cleavage and was associated with loss of adducins from adherens junctions; this was not affected by z-VAD-fmk. In conclusion, the data support a model in which increased phosphorylation of alpha-adducin due to cisplatin leads to dissociation from the cytoskeleton, a situation rendered irreversible by caspase-3-mediated cleavage of alpha-adducin at Asp-Asp-Ser-Asp(633)-Ala.

An Exploratory Study of Alpha Contracting: Antecedents, Processes, Issues, Success Factors and Consequences

DTIC Science & Technology

2009-09-01

ABSTRACT (maximum 200 words) Alpha contracting is a collaborative effort between a buyer and supplier during contract formation to maximize efficiency...experienced Alpha contracting teams, to include contracting officers, DCAA, DCMA, end users/ customers , program managers and acquisition directors to better...PROCESSES, ISSUES, SUCCESS FACTORS AND CONSEQUENCES ABSTRACT Alpha contracting is a collaborative effort between a buyer and supplier

La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs.

PubMed

Lahr, Roni M; Fonseca, Bruno D; Ciotti, Gabrielle E; Al-Ashtal, Hiba A; Jia, Jian-Jun; Niklaus, Marius R; Blagden, Sarah P; Alain, Tommy; Berman, Andrea J

2017-04-07

The 5'terminal oligopyrimidine (5'TOP) motif is a cis -regulatory RNA element located immediately downstream of the 7-methylguanosine [m 7 G] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, a cap analog (m 7 GTP), and a capped cytidine (m 7 GpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5'TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5'TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis.

Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS).

PubMed

Hoffman, Hal M

2009-04-01

Cryopyrin-associated periodic syndromes (CAPS) encompass a group of rare inherited, autoinflammatory disorders that represent a spectrum of one disease with varying degrees of severity. Until recently, there was no effective treatment for CAPS, but identification of the genetic basis of CAPS highlighted the pathogenic role of IL-1beta. Rilonacept is a recently FDA approved biologic therapy for CAPS with high affinity for IL-1beta. Limited pharmacological data has been reported to date. A review of the phamacokinetics and pharmacodynamics data as well as the results of a pilot study and Phase III placebo-controlled trials of rilonacept in CAPS. Unpublished data on an open-label extension study in adult and pediatric subjects is also reviewed. Rilonacept produced rapid and profound improvements in symptoms and also reduced high-sesitivity C-reactive protein levels and normalized elevated serum amyloid A concentrations, an important risk factor for amyloidosis. The primary adverse events were injection- site reactions and upper respiratory tract infections. Rilonacept, the only IL-1 Trap, is the first of many novel IL-1-targeted therapies being developed. In a very short time it has changed the lives of CAPS patients.

Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability

PubMed Central

Seal, Ruth; Temperley, Richard; Wilusz, Jeffrey; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M. A.

2005-01-01

PARN, a poly(A)-specific ribonuclease, binds the 5′ cap-structure of mRNA and initiates deadenylation-dependent decay. Eukaryotic initiation factor 4E (eIF4E) also binds to the cap structure, an interaction that is critical for initiating cap-dependent translation. The stability of various mRNA transcripts in human cell lines is reduced under conditions of serum starvation as determined by both functional and chemical half-lives. Serum starvation also leads to enhanced cap association by PARN. In contrast, the 5′ cap occupancy by eIF4E decreases under serum-deprivation, as does the translation of reporter transcripts. Further, we show that PARN is a phosphoprotein and that this modification can be modulated by serum status. Taken together, these data are consistent with a natural competition existing at the 5′ cap structure between PARN and eIF4E that may be regulated by changes in post-translational modifications. These phosphorylation-induced changes in the interplay of PARN and eIF4E may determine whether the mRNA is translated or decayed. PMID:15653638

Tumor necrosis factor-alpha converting enzyme in the human placenta throughout gestation.

PubMed

Hung, Tai-Ho; Chen, Szu-Fu; Hsieh, Ching-Chang; Hsu, Jenn-Jeih; Li, Meng-Jen; Yeh, Yi-Lin; Hsieh, T'sang-T'ang

2008-02-01

Ectodomain shedding of epidermal growth factor receptor ligands such as transforming growth factor- alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HBEGF), and amphiregulin (AREG) is considered to be important during implantation. Tumor necrosis factor-alpha converting enzyme (TACE) has been suggested as the major sheddase for these molecules. The objectives of this study are (1) to characterize the expression of TACE in the human placenta throughout gestation; (2) to determine the association between the expression of TACE with TGF-alpha, HBEGF, and AREG; (3) to ascertain whether TACE mediates TGF-alpha, HBEGF, and AREG shedding; and (4) to examine the effect of hypoxia on the expression of TACE. By analyzing a total of 55 villous samples representing different gestational ages, the authors found that TACE was continuously expressed in the placentas throughout gestation and that the levels of TACE were positively correlated with the levels of TGF-alpha, HBEGF, and AREG. Preadministration of a TACE inhibitor in villous explant cultures or transfection of cytotrophoblastic cells with TACE-specific small interference RNA decreased the shedding of HBEGF and AREG. Moreover, hypoxia (2% O(2)) caused an increase in the levels of TACE mRNA and protein in villous explants and primary cytotrophoblastic cells in vitro. These results indicate that oxygen regulates the expression of TACE and that TACE may be important for placental development during human pregnancy.

Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.

PubMed

Morisset, M; Richard, C; Astier, C; Jacquenet, S; Croizier, A; Beaudouin, E; Cordebar, V; Morel-Codreanu, F; Petit, N; Moneret-Vautrin, D A; Kanny, G

2012-05-01

Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.

Community-acquired pneumonia and positive urinary antigen tests: Factors associated with targeted antibiotic therapy.

PubMed

Mothes, A; Léotard, S; Nicolle, I; Smets, A; Chirio, D; Rotomondo, C; Tiger, F; Del Giudice, P; Perrin, C; Néri, D; Foucault, C; Della Guardia, M; Hyvernat, H; Roger, P-M

2016-10-01

The use of rapid microbiological tests is supported by antimicrobial stewardship policies. Targeted antibiotic therapy (TAT) for community-acquired pneumonia (CAP) with positive urinary antigen test (UAT) has been associated with a favorable impact on outcome. We aimed to determine the factors associated with TAT prescription. We conducted a retrospective multicenter study including all patients presenting with CAP and positive UAT for Streptococcus pneumoniae or Legionella pneumophila from January 2010 to December 2013. Patients presenting with aspiration pneumonia, coinfection, and neutropenia were excluded. CAP severity was assessed using the Pneumonia Severity Index (PSI). TAT was defined as the administration of amoxicillin for pneumococcal infection and either macrolides or fluoroquinolones (inactive against S. pneumoniae) for Legionella infection. A total of 861 patients were included, including 687 pneumococcal infections and 174 legionellosis from eight facilities and 37 medical departments. TAT was prescribed to 273 patients (32%). Four factors were found independently associated with a lower rate of TAT: a PSI score≥4 (OR 0.37), Hospital A (OR 0.41), hospitalization in the intensive care unit (OR 0.44), and cardiac comorbidities (OR 0.60). Four other factors were associated with a high rate of TAT: positive blood culture for S. pneumoniae (OR 2.32), Hospitals B (OR 2.34), E (OR 2.68), and H (OR 9.32). TAT in CAP with positive UAT was related to the hospitals as well as to patient characteristics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluating the use of blood cultures in the management of children hospitalized for community-acquired pneumonia.

PubMed

McCulloh, Russell J; Koster, Michael P; Yin, Dwight E; Milner, Tiffany L; Ralston, Shawn L; Hill, Vanessa L; Alverson, Brian K; Biondi, Eric A

2015-01-01

Blood cultures are often recommended for the evaluation of community-acquired pneumonia (CAP). However, institutions vary in their use of blood cultures, and blood cultures have unclear utility in CAP management in hospitalized children. To identify clinical factors associated with obtaining blood cultures in children hospitalized with CAP, and to estimate the association between blood culture obtainment and hospital length of stay (LOS). We performed a multicenter retrospective cohort study of children admitted with a diagnosis of CAP to any of four pediatric hospitals in the United States from January 1, 2011-December 31, 2012. Demographics, medical history, diagnostic testing, and clinical outcomes were abstracted via manual chart review. Multivariable logistic regression evaluated patient and clinical factors for associations with obtaining blood cultures. Propensity score-matched Kaplan-Meier analysis compared patients with and without blood cultures for hospital LOS. Six hundred fourteen charts met inclusion criteria; 390 children had blood cultures obtained. Of children with blood cultures, six (1.5%) were positive for a pathogen and nine (2.3%) grew a contaminant. Factors associated with blood culture obtainment included presenting with symptoms of systemic inflammatory response syndrome (OR 1.78, 95% CI 1.10-2.89), receiving intravenous hydration (OR 3.94, 95% CI 3.22-4.83), receiving antibiotics before admission (OR 1.49, 95% CI 1.17-1.89), hospital admission from the ED (OR 1.65, 95% CI 1.05-2.60), and having health insurance (OR 0.42, 95% CI 0.30-0.60). In propensity score-matched analysis, patients with blood cultures had median 0.8 days longer LOS (2.0 vs 1.2 days, P < .0001) without increased odds of readmission (OR 0.94, 95% CI 0.45-1.97) or death (P = .25). Obtaining blood cultures in children hospitalized with CAP rarely identifies a causative pathogen and is associated with increased LOS. Our results highlight the need to refine the role of obtaining blood cultures in children hospitalized with CAP.

Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E

PubMed Central

Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Osborne, Michael J.; Ramteke, Anup; Sun, Qingxiang; Niesman, Ashley; Chook, Yuh Min; Borden, Katherine L. B.

2016-01-01

Regulation of nuclear-cytoplasmic trafficking of oncoproteins is critical for growth homeostasis. Dysregulated trafficking contributes to malignancy, whereas understanding the process can reveal unique therapeutic opportunities. Here, we focus on eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many cancers, including acute myeloid leukemia (AML). Typically, eIF4E is localized to both the nucleus and cytoplasm, where it acts in export and translation of specific methyl 7-guanosine (m7G)–capped mRNAs, respectively. Nuclear accumulation of eIF4E in patients who have AML is correlated with increased eIF4E-dependent export of transcripts encoding oncoproteins. The subcellular localization of eIF4E closely correlates with patients’ responses. During clinical responses to the m7G-cap competitor ribavirin, eIF4E is mainly cytoplasmic. At relapse, eIF4E reaccumulates in the nucleus, leading to elevated eIF4E-dependent mRNA export. We have identified importin 8 as a factor that directly imports eIF4E into the nucleus. We found that importin 8 is highly elevated in untreated patients with AML, leading to eIF4E nuclear accumulation. Importin 8 only imports cap-free eIF4E. Cap-dependent changes to the structure of eIF4E underpin this selectivity. Indeed, m7G cap analogs or ribavirin prevents nuclear entry of eIF4E, which mirrors the trafficking phenotypes observed in patients with AML. Our studies also suggest that nuclear entry is important for the prooncogenic activity of eIF4E, at least in this context. These findings position nuclear trafficking of eIF4E as a critical step in its regulation and position the importin 8–eIF4E complex as a novel therapeutic target. PMID:27114554

Reliability and validity of the faculty evaluation instrument used at King Saud bin Abdulaziz University for Health Sciences: Results from the Haematology Course.

PubMed

Al-Eidan, Fahad; Baig, Lubna Ansari; Magzoub, Mohi-Eldin; Omair, Aamir

2016-04-01

To assess reliability and validity of evaluation tool using Haematology course as an example. The cross-sectional study was conducted at King Saud Bin Abdul Aziz University of Health Sciences, Riyadh, Saudi Arabia, in 2012, while data analysis was completed in 2013. The 27-item block evaluation instrument was developed by a multidisciplinary faculty after a comprehensive literature review. Validity of the questionnaire was confirmed using principal component analysis with varimax rotation and Kaiser normalisation. Identified factors were combined to get the internal consistency reliability of each factor. Student's t-test was used to compare mean ratings between male and female students for the faculty and block evaluation. Of the 116 subjects in the study, 80(69%) were males and 36(31%) were females. Reliability of the questionnaire was Cronbach's alpha 0.91. Factor analysis yielded a logically coherent 7 factor solution that explained 75% of the variation in the data. The factors were group dynamics in problem-based learning (alpha0.92), block administration (alpha 0.89), quality of objective structured clinical examination (alpha 0.86), block coordination (alpha 0.81), structure of problem-based learning (alpha 0.84), quality of written exam (alpha 0.91), and difficulty of exams (alpha0.41). Female students' opinion on depth of analysis and critical thinking was significantly higher than that of the males (p=0.03). The faculty evaluation tool used was found to be reliable, but its validity, as assessed through factor analysis, has to be interpreted with caution as the responders were less than the minimum required for factor analysis.

Risk of community-acquired pneumonia in chronic obstructive pulmonary disease stratified by smoking status: a population-based cohort study in the United Kingdom.

PubMed

Braeken, Dionne Cw; Rohde, Gernot Gu; Franssen, Frits Me; Driessen, Johanna Hm; van Staa, Tjeerd P; Souverein, Patrick C; Wouters, Emiel Fm; de Vries, Frank

2017-01-01

Smoking increases the risk of community-acquired pneumonia (CAP) and is associated with the development of COPD. Until now, it is unclear whether CAP in COPD is due to smoking-related effects, or due to COPD pathophysiology itself. To evaluate the association between COPD and CAP by smoking status. In total, 62,621 COPD and 191,654 control subjects, matched by year of birth, gender and primary care practice, were extracted from the Clinical Practice Research Datalink (2005-2014). Incidence rates (IRs) were estimated by dividing the total number of CAP cases by the cumulative person-time at risk. Time-varying Cox proportional hazard models were used to estimate the hazard ratios (HRs) for CAP in COPD patients versus controls. HRs of CAP by smoking status were calculated by stratified analyses in COPD patients versus controls and within both subgroups with never smoking as reference. IRs of CAP in COPD patients (32.00/1,000 person-years) and controls (6.75/1,000 person-years) increased with age and female gender. The risk of CAP in COPD patients was higher than in controls (HR 4.51, 95% CI: 4.27-4.77). Current smoking COPD patients had comparable CAP risk (HR 0.92, 95% CI: 0.82-1.02) as never smoking COPD patients (reference), whereas current smoking controls had a higher risk (HR 1.23, 95% CI: 1.13-1.34) compared to never smoking controls. COPD patients have a fourfold increased risk to develop CAP, independent of smoking status. Identification of factors related with the increased risk of CAP in COPD is warranted, in order to improve the management of patients at risk.

A synthetic peptide derived from A1 module in CRD4 of human TNF receptor-1 inhibits binding and proinflammatory effect of human TNF-alpha.

PubMed

Cao, Yingnan; Wang, Zhaohe; Bu, Xianzhang; Tang, Shu; Mei, Zhengrong; Liu, Peiqing

2009-06-01

Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine, which has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Proinflammatory effect of TNF-alpha is activated mainly through human TNF receptor-1 (TNF-R1). However, the role of the fourth cystein-rich domain (CRD4) of TNF-R1 extracellular portion in the interaction of TNF-alpha with TNF-R1 is still unclear. In the present study, binding activity of TNF-alpha to TNF-R1 and protein levels of IkappaB-alpha and nuclear transcription factor kappa B (NF-kappaB) p65 subunit in HeLa cells were measured using enzyme-linked immunosorbent assay (ELISA) and western-blot analysis. Pep 3 (LRENECVS) which was derived from the hydrophilic region of A1 module in CRD4 remarkably inhibited the binding of TNF-alpha to TNF-R1, and also reversed TNF-alpha-induced degradation of IkappaB-alpha and nuclear translocation of NF-kappaB p65 subunit in HeLa cells. Our results confirmed that the hydrophilic region of A1 module in CRD4 participated in the interaction of TNF-alpha with TNF-R1, and demonstrated the potential of small-molecule TNF-alpha extracellular inhibitors targeting at A1 module in CRD4 of TNF-R1 in suppressing proinflammatory effect of TNF-alpha.

NMR study of the transforming growth factor-alpha (TGF-alpha)-epidermal growth factor receptor complex. Visualization of human TGF-alpha binding determinants through nuclear Overhauser enhancement analysis.

PubMed

McInnes, C; Hoyt, D W; Harkins, R N; Pagila, R N; Debanne, M T; O'Connor-McCourt, M; Sykes, B D

1996-12-13

The study of human transforming growth factor-alpha (TGF-alpha) in complex with the epidermal growth factor (EGF) receptor extracellular domain has been undertaken in order to generate information on the interactions of these molecules. Analysis of 1H NMR transferred nuclear Overhauser enhancement data for titration of the ligand with the receptor has yielded specific data on the residues of the growth factor involved in contact with the larger protein. Significant increases and decreases in nuclear Overhauser enhancement cross-peak intensity occur upon complexation, and interpretation of these changes indicates that residues of the A- and C-loops of TGF-alpha form the major binding interface, while the B-loop provides a structural scaffold for this site. These results corroborate the conclusions from NMR relaxation studies (Hoyt, D. W., Harkins, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1994) Biochemistry 33, 15283-15292), which suggest that the C-terminal residues of the polypeptide are immobilized upon receptor binding, while the N terminus of the molecule retains considerable flexibility, and are consistent with structure-function studies of the TGF-alpha/EGF system indicating a multidomain binding model. These results give a visualization, for the first time, of native TGF-alpha in complex with the EGF receptor and generate a picture of the ligand-binding site based upon the intact molecule. This will undoubtedly be of utility in the structure-based design of TGF-alpha/EGF agonists and/or antagonists.

Condensin II Regulates Interphase Chromatin Organization Through the Mrg-Binding Motif of Cap-H2

PubMed Central

Wallace, Heather A.; Klebba, Joseph E.; Kusch, Thomas; Rogers, Gregory C.; Bosco, Giovanni

2015-01-01

The spatial organization of the genome within the eukaryotic nucleus is a dynamic process that plays a central role in cellular processes such as gene expression, DNA replication, and chromosome segregation. Condensins are conserved multi-subunit protein complexes that contribute to chromosome organization by regulating chromosome compaction and homolog pairing. Previous work in our laboratory has shown that the Cap-H2 subunit of condensin II physically and genetically interacts with the Drosophila homolog of human MORF4-related gene on chromosome 15 (MRG15). Like Cap-H2, Mrg15 is required for interphase chromosome compaction and homolog pairing. However, the mechanism by which Mrg15 and Cap-H2 cooperate to maintain interphase chromatin organization remains unclear. Here, we show that Cap-H2 localizes to interband regions on polytene chromosomes and co-localizes with Mrg15 at regions of active transcription across the genome. We show that co-localization of Cap-H2 on polytene chromosomes is partially dependent on Mrg15. We have identified a binding motif within Cap-H2 that is essential for its interaction with Mrg15, and have found that mutation of this motif results in loss of localization of Cap-H2 on polytene chromosomes and results in partial suppression of Cap-H2-mediated compaction and homolog unpairing. Our data are consistent with a model in which Mrg15 acts as a loading factor to facilitate Cap-H2 binding to chromatin and mediate changes in chromatin organization. PMID:25758823

Diabetes hinders community-acquired pneumonia outcomes in hospitalized patients.

PubMed

Martins, M; Boavida, J M; Raposo, J F; Froes, F; Nunes, B; Ribeiro, R T; Macedo, M P; Penha-Gonçalves, C

2016-01-01

This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and in-hospital mortality. We carried out a retrospective, nationwide register analysis of CAP in adult patients admitted to Portuguese hospitals between 2009 and 2012. Anonymous data from 157 291 adult patients with CAP were extracted from the National Hospital Discharge Database and we performed a DM-conditioned analysis stratified by age, sex and year of hospitalization. The 74 175 CAP episodes that matched the inclusion criteria showed a high burden of DM that tended to increase over time, from 23.7% in 2009 to 28.1% in 2012. Interestingly, patients with CAP had high DM prevalence in the context of the national DM prevalence. Episodes of CAP in patients with DM had on average 0.8 days longer hospital stay as compared to patients without DM (p<0.0001), totaling a surplus of 15 370 days of stay attributable to DM in 19 212 admissions. In-hospital mortality was also significantly higher in patients with CAP who have DM (15.2%) versus those who have DM (13.5%) (p=0.002). Our analysis revealed that DM prevalence was significantly increased within CAP hospital admissions, reinforcing other studies' findings that suggest that DM is a risk factor for CAP. Since patients with CAP who have DM have longer hospitalization time and higher mortality rates, these results hold informative value for patient guidance and healthcare strategies.

Consideration of Real World Factors Influencing Greenhouse Gas Emissions in ALPHA

EPA Science Inventory

Discuss a variety of factors that influence the simulated fuel economy and GHG emissions that are often overlooked and updates made to ALPHA based on actual benchmarking data observed across a range of vehicles and transmissions. ALPHA model calibration is also examined, focusin...

Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

PubMed

Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

2001-06-01

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

Identification of Actin-Binding Proteins from Maize Pollen

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

Staiger, C.J.

Specific Aims--The goal of this project was to gain an understanding of how actin filament organization and dynamics are controlled in flowering plants. Specifically, we proposed to identify unique proteins with novel functions by investigating biochemical strategies for the isolation and characterization of actin-binding proteins (ABPs). In particular, our hunt was designed to identify capping proteins and nucleation factors. The specific aims included: (1) to use F-actin affinity chromatography (FAAC) as a general strategy to isolate pollen ABPs (2) to produce polyclonal antisera and perform subcellular localization in pollen tubes (3) to isolate cDNA clones for the most promising ABPsmore » (4) to further purify and characterize ABP interactions with actin in vitro. Summary of Progress By employing affinity chromatography on F-actin or DNase I columns, we have identified at least two novel ABPs from pollen, PrABP80 (gelsolin-like) and ZmABP30, We have also cloned and expressed recombinant protein, as well as generated polyclonal antisera, for 6 interesting ABPs from Arabidopsis (fimbrin AtFIM1, capping protein a/b (AtCP), adenylyl cyclase-associated protein (AtCAP), AtCapG & AtVLN1). We performed quantitative analyses of the biochemical properties for two of these previously uncharacterized ABPs (fimbrin and capping protein). Our studies provide the first evidence for fimbrin activity in plants, demonstrate the existence of barbed-end capping factors and a gelsolin-like severing activity, and provide the quantitative data necessary to establish and test models of F-actin organization and dynamics in plant cells.« less

MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-catenin Signaling Transcripts by Recruiting CDK7 and RNA Methyltransferase

PubMed Central

Posternak, Valeriya; Ung, Matthew H.; Cheng, Chao; Cole, Michael D.

2016-01-01

MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/β-catenin signaling. Elevated mRNA cap methylation of Wnt signaling transcripts in response to MYC leads to augmented translational capacity, elevated protein levels, and enhanced Wnt signaling activity. Mechanistic evidence indicates that MYC promotes recruitment of RNA methyltransferase (RNMT) to Wnt signaling gene promoters by enhancing phosphorylation of serine 5 on the RNA Polymerase II Carboxy-Terminal Domain, mediated in part through an interaction between the TIP60 acetyltransferase complex and TFIIH. Implications MYC enhances mRNA cap methylation above and beyond transcriptional induction. PMID:27899423

Thermal infrared and visual observations of a water ice lag in the Mars southern summer

USGS Publications Warehouse

Titus, T.N.

2005-01-01

We present thermal infrared and visual evidence for the existence of water ice lags in the early southern summer. The observed H2O-ice lags lay in and near a chasma and appears to survive between 6-8 sols past the sublimation of the CO2. Possible sources of the H2O that compose the lag are (1) atmospheric H2O that is incorporated into the seasonal cap during condensation, (2) cold trapping of atmospheric water vapor onto the surface of the cap in the spring, or (3) a combination of the 2 processes where water is released from the sublimating cap only to be transported back over the cap edge and cold trapped. We refer to this later process as the "Houben" effect which may enrich the amount of water contained in the seasonal cap at 85??S by as much as a factor of 15. This phenomenon, which has already been identified for the northern retreating cap, may present an important water transport mechanism in the Southern Hemisphere.

Redox Control and Hydrogen Production in Sediment Caps Using Carbon Cloth Electrodes

PubMed Central

Sun, Mei; Yan, Fei; Zhang, Ruiling; Reible, Danny D.; Lowry, Gregory V.; Gregory, Kelvin B.

2010-01-01

Sediment caps that degrade contaminants can improve their ability to contain contaminants relative to sand and sorbent-amended caps, but few methods to enhance contaminant degradation in sediment caps are available. The objective of this study was to determine if, carbon electrodes emplaced within a sediment cap at poised potential could create a redox gradient and provide electron donor for the potential degradation of contaminants. In a simulated sediment cap overlying sediment from the Anacostia River (Washington, DC), electrochemically induced redox gradients were developed within 3 days and maintained over the period of the test (~100 days). Hydrogen and oxygen were produced by water electrolysis at the electrode surfaces and may serve as electron donor and acceptor for contaminant degradation. Electrochemical and geochemical factors that may influence hydrogen production were studied. Hydrogen production displayed zero order kinetics with ~75% coulombic efficiency and rates were proportional to the applied potential between 2.5V to 5V and not greatly affected by pH. Hydrogen production was promoted by increasing ionic strength and in the presence of natural organic matter. Graphite electrode-stimulated degradation of tetrachlorobenzene in a batch reactor was dependent on applied voltage and production of hydrogen to a concentration above the threshold for biological dechlorination. These findings suggest that electrochemical reactive capping can potentially be used to create “reactive” sediments caps capable of promoting chemical or biological transformations of contaminants within the cap. PMID:20879761

Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor.

PubMed

Matsuura, Takashi; Uematsu, Takashi; Yamaoka, Minoru; Furusawa, Kiyofumi

2004-03-01

The aim of this study was to clarify the effects of alpha-N-acetylgalactosaminidase (alpha-NaGalase) produced by human salivary gland adenocarcinoma (SGA) cells on the bioactivity of macrophage-activating factor (GcMAF). High exo-alpha-NaGalase activity was detected in the SGA cell line HSG. HSG alpha-NaGalase had both exo- and endo-enzyme activities, cleaving the Gal-GalNAc and GalNAc residues linked to Thr/Ser but not releasing the [NeuAc2-6]GalNac residue. Furthermore, GcMAF enzymatically prepared from the Gc protein enhanced the superoxide-generation capacity and phagocytic activity of monocytes/macrophages. However, GcMAF treated with purified alpha-NaGalase did not exhibit these effects. Thus, HSG possesses the capacity to produce larger quantities of alpha-NaGalase, which inactivates GcMAF produced from Gc protein, resulting in reduced phagocytic activity and superoxide-generation capacity of monocytes/macrophages. The present data strongly suggest that HSG alpha-NaGalase acts as an immunodeficiency factor in cancer patients.

Immunoreactive transforming growth factor alpha is commonly present in colorectal neoplasia.

PubMed Central

Tanaka, S.; Imanishi, K.; Yoshihara, M.; Haruma, K.; Sumii, K.; Kajiyama, G.; Akamatsu, S.

1991-01-01

Surgical specimens from 19 patients with invasive colorectal cancers and 12 specimens of normal mucosa from the same patients were examined immunohistochemically for the production of the immunoreactive (IR-) transforming growth factor (TGF)-alpha and IR-epidermal growth factor (EGF) with an anti-TGF-alpha monoclonal antibody (MAb) OAL-MTG01 and anti-EGF MAb KEM-10. Immunoreactive TGF-alpha was detected in 16 (84.2%) of 19 colorectal cancers. In contrast, there was no IR-TGF-alpha in the gland cells of normal mucosa. Immunoreactive EGF was detected in 7 (36.8%) of 19 colorectal cancers and 1 (8.3%) of 12 cases of normal mucosa. The production of both IR-TGF-alpha and IR-EGF in colorectal cancer did not differ by histologic type and Dukes' stage. Immunoreactive TGF-alpha was detected at significantly higher incidence than IR-EGF in colorectal cancer. These results indicate that IR-TGF-alpha should prove valuable as a possible tumor marker in colorectal cancers, and it may be very useful in understanding the biology of colorectal cancer. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1853928

Production and action of cytokines in space

NASA Technical Reports Server (NTRS)

Chapes, Stephen K.; Morrison, Dennis R.; Guikema, James A.; Lewis, Marian L.; Spooner, Brian S.

1994-01-01

B6MP102 cells, a continuously cultured murine bone marrow macrophage cell line, were tested for secretion of tumor necrosis factor-alpha and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis factor-alpha and interleukin-1 when stimulated in space with lipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor-alpha, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-alpha, was inhibited.

Consideration of Real World Factors Influencing Greenhouse ...

EPA Pesticide Factsheets

Discuss a variety of factors that influence the simulated fuel economy and GHG emissions that are often overlooked and updates made to ALPHA based on actual benchmarking data observed across a range of vehicles and transmissions. ALPHA model calibration is also examined, focusing on developing generic calibrations for driver behavior, transmission gear selection and torque converter lockup. In addition, show the derivation of correction factors needed to estimate cold start emission results. To provide an overview of the ALPHA tool with additional focus on recent updates by presenting the approach for validating and calibrating ALPHA to match particular vehicles in a general sense, then by looking at the individual losses, and calibration factors likely to influence fuel economy.

The Role of Internet Addiction and Social Media Membership on University Students' Psychological Capital

ERIC Educational Resources Information Center

Simsek, Eylem; Sali, Jale Balaban

2014-01-01

How Internet addiction affects happiness of university students in terms of their cognitive and emotional resources was not adequately investigated. One of the inner resources of life satisfaction and happiness is defined as psychological capital (PsyCap), under the paradigm of positive psychology. PsyCap consists of four main sub-factors: hope,…

Androgen receptor requires JunD as a coactivator to switch on an oxidative stress generation pathway in prostate cancer cells.

PubMed

Mehraein-Ghomi, Farideh; Basu, Hirak S; Church, Dawn R; Hoffmann, F Michael; Wilding, George

2010-06-01

Relatively high oxidative stress levels in the prostate are postulated to be a major factor for prostate carcinogenesis and prostate cancer (CaP) progression. We focused on elucidating metabolic pathways of oxidative stress generation in CaP cells. Previously, we showed that the transcription factor JunD is essential for androgen-induced reactive oxygen species (ROS) production in androgen-dependent human CaP cells. We also recently showed that androgen induces the first and regulatory enzyme spermidine/spermine N1-acetyltransferase (SSAT) in a polyamine catabolic pathway that produces copious amounts of metabolic ROS. Here, we present coimmunoprecipitation and Gaussia luciferase reconstitution assay data that show that JunD forms a complex with androgen-activated androgen receptor (AR) in situ. Our chromatin immunoprecipitation assay data show that JunD binds directly to a specific SSAT promoter sequence only in androgen-treated LNCaP cells. Using a vector containing a luciferase reporter gene connected to the SSAT promoter and a JunD-silenced LNCaP cell line, we show that JunD is essential for androgen-induced SSAT gene expression. The elucidation of JunD-AR complex inducing SSAT expression leading to polyamine oxidation establishes the mechanistic basis of androgen-induced ROS production in CaP cells and opens up a new prostate-specific target for CaP chemopreventive/chemotherapeutic drug development. Copyright 2010 AACR.

Free Body Dynamics of a Spinning Cylinder With Planar Restraint (a.k.a. Barrel of Fun)

NASA Technical Reports Server (NTRS)

Moraru, Laurentiu; Dimofte, Florin; Hendricks, Robert C.

2006-01-01

The dynamic motion of a cylinder on a floor or hard surface is both entertaining and instructive. With maintenance torques, motion can be sustained and controlled as illustrated in a video clip that can be viewed in the PDF file of this document. The analysis of such a cylinder with and without end caps is burned on rotation about its center of mass and restrained by a plane normal to the axis passing through its center of mass at an angle alpha. For small values of alpha, the governing equations are simplified, and for symmetric bodies, stability requires rotation greater than [2 square root of(JWL*)]/J(sub X), where J is the transverse mass moment of inertia, W is the weight of the cylinder, L* is the cylinder length from the base to the center of mass, and JX is the mass moment of inertia about the longitudinal axis OX of the barrel. Comparisons to data are made and some applications are discussed.

Identification of high-mannose and multiantennary complex-type N-linked glycans containing alpha-galactose epitopes from Nurse shark IgM heavy chain.

PubMed

Harvey, David J; Crispin, Max; Moffatt, Beryl E; Smith, Sylvia L; Sim, Robert B; Rudd, Pauline M; Dwek, Raymond A

2009-11-01

MALDI-TOF mass spectrometry, negative ion nano-electrospray MS/MS and exoglycosidase digestion were used to identify 36 N-linked glycans from 19S IgM heavy chain derived from the nurse shark (Ginglymostoma cirratum). The major glycan was the high-mannose compound, Man(6)GlcNAc(2) accompanied by small amounts of Man(5)GlcNAc(2), Man(7)GlcNAc(2) and Man(8)GlcNAc(2). Bi- and tri-antennary (isomer with a branched 3-antenna) complex-type glycans were also abundant, most contained a bisecting GlcNAc residue (beta1-->4-linked to the central mannose) and with varying numbers of alpha-galactose residues capping the antennae. Small amounts of monosialylated glycans were also found. This appears to be the first comprehensive study of glycosylation in this species of animal. The glycosylation pattern has implications for the mechanism of activation of the complement system by nurse shark IgM.

The ionosphere of Uranus - A myriad of possibilities

NASA Astrophysics Data System (ADS)

Chandler, M. O.; Waite, J. H.

1986-01-01

A one-dimensional model has been used to study the effects of exospheric temperature, methane and water influx, ionospheric outflow, and electron precipitation on the composition and structure of the ionosphere of Uranus. Peak ion concentrations range from 1000 to 1 million per cu cm with a wide variation in peak altitude, which depends strongly on the exospheric temperature. In all the cases considered, H(+) is the major ion in the topside ionosphere. At altitudes near or below the peak, H3(+) and CH5(+) can dominate, depending on the magnitude of CH4 and H2O influx. Atomic hydrogen column depths above the methane absorbing layer exceed 10 to the 17th per sq cm and can produce large (400 R) emissions of resonantly scattered Lyman-alpha. In the sunlit polar cap, electron precipitation with energy fluxes of 0.6 to 1.0 erg/sq cm s results in direct production of Lyman-alpha emissions that exceed 1 kR.

Enzymatic transformation of nonfood biomass to starch

PubMed Central

You, Chun; Chen, Hongge; Myung, Suwan; Sathitsuksanoh, Noppadon; Ma, Hui; Zhang, Xiao-Zhou; Li, Jianyong; Zhang, Y.-H. Percival

2013-01-01

The global demand for food could double in another 40 y owing to growth in the population and food consumption per capita. To meet the world’s future food and sustainability needs for biofuels and renewable materials, the production of starch-rich cereals and cellulose-rich bioenergy plants must grow substantially while minimizing agriculture’s environmental footprint and conserving biodiversity. Here we demonstrate one-pot enzymatic conversion of pretreated biomass to starch through a nonnatural synthetic enzymatic pathway composed of endoglucanase, cellobiohydrolyase, cellobiose phosphorylase, and alpha-glucan phosphorylase originating from bacterial, fungal, and plant sources. A special polypeptide cap in potato alpha-glucan phosphorylase was essential to push a partially hydrolyzed intermediate of cellulose forward to the synthesis of amylose. Up to 30% of the anhydroglucose units in cellulose were converted to starch; the remaining cellulose was hydrolyzed to glucose suitable for ethanol production by yeast in the same bioreactor. Next-generation biorefineries based on simultaneous enzymatic biotransformation and microbial fermentation could address the food, biofuels, and environment trilemma. PMID:23589840

Formation and self-organization kinetics of alpha-CD/PEO-based pseudo-polyrotaxanes in water. A specific behavior at 30 degrees C.

PubMed

Travelet, Christophe; Schlatter, Guy; Hébraud, Pascal; Brochon, Cyril; Lapp, Alain; Hadziioannou, Georges

2009-08-04

alpha-Cyclodextrins (alpha-CDs) have the ability to form inclusion complexes with poly(ethylene oxide) (PEO) polymer chains. These pseudo-polyrotaxanes (PPRs) can be obtained by quenching an alpha-CD/PEO mixture in water from 70 degrees C down to a lower temperature (typically in the range from 5 to 30 degrees C) thanks to favorable interactions between alpha-CD cavities and PEO chains. Moreover, starting from a liquid alpha-CD/PEO mixture at a total mass fraction of 15% w/w at 70 degrees C, the formation of PPRs with time at a lower temperature induces a white physical gel with time, and phase separation is observed. We established that PPR molecules are exclusively found in the precipitated phase although unthreaded alpha-CD molecules and unthreaded PEO chains are in the liquid phase. At 30 degrees C, the physical gel formation is much slower than at 5 degrees C. At 30 degrees C, we established that, in a first step, alpha-CDs thread onto PEO chains, forming PPR molecules which are not in good solvent conditions in water. At a higher length scale, rapid aggregation of the PPR molecules occurs, and threaded alpha-CD-based nanocylinders form (cylinder length L = 5.7 nm and cylinder radius R = 4.7 nm). At a higher length scale, alpha-CD-based nanocylinders associate in a Gaussian way, engendering the formation of precipitated domains which are responsible for the high turbidity of the studied system. At the end of this first step (i.e., after 20 min), the system still remains liquid and the PPRs are totally formed. Then, in a second step (i.e., after 150 min), the system undergoes its reorganization characterized by a compacity increase of the precipitated domains and forms a physical gel. We found that PPRs are totally formed after 20 min at 30 degrees C and that the system stays in a nongel state up to 150 min. This opens new perspectives regarding the PPR chemical modification: between these two characteristic times, we can easily envisage an efficient chemical modification of the PPR molecules in water, as for instance an end-capping reaction leading to the synthesis of polyrotaxanes.

Induction of VEGF expression by alpha-tocopherol and alpha-tocopheryl phosphate via PI3Kgamma/PKB and hTAP1/SEC14L2-mediated lipid exchange

USDA-ARS?s Scientific Manuscript database

In several studies, vitamin E has been observed to influence angiogenesis and vasculogenesis. We recently showed that the phosphorylated form of alpha-tocopherol (alphaT), alpha-tocopheryl phosphate (alphaTP), increases the expression of the vascular endothelial growth factor (VEGF). Thus, alphaTP m...

Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements.

PubMed

Chen, Zhilin; Eadie, Ashley L; Hall, Sean R; Ballantyne, Laurel; Ademidun, David; Tse, M Yat; Pang, Stephen C; Melo, Luis G; Ward, Christopher A; Brunt, Keith R

2017-01-01

Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha, in vitro and in vivo . Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.

Kruppel-like factor 2 inhibits hypoxia-inducible factor 1alpha expression and function in the endothelium.

PubMed

Kawanami, Daiji; Mahabeleshwar, Ganapati H; Lin, Zhiyong; Atkins, G Brandon; Hamik, Anne; Haldar, Saptarsi M; Maemura, Koji; Lamanna, Joseph C; Jain, Mukesh K

2009-07-31

Hypoxia-inducible factor 1 (HIF-1) is a central regulator of the hypoxic response in many cell types. In endothelial cells, HIF-1 induces the expression of key proangiogenic factors to promote angiogenesis. Recent studies have identified Kruppel-like factor 2 (KLF2) as a potent inhibitor of angiogenesis. However, the role of KLF2 in regulating HIF-1 expression and function has not been evaluated. KLF2 expression was induced acutely by hypoxia in endothelial cells. Adenoviral overexpression of KLF2 inhibited hypoxia-induced expression of HIF-1alpha and its target genes such as interleukin 8, angiopoietin-2, and vascular endothelial growth factor in endothelial cells. Conversely, knockdown of KLF2 increased expression of HIF-1alpha and its targets. Furthermore, KLF2 inhibited hypoxia-induced endothelial tube formation, whereas endothelial cells from mice with haploinsufficiency of KLF2 showed increased tube formation in response to hypoxia. Consistent with this ex vivo observation, KLF2 heterozygous mice showed increased microvessel density in the brain. Mechanistically, KLF2 promoted HIF-1alpha degradation in a von Hippel-Lindau protein-independent but proteasome-dependent manner. Finally, KLF2 disrupted the interaction between HIF-1alpha and its chaperone Hsp90, suggesting that KLF2 promotes degradation of HIF-1alpha by affecting its folding and maturation. These observations identify KLF2 as a novel inhibitor of HIF-1alpha expression and function. Therefore, KLF2 may be a target for modulating the angiogenic response in disease states.

Community-acquired bacterial pneumonia in human immunodeficiency virus-infected patients: validation of severity criteria. The Grupo Andaluz para el Estudio de las Enfermedades Infecciosas.

PubMed

Cordero, E; Pachón, J; Rivero, A; Girón, J A; Gómez-Mateos, J; Merino, M D; Torres-Tortosa, M; González-Serrano, M; Aliaga, L; Collado, A; Hernández-Quero, J; Barrera, A; Nuño, E

2000-12-01

Severity criteria for community-acquired pneumonia (CAP) have always excluded patients with human immunodeficiency virus (HIV) infection. A 1-yr, multicenter, prospective observational study of HIV-infected patients with bacterial CAP was done to validate the criteria used in the American Thoracic Society (ATS) guidelines for CAP, and to determine the prognosis-associated factors in the HIV-infected population with bacterial CAP. Overall, 355 cases were included, with an attributable mortality of 9.3%. Patients who met the ATS criteria had a longer hospital stay (p = 0.01), longer duration of fever (p < 0.001), and higher attributable mortality (13.1% versus 3.5%, p = 0.02) than those who did not. Three factors were independently related to mortality: CD4(+) cell count < 100/microl, radiologic progression of disease, and shock. Pleural effusion, cavities, and/or multilobar infiltrates at admission were independently associated with radiologic progression. A prognostic rule based on the five criteria of shock, CD4(+) cell count < 100/microl, pleural effusion, cavities, and multilobar infiltrates had a high negative predictive value for mortality (97.1%). The attributable mortality for severe pneumonia was 11.3%, as compared with 1.3% for nonsevere disease (p = 0.008). The ATS severity criteria are valid in HIV-infected patients with bacterial CAP. Our study provides the basis for identification of patients who may require hospitalization determined by clinical judgment and the five clinical criteria of shock, a CD4(+) cell count < 100/microl, pleural effusion, cavities, and multilobar involvement. These prognostic factors should be validated in independent cohort studies.

c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line.

PubMed

Iglesias, T; Llanos, S; López-Barahona, M; Pérez-Aranda, A; Rodríguez-Peña, A; Bernal, J; Höhne, A; Seliger, B; Muñoz, A

1994-07-01

The c-erbA alpha protooncogene coding for the thyroid hormone (T3) receptor (TR alpha 1) and the viral, mutated v-erbA oncogene were expressed in an immortal mouse glial cell line (B3.1) using retroviral vectors. c-erbA alpha expression led to a decrease in cell proliferation in high and low serum conditions, both in the presence and in the absence of T3. In serum-free medium, c-erbA-expressing cells (B3.1 + TR alpha 1) were completely arrested, whereas cells expressing v-erbA (B3.1 + v-erbA) showed a higher DNA synthesis rate than normal B3.1 cells. Although proliferation of all three cell types was stimulated by platelet-derived growth factor and basic fibroblast growth factor, differences were also observed in the response to these agents. B3.1 + TR alpha 1 cells were more sensitive to platelet-derived growth factor than B3.1 and B3.1 + v-erbA cells. In contrast, B3.1 cells responded to basic fibroblast growth factor better than B3.1 + TR alpha 1 or B3.1 + v-erbA cells. Insulin-like growth factor I potentiated the action of platelet-derived growth factor and basic fibroblast growth factor. Again, different responses to treatment with insulin-like growth factor I alone were observed; B3.1 + TR alpha 1 cells did not respond to it, whereas B3.1 + v-erbA cells showed a dramatic stimulation by this agent. Interestingly, in the presence of T3, the blockade in B3.1 + TR alpha 1 cell proliferation was accompanied by the down-regulation of the typical astrocytic genes, glial fibrillary acidic protein and vimentin. These hormone effects were not found in v-erbA-expressing cells. In addition, v-erbA inhibited the basal expression of the cyclic nucleotide phosphodiesterase gene, an oligodendrocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)

Measuring alcohol-related consequences and motives among students attending Historically Black Colleges and Universities.

PubMed

Messina, Bryan G; Tseng, Andy; Correia, Christopher J

2015-07-01

College student drinkers have the propensity to engage in heavy alcohol consumption. These consumption patterns can be problematic given the well-established relationship between heavy drinking and negative consequences of alcohol consumption. Though the research on college student drinking is abundant, much of the work conducted has been with Caucasian samples and less so with African American samples or at Historically Black Colleges and Universities (HBCUs). The current paper assessed the internal reliability and concurrent validity of two popular measures of alcohol related negative consequences (CAPS-r and YAACQ) and a measure of drinking motives (DMQ-R) within a HBCU sample. Total scores for the CAPS-r and YAACQ and all five subscales of the DMQ-R were internally reliable as determined by Cronbach's alpha. Correlations and regressions established concurrent validity for both measures of negative consequences as well as the subscales for the DMQ-R. Findings support the use of these measures in the assessment of negative consequences and motivations for alcohol consumption within a HBCU population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dose Comparisons for a Site-specific Representative Person Using the Age-dependent Dose Coefficients in CAP88-PC Version 4.

PubMed

Stagich, Brooke H; Moore, Kelsey R; Newton, Joseph R; Dixon, Kenneth L; Jannik, G Timothy

2017-04-01

Most U.S. Department of Energy (DOE) facilities with radiological airborne releases use the U.S. Environmental Protection Agency's (EPA) environmental dosimetry code CAP88-PC to demonstrate compliance with regulations in 40CFR61, subpart H [National Emission Standards for Hazardous Air Pollutants: Radiological (NESHAP)]. In 2015, EPA released Version 4 of CAP88-PC, which included significant modifications that improved usability and age-dependent dose coefficients and usage factors for six age groups (infant, 1 y, 5 y, 10 y, 15 y, and adult). However, EPA has not yet provided specific guidance on how to use these age-dependent factors. For demonstrating compliance with DOE public dose regulations, the Savannah River Site (SRS) recently changed from using the maximally exposed individual (MEI) concept (adult male) to the representative person concept (age- and gender-averaged reference person). In this study, dose comparisons are provided between the MEI and a SRS-specific representative person using the age-specific dose coefficients and usage factors in CAP88-PC V.4. Dose comparisons also are provided for each of the six age groups using five radionuclides of interest at SRS (tritium oxide, Cs, Sr, Pu, and I). In general, the total effective dose increases about 11% for the representative person as compared to the current NESHAP MEI because of the inclusion of the more radiosensitive age groups.

A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement.

PubMed

Chuang, Tzu-Wei; Lee, Kuo-Ming; Lou, Yuan-Chao; Lu, Chia-Chen; Tarn, Woan-Yuh

2016-04-15

Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Spinal neurons require Islet1 for subtype-specific differentiation of electrical excitability

PubMed Central

2014-01-01

Background In the spinal cord, stereotypic patterns of transcription factor expression uniquely identify neuronal subtypes. These transcription factors function combinatorially to regulate gene expression. Consequently, a single transcription factor may regulate divergent development programs by participation in different combinatorial codes. One such factor, the LIM-homeodomain transcription factor Islet1, is expressed in the vertebrate spinal cord. In mouse, chick and zebrafish, motor and sensory neurons require Islet1 for specification of biochemical and morphological signatures. Little is known, however, about the role that Islet1 might play for development of electrical membrane properties in vertebrates. Here we test for a role of Islet1 in differentiation of excitable membrane properties of zebrafish spinal neurons. Results We focus our studies on the role of Islet1 in two populations of early born zebrafish spinal neurons: ventral caudal primary motor neurons (CaPs) and dorsal sensory Rohon-Beard cells (RBs). We take advantage of transgenic lines that express green fluorescent protein (GFP) to identify CaPs, RBs and several classes of interneurons for electrophysiological study. Upon knock-down of Islet1, cells occupying CaP-like and RB-like positions continue to express GFP. With respect to voltage-dependent currents, CaP-like and RB-like neurons have novel repertoires that distinguish them from control CaPs and RBs, and, in some respects, resemble those of neighboring interneurons. The action potentials fired by CaP-like and RB-like neurons also have significantly different properties compared to those elicited from control CaPs and RBs. Conclusions Overall, our findings suggest that, for both ventral motor and dorsal sensory neurons, Islet1 directs differentiation programs that ultimately specify electrical membrane as well as morphological properties that act together to sculpt neuron identity. PMID:25149090

Internal and External Factors Related to Burnout among Iron and Steel Workers: A Cross-Sectional Study in Anshan, China.

PubMed

Guo, Haiqiang; Guo, Huifang; Yang, Yilong; Sun, Baozhi

2015-01-01

Burnout is a syndrome of emotional exhaustion, cynicism and reduced professional efficacy, which can result from long-term work stress. Although the burnout level is high among iron and steel workers, little is known concerning burnout among iron and steel worker. This study aimed to evaluate the burnout and to explore its associated internal and external factors in iron and steel workers. A cross-sectional survey was conducted in iron and steel workers at the Anshan iron-steel complex in Anshan, northeast China. Self-administered questionnaires were distributed to 1,600 workers, and finally 1,300 questionnaires were returned. Burnout was measured using the Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS). Effort-reward imbalance (ERI), perceived organizational support (POS), and psychological capital (PsyCap) were measured anonymously. A hierarchical regression model was applied to explore the internal and external factors associated with burnout. Mean MBI-GS scores were 13.11±8.06 for emotional exhaustion, 6.64±6.44 for cynicism, and 28.96±10.39 for professional efficacy. Hierarchical linear regression analysis showed that ERI and POS were the most powerful predictors for emotional exhaustion and cynicism, and PsyCap was the most robust predictor for high professional efficacy. Chinese iron and steel workers have a high level of burnout. Burnout might be associated with internal and external factors, including ERI, POS, and PsyCap. Further studies are recommended to develop an integrated model including both internal and external factors, to reduce the level of ERI, and improve POS and workers' PsyCap, thereby alleviating the level of burnout among iron and steel workers.

Internal and External Factors Related to Burnout among Iron and Steel Workers: A Cross-Sectional Study in Anshan, China

PubMed Central

Guo, Haiqiang; Guo, Huifang; Yang, Yilong; Sun, Baozhi

2015-01-01

Background Burnout is a syndrome of emotional exhaustion, cynicism and reduced professional efficacy, which can result from long-term work stress. Although the burnout level is high among iron and steel workers, little is known concerning burnout among iron and steel worker. This study aimed to evaluate the burnout and to explore its associated internal and external factors in iron and steel workers. Methods A cross-sectional survey was conducted in iron and steel workers at the Anshan iron-steel complex in Anshan, northeast China. Self-administered questionnaires were distributed to 1,600 workers, and finally 1,300 questionnaires were returned. Burnout was measured using the Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS). Effort-reward imbalance (ERI), perceived organizational support (POS), and psychological capital (PsyCap) were measured anonymously. A hierarchical regression model was applied to explore the internal and external factors associated with burnout. Results Mean MBI-GS scores were 13.11±8.06 for emotional exhaustion, 6.64±6.44 for cynicism, and 28.96±10.39 for professional efficacy. Hierarchical linear regression analysis showed that ERI and POS were the most powerful predictors for emotional exhaustion and cynicism, and PsyCap was the most robust predictor for high professional efficacy. Conclusions Chinese iron and steel workers have a high level of burnout. Burnout might be associated with internal and external factors, including ERI, POS, and PsyCap. Further studies are recommended to develop an integrated model including both internal and external factors, to reduce the level of ERI, and improve POS and workers’ PsyCap, thereby alleviating the level of burnout among iron and steel workers. PMID:26575031

Technical Note: Dosimetry of Leipzig and Valencia applicators without the plastic cap

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

Granero, D., E-mail: dgranero@eresa.com; Candela-Juan, C.; Vijande, J.

2016-05-15

Purpose: High dose rate (HDR) brachytherapy for treatment of small skin lesions using the Leipzig and Valencia applicators is a widely used technique. These applicators are equipped with an attachable plastic cap to be placed during fraction delivery to ensure electronic equilibrium and to prevent secondary electrons from reaching the skin surface. The purpose of this study is to report on the dosimetric impact of the cap being absent during HDR fraction delivery, which has not been explored previously in the literature. Methods: GEANT4 Monte Carlo simulations (version 10.0) have been performed for the Leipzig and Valencia applicators with andmore » without the plastic cap. In order to validate the Monte Carlo simulations, experimental measurements using radiochromic films have been done. Results: Dose absorbed within 1 mm of the skin surface increases by a factor of 1500% for the Leipzig applicators and of 180% for the Valencia applicators. Deeper than 1 mm, the overdosage flattens up to a 10% increase. Conclusions: Differences of treating with or without the plastic cap are significant. Users must check always that the plastic cap is in place before any treatment in order to avoid overdosage of the skin. Prior to skin HDR fraction delivery, the timeout checklist should include verification of the cap placement.« less

La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs

PubMed Central

Lahr, Roni M; Fonseca, Bruno D; Ciotti, Gabrielle E; Al-Ashtal, Hiba A; Jia, Jian-Jun; Niklaus, Marius R; Blagden, Sarah P; Alain, Tommy; Berman, Andrea J

2017-01-01

The 5’terminal oligopyrimidine (5’TOP) motif is a cis-regulatory RNA element located immediately downstream of the 7-methylguanosine [m7G] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5’TOP motif, a cap analog (m7GTP), and a capped cytidine (m7GpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5’TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5’TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis. DOI: http://dx.doi.org/10.7554/eLife.24146.001 PMID:28379136

Proecdysial changes in serum ecdysone titers, gastrolith formation, and limb regeneration following molt induction by limb autotomy and/or eyestalk removal in the land crab, Gecarcinus lateralis

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

McCarthy, J.F.; Skinner, D.M.

1977-01-01

The changes in serum ecdysone titers, gastrolith deposition, and limb regeneration were monitored at each stage of the molt cycle in the land crab, Gecarcinus lateralis. Animals were induced to molt by multiple-limb autotomy or eyestalk removal. The presence of ..cap alpha..-ecdysone and b-ecdysone (20-hydroxyecdysone) in the animals' serum was demonstrated chromatographically. ..beta..-ecdysone was the major circulating ecdysone, while ..cap alpha..-ecdysone was present only at very low concentrations. Four other components reacting with the ecdysone antiserum were separated chromatographically; one of these, a nonpolar compound, became a major component of the serum ecdysones at the time of maximum hormone titers.more » Ecdysone titers in the serum remained at the level characteristic of intermolt (approximately 10 ng/ml) during basal regeneration and rose linearly during the premolt period, reaching a maximum when regeneration of limbs had ceased and exoskeleton was deposited. Ecdysone decreased during stages D/sub 3/ and D/sub 4/, approaching intermolt levels at the time of ecdysis, where they remained through postmolt stages A and B. The patterns of premolt changes in ecdysone titers, gastroliths, and regeneration were very similar in ''normal'' animals (stimulated to molt by the loss of eight pereiopods) and in animals without eyestalks; however, in crabs without eyestalks, the changes were completed in about half the time as in crabs with eyestalks. Basal regeneration is associated with low ecdysone levels even in crabs without eyestalks. The normal sequence of proecdysial events is not initiated until the completion of basal regeneration. It is suggested that there exists a yet-unidentified mechanism outside the eyestalk capable of preventing increases in ecdysone titers while limbs engage in basal regeneration.« less

Interaction of tachykinins with their receptors studied with cyclic analogues of substance P and neurokinin B

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

Ploux, O.; Lavielle, S.; Chassaing, G.

1987-11-01

The activities of two groups of cyclic agonists of substance P (SP) have been studied. The disulfide bridge constraints have been designed on the basis of conformational studies on SP and physalaemin indicating an ..cap alpha..-helical structure for the core of these two tachykinins (group I) and a folding of the C-terminal carboxamide towards the side chains of the glutamines 5 and 6 (group II). Only peptides simulating the ..cap alpha..-helix present substantial potencies. (Cys/sup 3,6/)SP is as active as SP in inhibiting /sup 125/I-labeled Bolton and Hunter SP-specific binding on rat brain synaptosomes and on dog carotid bioassay, twomore » assays specific for the neurokinin 1 receptor. Moreover, (Cys/sup 3,6/)SP is a potent as neurokinin B in inhibiting /sup 125/I-labeled Bolton and Hunter eledoisin-specific binding on rat cortical synaptosomes as well as in stimulating rat portal vein, two tests specific for the neurokinin 3 receptor. Interestingly, in contrast to neurokinin B, (Cys/sup 3,6/)SP is a weak agonist of the neurokinin 2 receptor subtype, as evidenced by its binding potency in inhibiting /sup 3/H-labeled neurokinin A-specific binding on rat duodenum and in inducing the contractions of the rabbit pulmonary artery, a neurokinin 2-type bioassay. To increase the specificity of the cyclic analogue (Cys/sup 3,6/)SP positions 8 and 9 were modified. Collectively, these results suggest that the neurokinin 1 and neurokinin 3 tachykinin receptors may recognize a similar three-dimensional structure of the core of the tachykinins. Different orientations of the common C-terminal tripeptide may be related to the selectivity for the different receptor subtypes.« less

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

Inbar, S.; Linschitz, H.; Cohen, S.G.

Nanosecond flash photolysis, steady irradiation, and deuterium substitution studies have been carried out on solutions of benzophenone with added reductants. Quantum yields (phi/sub ketyl/) for reduction in benzene of benzophenone triplet to ketyl radical, based on phi = 2 for benzhydrol (I), were approx. 1 for cyclohexane (II), tert-butylamine (III), 2-aminobutane (IV), cyclohexylamine (V), di-n-propylamine (VI), and triethylamine (VII), approx. 0.7 for 1,4-diazabicyclo(2.2.2)octane (VIII), and approx. 0 for tert-butyl alcohol (IX). Thus, quenching, without radical formation by H abstraction from N and/or ..cap alpha..-C, does not occur with common aliphatic amines but does with Dabco (VIII). The latter quenching ismore » markedly increased by small additions of acetonitrile; the flash spectrum from this compound indicates formation of a triplet amine CT complex or radical ion pair. Triplet-reductant interaction rate constants, k/sur ir/, are high for the amines (approx. 10/sup 8/-10/sup 9/ M/sup -1/ s/sup -1/) but also show significant deuterium kinetic isotope effects: 1.9 with III-N-d/sub 2/; 1.4 with IV-N-d/sub 2/; 1.2-1.3 with IV-..cap alpha..-C-d. It is proposed that k/sub ir/ measures H atom abstraction, favored in the transition state by an initial charge-transfer interaction. Overall steady irradiation quantum yields of reduction by amines, phi/sub Red/, are much lower than phi/sub ketyl/. This is attributed to disproportionationreactions of ketyl and alkylaminyl radicals for primary and secondary amines, and, possibly, aminoalkyl radicals for tertiary amines. In the case of tert-butylamine, the rate constant for disproportionation is obtained from the decay kinetics of ketyl radical and leads to phi/sub Red/ in agreement with that directly measured.« less

The Structure of RalF, an ADP-Ribosylation Factor Guanine Nucleotide Exchange Factor from Legionella pneumophila, Reveals the Presence of a Cap over the Active Site

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

Amor,J.; Swails, J.; Zhu, X.

2005-01-01

The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms amore » cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the 'glutamic finger,' conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.« less

Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.

PubMed

Wong, Vincent Wai-Sun; Petta, Salvatore; Hiriart, Jean-Baptiste; Cammà, Calogero; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Tuttolomondo, Antonino; Merrouche, Wassil; Chan, Henry Lik-Yuen; Le Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Lédinghen, Victor

2017-09-01

Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n=340; validation cohort, n=414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52±14; body mass index 27.2±5.3kg/m 2 ). The primary outcome was the diagnosis of fatty liver, defined as steatosis involving ≥5% of hepatocytes. The area under the receiver-operating characteristics curve (AUROC) for CAP diagnosis of fatty liver was 0.85 (95% CI 0.82-0.88). The interquartile range (IQR) of CAP had a negative correlation with CAP (r=-0.32, p<0.001), suggesting the IQR-to-median ratio of CAP would be an inappropriate validity parameter. In the derivation cohort, the IQR of CAP was associated with the accuracy of CAP (AUROC 0.86, 0.89 and 0.76 in patients with IQR of CAP <20 [15% of patients], 20-39 [51%], and ≥40dB/m [33%], respectively). Likewise, the AUROC of CAP in the validation cohort was 0.90 and 0.77 in patients with IQR of CAP <40 and ≥40dB/m, respectively (p=0.004). The accuracy of CAP in detecting grade 2 and 3 steatosis was lower among patients with body mass index ≥30kg/m 2 and F3-4 fibrosis. The validity of CAP for the diagnosis of fatty liver is lower if the IQR of CAP is ≥40dB/m. Lay summary: Controlled attenuation parameter (CAP) is measured by transient elastography (TE) for the detection of fatty liver. In this large study, using liver biopsy as a reference, we show that the variability of CAP measurements based on its interquartile range can reflect the accuracy of fatty liver diagnosis. In contrast, other clinical factors such as adiposity and liver enzyme levels do not affect the performance of CAP. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis.

PubMed Central

Lemassu, A; Daffé, M

1994-01-01

The cell envelope which surrounds pathogenic mycobacteria is postulated to be a defence barrier against phagocytic cells and its outermost constituents have a tendency to accumulate in the culture medium. The present work demonstrates that the exocellular material of Mycobacterium tuberculosis contains large amounts of polysaccharides with only traces, if any at all, of lipids. Three types of polysaccharides were purified by anion-exchange and gel-filtration chromatography; all were found to be neutral compounds devoid of acyl substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 123, 13 and 4 kDa respectively. Their predominant structural features were determined by the characterization of the per-O-methyl derivatives of enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r. spectroscopy of the purified polysaccharides, using mono- and two-dimensional homonuclear chemical-shift correlated spectroscopy and two-dimensional heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of the polysaccharides was composed of repeating units of five or six-->4-alpha-D-Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to the so-called polysaccharide-II previously identified in tuberculin. The arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1--> core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini of the arabinomannan were found to be extensively capped with mannosyl residues. The possibility that these polysaccharides contribute to the persistence of the tubercle bacillus in the macrophage by molecular mimicry is discussed. PMID:8297342

Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis.

PubMed

Lemassu, A; Daffé, M

1994-01-15

The cell envelope which surrounds pathogenic mycobacteria is postulated to be a defence barrier against phagocytic cells and its outermost constituents have a tendency to accumulate in the culture medium. The present work demonstrates that the exocellular material of Mycobacterium tuberculosis contains large amounts of polysaccharides with only traces, if any at all, of lipids. Three types of polysaccharides were purified by anion-exchange and gel-filtration chromatography; all were found to be neutral compounds devoid of acyl substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 123, 13 and 4 kDa respectively. Their predominant structural features were determined by the characterization of the per-O-methyl derivatives of enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r. spectroscopy of the purified polysaccharides, using mono- and two-dimensional homonuclear chemical-shift correlated spectroscopy and two-dimensional heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of the polysaccharides was composed of repeating units of five or six-->4-alpha-D-Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to the so-called polysaccharide-II previously identified in tuberculin. The arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1--> core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini of the arabinomannan were found to be extensively capped with mannosyl residues. The possibility that these polysaccharides contribute to the persistence of the tubercle bacillus in the macrophage by molecular mimicry is discussed.

Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients

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

Gatanaga, Tetsuya; Whang, Chenduen; Cappuccini, F.

1990-11-01

Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor {alpha} (TNF-{alpha}) in vitro. BF is a protein with a molecular mass of 28kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-{alpha} and recombinant human lymphotoxin activity of TNF-{alpha} andmore » recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-{alpha} more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-{alpha} when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-{alpha} and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-{alpha} in clinical trials with human cancer patients.« less

Endogenous circulating sympatholytic factor in orthostatic intolerance

NASA Technical Reports Server (NTRS)

Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.

2000-01-01

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Dissecting and Culturing Animal Cap Explants.

PubMed

Dingwell, Kevin S; Smith, James C

2018-05-16

The animal cap explant is a simple but adaptable tool available to developmental biologists. The use of animal cap explants in demonstrating the presence of mesoderm-inducting activity in the Xenopus embryo vegetal pole is one of many elegant examples of their worth. Animal caps respond to a range of growth factors (e.g., Wnts, FGF, TGF-β), making them especially useful for studying signal transduction pathways and gene regulatory networks. Explants are also suitable for examining cell behavior and have provided key insights into the molecular mechanisms controlling vertebrate morphogenesis. In this protocol, we outline two methods to isolate animal cap explants from Xenopus laevis , both of which can be applied easily to Xenopus tropicalis The first method is a standard manual method that can be used in any laboratory equipped with a standard dissecting microscope. For labs planning on dissecting large numbers of explants on a regular basis, a second, high throughput method is described that uses a specialized microcautery surgical instrument. © 2018 Cold Spring Harbor Laboratory Press.

Cap-independent translation of plant viral RNAs

PubMed Central

Pettit Kneller, Elizabeth L.; Rakotondrafara, Aurélie M.; Miller, W. Allen

2007-01-01

The RNAs of many plant viruses lack a 5′ cap and must be translated by a cap-independent mechanism. Here, we discuss the remarkably diverse cap-independent translation elements that have been identified in members of the Potyviridae, Luteoviridae, and Tombusviridae families, and genus Tobamovirus. Many other plant viruses have uncapped RNAs but their translation control elements are uncharacterized. Cap-independent translation elements of plant viruses differ strikingly from those of animal viruses: they are smaller (<200 nt), some are located in the 3′ untranslated region, some require ribosome scanning from the 5′ end of the mRNA, and the 5′ UTR elements are much less structured than those of animal viruses. We discuss how these elements may interact with host translation factors, and speculate on their mechanism of action and their roles in the virus replication cycle. Much remains to be learned about how these elements enable plant viruses to usurp the host translational machinery. PMID:16360925

STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.

PubMed

Woroniuk, Anna; Porter, Andrew; White, Gavin; Newman, Daniel T; Diamantopoulou, Zoi; Waring, Thomas; Rooney, Claire; Strathdee, Douglas; Marston, Daniel J; Hahn, Klaus M; Sansom, Owen J; Zech, Tobias; Malliri, Angeliki

2018-05-29

The perinuclear actin cap is an important cytoskeletal structure that regulates nuclear morphology and re-orientation during front-rear polarisation. The mechanisms regulating the actin cap are currently poorly understood. Here, we demonstrate that STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. We show that STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), increases nuclear height and impairs nuclear re-orientation. STEF down-regulation also reduces perinuclear pMLC and decreases myosin-generated tension at the nuclear envelope, suggesting that STEF-mediated Rac1 activity regulates NMMIIB activity to promote stabilisation of the perinuclear actin cap. Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.

Tumor necrosis factor-alpha stimulates the production of squamous cell carcinoma antigen in normal squamous cells.

PubMed

Numa, F; Takeda, O; Nakata, M; Nawata, S; Tsunaga, N; Hirabayashi, K; Suminami, Y; Kato, H; Hamanaka, S

1996-01-01

Squamous cell carcinoma (SCC) antigen, a tumor marker of squamous cell carcinoma, is also increased in several nonmalignant skin lesions, e.g. pemphigus. The aim of the present investigation was to determine if tumor necrosis factor-alpha (TNF-alpha), one of the important environmental factors, stimulated the production of SCC antigen in the normal squamous cells. The exposure of normal human epidermal keratinocytes to TNF-alpha (100 IU/ml) for 72 h greatly increased the SCC antigen production. The stimulatory effect of TNF-alpha (1,000 IU/ml) on the production of SCC antigen was also observed in the normal squamous epithelium tissue. These results would be helpful for understanding the increase of SCC antigen in several nonmalignant skin disorders.

Aetiology and risk factors of community-acquired pneumonia in hospitalized patients in Norway.

PubMed

Røysted, Wenche; Simonsen, Øystein; Jenkins, Andrew; Sarjomaa, Marjut; Svendsen, Martin Veel; Ragnhildstveit, Eivind; Tveten, Yngvar; Kanestrøm, Anita; Waage, Halfrid; Ringstad, Jetmund

2016-11-01

In Norway, data on the aetiology of community-acquired pneumonia (CAP) in hospitalized patients are limited. The aims of this study were to investigate the bacterial aetiology of CAP in hospitalized patients in Norway, risk factors for CAP and possible differences in risk factors between patients with Legionnaire's disease and pneumonia because of other causes. Adult patients with radiologically confirmed CAP admitted to hospital were eligible for the study. Routine aerobic and Legionella culture of sputum, blood culture, urinary antigen test for Legionella pneumophila and Streptococcus pneumoniae, polymerase chain reaction detection of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis from throat specimens, and serology for L. pneumophila serogroup 1-6 were performed. A questionnaire, which included demographic and clinical data, risk factors and treatment, was completed. We included 374 patients through a 20-month study period in 2007-2008. The aetiological agent was detected in 37% of cases. S. pneumoniae (20%) was the most prevalent agent, followed by Haemophilus influenzae (6%) and Legionella spp. (6%). Eight Legionella cases were diagnosed by urinary antigen test, of which four also had positive serology. In addition, 13 Legionella cases were diagnosed by serology. The degree of comorbidity was high. An increased risk of hospital-diagnosed Legionella pneumonia was found among patients with a diagnosis of chronic congestive heart failure. Our results indicate that S. pneumoniae is the most common bacterial cause of pneumonia in hospitalized patients, and the prevalence of Legionella pneumonia is probably higher in Norway than recognized previously. © 2015 John Wiley & Sons Ltd.

Lactose intolerance in prostate cancer patients: incidence and associated factors.

PubMed

Agarwal, Mayank Mohan; Rana, Satyavati V; Mandal, Arup Kumar; Malhotra, Sunita; Khandelwal, Niranjan; Kumar, Santosh; Acharya, Naveen Chandra; Singh, Shrawan Kumar

2008-03-01

Osteoporosis is common in prostate cancer (CaP) patients both before and after institution of androgen deprivation therapy and is associated with significant morbidity. Lactose intolerance (LI) can affect bone mass but has not been studied in this group of patients. The objective of this study was to compare the incidence of LI in CaP patients with that in the general population and to identify factors affecting lactose intolerance in CaP patients. Fifty-five men with CaP planned for bilateral orchidectomy were enrolled in the study and their baseline characteristics including age, weight, height, body mass index (BMI), prostate-specific antigen, serum calcium profile, lactose tolerance status, physical activity, alcohol intake and smoking, bone mineral density and calcium intake were registered. The data on lactose tolerance in these patients were compared with those of 81 age-matched controls (data taken from the available database). The incidence of LI in CaP patients was significantly less than that in the control group (36.2% and 58.3%, respectively, p = 0.027). A significantly greater number of CaP patients in the lactose-tolerant group had a calcium intake of >1500 mg/day (p = 0.03) and that of milk >500 ml/day (p = 0.05) than those in the intolerant group. Age >70 years, BMI <25 kg/m2, height >163 cm, lower physical activity and co-abuse of alcohol and smoking significantly correlated with the presence of LI (p < or = 0.05). Patients with serum calcium <9 mg/dl had higher fasting breath H2 levels and a higher proportion had a BMI >25 kg/m2 and weight >65 kg. The incidence of LI in CaP patients is less than that in the general population despite a higher incidence of osteoporosis, indicating a complex etiology of CaP-related osteoporosis. Certain physical characteristics and personal habits are important in determining lactose-tolerant status.

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

NASA Technical Reports Server (NTRS)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Cuprophane but not synthetic membrane induces increases in serum tumor necrosis factor-alpha levels during hemodialysis.

PubMed

Canivet, E; Lavaud, S; Wong, T; Guenounou, M; Willemin, J C; Potron, G; Chanard, J

1994-01-01

Cytokine synthesis and secretion by blood mononuclear cells is a well-documented phenomenon in hemodialyzed patients. The present study was conducted in 17 chronically hemodialyzed patients to test the relative effect of uremic toxicity, membrane biocompatibility, dialysate composition, and the risk of endotoxinemia on the serum level of tumor necrosis factor-alpha (TNF-alpha). The only significant parameter that influenced circulating TNF-alpha was the chemical characteristics of the dialyzer membrane. Tumor necrosis factor-alpha levels significantly increased during the session with cuprophane, whereas they decreased with AN69. The TNF-alpha increase was documented whatever the dialysate buffer and the presence or absence (negative Limulus amoebocyte lysate test) of endotoxin in the dialysate. In the subgroup of patients treated with a contaminated dialysate and AN69, none had clinical symptoms and the central body temperature remained constant throughout the session. In these patients, serum TNF-alpha levels did not change after priming the dialyzer with sterile saline. In conclusion, the serum TNF-alpha level during hemodialysis appears to be modulated by biocompatibility, permeability, and binding properties of dialysis membrane rather than dialysate composition. Endotoxin in the dialysate did not result in positive TNF-alpha balance no matter what its possible priming effect on mononucleated blood cells.

Variation in structure of proteins by adjusting reactive oxygen and nitrogen species generated from dielectric barrier discharge jet

NASA Astrophysics Data System (ADS)

Park, Ji Hoon; Kim, Minsup; Shiratani, Masaharu; Cho, Art. E.; Choi, Eun Ha; Attri, Pankaj

2016-10-01

Over the last few years, the variation in liquid chemistry due to the development of radicals generated by cold atmospheric plasma (CAP) has played an important role in plasma medicine. CAP direct treatment or CAP activated media treatment in cancer cells shows promising anticancer activity for both in vivo and in vitro studies. However, the anticancer activity or antimicrobial activity varies between plasma devices due to the different abilities among plasma devices to generate the reactive oxygen and nitrogen species (RONS) at different ratios and in different concentrations. While the generation of RONS depends on many factors, the feeding gas plays the most important role among the factors. Hence, in this study we used different compositions of feeding gas while fixing all other plasma characteristics. We used Ar, Ar-O2 (at different ratios), and Ar-N2 (at different ratios) as the working gases for CAP and investigated the structural changes in proteins (Hemoglobin (Hb) and Myoglobin (Mb)). We then analyzed the influence of RONS generated in liquid on the conformations of proteins. Additionally, to determine the influence of H2O2 on the Hb and Mb structures, we used molecular dynamic simulation.

CAP - JET PROPULSION LABORATORY CONTAMINATION ANALYSIS PROGRAM

NASA Technical Reports Server (NTRS)

Millard, J. M.

1994-01-01

The Jet Propulsion Laboratory Contamination Analysis Program (CAP) is a generalized transient executive analysis computer code which solves realistic mass transport problems in the free molecular flow environment. These transport problems involve mass flux from surface source emission and re-emission, venting, and engine emission. CAP solution capability allows for one-bounce mass reflections if required. CAP was developed to solve thin-film contamination problems in the free molecular flow environment, the intent being to provide a powerful analytic tool for evaluating spacecraft contamination problems. The solution procedure uses an enclosure method based on a lumped-parameter multinodal approach with mass exchange between nodes. Transient solutions are computed by the finite difference Euler method. First-order rate theory is used to represent surface emission and reemission (user care must be taken to insure the problem is appropriate for such behavior), and all surface emission and reflections are assumed diffuse. CAP does not include the effects of post-deposition chemistry or interaction with the ambient atmosphere. CAP reads in a model represented by a multiple-block data stream. CAP allows the user to edit the input data stream and stack sequential editing operations (or cases) in order to make complex changes in behavior (surface temperatures, engine start-up and shut-down, etc.) in a single run if desired. The eight data blocks which make up the input data stream consist of problem control parameters, nodal data (area, temperature, mass, etc.), engine or vent distribution factors (based upon plume definitions), geometric configuration factors (diffuse surface emission), surface capture coefficient tables, source emission rate constant tables, reemission rate constant tables, and partial node to body collapse capability (for deposition rates only). The user must generate this data stream, since neither the problem-specific geometric relationships, the constituents involved, nor plume distribution functions are a part of CAP. Instead, these are used to generate the data stream model CAP solves. Outputs vary from individual deposition rates of exchange, on an internodal basis and on a constituent basis as a function of time, to deposition on each surface on a constituent basis as a function of time. The type of outputs may be user-specified by control parameters. CAP allows the user to select output intervals within the solution interval and to generate restart nodal data blocks. CAP is composed of several FORTRAN subroutines which serve specific functions and can be easily edited. The code is relatively small (2152 statements), and contains comment statements for all operations. It is written in relatively generic FORTRAN to be adaptable to a variety of computers. CAP was implemented on a DEC VAX 11/780 computer, and is distributed on a 9-track DEC VAX BACKUP format magnetic tape. Virtual memory required is 4.6 MB, which corresponds to a 900 node model capacity. CAP was originally developed under contract for NASA/Goddard Space Flight Center in 1979 by JPL, and was subsequently modified as required for project support at JPL. CAP is a copyrighted work with all copyright vested in NASA.

Lamina-associated polypeptide 2alpha loss impairs heart function and stress response in mice.

PubMed

Gotic, Ivana; Leschnik, Michael; Kolm, Ursula; Markovic, Mato; Haubner, Bernhard J; Biadasiewicz, Katarzyna; Metzler, Bernhard; Stewart, Colin L; Foisner, Roland

2010-02-05

Lamina-associated polypeptide (LAP)2alpha is a mammalian chromatin-binding protein that interacts with a fraction of A-type lamins in the nuclear interior. Because mutations in lamins and LAP2alpha lead to cardiac disorders in humans, we hypothesized that these factors may play important roles in heart development and adult tissue homeostasis. We asked whether the presence of LAP2alpha was required for normal cardiac function. To study the molecular mechanisms of the disease, we analyzed heart structure and function in complete and conditional Lap2alpha(-/-) mice as well as Lap2alpha(-/-)/Mdx mutants. Unlike conditional deletion of LAP2alpha in late embryonic striated muscle, its complete knockout caused systolic dysfunction in young mice, accompanied by sporadic fibrosis in old animals, as well as deregulation of major cardiac transcription factors GATA4 and myocyte enhancer factor 2c. Activation of compensatory pathways, including downregulation of beta-adrenergic receptor signaling, resulted in reduced responsiveness of the myocardium to chronic beta-adrenergic stimulation and stalled the progression of LAP2alpha-deficient hearts from hypertrophy toward cardiac failure. Dystrophin deficiency in an Mdx background resulted in a transient rescue of the Lap2alpha(-/-) phenotype. Our data suggest a novel role of LAP2alpha in the maintenance of cardiac function under normal and stress conditions.

Catastrophic antiphospholipid syndrome: a clinical review.

PubMed

Nayer, Ali; Ortega, Luis M

2014-01-01

Catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening autoimmune disease characterized by disseminated intravascular thrombosis resulting in multiorgan failure. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. CAPS is due to antiphospholipid antibodies directed against a heterogeneous group of proteins that are associated with phospholipids. These autoantibodies activate endothelial cells, platelets, and immune cells, thereby promoting a proinflammatory and prothrombotic phenotype. Furthermore, antiphospholipid antibodies inhibit anticoagulants, impair fibrinolysis, and activate complements. Although CAPS can affect a variety of organs and tissues, the kidneys, lungs, central nervous system, heart, skin, liver, and gastrointestinal tract are most commonly affected. The systemic inflammatory response syndrome, likely to extensive tissue damage, accompanies CAPS. The most frequent renal manifestations are hypertension, proteinuria, hematuria, and acute renal failure.In the majority of patients with CAPS, a precipitating factor such as infection, surgery, or medication can be identified. Antiphospholipid antibodies such as lupus anticoagulant and antibodies against cardiolipin, β2-glycoprotein I, and prothrombin are serological hallmark of CAPS. Laboratory tests often reveal antinuclear antibodies, thrombocytopenia, and anemia. Despite widespread intravascular coagulation, blood films reveal only a small number of schistocytes. In addition, severe thrombocytopenia is uncommon. Histologically, CAPS is characterized by acute thrombotic microangiopathy. CAPS must be distinguished from other forms of thrombotic microangiopathies such as hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and heparin-induced thrombocyt openia. CAPS is associated with high morbidity and mortality. Therefore, an aggressive multidisciplinary treatment strategy is indicated. Anticoagulation, immunosuppression, plasma exchange, intravenous immunoglobulins, and anti-platelet agents, used in various combinations, have resulted in improved patient outcome.

[Building immune microsphere against tumor necrosis factor-alpha (TNF-alpha)].

PubMed

Wang, Qin; Wu, Xiongfei; Wang, Junxia; Liu, Hong; Li, Lian; Jin, Xiyu

2005-12-01

We have constructed the immune microsphere against tumor necrosis factor-alpha (TNF-alpha) prospectively, hoping to establish the experiment groundwork in more researches which could be used in specific elimination of the TNF-alpha by blood purification method for the future. The recombinant human tumor necrosis factor-alpha monoclonal antibody (rHTNF-alpha McAb) was wrapped on the polystyrene microsphere (PSM) carrier connecting poly-L-lysine (PLL) beforehand. They were earmarked by the fluorescein isothiocyanate (FITC) respectively. The packing conditions were examined using the inversted and fluorescence microscopes and the spectrophotometer. The results showed that the best conditions for wrapping were 20 degrees C, pH9.5 and 60 minutes. The PLL content was not changed in the washing fluid after coating, which indicated the wrapping was quite firm. At the same temperature and same coating time, the rHTNF-alpha McAb coated on the PLL was obviously substantial when the concentration of glutaraldehyde solution was 0.2%. The findings demonstrated that the built immune microsphers can be used as a novel adsorption material. This method is simple and economic, and it offers a new approach to the related studies.

Angiotensin II type 1 receptor blockers prevent tumor necrosis factor-alpha-mediated endothelial nitric oxide synthase reduction and superoxide production in human umbilical vein endothelial cells.

PubMed

Kataoka, Hiroki; Murakami, Ryuichiro; Numaguchi, Yasushi; Okumura, Kenji; Murohara, Toyoaki

2010-06-25

Decrease in endothelial nitric oxide synthase (eNOS) expression is one of the adverse outcomes of endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha) is known to decrease eNOS expression and is an important mediator of endothelial dysfunction. We hypothesized that an angiotensin II type 1 (AT1) receptor blocker would improve endothelial function via not only inhibition of the angiotensin II signaling but also inhibition of the TNF-alpha-mediated signaling. Therefore we investigated whether an AT1 receptor blocker would restore the TNF-alpha-induced decrease in eNOS expression in cultured human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with an antioxidant (superoxide dismutase, alpha-tocopherol) or AT1 receptor blockers (olmesartan or candesartan) restored the TNF-alpha-dependent reduction of eNOS. The AT1 receptor blocker decreased the TNF-alpha-dependent increase of 8-isoprostane. The superoxide dismutase activities in HUVEC were stable during AT1 receptor blocker treatment, and the AT1 receptor blocker did not scavenge superoxide directly. The AT1 receptor blocker also decreased TNF-alpha-induced phosphorylation of I kappaB alpha and cell death. These results suggest that AT1 receptor blockers are able to ameliorate TNF-alpha-dependent eNOS reduction or cell injury by inhibiting superoxide production or nuclear factor-kappaB activation. (c) 2010 Elsevier B.V. All rights reserved.

Immunohistochemical detection of HIF-1alpha and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters.

PubMed

Kappler, Matthias; Taubert, Helge; Holzhausen, Hans-Jürgen; Reddemann, Rolf; Rot, Swetlann; Becker, Axel; Kuhnt, Thomas; Dellas, Kathrin; Dunst, Jürgen; Vordermark, Dirk; Hänsgen, Gabriele; Bache, Matthias

2008-08-01

Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant Levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Tumortissue sections of 34 patients with advanced head-and-neck cancertreated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1alpha and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Bivariate analysis showed a significant correlation of HIF-1alpha expression with high P53 and high OPN expression, high serum VEGF Levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1alpha and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1alpha or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1alpha or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Expression of HIF-1alpha and CAIX was correlated with different tumor parameters. Only combined HIF-1alpha and CAIX expression was significantly predictive of patients' overall survival.

Chondrogenic differentiation of growth factor-stimulated precursor cells in cartilage repair tissue is associated with increased HIF-1alpha activity.

PubMed

Gelse, K; Mühle, C; Knaup, K; Swoboda, B; Wiesener, M; Hennig, F; Olk, A; Schneider, H

2008-12-01

To investigate the chondrogenic potential of growth factor-stimulated periosteal cells with respect to the activity of Hypoxia-inducible Factor 1alpha (HIF-1alpha). Scaffold-bound autologous periosteal cells, which had been activated by Insulin-like Growth Factor 1 (IGF-1) or Bone Morphogenetic Protein 2 (BMP-2) gene transfer using both adeno-associated virus (AAV) and adenoviral (Ad) vectors, were applied to chondral lesions in the knee joints of miniature pigs. Six weeks after transplantation, the repair tissues were investigated for collagen type I and type II content as well as for HIF-1alpha expression. The functional role of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling on BMP-2/IGF-1-induced HIF-1alpha expression was assessed in vitro by employing specific inhibitors. Unstimulated periosteal cells formed a fibrous extracellular matrix in the superficial zone and a fibrocartilaginous matrix in deep zones of the repair tissue. This zonal difference was reflected by the absence of HIF-1alpha staining in superficial areas, but moderate HIF-1alpha expression in deep zones. In contrast, Ad/AAVBMP-2-stimulated periosteal cells, and to a lesser degree Ad/AAVIGF-1-infected cells, adopted a chondrocyte-like phenotype with strong intracellular HIF-1alpha staining throughout all zones of the repair tissue and formed a hyaline-like matrix. In vitro, BMP-2 and IGF-1 supplementation increased HIF-1alpha protein levels in periosteal cells, which was based on posttranscriptional mechanisms rather than de novo mRNA synthesis, involving predominantly the MEK/ERK pathway. This pilot experimental study on a relatively small number of animals indicated that chondrogenesis by precursor cells is facilitated in deeper hypoxic zones of cartilage repair tissue and is stimulated by growth factors which enhance HIF-1alpha activity.

Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival.

PubMed

Schipani, E; Ryan, H E; Didrickson, S; Kobayashi, T; Knight, M; Johnson, R S

2001-11-01

Breakdown or absence of vascular oxygen delivery is a hallmark of many common human diseases, including cancer, myocardial infarction, and stroke. The chief mediator of hypoxic response in mammalian tissues is the transcription factor hypoxia-inducible factor 1 (HIF-1), and its oxygen-sensitive component HIF-1alpha. A key question surrounding HIF-1alpha and the hypoxic response is the role of this transcription factor in cells removed from a functional vascular bed; in this regard there is evidence indicating that it can act as either a survival factor or induce growth arrest and apoptosis. To study more closely how HIF-1alpha functions in hypoxia in vivo, we used tissue-specific targeting to delete HIF-1alpha in an avascular tissue: the cartilaginous growth plate of developing bone. We show here the first evidence that the developmental growth plate in mammals is hypoxic, and that this hypoxia occurs in its interior rather than at its periphery. As a result of this developmental hypoxia, cells that lack HIF-1alpha in the interior of the growth plate die. This is coupled to decreased expression of the CDK inhibitor p57, and increased levels of BrdU incorporation in HIF-1alpha null growth plates, indicating defects in HIF-1alpha-regulated growth arrest occurs in these animals. Furthermore, we find that VEGF expression in the growth plate is regulated through both HIF-1alpha-dependent and -independent mechanisms. In particular, we provide evidence that VEGF expression is up-regulated in a HIF-1alpha-independent manner in chondrocytes surrounding areas of cell death, and this in turn induces ectopic angiogenesis. Altogether, our findings have important implications for the role of hypoxic response and HIF-1alpha in development, and in cell survival in tissues challenged by interruption of vascular flow; they also illustrate the complexities of HIF-1alpha response in vivo, and they provide new insights into mechanisms of growth plate development.

A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia

PubMed Central

Laterre, Pierre-François; Opal, Steven M; Abraham, Edward; LaRosa, Steven P; Creasey, Abla A; Xie, Fang; Poole, Lona; Wunderink, Richard G

2009-01-01

Introduction The purpose of this analysis was to determine the potential efficacy of recombinant human tissue factor pathway inhibitor (tifacogin) in a subpopulation of patients with community-acquired pneumonia (CAP) from a phase III study of severe sepsis. Methods A retrospective review of patients with suspected pneumonia was conducted by an independent clinical evaluation committee (CEC) blinded to treatment assignment. The CEC reanalyzed data from patients enrolled in an international multicenter clinical trial of sepsis who had a diagnosis of pneumonia as the probable source of sepsis. The primary efficacy measure was all-cause 28-day mortality. Results Of 847 patients identified on case report forms with a clinical diagnosis of pneumonia, 780 (92%) were confirmed by the CEC to have pneumonia. Of confirmed pneumonia cases, 496 (63.6%) met the definition for CAP. In the CEC CAP population, the mortality rates of the tifacogin and placebo groups were 70/251 (27.9%) and 80/245 (32.7%), respectively. The strongest signals were seen in patients with CAP not receiving concomitant heparin, having microbiologically confirmed infection, or having the combination of documented infection and no heparin. The reduction in mortality in this narrowly defined subgroup when treated with tifacogin compared with placebo was statistically significant (17/58 [29.3%] with tifacogin and 28/54 [51.9%] with placebo; unadjusted P value of less than 0.02). Conclusions Tifacogin administration did not significantly reduce mortality in any severe CAP patient. Exploratory analyses showed an improved survival in patients who did not receive concomitant heparin with microbiologically confirmed infections. These data support the rationale of an ongoing phase III study exploring the potential benefit of tifacogin in severe CAP. Trial Registration ClinicalTrials.gov identifier NCT00084071. PMID:19284881

Inhibition of Mitogen-activated Protein Kinase (MAPK)-interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing Both a 5'-Terminal Cap and Hairpin.

PubMed

Korneeva, Nadejda L; Song, Anren; Gram, Hermann; Edens, Mary Ann; Rhoads, Robert E

2016-02-12

The MAPK-interacting kinases 1 and 2 (MNK1 and MNK2) are activated by extracellular signal-regulated kinases 1 and 2 (ERK1/2) or p38 in response to cellular stress and extracellular stimuli that include growth factors, cytokines, and hormones. Modulation of MNK activity affects translation of mRNAs involved in the cell cycle, cancer progression, and cell survival. However, the mechanism by which MNK selectively affects translation of these mRNAs is not understood. MNK binds eukaryotic translation initiation factor 4G (eIF4G) and phosphorylates the cap-binding protein eIF4E. Using a cell-free translation system from rabbit reticulocytes programmed with mRNAs containing different 5'-ends, we show that an MNK inhibitor, CGP57380, affects translation of only those mRNAs that contain both a cap and a hairpin in the 5'-UTR. Similarly, a C-terminal fragment of human eIF4G-1, eIF4G(1357-1600), which prevents binding of MNK to intact eIF4G, reduces eIF4E phosphorylation and inhibits translation of only capped and hairpin-containing mRNAs. Analysis of proteins bound to m(7)GTP-Sepharose reveals that both CGP and eIF4G(1357-1600) decrease binding of eIF4E to eIF4G. These data suggest that MNK stimulates translation only of mRNAs containing both a cap and 5'-terminal RNA duplex via eIF4E phosphorylation, thereby enhancing the coupled cap-binding and RNA-unwinding activities of eIF4F. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A Dual Interaction Between the 5'- and 3'-Ends of the Melon Necrotic Spot Virus (MNSV) RNA Genome Is Required for Efficient Cap-Independent Translation.

PubMed

Miras, Manuel; Rodríguez-Hernández, Ana M; Romero-López, Cristina; Berzal-Herranz, Alfredo; Colchero, Jaime; Aranda, Miguel A; Truniger, Verónica

2018-01-01

In eukaryotes, the formation of a 5'-cap and 3'-poly(A) dependent protein-protein bridge is required for translation of its mRNAs. In contrast, several plant virus RNA genomes lack both of these mRNA features, but instead have a 3'-CITE (for cap-independent translation enhancer), a RNA element present in their 3'-untranslated region that recruits translation initiation factors and is able to control its cap-independent translation. For several 3'-CITEs, direct RNA-RNA long-distance interactions based on sequence complementarity between the 5'- and 3'-ends are required for efficient translation, as they bring the translation initiation factors bound to the 3'-CITE to the 5'-end. For the carmovirus melon necrotic spot virus (MNSV), a 3'-CITE has been identified, and the presence of its 5'-end in cis has been shown to be required for its activity. Here, we analyze the secondary structure of the 5'-end of the MNSV RNA genome and identify two highly conserved nucleotide sequence stretches that are complementary to the apical loop of its 3'-CITE. In in vivo cap-independent translation assays with mutant constructs, by disrupting and restoring sequence complementarity, we show that the interaction between the 3'-CITE and at least one complementary sequence in the 5'-end is essential for virus RNA translation, although efficient virus translation and multiplication requires both connections. The complementary sequence stretches are invariant in all MNSV isolates, suggesting that the dual 5'-3' RNA:RNA interactions are required for optimal MNSV cap-independent translation and multiplication.

Relationship between the Use of Inhaled Steroids for Chronic Respiratory Diseases and Early Outcomes in Community-Acquired Pneumonia

PubMed Central

Almirall, Jordi; Bolíbar, Ignasi; Serra-Prat, Mateu; Palomera, Elisabet; Roig, Jordi; Hospital, Imma; Carandell, Eugenia; Agustí, Mercè; Ayuso, Pilar; Estela, Andreu; Torres, Antoni

2013-01-01

Background The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP). We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. Methods Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality). Results Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%). In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542), with COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. Conclusions Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis. PMID:24039899

Interaction of insulin with colloidal ZnS quantum dots functionalized by various surface capping agents.

PubMed

Hosseinzadeh, Ghader; Maghari, Ali; Farniya, Seyed Morteza Famil; Keihan, Amir Homayoun; Moosavi-Movahedi, Ali A

2017-08-01

Interaction of quantum dots (QDs) and proteins strongly influenced by the surface characteristics of the QDs at the protein-QD interface. For a precise control of these surface-related interactions, it is necessary to improve our understanding in this field. In this regard, in the present work, the interaction between the insulin and differently functionalized ZnS quantum dots (QDs) were studied. The ZnS QDs were functionalized with various functional groups of hydroxyl (OH), carboxyl (COOH), amine (NH 2 ), and amino acid (COOH and NH 2 ). The effect of surface hydrophobicity was also studied by changing the alkyl-chain lengths of mercaptocarboxylic acid capping agents. The interaction between insulin and the ZnS QDs were investigated by fluorescence quenching, synchronous fluorescence, circular dichroism (CD), and thermal aggregation techniques. The results reveal that among the studied QDs, mercaptosuccinic acid functionalized QDs has the strongest interaction (∆G ° =-51.50kJ/mol at 310K) with insulin, mercaptoethanol functionalized QDs destabilize insulin by increasing the beta-sheet contents, and only cysteine functionalized QDs improves the insulin stability by increasing the alpha-helix contents of the protein, and. Our results also indicate that by increasing the alkyl-chain length of capping agents, due to an increase in hydrophobicity of the QDs surface, the beta-sheet contents of insulin increase which results in the enhancement of insulin instability. Copyright © 2017 Elsevier B.V. All rights reserved.

Venus 2004: east and west elongations and solar transit

NASA Astrophysics Data System (ADS)

McKim, R. J.; Blaxall, K.; Heath, A.

2007-04-01

The year 2004 was exceptional in producing the first solar transit of Venus since the late Victorian era. The bright aureole and atmospheric ring were re-observed, and the entire phenomenon was witnessed for the first time ever in hydrogen alpha light. Although routine observations throughout 2004 were unexceptional, patterns of visibility of bright and dark markings, cusp extensions and cusp-caps were recorded. No correlation was found between the latitude of the sub-Earth point and the visibility of either cusp-cap, with the S. cap predominating for most of the year. It was possible to accurately follow individual ultraviolet dark markings over many consecutive rotations, extending from the E. to W. elongations, and thereby to make a current measurement of the synodic atmospheric rotation period for the near-equatorial features: 3.996 ± 0.001 days. The true Ashen Light was reported visually on only a few occasions, but these correspond closely to times when infrared emission from the surface of the dark side was recorded in 1-micron waveband images. Some of the stable dark side albedo features were also visible upon the 1-micron images, and have been tentatively identified with known surface features. Infrared imaging at the same waveband showed little detail on the sunlit disk, but a few bright spots were sufficiently well observed to suggest a synodic rotation period close to 5.0 days, not atypical for the lower cloud decks.

Online self-report questionnaire on computer work-related exposure (OSCWE): validity and internal consistency.

PubMed

Mekhora, Keerin; Jalayondeja, Wattana; Jalayondeja, Chutima; Bhuanantanondh, Petcharatana; Dusadiisariyavong, Asadang; Upiriyasakul, Rujiret; Anuraktam, Khajornyod

2014-07-01

To develop an online, self-report questionnaire on computer work-related exposure (OSCWE) and to determine the internal consistency, face and content validity of the questionnaire. The online, self-report questionnaire was developed to determine the risk factors related to musculoskeletal disorders in computer users. It comprised five domains: personal, work-related, work environment, physical health and psychosocial factors. The questionnaire's content was validated by an occupational medical doctor and three physical therapy lecturers involved in ergonomic teaching. Twenty-five lay people examined the feasibility of computer-administered and the user-friendly language. The item correlation in each domain was analyzed by the internal consistency (Cronbach's alpha; alpha). The content of the questionnaire was considered congruent with the testing purposes. Eight hundred and thirty-five computer users at the PTT Exploration and Production Public Company Limited registered to the online self-report questionnaire. The internal consistency of the five domains was: personal (alpha = 0.58), work-related (alpha = 0.348), work environment (alpha = 0.72), physical health (alpha = 0.68) and psychosocial factor (alpha = 0.93). The findings suggested that the OSCWE had acceptable internal consistency for work environment and psychosocial factors. The OSCWE is available to use in population-based survey research among computer office workers.

Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

PubMed

Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

2010-07-16

Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

Alpha-cluster preformation factor within cluster-formation model for odd-A and odd-odd heavy nuclei

NASA Astrophysics Data System (ADS)

Saleh Ahmed, Saad M.

2017-06-01

The alpha-cluster probability that represents the preformation of alpha particle in alpha-decay nuclei was determined for high-intensity alpha-decay mode odd-A and odd-odd heavy nuclei, 82 < Z < 114, 111 < N < 174. This probability was calculated using the energy-dependent formula derived from the formulation of clusterisation states representation (CSR) and the hypothesised cluster-formation model (CFM) as in our previous work. Our previous successful determination of phenomenological values of alpha-cluster preformation factors for even-even nuclei motivated us to expand the work to cover other types of nuclei. The formation energy of interior alpha cluster needed to be derived for the different nuclear systems with considering the unpaired-nucleon effect. The results showed the phenomenological value of alpha preformation probability and reflected the unpaired nucleon effect and the magic and sub-magic effects in nuclei. These results and their analyses presented are very useful for future work concerning the calculation of the alpha decay constants and the progress of its theory.

The development of novel inhibitors of tumor necrosis factor-alpha production based on substituted [5,5]-bicyclic pyrozolones

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

Laufersweiler, Matthew; Brugel, Todd; Clark, Michael

Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-{alpha} (TNF-{alpha}) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-{alpha} production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed.

Analysis of factors controlling sediment phosphorus flux potential of wetlands in Hulun Buir grassland by principal component and path analysis method.

PubMed

He, Jing; Su, Derong; Lv, Shihai; Diao, Zhaoyan; Ye, Shengxing; Zheng, Zhirong

2017-11-08

Phosphorus (P) flux potential can predict the trend of phosphorus release from wetland sediments to water and provide scientific parameters for further monitoring and management for phosphorus flux from wetland sediments to overlying water. Many studies have focused on factors affecting sediment P flux potential in sediment-water interface, but rarely on the relationship among these factors. In the present study, experiment on sediment P flux potential in sediment-water interface was conducted in six wetlands in Hulun Buir grassland, China and the relationships among sediment P flux potential in sediment-water interface, sediment physical properties, and sediment chemical characteristics were examined. Principal component analysis and path analysis were used to discuss these data in correlation coefficient, direct, and indirect effects on sediment P flux potential in sediment-water interface. Results indicated that the major factors affecting sediment P flux potential in sediment-water interface were amount of organophosphate-degradation bacterium in sediment, Ca-P content, and total phosphorus concentrations. The factors of direct influence sediment P flux potential were sediment Ca-P content, Olsen-P content, SOC content, and sediment Al-P content. The indirect influence sediment P flux potential in sediment-water interface was sediment Olsen-P content, sediment SOC content, sediment Ca-P content, and sediment Al-P content. And the standard multiple regression describing the relationship between sediment P flux potential in sediment-water interface and its major effect factors was Y = 5.849 - 1.025X 1  - 1.995X 2  + 0.188X 3  - 0.282X 4 (r = 0.9298, p < 0.01, n = 96), where Y is sediment P flux potential in sediment-water interface, X 1 is sediment Ca-P content, X 2 is sediment Olsen-P content, X 3 is sediment SOC content, and X 4 is sediment Al-P content. Therefore, future research will focus on these sediment properties to analyze the interrelation among sediment properties factors, main vegetable factors, and environment factors which influence the sediment P flux potential in sediment-water interface.

Connecting different TMD factorization formalisms in QCD

DOE PAGES

Collins, John; Rogers, Ted C.

2017-09-11

In the original Collins-Soper-Sterman (CSS) presentation of the results of transverse-momentum-dependent (TMD) factorization for the Drell-Yan process, results for perturbative coefficients can be obtained from calculations for collinear factorization. Here we show how to use these results, plus known results for the quark form factor, to obtain coefficients for TMD factorization in more recent formulations, e.g., that due to Collins, and apply them to known results at ordermore » $$\\alpha_s^2$$ and $$\\alpha_s^3$$. We also show that the ``non-perturbative'' functions as obtained from fits to data are equal in the two schemes. We compile the higher-order perturbative inputs needed for the updated CSS scheme by appealing to results obtained in a variety of different formalisms. In addition, we derive the connection between both versions of the CSS formalism and several formalisms based in soft-collinear effective theory (SCET). As a result, our work uses some important new results for factorization for the quark form factor, which we derive.« less

Connecting different TMD factorization formalisms in QCD

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

Collins, John; Rogers, Ted C.

In the original Collins-Soper-Sterman (CSS) presentation of the results of transverse-momentum-dependent (TMD) factorization for the Drell-Yan process, results for perturbative coefficients can be obtained from calculations for collinear factorization. Here we show how to use these results, plus known results for the quark form factor, to obtain coefficients for TMD factorization in more recent formulations, e.g., that due to Collins, and apply them to known results at ordermore » $$\\alpha_s^2$$ and $$\\alpha_s^3$$. We also show that the ``non-perturbative'' functions as obtained from fits to data are equal in the two schemes. We compile the higher-order perturbative inputs needed for the updated CSS scheme by appealing to results obtained in a variety of different formalisms. In addition, we derive the connection between both versions of the CSS formalism and several formalisms based in soft-collinear effective theory (SCET). As a result, our work uses some important new results for factorization for the quark form factor, which we derive.« less

Two DNA-binding factors recognize specific sequences at silencers, upstream activating sequences, autonomously replicating sequences, and telomeres in Saccharomyces cerevisiae

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

Buchman, A.R.; Kimmerly, W.J.; Rine, J.

1988-01-01

Two DNA-binding factors from Saccharomyces cerevisiae have been characterized, GRFI (general regulatory factor I) and ABFI (ARS-binding factor I), that recognize specific sequences within diverse genetic elements. GRFI bound to sequences at the negative regulatory elements (silencers) of the silent mating type loci HML E and HMR E and to the upstream activating sequence (UAS) required for transcription of the MAT ..cap alpha.. genes. A putative conserved UAS located at genes involved in translation (RPG box) was also recognized by GRFI. In addition, GRFI bound with high affinity to sequences within the (C/sub 1-3/A)-repeat region at yeast telomeres. Binding sitesmore » for GRFI with the highest affinity appeared to be of the form 5'-(A/G)(A/C)ACCCAN NCA(T/C)(T/C)-3', where N is any nucleotide. ABFI-binding sites were located next to autonomously replicating sequences (ARSs) at controlling elements of the silent mating type loci HMR E, HMR I, and HML I and were associated with ARS1, ARS2, and the 2..mu..m plasmid ARS. Two tandem ABFI binding sites were found between the HIS3 and DED1 genes, several kilobase pairs from any ARS, indicating that ABFI-binding sites are not restricted to ARSs. The sequences recognized by AFBI showed partial dyad-symmetry and appeared to be variations of the consensus 5'-TATCATTNNNNACGA-3'. GRFI and ABFI were both abundant DNA-binding factors and did not appear to be encoded by the SIR genes, whose product are required for repression of the silent mating type loci. Together, these results indicate that both GRFI and ABFI play multiple roles within the cell.« less

Hypoxia preconditioning protection of corneal stromal cells requires HIF1alpha but not VEGF.

PubMed

Xing, Dongmei; Bonanno, Joseph A

2009-05-18

Hypoxia preconditioning protects corneal stromal cells from stress-induced death. This study determined whether the transcription factor HIF-1alpha (Hypoxia Inducible Factor) is responsible and whether this is promulgated by VEGF (Vascular Endothelial Growth Factor). Cultured bovine stromal cells were preconditioned with hypoxia in the presence of cadmium chloride, a chemical inhibitor of HIF-1alpha, and HIF-1alpha siRNA to test if HIF-1alpha activity is needed for hypoxia preconditioning protection from UV-irradiation induced cell death. TUNEL assay was used to detect cell apoptosis after UV-irradiation. RT-PCR and western blot were used to detect the presence of HIF-1alpha and VEGF in transcriptional and translational levels. During hypoxia (0.5% O2), 5 muM cadmium chloride completely inhibited HIF-1alpha expression and reversed the protection by hypoxia preconditioning. HIF-1alpha siRNA (15 nM) reduced HIF-1alpha expression by 90% and produced a complete loss of protection provided by hypoxia preconditioning. Since VEGF is induced by hypoxia, can be HIF-1alpha dependent, and is often protective, we examined the changes in transcription of VEGF and its receptors after 4 h of hypoxia preconditioning. VEGF and its receptors Flt-1 and Flk-1 are up-regulated after hypoxia preconditioning. However, the transcription and translation of VEGF were paradoxically increased by siHIF-1alpha, suggesting that VEGF expression in stromal cells is not down-stream of HIF-1alpha. These findings demonstrate that hypoxia preconditioning protection in corneal stromal cells requires HIF-1alpha, but that VEGF is not a component of the protection.

SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

PubMed Central

McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

1992-01-01

The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

Role of tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and associated proteins in coronary artery disease and cardiac events.

PubMed

Chemaly, Melody; McGilligan, Victoria; Gibson, Mark; Clauss, Matthias; Watterson, Steven; Alexander, H Denis; Bjourson, Anthony John; Peace, Aaron

2017-12-01

Tumour necrosis factor alpha converting enzyme (TACE/ADAM17) is a member of the A disintegrin and metalloproteinase (ADAM) family of ectodomain shedding proteinases. It regulates many inflammatory processes by cleaving several transmembrane proteins, including tumour necrosis factor alpha (TNFα) and its receptors tumour necrosis factor alpha receptor 1 and tumour necrosis factor alpha receptor 2. There is evidence that TACE is involved in several inflammatory diseases, such as ischaemia, heart failure, arthritis, atherosclerosis, diabetes and cancer as well as neurological and immune diseases. This review summarizes the latest discoveries regarding the mechanism of action and regulation of TACE. It also focuses on the role of TACE in atherosclerosis and coronary artery disease (CAD), highlighting clinical studies that have investigated its expression and protein activity. The multitude of substrates cleaved by TACE make this enzyme an attractive target for therapy and a candidate for biomarker research and development in CAD. Crown Copyright © 2017. Published by Elsevier Masson SAS. All rights reserved.

Fluid core size of Mars from detection of the solar tide

NASA Technical Reports Server (NTRS)

Yoder, C. F.; Konopliv, A. S.; Yuan, D. N.; Standish, E. M.; Folkner, W. M.

2003-01-01

The solar tidal deformation of Mars, measured by its k2 potential Love number, has been obtained from an analysis of Mars Global Surveyor radio tracking. The observed k2 of 0.153 +/- 0.017 is large enough to rule out a solid iron core and so indicates that at least the outer part of the core is liquid. The inferred core radius is between 1520 and 1840 kilometers and is independent of many interior properties, although partial melt of the mantle is one factor that could reduce core size. Ice-cap mass changes can be deduced from the seasonal variations in air pressure and the odd gravity harmonic J3, given knowledge of cap mass distribution with latitude. The south cap seasonal mass change is about 30 to 40% larger than that of the north cap.

Fluid Core Size of Mars from Detection of the Solar Tide

NASA Astrophysics Data System (ADS)

Yoder, C. F.; Konopliv, A. S.; Yuan, D. N.; Standish, E. M.; Folkner, W. M.

2003-04-01

The solar tidal deformation of Mars, measured by its k2 potential Love number, has been obtained from an analysis of Mars Global Surveyor radio tracking. The observed k2 of 0.153 +/- 0.017 is large enough to rule out a solid iron core and so indicates that at least the outer part of the core is liquid. The inferred core radius is between 1520 and 1840 kilometers and is independent of many interior properties, although partial melt of the mantle is one factor that could reduce core size. Ice-cap mass changes can be deduced from the seasonal variations in air pressure and the odd gravity harmonic J3, given knowledge of cap mass distribution with latitude. The south cap seasonal mass change is about 30 to 40% larger than that of the north cap.

Update on the combination effect of macrolide antibiotics in community-acquired pneumonia.

PubMed

Emmet O'Brien, M; Restrepo, Marcos I; Martin-Loeches, Ignacio

2015-09-01

Community-acquired pneumonia (CAP) is a leading cause of death from an infectious cause worldwide. Guideline-concordant antibiotic therapy initiated in a timely manner is associated with improved treatment responses and patient outcomes. In the post-antibiotic era, much of the morbidity and mortality of CAP is as a result of the interaction between bacterial virulence factors and host immune responses. In patients with severe CAP, or who are critically ill, there is a lot of emerging observational evidence demonstrating improved survival rates when treatment using combination therapy with a β-lactam and a macrolide is initiated, as compared to other antibiotic regimes without a macrolide. Macrolides in combination with a β-lactam antibiotic provide broader coverage for the atypical organisms implicated in CAP, and may contribute to antibacterial synergism. However, it has been postulated that the documented immunomodulatory effects of macrolides are the primary mechanism for improved patient outcomes through attenuation of bacterial virulence factors and host systemic inflammatory responses. Despite concerns regarding the limitations of observational evidence and the lack of confirmatory randomized controlled trials, the potential magnitude of mortality benefits estimated at 20-50% cannot be overlooked. In light of recent data from a number of trials showing that combination treatment with a macrolide and a suitable second agent is justified in all patients with severe CAP, such treatment should be obligatory for those admitted to an intensive care setting. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Orientation dependence of grain-boundary energy in metals in the view of a pseudoheterophase dislocation core model

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

Missol, W.

A new dislocation model for symmetric tilt grain boundaries was developed as a basis for deriving the quantitative dependence of grain-boundary energy upon misorientation angle in the form of an expression similar to that given by Read and Shockley (Phys. Rev. 78: 275(1950)). The range of applicability of this equation was extended to over 20 degrees. A comparison of theory and experiment was made for Bi, Ag, Cu, and Fe--Si 3 percent in the teen-degree range of misorientation angles and for Au, ..cap alpha..-Fe, Mo, and W in the high-angle range.

Prediction of alpha factor values for fine pore aeration systems.

PubMed

Gillot, S; Héduit, A

2008-01-01

The objective of this work was to analyse the impact of different geometric and operating parameters on the alpha factor value for fine bubble aeration systems equipped with EPDM membrane diffusers. Measurements have been performed on nitrifying plants operating under extended aeration and treating mainly domestic wastewater. Measurements performed on 14 nitrifying plants showed that, for domestic wastewater treatment under very low F/M ratios, the alpha factor is comprised between 0.44 and 0.98. A new composite variable (the Equivalent Contact Time, ECT) has been defined and makes it possible for a given aeration tank, knowing the MCRT, the clean water oxygen transfer coefficient and the supplied air flow rate, to predict the alpha factor value. ECT combines the effect on mass transfer of all generally accepted factors affecting oxygen transfer performances (air flow rate, diffuser submergence, horizontal flow). (c) IWA Publishing 2008.

Calcium phosphate ceramics in drug delivery

NASA Astrophysics Data System (ADS)

Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

2011-04-01

Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

PubMed

Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

2003-07-20

Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.

Apatite formation on bioactive calcium-silicate cements for dentistry affects surface topography and human marrow stromal cells proliferation.

PubMed

Gandolfi, Maria Giovanna; Ciapetti, Gabriela; Taddei, Paola; Perut, Francesca; Tinti, Anna; Cardoso, Marcio Vivan; Van Meerbeek, Bart; Prati, Carlo

2010-10-01

The effect of ageing in phosphate-containing solution of bioactive calcium-silicate cements on the chemistry, morphology and topography of the surface, as well as on in vitro human marrow stromal cells viability and proliferation was investigated. A calcium-silicate cement (wTC) mainly based on dicalcium-silicate and tricalcium-silicate was prepared. Alpha-TCP was added to wTC to obtain wTC-TCP. Bismuth oxide was inserted in wTC to prepare a radiopaque cement (wTC-Bi). A commercial calcium-silicate cement (ProRoot MTA) was tested as control. Cement disks were aged in DPBS for 5 h ('fresh samples'), 14 and 28 days, and analyzed by ESEM/EDX, SEM/EDX, ATR-FTIR, micro-Raman techniques and scanning white-light interferometry. Proliferation, LDH release, ALP activity and collagen production of human marrow stromal cells (MSC) seeded for 1-28 days on the cements were evaluated. Fresh samples exposed a surface mainly composed of calcium-silicate hydrates CSH (from the hydration of belite and alite), calcium hydroxide, calcium carbonate, and ettringite. Apatite nano-spherulites rapidly precipitated on cement surfaces within 5 h. On wTC-TCP the Ca-P deposits appeared thicker than on the other cements. Aged cements showed an irregular porous calcium-phosphate (Ca-P) coating, formed by aggregated apatite spherulites with interspersed calcite crystals. All the experimental cements exerted no acute toxicity in the cell assay system and allowed cell growth. Using biochemical results, the scores were: fresh cements>aged cements for cell proliferation and ALP activity (except for wTC-Bi), whereas fresh cements

Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-{alpha}

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

Tsukasaki, Masayuki; Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp; Suzuki, Dai

2011-07-15

Highlights: {yields} TNF-{alpha} inhibits POEM gene expression. {yields} Inhibition of POEM gene expression is caused by NF-{kappa}B activation by TNF-{alpha}. {yields} Over-expression of POEM recovers inhibition of osteoblast differentiation by TNF-{alpha}. -- Abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-{alpha} (TNF-{alpha}), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-{alpha}-induced down-regulation of POEM gene expression occurred in both time- andmore » dose-dependent manners through the nuclear factor kappa B (NF-{kappa}B) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-{alpha} in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-{alpha}-induced inhibition of osteoblast differentiation. These results suggest that TNF-{alpha} inhibits POEM expression through the NF-{kappa}B signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-{alpha}.« less

Effect of transforming growth factor-alpha on enterocyte apoptosis is correlated with EGF receptor expression along the villus-crypt axis during methotrexate-induced intestinal mucositis in a rat.

PubMed

Sukhotnik, Igor; Shteinberg, Dan; Ben Lulu, Shani; Bashenko, Yulia; Mogilner, Jorge G; Ure, Benno M; Shaoul, Ron; Coran, Arnold G

2008-11-01

The purpose of the present study was to evaluate the effect of transforming-growth factor-alpha (TGF-alpha) on enterocyte apoptosis following methotrexate (MTX) induced intestinal mucositis in a rat and in Caco-2 cells. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of TGF-alpha. Cell apoptosis was determined by FACS cytometry. Adult rats were divided into four groups: Control, Control-TGF-alpha, MTX, and MTX- TGF-alpha rats. Three days later rats were sacrificed. Enterocyte apoptosis were measured at sacrifice. RT-PCR and Western Blotting was used to determine the level of Bax and Bcl-2 mRNA and protein. Real time PCR was used to measure epidermal growth factor receptor (EGFr) expression along the villus-crypt axis. The in vitro experiment has shown that treatment with TGF-alpha of Caco-2 cells results in a significant inhibition of cell apoptosis in a dose-dependent manner. In vivo experiment, a decreased levels of apoptosis in MTX- TGF-alpha rats corresponded with the decrease in Bax and with the increase in Bcl-2 at both mRNA and protein levels. The inhibiting effect of TGF-alpha on enterocyte apoptosis was strongly correlated with EGFr expression along the villus-crypt axis. In conclusion, treatment with TGF-alpha inhibits enterocyte apoptosis following MTX- injury in the rat.

Circulating tumour necrosis factor alpha & soluble TNF receptors in patients with Guillain-Barre syndrome.

PubMed

Radhakrishnan, V V; Sumi, M G; Reuben, S; Mathai, A; Nair, M D

2003-05-01

Tumour necrosis factor-alpha (TNF-alpha) is regarded as one of the immune factors that can induce demyelination of peripheral nerves in patients with Guillian-Barre syndrome (GBS). This present study was undertaken to find out the role of TNF-alpha and soluble TNF receptors in the pathogenesis of GBS; and to study the effect of intravenous immunoglobulin (ivIg) therapy on the serum TNF-alpha and soluble TNF receptors in patients with GBS. Thirty six patients with GBS in progressive stages of motor weakness were included in this study. The serum TNF-alpha and soluble TNF receptors (TNF-RI, TNF-RII) were measured in the serum samples of these patients before and after ivIg therapy by a sandwich ELISA. Of the 36 patients with GBS, 26 (72.2%) showed elevated serum TNF-alpha levels prior to ivIg therapy. Following a complete course of ivIg therapy there was a progressive decrease in the serum TNF-alpha concentrations in these 26 patients. On the other hand, the soluble TNF receptors, particularly TNF-RII showed an increase in the serum of GBS patients following ivIg therapy. The results indicate that ivIg reduces the serum TNF-alpha concentrations in the GBS patients having elevated levels prior to ivIg therapy. Elevated serum levels of soluble TNF receptors following ivIg therapy may play a protective role by inhibiting the demyelinating effect of TNF-alpha in the peripheral nerves of patients with GBS.

Biomarkers in Pediatric Community-Acquired Pneumonia.

PubMed

Principi, Nicola; Esposito, Susanna

2017-02-19

Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon-γ protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended.

TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

EPA Science Inventory

TITLE:
TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

A Factor Analysis of Learning Data and Selected Ability Test Scores

ERIC Educational Resources Information Center

Jones, Dorothy L.

1976-01-01

A verbal concept-learning task permitting the externalizing and quantifying of learning behavior and 16 ability tests were administered to female graduate students. Data were analyzed by alpha factor analysis and incomplete image analysis. Six alpha factors and 12 image factors were extracted and orthogonally rotated. Four areas of cognitive…

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

Arpiainen, Satu; Jaervenpaeae, Sanna-Mari; Manninen, Aki

The nutritional state of organisms and energy balance related diseases such as diabetes regulate the metabolism of xenobiotics such as drugs, toxins and carcinogens. However, the mechanisms behind this regulation are mostly unknown. The xenobiotic-metabolizing cytochrome P450 (CYP) 2A5 enzyme has been shown to be induced by fasting and by glucagon and cyclic AMP (cAMP), which mediate numerous fasting responses. Peroxisome proliferator-activated receptor {gamma} coactivator (PGC)-1{alpha} triggers many of the important hepatic fasting effects in response to elevated cAMP levels. In the present study, we were able to show that cAMP causes a coordinated induction of PGC-1{alpha} and CYP2A5 mRNAsmore » in murine primary hepatocytes. Furthermore, the elevation of the PGC-1{alpha} expression level by adenovirus mediated gene transfer increased CYP2A5 transcription. Co-transfection of Cyp2a5 5' promoter constructs with the PGC-1{alpha} expression vector demonstrated that PGC-1{alpha} is able to activate Cyp2a5 transcription through the hepatocyte nuclear factor (HNF)-4{alpha} response element in the proximal promoter of the Cyp2a5 gene. Chromatin immunoprecipitation assays showed that PGC-1{alpha} binds, together with HNF-4{alpha}, to the same region at the Cyp2a5 proximal promoter. In conclusion, PGC-1{alpha} mediates the expression of CYP2A5 induced by cAMP in mouse hepatocytes through coactivation of transcription factor HNF-4{alpha}. This strongly suggests that PGC-1{alpha} is the major factor mediating the fasting response of CYP2A5.« less

Interleukin-10 to tumor necrosis factor-alpha ratio is a predictive biomarker in nonalcoholic fatty liver disease: interleukin-10 to tumor necrosis factor-alpha ratio in steatohepatitis.

PubMed

Hashem, Reem M; Mahmoud, Mona F; El-Moselhy, Mohamed A; Soliman, Hala M

2008-10-01

Fatty liver disease is commonly associated with diabetes mellitus (DM). Insulin resistance (IR) as an investigative biomarker is only concerned with fatty liver that results from DM type 2 associated with metabolic syndrome. Irrespective of IR, DM is generally characterized by overproduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), whereas action of the latter is modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). The aim of this study was to investigate the efficacy of using TNF-alpha alone or IL-10/TNF-alpha ratio compared to IR, as a promising biomarker for fatty liver assessment in DM. Furthermore, we hypothesized that using garlic as an immunomodulator may decrease TNF-alpha and increase IL-10 production to improve steatohepatitis. DM was induced metabolically by a high-fat diet to bring about IR, or chemically by alloxan, producing insulin deficiency, in male albino rats. Garlic powder was supplemented (15 mg/kg per day) for 3 weeks. Fatty liver was depicted histologically and biochemically (aspartic aminotransferase, alanine aminotransferase, HOMA-IR, TNF-alpha, IL-10, IL-10/TNF-alpha ratio). We found that, in contrast to obese rats, garlic decreased IL-10/TNF-alpha ratio, despite decreasing TNF-alpha in alloxan diabetic rats in agreement with the histology, which revealed more prominent improvement in the obese group. Moreover, the effect of garlic was not linked to improvement of IR in obese rats. We conclude that IL-10/TNF-alpha ratio may be considered as a convenient biomarker for investigation of fatty liver of different grades, apart from being associated with IR, and immunomodulation of this ratio in favor of increasing it may exert significant improvement.

Toward the mechanism of eIF4F-mediated ribosomal attachment to mammalian capped mRNAs.

PubMed

Kumar, Parimal; Hellen, Christopher U T; Pestova, Tatyana V

2016-07-01

Ribosomal attachment to mammalian capped mRNAs is achieved through the cap-eukaryotic initiation factor 4E (eIF4E)-eIF4G-eIF3-40S chain of interactions, but the mechanism by which mRNA enters the mRNA-binding channel of the 40S subunit remains unknown. To investigate this process, we recapitulated initiation on capped mRNAs in vitro using a reconstituted translation system. Formation of initiation complexes at 5'-terminal AUGs was stimulated by the eIF4E-cap interaction and followed "the first AUG" rule, indicating that it did not occur by backward scanning. Initiation complexes formed even at the very 5' end of mRNA, implying that Met-tRNAi (Met) inspects mRNA from the first nucleotide and that initiation does not have a "blind spot." In assembled initiation complexes, the cap was no longer associated with eIF4E. Omission of eIF4A or disruption of eIF4E-eIF4G-eIF3 interactions converted eIF4E into a specific inhibitor of initiation on capped mRNAs. Taken together, these results are consistent with the model in which eIF4E-eIF4G-eIF3-40S interactions place eIF4E at the leading edge of the 40S subunit, and mRNA is threaded into the mRNA-binding channel such that Met-tRNAi (Met) can inspect it from the first nucleotide. Before entering, eIF4E likely dissociates from the cap to overcome steric hindrance. We also found that the m(7)G cap specifically interacts with eIF3l. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

Impaired cytokine responses in patients with cryopyrin-associated periodic syndrome (CAPS)

PubMed Central

Haverkamp, M H; van de Vosse, E; Goldbach-Mansky, R; Holland, S M

2014-01-01

Cryopyrin-associated periodic syndrome (CAPS) is characterized by dysregulated inflammation with excessive interleukin (IL)-1β activation and secretion. Neonatal-onset multi-system inflammatory disease (NOMID) is the most severe form. We explored cytokine responses in 32 CAPS patients before and after IL-1β blocking therapy. We measured cytokines produced by activated peripheral blood monuclear cells (PBMCs) from treated and untreated CAPS patients after stimulation for 48 h with phytohaemagglutinin (PHA), PHA plus IL-12, lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ. We measured IL-1β, IL-6, IL-10, tumour necrosis factor (TNF), IL-12p70 and IFN-γ in the supernatants. PBMCs from three untreated CAPS patients were cultured in the presence of the IL-1β blocker Anakinra. Fifty healthy individuals served as controls. CAPS patients had high spontaneous production of IL-1β, IL-6, TNF and IFN-γ by unstimulated cells. However, stimulation indexes (SIs, ratio of stimulated to unstimulated production) of these cytokines to PHA and LPS were low in NOMID patients compared to controls. Unstimulated IL-10 and IL-12p70 production was normal, but up-regulation after PHA and LPS was also low. LPS plus IFN-γ inadequately up-regulated the production of IL-1β, IL-6, TNF and IL-10 in CAPS patients. In-vitro but not in-vivo treatment with Anakinra improved SIs by lowering spontaneous cytokine production. However, in-vitro treatment did not improve the low stimulated cytokine levels. Activating mutations in NLRP3 in CAPS are correlated with poor SIs to PHA, LPS and IFN-γ. The impairment in stimulated cytokine responses in spite of IL-1β blocking therapy suggests a broader intrinsic defect in CAPS patients, which is not corrected by targeting IL-1β. PMID:24773462

[Factors influencing bonding fixed restorations].

PubMed

Medić, Vesna; Obradović-Djuricić, Kosovka

2008-01-01

Crown displacement often occurs because the features of tooth preparations do not counteract the forces directed against restorations. The purpose of this study was to evaluate the effect of preparation designs on retention and resistance of fixed restorations. The study was performed on 64 differently sized stainless steel dies. Also, caps which were used for evaluated retention were made of stainless steel for each die. After cementing the caps on experimental dies, measuring of necessary tensile forces to separate cemented caps from dies was done. Caps, which were made of a silver-palladium alloy with a slope of 600 to the longitudinal axis formed on the occlusal surface, were used for evaluating resistance. A sudden drop in load pressure recorded by the test machine indicated failure for that cap. A significant difference was found between the tensile force required to remove the caps from the dies with different length (p < 0.05) and different taper (p < 0.01). The greatest retentive strengths (2579.2 N and 2989.8 N) were noticed in experimental dies with the greatest length and smallest taper. No statistically significant (p > 0.05) differences were found between tensile loads for caps cemented on dies with different diameter. Although there was an apparent slight increase in resistance values for caps on dies with smaller tapers, the increase in resistance for those preparation designs was not statistically significant. There was a significant difference among the resistance values for caps on dies with different length (p < 0.01) and diameter (p < 0.05). In the light of the results obtained, it could be reasonably concluded that retention and resistance of the restoration is in inverse proportion to convergence angle of the prepared teeth. But, at a constant convergence angle, retention and resistance increase with rising length and diameter.

In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

PubMed

Limentani, S A; Gowell, K P; Deitcher, S R

1995-04-01

This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor VIIa could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Improving job satisfaction of Chinese doctors: the positive effects of perceived organizational support and psychological capital.

PubMed

Fu, J; Sun, W; Wang, Y; Yang, X; Wang, L

2013-10-01

The huge population basic and the transformational changes to healthcare system in China have gained wide public attention in recent years. Along with these issues is a growing literature about doctor's job satisfaction; however, more is known about its negative related factors. Thus, this study was an attempt to assess the level of job satisfaction among Chinese doctors and to explore factors that enhance their job satisfaction. Cross-sectional questionnaire-based survey. A cross-sectional study was conducted during the period of September/October 2010. A questionnaire containing job satisfaction assessed by Minnesota Satisfaction Questionnaire (MSQ), demographic characteristics, work conditions, psychological capital (PsyCap) and perceived organizational support (POS) was distributed to 1300 registered doctors in Liaoning province. A total of 984 respondents became our subjects (effective response rate 75.7%). Hierarchical regression was performed to explore the factors associated with satisfaction. The average MSQ score was 65.86 (level ranking for MSQ, 20-100) in our study population. Hierarchical regression analysis showed that POS (β = 0.412, P < 0.001), PsyCap (β = 0.255, P < 0.001), incentive system (β = 0.119, P < 0.001) and educational background (β = 0.056, P = 0.042) were positively associated with job satisfaction. The job satisfaction of Chinese doctors was at a moderate level. POS and PsyCap seemed to be the most crucial factors in relation to job satisfaction. Therefore, efficient measures such as building a supportive work environment and developing doctors' PsyCap should be considered by health administrators in order to promote job satisfaction among Chinese doctors. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Effects of titanium surface anodization with CaP incorporation on human osteoblastic response

PubMed Central

OLIVEIRA, Natássia Cristina Martins; MOURA, Camilla Christian Gomes; ZANETTA-BARBOSA, Darceny; MENDONÇA, Daniela Baccelli Silveira; MENDONÇA, Gustavo; DECHICHI, Paula

2015-01-01

In this study we investigated whether anodization with calcium phosphate (CaP) incorporation (Vulcano®) enhances growth factors secretion, osteoblast-specific gene expression, and cell viability, when compared to acid etched surfaces (Porous®) and machined surfaces (Screw®) after 3 and 7 days. Results showed significant cell viability for Porous and Vulcano at day 7, when compared with Screw (p=0.005). At the same time point, significant differences regarding runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and bone sialoprotein (BSP) expression were found for all surfaces (p<0.05), but with greater fold induction for Porous and Vulcano. The secretion of transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) was not significantly affected by surface treatment in any experimental time (p>0.05). Although no significant correlation was found for growth factors secretion and Runx2 expression, a significant positive correlation between this gene and ALP/BSP expression showed that their strong association is independent on the type of surface. The incorporation of CaP affected the biological parameters evaluated similar to surfaces just acid etched. The results presented here support the observations that roughness also may play an important role in determining cell response. PMID:23498218

The fibroblast growth factor receptor (FGFR) agonist FGF1 and the neural cell adhesion molecule-derived peptide FGL activate FGFR substrate 2alpha differently.

PubMed

Chen, Yongshuo; Li, Shizhong; Berezin, Vladimir; Bock, Elisabeth

2010-07-01

Activation of fibroblast growth factor (FGF) receptors (FGFRs) both by FGFs and by the neural cell adhesion molecule (NCAM) is crucial in the development and function of the nervous system. We found that FGFR substrate 2alpha (FRS2alpha), Src homologous and collagen A (ShcA), and phospholipase-Cgamma (PLCgamma) were all required for neurite outgrowth from cerebellar granule neurons (CGNs) induced by FGF1 and FGL (an NCAM-derived peptide agonist of FGFR1). Like FGF1, FGL induced tyrosine phosphorylation of FGFR1, FRS2alpha, ShcA, and PLCgamma in a time- and dose-dependent manner. However, the activation of FRS2alpha by FGL was significantly lower than the activation by FGF1, indicating a differential signaling profile induced by NCAM compared with the cognate growth factor.

Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production via down-regulation of MyD88 expression.

PubMed

Noman, Abu Shadat M; Koide, Naoki; Hassan, Ferdaus; I-E-Khuda, Imtiaz; Dagvadorj, Jargalsaikhan; Tumurkhuu, Gantsetseg; Islam, Shamima; Naiki, Yoshikazu; Yoshida, Tomoaki; Yokochi, Takashi

2009-02-01

The effect of thalidomide on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production was studied by using RAW 264.7 murine macrophage-like cells. Thalidomide significantly inhibited LPS-induced TNF-alpha production. Thalidomide prevented the activation of nuclear factor (NF)-KB by down-regulating phosphorylation of inhibitory KB factor (IKB), and IKB kinase (IKK)-alpha and IKK-beta Moreover, thalidomide inhibited LPS-induced phosphorylation of AKT, p38 and stress-activated protein kinase (SAPK)/JNK. The expression of myeloid differentiation factor 88 (MyD88) protein and mRNA was markedly reduced in thalidomide-treated RAW 264.7 cells but there was no significant alteration in the expression of interleukin-1 receptor-associated kinase (IRAK) 1 and TNF receptor-associated factor (TRAF) 6 in the cells. Thalidomide did not affect the cell surface expression of Toll-like receptor (TLR) 4 and CD14, suggesting the impairment of intracellular LPS signalling in thalidomide-treated RAW 264.7 cells. Thalidomide significantly inhibited the TNF-alpha production in response to palmitoyl-Cys(RS)-2,3-di(palmitoyloxy) propyl)-Ala-Gly-OH (Pam(3)Cys) as a MyD88-dependent TLR2 ligand. Therefore, it is suggested that thalidomide might impair LPS signalling via down-regulation of MyD88 protein and mRNA and inhibit LPS-induced TNF-alpha production. The putative mechanism of thalidomide-induced MyD88 down-regulation is discussed.

Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway.

PubMed

Yang, Yi; Li, Wang; Liu, Yang; Sun, Yuning; Li, Yan; Yao, Qing; Li, Jianning; Zhang, Qian; Gao, Yujing; Gao, Ling; Zhao, Jiajun

2014-11-01

Understanding the mechanism by which alpha-lipoic acid supplementation has a protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha-lipoic acid. The lipid-lowering effects were measured. The protein expression and distribution were analyzed by Western blot, immunoprecipitation and immunofluorescence, respectively. We found that alpha-lipoic acid enhanced sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP-activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP-activated protein kinase pathway, the translocation of sterol regulatory element-binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression and decreased fatty acid synthase abundance. In in vivo and in vitro studies, alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually reduced intrahepatic and serum triglyceride content. The protective effects of alpha-lipoic acid on hepatic steatosis appear to be associated with the transcription factors sterol regulatory element-binding protein-1, forkhead box O1 and NF-E2-related factor 2. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha.

PubMed

Leibovich, S J; Polverini, P J; Shepard, H M; Wiseman, D M; Shively, V; Nuseir, N

Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth. We show here that tumour necrosis factor-alpha (TNF-alpha), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-alpha induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-alpha stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures. The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-alpha, suggesting immunological features are common to TNF-alpha and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-alpha could augment repair by stimulating new blood vessel growth; in tumours, TNF-alpha might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity.

The effect of PVP on morphology, optical properties and electron paramagnetic resonance of Zn0.5Co0.5Fe2-xPrxO4 nanoparticles

NASA Astrophysics Data System (ADS)

Bitar, Z.; El-Said Bakeer, D.; Awad, R.

2017-07-01

Zinc Cobalt nano ferrite doped with Praseodymium, Zn0.5Co0.5Fe2-xPrxO4 (0 ≤ x ≤ 0.2), were prepared by co-precipitation method from an aqueous solution containing metal chlorides and two concentrations of poly(vinylpyrrolidone) (PVP) 0 and 30g/L as capping agent. The samples were characterized using X-ray powder diffraction (XRD), Transmission Electron Microscope (TEM), UV-visible optical spectroscopy, Fourier transform infrared (FTIR) and Electron Paramagnetic Resonance (EPR). XRD results display the formation of cubic spinel structure with space group Fd3m and the lattice parameter (a) is slightly decreased for PVP capping samples. The particle size that determined by TEM, decreases for PVP capping samples. The optical band energy Eg increases for PVP capping samples, confirming the variation of energy gap with the particle size. The FTIR results indicate that the metal oxide bands were shifted for the PVP capping samples. EPR data shows that the PVP addition increases the magnetic resonance field and hence decreases the g-factor.

Sequestration by IFIT1 Impairs Translation of 2′O-unmethylated Capped RNA

PubMed Central

Lacerda, Livia; Benda, Christian; Holze, Cathleen; Eberl, Christian H.; Mann, Angelika; Kindler, Eveline; Gil-Cruz, Cristina; Ziebuhr, John; Thiel, Volker; Pichlmair, Andreas

2013-01-01

Viruses that generate capped RNA lacking 2′O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2′O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2′O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2′O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2′O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells. PMID:24098121

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

PubMed

Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Variable pulmonary responses from exposure to concentrated ambient air particles in a rat model of bronchitis.

PubMed

Kodavanti, U P; Mebane, R; Ledbetter, A; Krantz, T; McGee, J; Jackson, M C; Walsh, L; Hilliard, H; Chen, B Y; Richards, J; Costa, D L

2000-04-01

Chronic bronchitis may be considered a risk factor in particulate matter (PM)-induced morbidity. We hypothesized that a rat model of human bronchitis would be more susceptible to the pulmonary effects of concentrated ambient particles (CAPs) from Research Triangle Park, NC. Bronchitis was induced in male Sprague-Dawley rats (90-100 days of age) by exposure to 200 ppm sulfur dioxide (SO2), 6 h/day x 5 days/week x 6 weeks. One day following the last SO2 exposure, both healthy (air-exposed) and bronchitic (SO2-exposed) rats were exposed to filtered air (three healthy; four bronchitic) or CAPs (five healthy; four bronchitic) by whole-body inhalation, 6 h/day x 2 or 3 days. Pulmonary injury was determined either immediately (0h) or 18 h following final CAPs exposure. The study protocol involving 0 h time point was repeated four times (study #A, November, 1997; #B, February, 1998; #C and #D, May, 1998), whereas the study protocol involving 18 h time point was done only once (#F). In an additional study (#E), rats were exposed to residual oil fly ash (ROFA), approximately 1 mg/ m(3)x6 h/day x 3 days to mimic the CAPs protocol (February, 1998). The rats allowed 18 h recovery following CAPs exposure (#F) did not depict any CAPs-related differences in bronchoalveolar lavage fluid (BALF) injury markers. Of the four CAPs studies conducted (0 h time point), the first (#A) study (approximately 650 microg/m3 CAPs) revealed significant changes in the lungs of CAPs-exposed bronchitic rats compared to the clean air controls. These rats had increased BALF protein, albumin, N-acetyl glutaminidase (NAG) activity and neutrophils. The second (#B) study (approximately 475 microg/m3 CAPs) did not reveal any significant effects of CAPs on BALF parameters. Study protocols #C (approximately 869 microg/m3 CAPs) and #D (approximately 907 microg/m3 CAPs) revealed only moderate increases in the above mentioned BALF parameters in bronchitic rats exposed to CAPs. Pulmonary histologic evaluation of studies #A, #C, #D, and #F revealed marginally higher congestion and perivascular cellularity in CAPs-exposed bronchitic rats. Healthy and bronchitic rats exposed to ROFA (approximately 1 mg/m3) did not show significant pulmonary injury (#E). Analysis of leachable elemental components of CAPs revealed the presence of sulfur, zinc, manganese, and iron. There was an apparent lack of association between pulmonary injury and CAPs concentration, or its leachable sulfate or elemental content. In summary, real-time atmospheric PM may result in pulmonary injury, particularly in susceptible models. However, the variability observed in pulmonary responses to CAPs emphasizes the need to conduct repeated studies, perhaps in relation to the season, as composition of CAPs may vary. Additionally, potential variability in pathology of induced bronchitis or other lung disease may decrease the ability to distinguish toxic injury due to PM.

Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP)

PubMed Central

Park, Kyoung Un; Lee, Sang Hoon; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Lee, Choon-Taek

2018-01-01

Background Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. Methods Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). Results Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral–bacterial coinfection and bacterial infection, and the CAP group showed similar results. Conclusions The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral–bacterial coinfection or bacterial infection. PMID:29447204

Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP).

PubMed

Kim, Eun Sun; Park, Kyoung Un; Lee, Sang Hoon; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Lee, Choon-Taek; Lee, Jae Ho

2018-01-01

Although viruses are known to be the second most common etiological factor in community-acquired pneumonia (CAP), the respiratory viral profile of the patients with healthcare-associated pneumonia (HCAP) has not yet been elucidated. We investigated the prevalence and the clinical impact of respiratory virus infection in adult patients with HCAP. Patients admitted with HCAP or CAP, between January and December 2016, to a tertiary referral hospital in Korea, were prospectively enrolled, and virus identification was performed using reverse-transcription polymerase chain reaction (RT-PCR). Among 452 enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%) patients had a viral infection, and the proportion of those with viral infection was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p = 0.004). In both the HCAP and CAP groups, influenza A was the most common respiratory virus, followed by entero-rhinovirus. The seasonal distributions of respiratory viruses were also similar in both groups. In the HCAP group, the viral infection resulted in a similar length of hospital stay and in-hospital mortality as viral-bacterial coinfection and bacterial infection, and the CAP group showed similar results. The prevalence of viral infection in patients with HCAP was lower than that in patients with CAP, and resulted in a similar prognosis as viral-bacterial coinfection or bacterial infection.

Noninvasive detection of hepatic steatosis in patients without ultrasonographic evidence of fatty liver using the controlled attenuation parameter evaluated with transient elastography.

PubMed

Yilmaz, Yusuf; Ergelen, Rabia; Akin, Hakan; Imeryuz, Nese

2013-11-01

Although ultrasound is a useful technique for detecting hepatic steatosis, it cannot provide a precise determination of hepatic fat content. A novel attenuation parameter named controlled attenuation parameter (CAP) has been developed to process the raw ultrasonic signals acquired by Fibroscan. The aim of this study was to determine the percentage of hepatic steatosis in apparently healthy Turkish individuals using the proposed diagnostic cut-off points for CAP. In addition, we sought to investigate the association of CAP with the traditional risk factors for nonalcoholic fatty liver disease in a screening setting. In the present study, 102 Turkish individuals without evidence of fatty liver on ultrasound and normal aminotransferase levels underwent CAP measurements by means of Fibroscan. The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CAP values in this cohort of 102 individuals were 206.99 (48.12), 210.5 (100.0-314.0), 113.4 and 280.2 dB/m, respectively. Using the cut-offs of 222, 238, and 283 dB/m for CAP, there were 39 (38.2%), 23 (22.5%), and five (4.9%) individuals out of 102 who had at least 10% steatosis despite normal liver findings on ultrasound. After allowance for potential confounders, CAP was independently associated with BMI (β=0.39, t=3.5, P<0.001) and the number of metabolic syndrome criteria (β=0.24, t=2.1, P<0.05). These results hold promise for early noninvasive detection of hepatic steatosis on the basis of CAP assessment.

Involvement of reactive oxygen species in endosperm cap weakening and embryo elongation growth during lettuce seed germination

PubMed Central

Zhang, Yu; Chen, Bingxian; Xu, Zhenjiang; Shi, Zhaowan; Chen, Shanli; Huang, Xi; Chen, Jianxun; Wang, Xiaofeng

2014-01-01

Endosperm cap (CAP) weakening and embryo elongation growth are prerequisites for the completion of lettuce seed germination. Although it has been proposed that the cell wall loosening underlying these processes results from an enzymatic mechanism, it is still unclear which enzymes are involved. Here it is shown that reactive oxygen species (ROS), which are non-enzymatic factors, may be involved in the two processes. In Guasihong lettuce seeds imbibed in water, O2·– and H2O2 accumulated and peroxidase activity increased in the CAP, whereas its puncture force decreased. In addition, in the radicle, the increase in embryo growth potential was accompanied by accumulation of O2·– and an increase in peroxidase activity. Imbibing seeds in 0.3% sodium dichloroisocyanurate (SDIC) reduced endosperm viability and the levels of O2·–, H2O2, and peroxidase activity in the CAP, whereas the decrease in its puncture force was inhibited. However, in the embryo, SDIC did not affect the accumulation of O2·–, peroxidase activity, and the embryo growth potential. As a result, SDIC caused atypical germination, in which the endosperm ruptured at the boundary between the CAP and lateral endosperm. ROS scavengers and ROS generation inhibitors inhibited the CAP weakening and also decreased the embryo growth potential, thus decreasing the percentage of seed germination. Exogenous ROS and ROS generation inducers increased the percentage of CAP rupture to some extent, and the addition of H2O2 to 0.3% SDIC enabled some seeds to undergo typical germination. PMID:24744430

Hepatocyte nuclear factor 4alpha contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Kruppel-like transcription factor 9.

PubMed

Ohguchi, Hiroto; Tanaka, Toshiya; Uchida, Aoi; Magoori, Kenta; Kudo, Hiromi; Kim, Insook; Daigo, Kenji; Sakakibara, Iori; Okamura, Masashi; Harigae, Hideo; Sasaki, Takeshi; Osborne, Timothy F; Gonzalez, Frank J; Hamakubo, Takao; Kodama, Tatsuhiko; Sakai, Juro

2008-06-01

Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4alpha-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4alpha site (direct repeat 1 [TGGACAAAGGTGC]; HNF4alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4alpha-RE. Furthermore, KLF9 functions together with HNF4alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9.

Validez Convergente de la Version Espanola Preliminar del Child Abuse Potential Inventory: Depresion y Aduste Marital (Convergent Validity of the Preliminary Spanish Version of the Child Abuse Potential Inventory: Depression and Marital Adjustment).

ERIC Educational Resources Information Center

Arruabarrena, M. Ignacia; de Paul, Joaquin

1992-01-01

"Convergent validity" of preliminary Spanish version of Child Abuse Potential (CAP) Inventory was studied. CAP uses ecological-systemic model of child maltreatment to evaluate individual, family, and social factors facilitating physical child abuse. Depression and marital adjustment were measured in three groups of mothers. Results found…

NESHAP Dose-Release Factor Isopleths for Five Source-to-Receptor Distances from the Center of Site and H-Area for all Compass Sectors at SRS using CAP88-PC Version 4.0

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

Trimor, P.

The Environmental Protection Agency (EPA) requires the use of the computer model CAP88-PC to estimate the total effective doses (TED) for demonstrating compliance with 40 CFR 61, Subpart H (EPA 2006), the National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. As such, CAP88 Version 4.0 was used to calculate the receptor dose due to routine atmospheric releases at the Savannah River Site (SRS). For estimation, NESHAP dose-release factors (DRFs) have been supplied to Environmental Compliance and Area Closure Projects (EC&ACP) for many years. DRFs represent the dose to a maximum receptor exposed to 1 Ci of a specified radionuclidemore » being released into the atmosphere. They are periodically updated to include changes in the CAP88 version, input parameter values, site meteorology, and location of the maximally exposed individual (MEI). This report presents the DRFs of tritium oxide released at two onsite locations, center-of-site (COS) and H-Area, at 0 ft. elevation to maximally exposed individuals (MEIs) located 1000, 3000, 6000, 9000, and 12000 meters from the release areas for 16 compass sectors. The analysis makes use of area-specific meteorological data (Viner 2014).« less

A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan.

PubMed

Raskind, Murray A; Peterson, Kris; Williams, Tammy; Hoff, David J; Hart, Kimberly; Holmes, Hollie; Homas, Dallas; Hill, Jeffrey; Daniels, Colin; Calohan, Jess; Millard, Steven P; Rohde, Kirsten; O'Connell, James; Pritzl, Denise; Feiszli, Kevin; Petrie, Eric C; Gross, Christopher; Mayer, Cynthia L; Freed, Michael C; Engel, Charles; Peskind, Elaine R

2013-09-01

The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan. Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire-9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant. Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups. Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.

Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement.

PubMed

Brachmann, Saskia M; Yballe, Claudine M; Innocenti, Metello; Deane, Jonathan A; Fruman, David A; Thomas, Sheila M; Cantley, Lewis C

2005-04-01

Class Ia phosphoinositide 3-kinases (PI3Ks) are heterodimers of p110 catalytic and p85 regulatory subunits that mediate a variety of cellular responses to growth and differentiation factors. Although embryonic development is not impaired in mice lacking all isoforms of the p85alpha gene (p85alpha-/- p55alpha-/- p50alpha-/-) or in mice lacking the p85beta gene (p85beta-/-) (D. A. Fruman, F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, R. T. Bronson, C. R. Kahn, and L. C. Cantley, Nat Genet. 26:379-382, 2000; K. Ueki, C. M. Yballe, S. M. Brachmann, D. Vicent, J. M. Watt, C. R. Kahn, and L. C. Cantley, Proc. Natl. Acad. Sci. USA 99:419-424, 2002), we show here that loss of both genes results in lethality at embryonic day 12.5 (E12.5). The phenotypes of these embryos, including subepidermal blebs flanking the neural tube at E8 and bleeding into the blebs during the turning process, are similar to defects observed in platelet-derived growth factor receptor alpha null (PDGFRalpha-/-) mice (P. Soriano, Development 124:2691-2700, 1997), suggesting that PI3K is an essential mediator of PDGFRalpha signaling at this developmental stage. p85alpha-/- p55alpha+/+ p50alpha+/+ p85beta-/- mice had similar but less severe defects, indicating that p85alpha and p85beta have a critical and redundant function in development. Mouse embryo fibroblasts deficient in all p85alpha and p85beta gene products (p85alpha-/- p55alpha-/- p50alpha-/- p85beta-/-) are defective in PDGF-induced membrane ruffling. Overexpression of the Rac-specific GDP-GTP exchange factor Vav2 or reintroduction of p85alpha or p85beta rescues the membrane ruffling defect. Surprisingly, reintroduction of p50alpha also restored PDGF-dependent membrane ruffling. These results indicate that class Ia PI3K is critical for PDGF-dependent actin rearrangement but that the SH3 domain and the Rho/Rac/Cdc42-interacting domain of p85, which lacks p50alpha, are not required for this response.

76 FR 13576 - Jurisdictional Separations and Referral to the Federal-State Joint Board

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... relationships and jurisdictional cost allocation factors used in jurisdictional separations. Extending the... allocation factors used in jurisdictional separations, which freeze would otherwise expire on June 30, 2011... factors for price cap carriers and all allocation factors for rate-of-return carriers. Rate-of-return...

77 FR 30410 - Jurisdictional Separations and Referral to the Federal-State Joint Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... jurisdictional cost allocation factors used in jurisdictional separations until June 30, 2014. Extending the... relationships and allocation factors for price cap carriers and all allocation factors for rate-of-return... extending the current freeze of part 36 category relationships and jurisdictional cost allocation factors...

Temporal expression of the human alcohol dehydrogenase gene family during liver development correlates with differential promoter activation by hepatocyte nuclear factor 1, CCAAT/enhancer-binding protein alpha, liver activator protein, and D-element-binding protein.

PubMed Central

van Ooij, C; Snyder, R C; Paeper, B W; Duester, G

1992-01-01

The human class I alcohol dehydrogenase (ADH) gene family consists of ADH1, ADH2, and ADH3, which are sequentially activated in early fetal, late fetal, and postnatal liver, respectively. Analysis of ADH promoters revealed differential activation by several factors previously shown to control liver transcription. In cotransfection assays, the ADH1 promoter, but not the ADH2 or ADH3 promoter, was shown to respond to hepatocyte nuclear factor 1 (HNF-1), which has previously been shown to regulate transcription in early liver development. The ADH2 promoter, but not the ADH1 or ADH3 promoter, was shown to respond to CCAAT/enhancer-binding protein alpha (C/EBP alpha), a transcription factor particularly active during late fetal liver and early postnatal liver development. The ADH1, ADH2, and ADH3 promoters all responded to the liver transcription factors liver activator protein (LAP) and D-element-binding protein (DBP), which are most active in postnatal liver. For all three promoters, the activation by LAP or DBP was higher than that seen by HNF-1 or C/EBP alpha, and a significant synergism between C/EBP alpha and LAP was noticed for the ADH2 and ADH3 promoters when both factors were simultaneously cotransfected. A hierarchy of ADH promoter responsiveness to C/EBP alpha and LAP homo- and heterodimers is suggested. In all three ADH genes, LAP bound to the same four sites previously reported for C/EBP alpha (i.e., -160, -120, -40, and -20 bp), but DBP bound strongly only to the site located at -40 bp relative to the transcriptional start. Mutational analysis of ADH2 indicated that the -40 bp element accounts for most of the promoter regulation by the bZIP factors analyzed. These studies suggest that HNF-1 and C/EBP alpha help establish ADH gene family transcription in fetal liver and that LAP and DBP help maintain high-level ADH gene family transcription in postnatal liver. Images PMID:1620113

Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.

PubMed Central

Pontoglio, M; Sreenan, S; Roe, M; Pugh, W; Ostrega, D; Doyen, A; Pick, A J; Baldwin, A; Velho, G; Froguel, P; Levisetti, M; Bonner-Weir, S; Bell, G I; Yaniv, M; Polonsky, K S

1998-01-01

Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine. These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function. PMID:9593777

Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor alpha promoter in vivo.

PubMed

Staniforth, Vanisree; Wang, Sheng-Yang; Shyur, Lie-Fen; Yang, Ning-Sun

2004-02-13

Tumor necrosis factor alpha (TNF-alpha) contributes to the pathogenesis of both acute and chronic inflammatory diseases and has been a target for the development of new anti-inflammatory drugs. Shikonins, the naphthoquinone pigments present in the root tissues of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), have been reported to exert anti-inflammatory effects both in vitro and in vivo. In this study, we evaluated the effects of shikonin and its derivatives on the transcriptional activation of human TNF-alpha promoter in a gene gun-transfected mouse skin system by using a luciferase reporter gene assay. The crude plant extract of L. erythrorhizon as well as derived individual compounds shikonin, isobutyryl shikonin, acetyl shikonin, dimethylacryl shikonin and isovaleryl shikonin showed significant dose-dependent inhibition of TNF-alpha promoter activation. Among the tested compounds, shikonin and isobutyryl shikonin exhibited the highest inhibition of TNF-alpha promoter activation and also showed significant suppression of transgenic human TNF-alpha mRNA expression and protein production. We demonstrated that shikonin-inhibitory response was retained in the core TNF-alpha promoter region containing the TATA box and a 48-bp downstream sequence relative to the transcription start site. Further our results indicated that shikonin suppressed the basal transcription and activator-regulated transcription of TNF-alpha by inhibiting the binding of transcription factor IID protein complex (TATA box-binding protein) to TATA box. These in vivo results suggest that shikonins inhibit the transcriptional activation of the human TNF-alpha promoter through interference with the basal transcription machinery. Thus, shikonins may have clinical potential as anti-inflammatory therapeutics.

Phenotypic differences between oral and skin fibroblasts in wound contraction and growth factor expression.

PubMed

Shannon, Diane B; McKeown, Scott T W; Lundy, Fionnuala T; Irwin, Chris R

2006-01-01

Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring compared with cutaneous wounds. The differences in healing outcome between oral mucosa and skin could be because of phenotypic differences between the respective fibroblast populations. This study compared paired mucosal and dermal fibroblasts in terms of collagen gel contraction, alpha-smooth muscle actin expression (alpha-SMA), and production of the epithelial growth factors: keratinocyte growth factor (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of transforming growth factor -beta1 and -beta3 on each parameter were also determined. Gel contraction in floating collagen lattices was determined over a 7-day period. alpha-SMA expression by fibroblasts was determined by Western blotting. KGF and HGF expression were determined by an enzyme-linked immunosorbent assay. Oral fibroblasts induced accelerated collagen gel contraction, yet surprisingly expressed lower levels of alpha-SMA. Oral cells also produced significantly greater levels of both KGF and HGF than their dermal counterparts. Transforming growth factor-beta1 and -beta3, over the concentration range of 0.1-10 ng/mL, had similar effects on cell function, stimulating both gel contraction and alpha-SMA production, but inhibiting KGF and HGF production by both cell types. These data indicate phenotypic differences between oral and dermal fibroblasts that may well contribute to the differences in healing outcome between these two tissues.

The German version of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): psychometric properties and diagnostic utility.

PubMed

Krüger-Gottschalk, Antje; Knaevelsrud, Christine; Rau, Heinrich; Dyer, Anne; Schäfer, Ingo; Schellong, Julia; Ehring, Thomas

2017-11-28

The Posttraumatic Stress Disorder (PTSD) Checklist (PCL, now PCL-5) has recently been revised to reflect the new diagnostic criteria of the disorder. A clinical sample of trauma-exposed individuals (N = 352) was assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the PCL-5. Internal consistencies and test-retest reliability were computed. To investigate diagnostic accuracy, we calculated receiver operating curves. Confirmatory factor analyses (CFA) were performed to analyze the structural validity. Results showed high internal consistency (α = .95), high test-retest reliability (r = .91) and a high correlation with the total severity score of the CAPS-5, r = .77. In addition, the recommended cutoff of 33 on the PCL-5 showed high diagnostic accuracy when compared to the diagnosis established by the CAPS-5. CFAs comparing the DSM-5 model with alternative models (the three-factor solution, the dysphoria, anhedonia, externalizing behavior and hybrid model) to account for the structural validity of the PCL-5 remained inconclusive. Overall, the findings show that the German PCL-5 is a reliable instrument with good diagnostic accuracy. However, more research evaluating the underlying factor structure is needed.

The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription

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

Shlomai, Amir, E-mail: amirsh@tasmc.health.gov.il; Institute for Gastroenterology and Liver disease, Tel-Aviv Sourasky Medical Center, 6 Weizmann street, Tel-Aviv; Shaul, Yosef

2009-04-17

Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1{alpha} coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1{alpha} coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4{alpha} and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1{alpha} coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhancedmore » in the presence of PGC-1{alpha}, implying that FOXO1 is a target for PGC-1{alpha} coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.« less

Artificial ligand binding within the HIF2[alpha] PAS-B domain of the HIF2 transcription factor

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

Scheuermann, Thomas H.; Tomchick, Diana R.; Machius, Mischa

2009-05-12

The hypoxia-inducible factor (HIF) basic helix-loop-helix Per-aryl hydrocarbon receptor nuclear translocator (ARNT)-Sim (bHLH-PAS) transcription factors are master regulators of the conserved molecular mechanism by which metazoans sense and respond to reductions in local oxygen concentrations. In humans, HIF is critically important for the sustained growth and metastasis of solid tumors. Here, we describe crystal structures of the heterodimer formed by the C-terminal PAS domains from the HIF2{alpha} and ARNT subunits of the HIF2 transcription factor, both in the absence and presence of an artificial ligand. Unexpectedly, the HIF2{alpha} PAS-B domain contains a large internal cavity that accommodates ligands identified frommore » a small-molecule screen. Binding one of these ligands to HIF2{alpha} PAS-B modulates the affinity of the HIF2{alpha}:ARNT PAS-B heterodimer in vitro. Given the essential role of PAS domains in forming active HIF heterodimers, these results suggest a presently uncharacterized ligand-mediated mechanism for regulating HIF2 activity in endogenous and clinical settings.« less

Hepatocyte nuclear factor-4alpha is a central transactivator of the mouse Ntcp gene.

PubMed

Geier, Andreas; Martin, Ina V; Dietrich, Christoph G; Balasubramaniyan, Natarajan; Strauch, Sonja; Suchy, Frederick J; Gartung, Carsten; Trautwein, Christian; Ananthanarayanan, Meenakshisundaram

2008-08-01

Sodium taurocholate cotransporting polypeptide (Ntcp) is the major uptake system for conjugated bile acids. Deletions of hepatocyte nuclear factor (HNF)-1alpha and retinoid X receptor-alpha:retinoic acid receptor-alpha binding sites in the mouse 5'-flanking region corresponding to putatively central regulatory elements of rat Ntcp do not significantly reduce promoter activity. We hypothesized that HNF-4alpha, which is increasingly recognized as a central regulator of hepatocyte function, may directly transactivate mouse (mNtcp). A 1.1-kb 5'-upstream region including the mouse Ntcp promoter was cloned and compared with the rat promoter. In contrast to a moderate 3.5-fold activation of mNtcp by HNF-1alpha, HNF-4alpha cotransfection led to a robust 20-fold activation. Deletion analysis of mouse and rat Ntcp promoters mapped a conserved HNF-4alpha consensus site at -345/-326 and -335/-316 bp, respectively. p-475bpmNtcpLUC is not transactivated by HNF-1alpha but shows a 50-fold enhanced activity upon cotransfection with HNF-4alpha. Gel mobility shift assays demonstrated a complex of the HNF-4alpha-element formed with liver nuclear extracts that was blocked by an HNF-4alpha specific antibody. HNF-4alpha binding was confirmed by chromatin immunoprecipitation. Using Hepa 1-6 cells, HNF-4alpha-knockdown resulted in a significant 95% reduction in NTCP mRNA. In conclusion, mouse Ntcp is regulated by HNF-4alpha via a conserved distal cis-element independently of HNF-1alpha.

The human interleukin-1 alpha gene is located on the long arm of chromosome 2 at band q13.

PubMed

Lafage, M; Maroc, N; Dubreuil, P; de Waal Malefijt, R; Pébusque, M J; Carcassonne, Y; Mannoni, P

1989-01-01

Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are two biochemically distinct, but distantly related, polypeptidic cytokines that play a key role in inflammation, immunologic reactions, and tissue repair. Recently, it has been shown that IL-1 alpha is identical to hematopoietin 1, which was described as a hematopoietic growth factor acting on early progenitor cells in synergy with other hematopoietic growth factors. In this report we discuss our use of in situ hybridization on human prometaphase cells with a human IL-1 alpha cDNA probe to localize the human IL-1 alpha gene on the proximal part of the long arm of chromosome 2 at band q13, in the same chromosomal region as the IL-1 beta gene.

Roles of the bacterial cell wall and capsule in induction of tumor necrosis factor alpha by type III group B streptococci.

PubMed Central

Vallejo, J G; Baker, C J; Edwards, M S

1996-01-01

Group B streptococci (GBS) are the major cause of sepsis and fatal shock in neonates in the United States. The precise role of tumor necrosis factor alpha (TNF-alpha) in the development of human GBS sepsis has not been defined; however, whole GBS have been shown to induce the production of this inflammatory cytokine. We sought to determine which bacterial cell wall components of GBS are responsible for triggering TNF-alpha production. Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG). Lipopolysaccharide from Escherichia coli served as a control. Supernatants were harvested at specific timed intervals, and TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Monocytes exposed to COH1 and COH1-13 induced similar amounts of TNF-alpha. III-PS, GB-PS, LTA, and PG each induced TNF-alpha in a time- and concentration-dependent manner. However, TNF-alpha release was significantly greater after stimulation by the GB-PS or PG than after stimulation by III-PS or LTA (P < 0.05). Our findings indicate that GB-PS and PG are the bacterial cell wall components primarily evoking TNF-alpha release. These, alone or in concert with other factors, may be responsible for septic shock accompanying GBS sepsis. PMID:8945544

Alpha Air Sample Counting Efficiency Versus Dust Loading: Evaluation of a Large Data Set

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

Hogue, M. G.; Gause-Lott, S. M.; Owensby, B. N.

Dust loading on air sample filters is known to cause a loss of efficiency for direct counting of alpha activity on the filters, but the amount of dust loading and the correction factor needed to account for attenuated alpha particles is difficult to assess. In this paper, correction factors are developed by statistical analysis of a large database of air sample results for a uranium and plutonium processing facility at the Savannah River Site. As is typically the case, dust-loading data is not directly available, but sample volume is found to be a reasonable proxy measure; the amount of dustmore » loading is inferred by a combination of the derived correction factors and a Monte Carlo model. The technique compares the distribution of activity ratios [beta/(beta + alpha)] by volume and applies a range of correction factors on the raw alpha count rate. The best-fit results with this method are compared with MCNP modeling of activity uniformly deposited in the dust and analytical laboratory results of digested filters. Finally, a linear fit is proposed to evenly-deposited alpha activity collected on filters with dust loading over a range of about 2 mg cm -2 to 1,000 mg cm -2.« less

Alpha Air Sample Counting Efficiency Versus Dust Loading: Evaluation of a Large Data Set

DOE PAGES

Hogue, M. G.; Gause-Lott, S. M.; Owensby, B. N.; ...

2018-03-03

Dust loading on air sample filters is known to cause a loss of efficiency for direct counting of alpha activity on the filters, but the amount of dust loading and the correction factor needed to account for attenuated alpha particles is difficult to assess. In this paper, correction factors are developed by statistical analysis of a large database of air sample results for a uranium and plutonium processing facility at the Savannah River Site. As is typically the case, dust-loading data is not directly available, but sample volume is found to be a reasonable proxy measure; the amount of dustmore » loading is inferred by a combination of the derived correction factors and a Monte Carlo model. The technique compares the distribution of activity ratios [beta/(beta + alpha)] by volume and applies a range of correction factors on the raw alpha count rate. The best-fit results with this method are compared with MCNP modeling of activity uniformly deposited in the dust and analytical laboratory results of digested filters. Finally, a linear fit is proposed to evenly-deposited alpha activity collected on filters with dust loading over a range of about 2 mg cm -2 to 1,000 mg cm -2.« less

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

PubMed

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

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

Kim, Nam Hee; Jung, Hye Jin; Shibasaki, Futoshi

2010-01-15

Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effectmore » of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.« less

Cardiopulmonary Toxicity Induced by Ambient Particulate Matter (BI City Concentrated Ambient Particle Study)

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

Annette Rohr; James Wagner Masako Morishita; Gerald Keeler

Alterations in heart rate variability (HRV) have been reported in rodents exposed to concentrated ambient particles (CAPs) from different regions of the United States. The goal of this study was to compare alterations in cardiac function induced by CAPs in two distinct regional atmospheres. AirCARE 1, a mobile laboratory with an EPA/Harvard fine particle (particulate matter <2.5 {micro}m; PM{sub 2.5}) concentrator was located in urban Detroit, MI, where the PM mixture is heavily influenced by motor vehicles, and in Steubenville, OH, where PM is derived primarily from long-range transport and transformation of power plant emissions, as well as from localmore » industrial operations. Each city was studied during both winter and summer months, for a total of four sampling periods. Spontaneously hypertensive rats instrumented for electrocardiogram (ECG) telemetry were exposed to CAPs 8 h/day for 13 consecutive days during each sampling period. Heart rate (HR), and indices of HRV (standard deviation of the average normal-to-normal intervals [SDNN]; square root of the mean squared difference of successive normal-to-normal intervals [rMSSD]), were calculated for 30-minute intervals during exposures. A large suite of PM components, including nitrate, sulfate, elemental and organic carbon, and trace elements, were monitored in CAPs and ambient air. In addition, a unique sampler, the Semi-Continuous Elements in Air Sampler (SEAS) was employed to obtain every-30-minute measurements of trace elements. Positive matrix factorization (PMF) methods were applied to estimate source contributions to PM{sub 2.5}. Mixed modeling techniques were employed to determine associations between pollutants/CAPs components and HR and HRV metrics. Mean CAPs concentrations in Detroit were 518 and 357 {micro}g/m{sup 3} (summer and winter, respectively) and 487 and 252 {micro}g/m{sup 3} in Steubenville. In Detroit, significant reductions in SDNN were observed in the summer in association with cement/lime, iron/steel, and gasoline/diesel factors, while associations with the sludge incineration factor and components were less consistent. In winter, increases in HR were associated with a refinery factor and its components. CAPs-associated HR decreases in winter were linked to sludge incineration, cement/lime, and coal/secondary factors and the majority of their associated components. Specific relationships for increased rMSSD in winter were difficult to determine due to lack of consistency between factors and associated constituents. In Steubenville, we observed significant changes in HR (both increases and decreases), SDNN, and rMSSD in the summer, but not in the winter. We examined associations between individual source factors/PM components and HRV metrics segregated by predominant wind direction (NE or SW). Changes in HR (both increases and decreases) were linked with metal processing, waste incineration, and iron/steel factors along with most of their associated elemental constituents. Reductions in SDNN were associated with metal processing, waste incineration, and mobile source factors and the majority of elements loading onto these factors. There were no consistent associations between changes in rMSSD and source factors/components. Despite the large number of coal-fired power plants in the region, and therefore the large contribution of secondary sulfate to overall PM mass, we did not observe any associations with the coal/secondary factor or with the majority of its associated components. There were several inconsistencies in our results which make definitive conclusions difficult. For example, we observed opposing signs of effect estimates with some components depending on season, and with others depending on wind direction. In addition, our extensive dataset clearly would be subject to issues of multiple comparisons, and the 'true' significant results are unknown. Overall, however, our results suggest that acute changes in cardiac function were most strongly associated with local industrial sources. Results for coal-fired power plant-derived PM were inconsistent and largely nonsignificant, whereas traffic and metal-related industries appeared to have stronger impacts. Importantly, our findings highlight the value of combining both factor analytical and component-specific analyses when interpreting results; relying on only one approach may not provide a complete picture of exposure-health relationships.« less

The development of measures of organizational citizenship behaviour and changes in job behaviours related to quality management in health care.

PubMed

Irvine, D

1995-08-01

A study was conducted at two tertiary care hospitals in Canada for the purpose of developing instruments to measure organizational citizenship behaviours (OCB) and changes in job behaviours that occur as a result of participation on hospital quality improvement (CQI) teams. Semi structured interviews were conducted among 52 hospital employees in order to elicit critical incidents of OCB and changes in job behaviours related to CQI. The results of the staff interviews were used to develop a measure of OCB in the hospital setting, and a measure of changes in job behaviours related to CQI. 39 employees, who were drawn from the major departments within the two hospitals on the basis of their membership on CQI teams, participated in a test of the psychometric properties of the two research instruments. Exploratory factor analysis, employing an orthogonal rotation, yielded two factors that accounted for 30% of the variation among the OCB items. The Cronbach alpha for items loading highly on the first factor was .88. The factor was labelled 'OCB directed towards individuals within the organization'. This factor was dominated by items reflecting the kinds of extra-role job behaviours employees engage in to assist patients, family members, visitors, and other employees within the organization. The Cronbach alpha for items loading highly on the second factor was 0.71. The second factor was labelled 'organizationally directed OCB', and consisted of behaviours that reflected an impersonal form of OCB in the hospital setting. Factor analysis, employing an orthogonal rotation, yielded four factors that accounted for 48% of the variation among the items measuring changes in job behaviours related to CQI. The four factors were labelled 'problem-solving', Cronbach alpha 0.82; 'customer awareness', Cronbach alpha 0.79; 'use of CQI knowledge', Cronbach alpha 0.77; and 'organizational interests', Cronbach alpha 0.79. The two OCB factors were moderately correlated, there were no significant correlations among any of the factors measuring changes in job behaviours related to CQI, and the problem-solving job behaviours factor was moderately correlated with the two OCB factors. Directions for future research are discussed.

Hydrogen absorption by thin Pd/Nb films deposited on glass

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

Reisfeld, G.; Jisrawi, N.M.; Ruckman, M.W.

Hydrogen absorption by 200{endash}2000-A-thick Pd-capped Nb films, between 5 and 110{degree}C, was studied by simultaneous four-probe resistivity and volumetric measurements. The resistivity as a function of hydrogen concentration was measured while charging the films with hydrogen, and was used to compute the change in hydrogen concentration in the film, during the reaction with oxygen. For the thinnest films (200 A thick), the hydrogen charging and discharging curves indicate that a first-order gas-liquid-like phase transition with a {ital T}{sub {ital c}} of 70{endash}75{degree}C takes place. The H-Nb phase diagram for the 200-A film looks like the H/bulk Nb {alpha}-{alpha}{prime} phase diagrammore » which has a higher {ital T}{sub {ital c}} (173{degree}C). We attribute the substantial modifications of the film{close_quote}s phase diagram to the clamping of the Nb film at its interfaces with glass and Pd and to the nanostructure of the films. {copyright} {ital 1996 The American Physical Society.}« less

Leiomodin and tropomodulin in smooth muscle

NASA Technical Reports Server (NTRS)

Conley, C. A.

2001-01-01

Evidence is accumulating to suggest that actin filament remodeling is critical for smooth muscle contraction, which implicates actin filament ends as important sites for regulation of contraction. Tropomodulin (Tmod) and smooth muscle leiomodin (SM-Lmod) have been found in many tissues containing smooth muscle by protein immunoblot and immunofluorescence microscopy. Both proteins cofractionate with tropomyosin in the Triton-insoluble cytoskeleton of rabbit stomach smooth muscle and are solubilized by high salt. SM-Lmod binds muscle tropomyosin, a biochemical activity characteristic of Tmod proteins. SM-Lmod staining is present along the length of actin filaments in rat intestinal smooth muscle, while Tmod stains in a punctate pattern distinct from that of actin filaments or the dense body marker alpha-actinin. After smooth muscle is hypercontracted by treatment with 10 mM Ca(2+), both SM-Lmod and Tmod are found near alpha-actinin at the periphery of actin-rich contraction bands. These data suggest that SM-Lmod is a novel component of the smooth muscle actin cytoskeleton and, furthermore, that the pointed ends of actin filaments in smooth muscle may be capped by Tmod in localized clusters.

The role of macrophages in the regulation of erythroid colony growth in vitro.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1992-10-01

Depletion of macrophages from murine marrow by the use of a monoclonal anti-macrophage antibody resulted in a significant increase in the number of erythroid burst forming units (BFU-E). This increase could be neutralized by the addition back to culture of macrophages or macrophage conditioned medium indicating that the suppression was mediated by soluble factors. To further characterize this effect, the addition to culture, either alone or in combination, of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage-containing and macrophage-depleted cultures. The addition of IL-1 alpha to culture stimulated the release of both TNF alpha and GM-CSF and acted synergistically with both cytokines, resulting in a dose-dependent suppression of BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by monoclonal antibodies the addition of IL-1 alpha resulted in a significant increase in BFU-E growth. The addition of GM-CSF to culture caused a dose-dependent suppression of BFU-E that was mediated by TNF alpha, as colony number was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were simultaneously added to culture. TNF alpha-induced suppression of BFU-E only occurred in the presence of macrophages. In macrophage-depleted cultures, a dose-dependent suppression of BFU-E could be induced if subinhibitory concentrations of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly synergistic so that the doses required to induce suppression when added simultaneously was only 10% of that required when either were added to culture alone. Suppression of BFU-E by GM-CSF or the combined addition of GM-CSF and TNF alpha did not require IL-1 alpha because inhibition was not neutralized by the addition of anti-IL-1 alpha antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of the transforming growth factor alpha protooncogene in differentiating human promyelocytic leukemia (HL-60) cells.

PubMed

Walz, T M; Malm, C; Wasteson, A

1993-01-01

The process of myeloid differentiation in human promyelocytic leukemia cells (HL-60) is accompanied by the coordinate expression of numerous protooncogenes. To investigate the expression of transforming growth factor alpha (TGF-alpha) in myeloid differentiation, HL-60 cells were induced to differentiate into granulocytes with 1.25% dimethyl sulfoxide, 0.2 microM all-trans retinoic acid, or 500 microM N6,O2-dibutyryladenosine-3'5'-cyclic monophosphate or differentiated along the monocyte/macrophage pathway with 0.1 microM phorbol-12-myristate-13-acetate. Using Northern blot analyses, TGF-alpha transcripts were detected within 24 h of treatment in cells differentiating toward granulocytes; maximal levels of gene expression were reached after 3 days or later and remained essentially constant throughout the observation period. These cells released TGF-alpha protein, as demonstrated by analysis of the incubation medium. In contrast, no TGF-alpha RNA or protein was detectable in HL-60 cell cultures when induced with phorbol-12-myristate-13-acetate. Epidermal growth factor receptor transcripts could not be detected either in undifferentiated or in differentiated HL-60 cells; therefore it appears as if an autocrine loop involving TGF-alpha in HL-60 cells is unlikely. In conclusion, the results demonstrate, for the first time, the expression of TGF-alpha in human granulocyte precursor cells. Our findings may indicate novel regulatory pathways in hematopoiesis.

A review of the alpha-1 foundation: its formation, impact, and critical success factors.

PubMed

Walsh, John W; Snider, Gordon L; Stoller, James K

2006-05-01

Patient-advocacy organizations have proliferated because they can be an effective method to advance research and clinical care for those with the index condition, and can produce substantial benefits for the affected community, especially when the condition is uncommon. To clarify critical success factors in organizing a patient-advocacy organization and to provide a blueprint for others, including the respiratory-care advocacy community, this report examines features of one highly successful organization, the Alpha-1 Foundation, which is committed to helping those with the genetic condition alpha-1 antitrypsin deficiency. Features of the Alpha-1 Foundation that underlie its success include: consistently creating partnerships with key stakeholders, including the scientific and clinical communities, government, and pharmaceutical manufacturers; bringing passion to the cause (eg, by assuring that organizational leadership is provided by individuals affected by alpha-1 antitrypsin deficiency); and developing strategic business partnerships, as with a company that administers alpha-1 antitrypsin treatment (so-called intravenous augmentation therapy) and employs individuals with alpha-1 antitrypsin deficiency. Funds allocated by the company help to underwrite the foundation's research-funding commitment. The foundation also recruits and retains talent, including alpha-1 patients, to leadership roles (eg, on the board of directors) and has a voluntary group of committed scientists and clinicians. We believe that attention to these factors can help assure the success of patient-advocacy groups.

Low susceptibility of NC/Nga mice to tumor necrosis factor-alpha-mediated lethality and hepatocellular damage with D-galactosamine sensitization.

PubMed

Koide, Naoki; Morikawa, Akiko; Naiki, Yoshikazu; Tumurkhuu, Gantsetseg; Yoshida, Tomoaki; Ikeda, Hiroshi; Yokochi, Takashi

2009-02-01

The susceptibility of NC/Nga mice to tumor necrosis factor (TNF)-alpha was examined by using sensitization with d-galactosamine (d-GalN). Administration of TNF-alpha and d-GalN killed none of the NC/Nga mice, whereas it killed all of the BALB/c mice. Treatment with TNF-alpha and d-GalN caused few hepatic lesions in NC/Nga mice but massive hepatocellular apoptosis in BALB/c mice. Unlike BALB/c mice, there was no elevation in caspase 3 and 8 activities in the livers of NC/Nga mice receiving TNF-alpha and d-GalN. On the other hand, administration of anti-Fas antibody definitely killed both NC/Nga and BALB/c mice via activation of caspases 3 and 8. Treatment with TNF-alpha and d-GalN led to translocation of nuclear factor (NF)-kappaB in NC/Nga and BALB/c mice. However, NF-kappaB translocation was sustained in NC/Nga mice, although it disappeared in BALB/c mice 7 h after the treatment. NF-kappaB inhibitors activated caspases 3 and 8, and enhanced TNF-alpha-mediated lethality in NC/Nga. Taken together, the low susceptibility of NC/Nga mice to TNF-alpha-mediated lethality was suggested to be responsible for the sustained NF-kappaB activation.

Heat-transfer test results for a .0275-scale space shuttle external tank with a 10 deg/40 deg double cone-ogive nose in the NASA/AMES 3.5-foot hypersonic wind tunnel (FH14), volume 2

NASA Technical Reports Server (NTRS)

Carroll, H. R.

1977-01-01

A .0275 scale forebody model of the new baseline configuration of the space shuttle external tank vent cap configuration was tested to determine the flow field due to the double cone configuration. The tests were conducted in a 3.5 foot hypersonic wind tunnel at alpha = -5 deg, -4.59 deg, 0 deg, 5 deg, and 10 deg; beta = 0 deg, -3 deg, -5.51 deg, -6 deg, -9 deg, and +6 deg; nominal freestream Reynolds numbers per foot of 1.5 x 1 million, 3.0 x 1 million, and 5.0 x 1 million; and a nominal Mach number of 5. Separation and reattached flow from thermocouple data, shadowgraphs, and oil flows indicate that separation begins about 80% from the tip of the 10 deg cone, then reattaches on the vent cap and produces fully turbulent flow over most of the model forebody. The hardware disturbs the flow over a much larger area than present TPS application has assumed. A correction to the flow disturbance was experimentally suggested from the results of an additional test run.

Evaluating the Quality of Competency Assessment in Pharmacy: A Framework for Workplace Learning.

PubMed

Shah, Shailly; McLaughlin, Jacqueline E; Eckel, Stephen F; Mangun, Jesica; Hawes, Emily

2016-01-19

Demonstration of achieved competencies is critical in the pharmacy workplace. The purpose of this study was to evaluate the quality of the competency assessment program for pharmacy residents at an academic medical center. The competency assessment program (CAP) survey is a validated, 48-item instrument that evaluates the quality of an assessment program based on 12 criteria, each measured by four questions on a scale of 0 to 100. The CAP was completed by residents ( n = 23) and preceptors ( n = 28) from the pharmacy residency program between 2010 and 2013. Results were analyzed using descriptive statistics, Cronbach's alpha, and non-parametric tests. Educational Consequences was the only quality criteria falling below the standard for "good quality." Participants that completed residency training elsewhere rated the Comparability (0.04) and Meaningfulness (0.01) of the assessment program higher than those that completed residency at the academic medical center. There were no significant differences between resident and preceptor scores. Overall, the quality of the assessment program was rated highly by residents and preceptors. The process described here provides a useful framework for understanding the quality of workplace learning assessments in pharmacy practice.

[Role of rostral ventrolateral medulla in the pressor response to intraventricular (4th) injection of substance P].

PubMed

Zhang, X H; Ni, H

1998-04-01

Experiments were done in rabbits anaesthetized with urethane and immobilized under artificial respiration. It was found that substance P (SP, 0.8 ng/kg dissolved in 100 microliters artificial cerebro-spinal fluid, CSF) injected into the 4th ventricle induced either a rise or a drop of pulmonary arterial pressure (PAP) with predominated pressor response. In addition, a rise in carotid arterial pressure (CAP) and reduction in heart rate (HR) were also observed, whereas no significant alteration in PAP, CAP and HR was observed. Microinjection of SP receptor antagonist [D-Pro2, D-Phe7, D-Trp9]--SP (5-10 ng dissolved in 0.5 microliter CSF) or phentolamine (2-3 micrograms dissolved in 0.5 microliter CSF) into the bilateral rostral ventrolateral medulla (rVLM) prior to intraventricular injection of SP could block the SP-induced pressor responses in pulmonary and carotid arteries, while microinjection of SP receptor antagonist or phentolamine into bilateral caudal ventrolateral medulla (cVLM) at the same dosage had no effect. The results show that SP-induced pulmonary and carotid pressor responses may be mediated through SP-receptor and alpha-adrenergic receptors in the rostral ventro-lateral medulla (rVLM).

ROLES OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-A) IN MEDIATION OF DIOXIN (TCDD)-INDUCED DELAYS IN DEVELOPMENT OF THE MOUSE MAMMARY GLAND

EPA Science Inventory

Roles of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a) in Mediation of Dioxin (TCDD)-Induced Delays in Development of the Mouse Mammary Gland.
Suzanne E. Fenton, Barbara Abbott, Lamont Bryant, and Angela Buckalew. U.S. EPA, NHEERL, Reproductive Tox...

Low-Temperature Stress during Capped Brood Stage Increases Pupal Mortality, Misorientation and Adult Mortality in Honey Bees

PubMed Central

Wang, Qing; Xu, Xinjian; Zhu, Xiangjie; Chen, Lin; Zhou, Shujing; Huang, Zachary Y.; Zhou, Bingfeng

2016-01-01

Honey bees (Apis mellifera) are key pollinators, playing a vital role in ecosystem maintenance and stability of crop yields. Recently, reduced honey bee survival has attracted intensive attention. Among all other honey bee stresses, temperature is a fundamental ecological factor that has been shown to affect honey bee survival. Yet, the impact of low temperature stress during capped brood on brood mortality has not been systematically investigated. In addition, little was known about how low temperature exposure during capped brood affects subsequent adult longevity. In this study, capped worker broods at 12 different developmental stages were exposed to 20°C for 12, 24, 36, 48, 60, 72, 84 and 96 hours, followed by incubation at 35°C until emergence. We found that longer durations of low temperature during capped brood led to higher mortality, higher incidences of misorientation inside cells and shorter worker longevity. Capped brood as prepupae and near emergence were more sensitive to low-temperature exposure, while capped larvae and mid-pupal stages showed the highest resistance to low-temperature stress. Our results suggest that prepupae and pupae prior to eclosion are the most sensitive stages to low temperature stress, as they are to other stresses, presumably due to many physiological changes related to metamorphosis happening during these two stages. Understanding how low-temperature stress affects honey bee physiology and longevity can improve honey bee management strategies. PMID:27149383

[Vaccination against community acquired pneumonia in adult patients. A position paper by Neumoexpertos en Prevención].

PubMed

Redondo, E; Rivero, I; Vargas, D A; Mascarós, E; Díaz-Maroto, J L; Linares, M; Valdepérez, J; Gil, A; Molina, J; Jimeno, I; Ocaña, D; Martinón-Torres, F

2016-10-01

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in adults. The annual incidence of CAP in adults in Spain ranges from 3 to 14 cases per 1,000 inhabitants. Current clinical guidelines primarily focus on the therapeutic approach to CAP rather than its prevention. The aim of this study is to develop and propose a practical guide for CAP prevention through vaccination in Spain according to available vaccines and evidence. A literature review and expert opinion. Pneumococcal and influenza vaccines are the main preventive tools available against CAP. Age, chronic diseases, and immunosuppression are risk factors for pneumonia, so these populations should be a priority for vaccination. In addition, influenza and pneumococcal vaccination is considered advisable in healthy adults under 60 years of age, and anyone with risk condition for CAP, irrespective of age. The influenza vaccine will be administered seasonally, while pneumococcal vaccination can be administered at any time of the year. Vaccination against pneumococcus and influenza in adults can help to reduce the burden of CAP and its associated complications. The available evidence supports the priority indications set out in this guide, and it would be advisable to try to achieve a wide circulation and practical implementation of these recommendations. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

PubMed Central

1993-01-01

Tumor necrosis factor alpha (TNF-alpha), a cytokine with pleiotropic biological effects, is produced by a variety of cell types in response to induction by diverse stimuli. In this paper, TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor (TCR) ligands or by calcium ionophores alone. Induction is rapid, does not require de novo protein synthesis, and is completely blocked by the immunosuppressant cyclosporin A (CsA). We have identified a human TNF-alpha promoter element, kappa 3, which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene. In electrophoretic mobility shift assays, an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells. These complexes appear in nuclear extracts only after T cell stimulation. Induction of the inducible nuclear complexes is rapid, independent of protein synthesis, and blocked by CsA, and thus, exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore. Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells. Thus, the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells. PMID:8376940

Cloning and characterization of the mouse alpha1C/A-adrenergic receptor gene and analysis of an alpha1C promoter in cardiac myocytes: role of an MCAT element that binds transcriptional enhancer factor-1 (TEF-1).

PubMed

O'Connell, T D; Rokosh, D G; Simpson, P C

2001-05-01

alpha1-Adrenergic receptor (AR) subtypes in the heart are expressed by myocytes but not by fibroblasts, a feature that distinguishes alpha1-ARs from beta-ARs. Here we studied myocyte-specific expression of alpha1-ARs, focusing on the subtype alpha1C (also called alpha1A), a subtype implicated in cardiac hypertrophic signaling in rat models. We first cloned the mouse alpha1C-AR gene, which consisted of two exons with an 18 kb intron, similar to the alpha1B-AR gene. The receptor coding sequence was >90% homologous to that of rat and human. alpha1C-AR transcription in mouse heart was initiated from a single Inr consensus sequence at -588 from the ATG; this and a putative polyadenylation sequence 8.5 kb 3' could account for the predominant 11 kb alpha1C mRNA in mouse heart. A 5'-nontranscribed fragment of 4.4 kb was active as a promoter in cardiac myocytes but not in fibroblasts. Promoter activity in myocytes required a single muscle CAT (MCAT) element, and this MCAT bound in vitro to recombinant and endogenous transcriptional enhancer factor-1. Thus, alpha1C-AR transcription in cardiac myocytes shares MCAT dependence with other cardiac-specific genes, including the alpha- and beta-myosin heavy chains, skeletal alpha-actin, and brain natriuretic peptide. However, the mouse alpha1C gene was not transcribed in the neonatal heart and was not activated by alpha1-AR and other hypertrophic agonists in rat myocytes, and thus differed from other MCAT-dependent genes and the rat alpha1C gene.