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Sintese e identificação de biomarcadores em oleos da Bacia de Campos e Bacia Potiguar : identificação de 3-alquil-esteranos; Synthesis and identification of biomarkers in oils of the Campos and Potiguar Basin: identification of 3-alkyl-steranes

Sidney Gonçalo de Lima
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 18/02/2005 Português
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Este trabalho relata o estudo de biomarcadores em óleos da Bacia de Campos (sudeste do Brasil) e da Bacia Potiguar (nordeste do Brasil), que se constituem nas duas principais bacias petrolíferas do país. O principal enfoque foi a análise de biomarcadores neutros e ácidos como indicador dos processos de biodegradação. Conseqüentemente, selecionamos amostras de óleos da mesma rocha geradora (Bacia de Canlpos) e localizada em diferentes reservatórios, a profundidade e características geológicas distintas A análise da fração neutra (óleos de Campos) revelou a presença de biomarcadores alquil-esteranos: 5a(H)-estigmastano, 5b(H)-estigmastano, 3a(metil)-5b(H)-estigmastano e 3b(metil)-5a(H)-estigmastano, cujas estruturas foram confirmadas com padrões de síntese. Em trabalhos anteriores sobre óleos da Bacia Potiguar, Lopes et aI. (1999, 1997) detectaram uma série de alquil-esteranos, incluindo a família estigmastano e ergostano. Suas estruturas foram propostas com base em estudo de massa, requerendo portanto a síntese total de dez padrões 5a(H)- e 5b(H)-estigmastano e alquil-estigmastano. As co-injeções desses padrões com as frações dos respectivos óleos confirmaram as estruturas propostas para esses biomarcadores. A re-análise dos óleos da Bacia de Potiguar mostrou-nos a identificação de vários biomarcadores aromáticos usados como indicadores de fonte...

Ventilatory Acclimatization to Moderate Hypoxemia in Man: THE ROLE OF SPINAL FLUID [H+]

Dempsey, J. A.; Forster, H. V.; Dopico, G. A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1974 Português
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This study has assessed the regulation of arterial blood and cerebrospinal fluid (CSF) pH and thereby their contribution to the control of breathing in normal man during various stages of ventilatory acclimatization to 3,100 m altitude. CSF acid-base status was determined: (a) from measurements of lumbar spinal fluid during steady-state conditions of chronic normoxia (250 m altitude) and at + 8 h and + 3-4 wk of hypobaric hypoxia; and (b) from changes in cerebral venous PCO2 at + 1 h hypoxic exposure. After 3-4 wk at 3,100 m, CSF [H+] remained significantly alkaline to values obtained in either chronic normoxia or with 1 h hypoxic exposure and was compensated to the same extent (∼66%) as was arterial blood [H+]. Ventilatory acclimatization to 3,100 m bore no positive relationship to accompanying changes in arterial PO2 and pH and CSF pH: (a) CSF pH either increased or remained constant at 8 h and at 3-4 wk hypoxic exposure, respectively, coincident with significant, progressive reductions in PaCO2; (b) arterial PO2 and pH increased progressively with time of exposure; and (c) in the steady-state of acclimatization to 3,100 m the combination of chemical stimuli present, i.e. PaO2 = 60 mm Hg, pHa and pHCSF = + 0.03-0.04 > control, was insufficient to produce the observed hyperventilation (PaCO2 = 32 mm Hg). It was postulated that ventilatory acclimatization to 3...

Characterization of methylation of rat liver cytosolic glutathione S-transferases by using reverse-phase h.p.l.c. and chromatofocusing.

Johnson, J A; Neal, T L; Collins, J H; Siegel, F L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/09/1990 Português
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Glutathione S-transferase (GST) subunits in rat liver cytosol were separated by reverse-phase h.p.l.c.; five major proteins were isolated and identified as subunits 1, 2, 3, 4 and 8. F.p.l.c. chromatofocusing resolved the affinity-purified GST pool into nine different isoenzymes. The five basic (Alpha class) dimeric peaks of GST activity were 1-1, 1-2a, 1-2b, 2-2a and 2-2b. Reverse-phase h.p.l.c. analysis revealed that subunit 8 was also present in the protein peaks designated 1-1, 1-2a and 1-2b. The four neutral (Mu class) isoenzymes were 3-3, 3-4, 3-6 and 4-4. The GST pool was methylated in vitro before reverse-phase h.p.l.c. or f.p.l.c. chromatofocusing. Chromatofocusing indicated that the Mu class isoforms (3-3, 3-4 and 4-4) were the primary GSTs methylated, and h.p.l.c. analysis confirmed that subunits 3 and 4 were the major methyl-accepting GST subunits. The addition of calmodulin stimulated the methylation in vitro of GST isoenzymes 3-3, 3-4 and 4-4 by 3.0-, 7.5- and 9.9-fold respectively. Reverse-phase h.p.l.c. also indicated that only the methylation of GST subunits 3 and 4 was stimulated by calmodulin. Basic GST isoenzymes were minimally methylated and the methylation was not enhanced by calmodulin. Investigation of the time course of methylation of GST subunits 3 and 4 indicated that at incubation times less than 4 h the methylation of both Mu class subunits was stimulated by calmodulin...

Complete beta-oxidation of valproate: cleavage of 3-oxovalproyl-CoA by a mitochondrial 3-oxoacyl-CoA thiolase.

Silva, Margarida F B; Ruiter, Jos P N; Overmars, Henk; Bootsma, Albert H; van Gennip, Albert H; Jakobs, Cornelis; Duran, Marinus; Tavares de Almeida, Isabel; Wanders, Ronald J A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/03/2002 Português
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The beta-oxidation of valproic acid (VPA; 2-n-propylpentanoic acid) was investigated in vitro in intact rat liver mitochondria incubated with (3)H-labelled VPA. The metabolism of [4,5-(3)H(2)]VPA and [2-(3)H]VPA was studied by analysing the different acyl-CoA intermediates formed by reverse-phase HPLC with radiochemical detection. Valproyl-CoA, Delta(2(E))-valproyl-CoA,3-hydroxyvalproyl-CoA and 3-oxovalproyl-CoA (labelled and non-labelled) were determined using continuous on-line radiochemical and UV detection. The formation of these intermediates was investigated using the two tritiated precursors in respiratory states 3 and 4. Valproyl-CoA was present at highest concentrations under both conditions. Two distinct labelled peaks were found, which were identified as (3)H(2)O and [4,5-(3)H(2)]3-oxo-VPA. The formation of (3)H(2)O strongly suggested that VPA underwent complete beta-oxidation and that [4,5-(3)H(2)]3-oxo-VPA was formed by hydrolysis of the corresponding thioester. The hypothesis that 3-oxovalproyl-CoA undergoes thiolytic cleavage was investigated further. For this purpose a mito chondrial lysate was incubated with synthetic 3-oxovalproyl-CoA, carnitine and carnitine acetyltransferase for subsequent monitoring of the formation of propionylcarnitine and pentanoylcarnitine using electrospray ionization tandem MS. The detection of these compounds demonstrated unequivocally that the intermediate 3-oxovalproyl-CoA is a substrate of a mitochondrial thiolase...

CNS-related performance and haemodynamics of metoprolol-Oros and propranolol after single and 3 days dosing in healthy volunteers.

van Steveninck, A L; Pieters, M S; Schoemaker, H C; Breimer, D D; Cohen, A F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1993 Português
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1. The effects of metoprolol-Oros 14/190 once daily, propranolol 80 mg twice daily and temazepam 10 mg once daily on central nervous system (CNS) related performance and haemodynamic variables were evaluated in a double-blind, randomized, placebo controlled, crossover study in 12 healthy volunteers. Drugs were administered for 3 consecutive days except for temazepam, which was administered on days 1 and 3 only. Treatment effects were evaluated at 0, 2, 5 and 8 h on days 1 and 3. 2. Neither beta-adrenoceptor blocker had significant effects in a battery of tests after single or 3 days dosing. Temazepam caused a decrease in saccadic peak velocity of 37.4 degrees s-1 (95% CI: 6.0, 68.9) at 2 h and an increase of auditory reaction times of 11.5 ms (0.2, 22.8) at 8 h on day 1. No significant effects of temazepam were detected on day 3. 3. Both beta-adrenoceptor blockers reduced exercise heart rate. Peak effects were measured at 2 h 40 min after propranolol but not metoprolol-Oros (difference, day 1:20 (11, 29) beats min-1, day 3:13 (8, 19) beats min-1). Both beta-adrenoceptor blockers significantly reduced baseline exercise heart rate on day 3. Compared with day 1, metoprolol-Oros caused larger reductions of exercise heart rate at all times on day 3. 4. Metoprolol-Oros and propranolol caused similar reductions of systolic- and diastolic blood pressure on days 1 and 3. Temazepam caused a small reduction in diastolic blood pressure at 5 h 40 min on day 1 but was otherwise devoid of haemodynamic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Photodissimilation of Fructose to H(inf2) and CO(inf2) by a Dinitrogen-Fixing Cyanobacterium, Anabaena variabilis

Reddy, P. M.; Spiller, H.; Albrecht, S. L.; Shanmugam, K. T.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1996 Português
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The ability of cyanobacteria to serve as biocatalysts in the production of H(inf2) as a fuel and chemical feedstock was investigated with Anabaena variabilis. The results show that A. variabilis, when incubated under argon, dissimilated fructose to H(inf2) and CO(inf2) in a light-dependent reaction. The H(inf2) production had an obligate requirement for fructose and was heterocyst dependent, since NH(inf4)(sup+)-grown cultures lacking heterocysts failed to produce H(inf2). Differential inhibition studies with CO showed that nitrogenase is the main enzyme catalyzing the H(inf2) production. Net H(inf2) yield increased with increasing concentrations of fructose up to 10 mM in the medium. The average apparent conversion efficiency of fructose to H(inf2) (net H(inf2) produced/fructose removed from the medium) was about 10, although higher conversion efficiencies of 15 to 17 could be obtained during shorter periods and at optimum fructose concentrations. Under the same conditions, the ratio of CO(inf2) released to fructose removed from the medium was about 3.5, suggesting that only a fraction of the fructose carbon was completely oxidized to CO(inf2). Under conditions of carbon excess, which prevents H(inf2) uptake, the maximum ratio of H(inf2) to CO(inf2) was found to be 3.0. This is higher than the expected value of 2.0...

Mutagenicity and tumorigenicity of the four enantiopure bay-region 3,4-diol-1,2-epoxide isomers of dibenz[a,h]anthracene

Chang, Richard L.; Wood, Alexander W.; Huang, Mou Tuan; Xie, Jian Guo; Cui, Xiao Xing; Reuhl, Kenneth R.; Boyd, D.R.; Lin, Yong; Shih, Weichung Joe; Balani, Suresh K.; Yagi, Haruhiko; Jerina, Donald M.; Conney, Allan H.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
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Each enantiomer of the diastereomeric pair of bay-region dibenz[a,h]anthracene 3,4-diol-1,2-epoxides in which the benzylic 4-hydroxyl group and epoxide oxygen are either cis (isomer 1) or trans (isomer 2) were evaluated for mutagenic activity. In strains TA 98 and TA 100 of Salmonella typhimurium, the diol epoxide with (1S,2R,3S,4R) absolute configuration [(–)-diol epoxide-1] had the highest mutagenic activity. In Chinese hamster V-79 cells, the diol epoxide with (1R,2S,3S,4R) absolute configuration [(+)-diol epoxide-2] had the highest mutagenic activity. The (1R,2S,3R,4S) diol epoxide [(+)-diol epoxide-1] also had appreciable activity, whereas the other two bay-region diol epoxide enantiomers had very low activity. In tumor studies, the (1R,2S,3S,4R) enantiomer was the only diol epoxide isomer tested that had strong activity as a tumor initiator on mouse skin and in causing lung and liver tumors when injected into newborn mice. This stereoisomer was about one-third as active as the parent hydrocarbon, dibenz[a,h]anthracene as a tumor initiator on mouse skin; it was several-fold more active than dibenz[a,h]anthracene as a lung and liver carcinogen when injected into newborn mice. (–)-(3R,4R)-3β,4α-dihydroxy-3,4-dihydro-dibenz[a...

Crystal structure of 1-(3-chloro­phen­yl)piperazin-1-ium picrate–picric acid (2/1)

Kavitha, Channappa N.; Jasinski, Jerry P.; Kaur, Manpreet; Anderson, Brian J.; Yathirajan, H. S.
Fonte: International Union of Crystallography Publicador: International Union of Crystallography
Tipo: Artigo de Revista Científica
Publicado em 31/10/2014 Português
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The title salt {systematic name: bis­[1-(3-chloro­phen­yl)piperazinium 2,4,6-tri­nitro­phenolate]–picric acid (2/1)}, 2C10H14ClN2 +·2C6H5N3O7 −·C6H6N3O7, crystallized with two independent 1-(3-chloro­phen­yl)piperazinium cations, two picrate anions and a picric acid mol­ecule in the asymmetric unit. The six-membered piperazine ring in each cation adopts a slightly distorted chair conformation and contains a protonated N atom. In the picric acid mol­ecule, the mean planes of the nitro groups in the ortho-, meta-, and para-positions are twisted from the benzene ring by 31.5 (3), 7.7 (1), and 3.8 (2)°, respectively. In the anions, the dihedral angles between the benzene ring and the ortho-, meta-, and para-nitro groups are 36.7 (1), 5.0 (6), 4.8 (2)°, and 34.4 (9), 15.3 (8), 4.5 (1)°, respectively. The nitro group in one anion is disordered and was modeled with two sites for one O atom with an occupancy ratio of 0.627 (7):0.373 (7). In the crystal, the picric acid mol­ecule inter­acts with the picrate anion through a trifurcated O—H⋯O four-centre hydrogen bond involving an intra­molecular O—H⋯O hydrogen bond and a weak C—H⋯O inter­action. Weak inter­molecular C—H⋯O inter­actions are responsible for the formation of cation–anion–cation trimers resulting in a chain along [010]. In addition...

O Teorema do h-cobordismo e a conjectura generalizada de Poincaré

Livin Barrera Bocanegra, Lord; Shirlippe Goes Leandro, Eduardo (Orientador)
Fonte: Universidade Federal de Pernambuco Publicador: Universidade Federal de Pernambuco
Tipo: Outros
Português
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O trabalho está apresentado da seguinte maneira: No primeiro capítulo se faz uma lista de definições e teoremas que achamos mais importantes sobre tópicos tais como Topologia, Variedades Diferenciáveis e aspectos da Topologia Algébrica, os quais serão utilizados ao longo dos capítulos seguintes. Consideramos conveniente indicar as provas dos teoremas assim como comentários da teoria na bibliografia correspondente citada após de cada resultado. O segundo capítulo dedica-se a estudar a estrutura cobordismo. Na seção 2.1 introduzimos o conceito de cobordismo e fazemos um resumo das propriedades gerais de funções de Morse sobre cobordismos. Com as definições e resultados da seção 2.1, construímos na seção 2.2 uma topologia que nos permitir a mostrar a existência de funções de Morse sobre um cobordismo e definir o número de Morse de um cobordismo. Funções de Morse fornecem por sua vez em 2.3 campos vetoriais de tipo-gradiente, resultado fundamental que nos ajudará a provar o teorema da vizinhança colar, que por sua vez, nos permitirá introduzir uma operação entre cobordismos. Na seção 2.3 também provaremos que um cobordismo com número de Morse zero é precisamente um cobordismo produto (teorema 2.3.3). Este resultado é crucial no teorema do h-cobordismo. A seção 2.4 está dedicada ao estudo de cobordismos com número de Morse 1. A homologia de tais cobordismos fornecerá informação sobre a decomposição de um cobordismo em cobordismos elementares. Finalmente terminamos o capítulo 2 mostrando que qualquer cobordismo pode-se reordenar como composição de cobordismos cada um deles com uma função de Morse e um nível crítico onde todos seus pontos críticos tem índice fixo. Este último resultado será fundamental para o cancelamento de pontos críticos de índices intermediários (teorema 3.3.7). O terceiro capítulo está baseado em quatro teoremas fundamentais que podemos dividir em dois grupos...

14-3-3:Shc scaffolds integrate phosphoserine and phosphotyrosine signaling to regulate phosphatidylinositol 3-kinase activation and cell survival

Barry, E.; Felquer, F.; Powell, J.; Biggs, L.; Stomski, F.; Urbani, A.; Ramshaw, H.; Hoffmann, P.; Wilce, M.; Grimbaldeston, M.; Lopez, A.; Guthridge, M.
Fonte: Amer Soc Biochemistry Molecular Biology Inc Publicador: Amer Soc Biochemistry Molecular Biology Inc
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
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Integrated cascades of protein tyrosine and serine/threonine phosphorylation play essential roles in transducing signals in response to growth factors and cytokines. How adaptor or scaffold proteins assemble signaling complexes through both phosphotyrosine and phosphoserine/threonine residues to regulate specific signaling pathways and biological responses is unclear. We show in multiple cell types that endogenous 14-3-3zeta is phosphorylated on Tyr(179) in response to granulocyte macrophage colony-stimulating factor. Importantly, 14-3-3zeta can function as an intermolecular bridge that couples to phosphoserine residues and also directly binds the SH2 domain of Shc via Tyr(179). The assembly of these 14-3-3:Shc scaffolds is specifically required for the recruitment of a phosphatidylinositol 3-kinase signaling complex and the regulation of CTL-EN cell survival in response to cytokine. The biological significance of these findings was further demonstrated using primary bone marrow-derived mast cells from 14-3-3zeta(-/-) mice. We show that cytokine was able to promote Akt phosphorylation and viability of primary mast cells derived from 14-3-3zeta(-/-) mice when reconstituted with wild type 14-3-3zeta, but the Akt phosphorylation and survival response was reduced in cells reconstituted with the Y179F mutant. Together...

NMR spectroscopy of 14-3-3ζ reveals a flexible C-terminal extension: Differentiation of the chaperone and phosphoserine-binding activities of 14-3-3ζ; NMR spectroscopy of 14-3-3zeta reveals a flexible C-terminal extension: Differentiation of the chaperone and phosphoserine-binding activities of 14-3-3zeta

Williams, D.; Ecroyd, H.; Goodwin, K.; Dai, H.; Fu, H.; Woodcock, J.; Zhang, L.; Carver, J.
Fonte: Portland Press Publicador: Portland Press
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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Intracellular 14-3-3 proteins bind to many proteins, via a specific phosphoserine motif, regulating diverse cellular tasks including cell signalling and disease progression. The 14-3- 3ζ isoform is a molecular chaperone, preventing the stressinduced aggregation of target proteins in a manner comparable with that of the unrelated sHsps (small heat-shock proteins). 1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3ζ and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3ζ, but has no direct role in chaperone action. Lys49 is an important functional residue within the ligand-binding groove of 14-3- 3ζ with K49E 14-3-3ζ exhibiting markedly reduced binding to phosphorylated and non-phosphorylated ligands. The R18 peptide binds to the binding groove of 14-3-3ζ with high affinity and also reduces the interaction of 14-3-3ζ ligands. However, neither the K49E mutation nor the presence of the R18 peptide affected the chaperone activity of 14-3-3ζ , implying that the C-terminal extension and binding groove of 14-3-3ζ do not mediate interaction with target proteins during chaperone action. Other region(s) in 14-3-3ζ are most likely to be involved...

Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency; Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3 zeta deficiency

Cheah, P.; Ramshaw, H.; Thomas, P.; Toyo-oka, K.; Xu, X.; Martin, S.; Coyle, P.; Guthridge, M.; Stomski, F.; van den Buuse, M.; Wynshaw-Boris, A.; Lopez, A.; Schwarz, Q.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
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Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-Deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.; P-S Cheah, HS Ramshaw, PQ Thomas, K Toyo-oka...

Locomotor hyperactivity in 14-3-3ζ KO mice is associated with dopamine transporter dysfunction; Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Ramshaw, H.; Xu, X.; Jaehne, E.; McCarthy, P.; Greenberg, Z.; Saleh, E.; McClure, B.; Woodcock, J.; Kabbara, S.; Wiszniak, S.; Wang, T.Y.; Parish, C.; van den Buuse, M.; Baune, B.; Lopez, A.; Schwarz, Q.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather...

14-3-3ε and ζ regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain; 14-3-3epsilon and zeta regulate neurogenesis and differentiation of neuronal progenitor cells in the developing brain

Toyo-oka, K.; Wachi, T.; Hunt, R.F.; Baraban, S.C.; Taya, S.; Ramshaw, H.; Kaibuchi, K.; Schwarz, Q.P.; Lopez, A.F.; Wynshaw-Boris, A.
Fonte: Society for Neuroscience Publicador: Society for Neuroscience
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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During brain development, neural progenitor cells proliferate and differentiate into neural precursors. These neural precursors migrate along the radial glial processes and localize at their final destination in the cortex. Numerous reports have revealed that 14-3-3 proteins are involved in many neuronal activities, although their functions in neurogenesis remain unclear. Here, using 14-3-3ε/ζ double knock-out mice, we found that 14-3-3 proteins are important for proliferation and differentiation of neural progenitor cells in the cortex, resulting in neuronal migration defects and seizures. 14-3-3 deficiency resulted in the increase of δ-catenin and the decrease of β-catenin and αN-catenin. 14-3-3 proteins regulated neuronal differentiation into neurons via direct interactions with phosphorylated δ-catenin to promote F-actin formation through a catenin/Rho GTPase/Limk1/cofilin signaling pathway. Conversely, neuronal migration defects seen in the double knock-out mice were restored by phosphomimic Ndel1 mutants, but not δ-catenin. Our findings provide new evidence that 14-3-3 proteins play important roles in neurogenesis and neuronal migration via the regulation of distinct signaling cascades.; Kazuhito Toyo-oka, Tomoka Wachi...

TeV γ-ray observations of the young synchrotron-dominated SNRs G1.9+0.3 and G330.2+1.0 with H.E.S.S.; TeV gamma-ray observations of the young synchrotron-dominated SNRs G1.9+0.3 and G330.2+1.0 with H.E.S.S.

H.E.S.S. Collaboration; Abramowski, A.; Aharonian, F.; Ait Benkhali, F.; Akhperjanian, A.G.; Angüner, E.; Anton, G.; Balenderan, S.; Balzer, A.; Barnacka, A.; Becherini, Y.; Becker Tjus, J.; Bernlöhr, K.; Birsin, E.; Bissaldi, E.; Biteau, J.; Böttcher,
Fonte: Published by Oxford University Press on behalf of the Royal Astronomical Society Publicador: Published by Oxford University Press on behalf of the Royal Astronomical Society
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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The non-thermal nature of the X-ray emission from the shell-type supernova remnants (SNRs) G1.9+0.3 and G330.2+1.0 is an indication of intense particle acceleration in the shock fronts of both objects. This suggests that the SNRs are prime candidates for very-high-energy (VHE; E > 0.1 TeV) γ-ray observations. G1.9+0.3, recently established as the youngest known SNR in the Galaxy, also offers a unique opportunity to study the earliest stages of SNR evolution in the VHE domain. The purpose of this work is to probe the level of VHE γ-ray emission from both SNRs and use this to constrain their physical properties. Observations were conducted with the H.E.S.S. (High Energy Stereoscopic System) Cherenkov Telescope Array over a more than six-year period spanning 2004–2010. The obtained data have effective livetimes of 67 h for G1.9+0.3 and 16 h for G330.2+1.0. The data are analysed in the context of the multiwavelength observations currently available and in the framework of both leptonic and hadronic particle acceleration scenarios. No significant γ-ray signal from G1.9+0.3 or G330.2+1.0 was detected. Upper limits (99 per cent confidence level) to the TeV flux from G1.9+0.3 and G330.2+1.0 for the assumed spectral index Γ = 2.5 were set at 5.6 × 10−13 cm−2 s−1 above 0.26 TeV and 3.2 × 10−12 cm−2 s−1 above 0.38 TeV...

BIS targeting induces cellular senescence through the regulation of 14-3-3 zeta/STAT3/SKP2/p27 in glioblastoma cells

Lee, J-J; Lee, J-S; Cui, M N; Yun, H H; Kim, H Y; Lee, S H; Lee, J-H
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
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Cellular senescence is an important mechanism for preventing tumor progression. The elevated expression of Bcl-2-interacting cell death suppressor (BIS), an anti-apoptotic and anti-stress protein, often correlates with poor prognosis in several cancers including glioblastoma; however, the role of BIS in the regulation of senescence has not been well defined. Here, we describe for the first time that the depletion of BIS induces G1 arrest and cellular senescence through the accumulation of p27 that is independent of p53, p21 or p16. The increase in p27 expression in BIS-depleted cells was attributable to an impairment of the ubiquitin-mediated degradation of p27, which was caused by a decrease in S-phase kinase-associated protein 2 (SKP2) at the transcriptional level. As an underlying molecular mechanism, we demonstrate that the loss of activity of signal transducer and activator of transcription 3 (STAT3) was specifically linked to the suppression of SKP2 expression. Despite a reduction in phospho-STAT3 levels, total STAT3 levels were unexpectedly increased by BIS depletion, specifically in the insoluble fraction. Our results show that 14-3-3ζ expression is decreased by BIS knockdown and that 14-3-3ζ depletion per se significantly induced senescence phenotypes. In addition...

Production of H$_3^+$ via photodissociation of organic molecules in interstellar clouds

Pilling, S.; Andrade, D. P. P.; Neves, R.; Ferreira-Rodrigues, A. M.; Santos, A. C. F.; Boechat-Roberty, H. M.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 14/12/2006 Português
Relevância na Pesquisa
46.313413%
We present experimental results obtained from photoionization and photodissociation processes of abundant interstellar CH$_3$-X type organic molecules like methanol (CH$_3$OH), methylamine (CH$_3$NH$_2$) and acetonitrile (CH$_3$CN) as alternative route for the production of H$_3^+$ in interstellar and star forming environments. The measurements were taken at the Brazilian Synchrotron Light Laboratory (LNLS), employing soft X-ray photons with energies between 200 and 310 eV and time of flight mass spectrometry. Mass spectra were obtained using the photoelectron-photoion coincidence techniques. Absolute averaged cross sections for H$_3^+$ production by soft X-rays were determined. We have found that, among the channels leading to molecular dissociation, the H$_3^+$ yield could reach values up to 0.7% for single photoionization process and up to 4% for process involving double photoionization. The H$_3^+$ photoproduction cross section due to the dissociation of the studied organic molecules by photons over the C1s edge (200-310 eV) were about 0.2-1.4 $\times$ 10$^{-18}$ cm$^2$. Adopting the typical X-ray luminosity $L_X \gtrsim 10^{31}$ erg s$^{-1}$ which best fit the observational data for AFGL 2591 (Stauber et al. 2005) we derive an estimative for the H$_3^+$ photoproduction rate due to methyl-compounds dissociation process. The highest value for the H$_3^+$ column density from methanol dissociation by soft X-rays...

The D/H ratio at z = 3.57 toward Q 1937-1009

Levshakov, Sergei A.; Kegel, Wilhelm H.; Takahara, Fumio
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 09/02/1998 Português
Relevância na Pesquisa
56.256177%
Deuterium abundance re-measurements by Burles and Tytler (1998; hereafter BT) yielded D/H = (3.3 +/- 0.3) 10^{-5} and the robust upper limit D/H < 3.9 10^{-5} from the z_a = 3.572 system toward Q1937-1009. In this new analysis BT adopted multicomponent microturbulent models together with the possibility to vary freely the local continuum level around each HI line to improve the fit. The procedure failed, however, to fit adequately D Ly-beta without recourse to an additional H Ly-alpha contamination at the position of D Ly-beta. We show that this obstacle may be successfully overcome within the framework of the mesoturbulent model accounting (in contrast to the microturbulent approximation) for a correlated structure of the large scale velocity field. Using the same observational data and the original continuum as determined by Tytler et al. (1996), we obtained good fits. The one-component mesoturbulent models provide D/H in the range (3.2 - 4.8) 10^{-5} and the total hydrogen column density N(HI) = (5.6 - 7.0) 10^{17} cm^{-2}. This result is consistent with that found by us from the z_a = 2.504 and z_a = 0.701 systems toward Q1009+2956 and Q1718+4807, respectively. The range for D/H common to all three analyses is D/H = (4.1 - 4.6) 10^{-5}. This value is consistent with standard big bang nucleosynthesis [SBBN] if the baryon-to-photon ratio...

Visualising Virtual Communities: From Erd\H{o}s to the Arts

Bowen, Jonathan P.; Wilson, Robin J.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 14/07/2012 Português
Relevância na Pesquisa
56.042427%
Monitoring communities has become increasingly easy on the web as the number of visualisation tools and amount of data available about communities increase. It is possible to visualise connections on social and professional networks such as Facebook in the form of mathematical graphs. It is also possible to visualise connections between authors of papers. In particular, Microsoft Academic Search now has a large corpus of information on publications, together with author and citation information, that can be visualised in a number of ways. In mathematical circles, the concept of the "Erd\H{o}s number" has been introduced, in honour of the Hungarian mathematician Paul Erd\H{o}s, measuring the "collaborative distance" of a person away from Erd\H{o}s through links by co-author. Similar metrics have been proposed in other fields, including acting. The possibility of exploring and visualising such links in arts fields is proposed in this paper.; Comment: 7 pages, 7 figures

Benzene C−H Bond Activation in Carboxylic Acids Catalyzed by O-Donor Iridium(III) Complexes: An Experimental and Density Functional Study

Bischof, Steven M.; Ess, Daniel H.; Meier, Steven K.; Oxgaard, Jonas; Nielsen, Robert J.; Bhalla, Gaurav; Goddard, William A., III; Periana, Roy A.
Fonte: American Chemical Society Publicador: American Chemical Society
Tipo: Article; PeerReviewed Formato: chemical/x-cif; application/pdf
Publicado em 22/02/2010 Português
Relevância na Pesquisa
46.31927%
The mechanism of benzene C−H bond activation by [Ir(μ-acac-O,O,C^3)(acac-O,O)(OAc)]_2 (4) and [Ir(μ-acac-O,O,C^3)(acac-O,O)(TFA)]_2 (5) complexes (acac = acetylacetonato, OAc = acetate, and TFA = trifluoroacetate) was studied experimentally and theoretically. Hydrogen−deuterium (H/D) exchange between benzene and CD_(3)COOD solvent catalyzed by 4 (ΔH^‡ = 28.3 ± 1.1 kcal/mol, ΔS^‡ = 3.9 ± 3.0 cal K^(−1) mol^(−1)) results in a monotonic increase of all benzene isotopologues, suggesting that once benzene coordinates to the iridium center, there are multiple H/D exchange events prior to benzene dissociation. B3LYP density functional theory (DFT) calculations reveal that this benzene isotopologue pattern is due to a rate-determining step that involves acetate ligand dissociation and benzene coordination, which is then followed by heterolytic C−H bond cleavage to generate an iridium-phenyl intermediate. A synthesized iridium-phenyl intermediate was also shown to be competent for H/D exchange, giving similar rates to the proposed catalytic systems. This mechanism nicely explains why hydroarylation between benzene and alkenes is suppressed in the presence of acetic acid when catalyzed by [Ir(μ-acac-O,O,C^3)(acac-O,O)(acac-C^3)]_2 (3) (Matsumoto et al. J. Am. Chem. Soc. 2000...