920 resultados para 4-TRIMETHYLPENTYL PHOSPHINIC ACID
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Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4(+) leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8(+) cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD. Bone Marrow Transplantation (2010) 45, 1562-1571; doi:10.1038/bmt.2010.6; published online 15 March 2010
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The effect of the solid and dissolved organic matter fractions, mineral composition and ionic strength of the soil solution on the sorption behaviour of pesticides were studied. A number of soils, chosen so as to have different clay mineral and organic carbon content, were used to study the sorption of the pesticides atrazine (6-chloro-N-2-ethyl-N-4-isopropyl-1,3,5-triazine-2,4-diamine), 2,4-D ((2,4-dichlorophenoxy) acetic acid), isoproturon (3-(4-isopropylphenyl)1,1-dimethylurea) and paraquat (1,1'-dimethyl-4,4'-bipyridinium) in the presence of low and high levels of dissolved organic carbon and different background electrolytes. The sorption behaviour of atrazine, isoproturon and paraquat was dominated by the solid state soil components and the presence of dissolved organic matter had little effect. The sorption of 2,4-D was slightly affected by the soluble organic matter in the soil. However, this effect may be due to competition for adsorption sites between the pesticide and the soluble organic matter rather than due to a positive interaction between the pesticide and the soluble fraction of soil organic matter. It is concluded that the major factor governing the sorption of these pesticides is the solid state organic fraction with the clay mineral content also making a significant contribution. The dissolved organic carbon fraction of the total organic carbon in the soil and the ionic strength of the soil solution appear to have little or no effect on the sorption/transport characteristics of these pesticides over the range of concentrations studied. (C) 2002 Elsevier Science B.V. All rights reserved.
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Two multinuclear complexes [Fe-6(mu(3)-O)(2)(mu(4)-O-2)L-10(OAc)(2)(H2O)(2)]center dot 2.625Et(2)O center dot 2.375H(2)O (1) and [(Fe11Cl)-Cl-III-(mu(4)-O)(3)(mu(3)-O)(5)L-16(dmf)(2.5)(H2O)(0.5)]center dot Et2O center dot 1.25dmf center dot 3.8H(2)O (2), where HL = 3,4,5-trimethoxybenzoic acid and dmf = dimethylformamide, have been prepared from trinuclear iron(III) carboxylates via their structural rearrangement in dimethylformamide or diethyl ether-dimethylformamide 9:1, respectively, and slow vapor diffusion of diethyl ether into the reaction mixture. Both compounds have been characterized by X-ray diffraction, optical, Mossbauer spectroscopy, and magnetic measurements. Complex 1 possesses a hexanuclear ferric peroxido-dioxido {Fe-6(O-2)(O)(2)}(12+) core unit, which adopts a recliner conformation, while complex 2 contains an unprecedented {Fe11O8Cl}(16+) core, in which 9 ferric ions are six-coordinate and the remaining two are five-coordinate. Another structural feature of note of the undecanuclear core is the presence of a deformed cubane entity {Fe-4(mu(3)-O)(mu(4)-O)(3)}(4+). Both complexes act as catalyst precursors for the oxidation of cyclohexane to cyclohexanol and cyclohexanone with aqueous H2O2, in the presence of pyrazinecarboxylic acid. Remarkable TONs and TOFs (the latter mainly for 1) with concomitant quite good yields have been achieved under mild conditions. Moreover, 1 exhibits remarkably high activity in an exceptionally short reaction time (45 min), being unprecedented for any metal catalyzed alkane oxidation by H2O2. The catalytic reactions proceed via Fenton type chemistry.
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O rio Febros é um pequeno curso de água, situado no concelho de Vila Nova de Gaia, com cerca de 15 km de extensão, cuja bacia hidrográfica ocupa uma área de aproximadamente 35,4 km2. Nasce em Seixezelo e desagua na margem esquerda do Rio Douro no Cais do Esteiro, em Avintes. Em Maio de 2008, um acidente de viação teve como consequência o derrame de cerca de quatro toneladas de ácido clorídrico que rapidamente convergiu às águas do rio. Apenas um dia depois, o pH desceu para três e muitos foram os peixes que morreram. A solução adoptada para evitar o desaire foi introduzir milhares de litros de água de modo a diluir o ácido presente, ao longo de todo o curso de água. Tal facto não evitou a destruição de parte de um ecossistema, que ainda nos dias de hoje se encontra em recuperação. De forma a avaliar-se o impacto destas possíveis perturbações sejam estas de origem antropogénica ou natural é necessário possuir conhecimentos dos processos químicos tais como a advecção, a mistura devida à dispersão e a transferência de massa ar/água. Estes processos irão determinar o movimento e destino das substâncias que poderão ser descarregadas no rio. Para tal, recorrer-se-á ao estudo hidrogeométrico do curso de água assim como ao estudo do comportamento de um marcador, simulando uma possível descarga. A rodamina WT será o marcador a ser utilizado devido à panóplia de características ambientalmente favoráveis. Os estudos de campo com este corante, realizados em sequência de descarga previamente estudada, fornecem uma das melhores fontes de informação para verificação e validação de modelos hidráulicos utilizados em estudos de qualidade de águas e protecção ambiental. Escolheram-se dois pontos de descarga no Febros, um em Casal Drijo e outro no Parque Biológico de Gaia, possuindo cada um deles, a jusante, duas estações de monitorização. Pelo modelo ADE os valores obtidos para o coeficiente de dispersão longitudinal para as estações Pontão d’ Alheira, Pinheiral, Menesas e Giestas foram, respectivamente, 0,3622; 0,5468; 1,6832 e 1,7504 m2/s. Para a mesma sequência de estações, os valores da velocidade de escoamento obtidos neste trabalho experimental foram de 0,0633; 0,0684; 0,1548 e 0,1645 m/s. Quanto ao modelo TS, os valores obtidos para o coeficiente de dispersão longitudinal para as estações Pontão d’ Alheira, Pinheiral, Menesas e Giestas foram, respectivamente, 0,2339; 0,1618; 0,5057e 1,1320 m2/s. Para a mesma sequência de estações, os valores da velocidade de escoamento obtidos neste trabalho experimental foram de 0,0652; 0,0775; 0,1891 e 0,1676 m/s. Os resultados foram ajustados por um método directo, o método dos momentos, e por dois métodos indirectos, os modelos ADE e TS. O melhor ajuste corresponde ao modelo TS onde os valores do coeficiente de dispersão longitudinal e da velocidade de escoamento são aqueles que melhor se aproximam da realidade. Quanto ao método dos momentos, o valor estimado para a velocidade é de 0,162 m/s e para o coeficiente de dispersão longitudinal de 9,769 m2/s. Não obstante, a compreensão da hidrodinâmica do rio e das suas características, bem como a adequação de modelos matemáticos no tratamento de resultados formam uma estratégia de protecção ambiental inerente a futuros impactos que possam suceder.
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O Biodiesel é uma fonte de energia renovável que actualmente se encontra em expansão. O Biodiesel é constituído por uma mistura de ésteres alquílicos de ácidos gordos. A existência de ácidos gordos insaturados torna o Biodiesel quimicamente menos estável, podendo ocorrer oxidação, degradação e polimerização do combustível, se este for inadequadamente armazenado ou transportado. O objectivo deste trabalho consistiu em avaliar a eficiência da utilização de antioxidantes fenólicos (ácido protocatecuico, ácido gálico, ácido 3,4 di-hidroxifenilacético, ácido cafeico, ácido hidrocafeico, ácido 3,4,5-tri-hidroxicinâmico, ácido m-coumárico e ácido p-coumárico), na estabilização do Biodiesel. O estudo envolveu a análise da influência do uso de cada um dos antioxidantes na inibição da peroxidação lipídica do ácido linoleico um dos principais ácidos gordos insaturados presentes na matéria-prima utilizada na produção de Biodiesel. A avaliação do efeito de inibição dos antioxidantes na peroxidação do ácido linoleico foi efetuada usando o método do tiocianato de ferro (III). Os resultados obtidos demonstraram, que todos os ácidos fenólicos estudados, apresentam uma elevada capacidade para inibir a peroxidação lipídica do ácido linoleico. As percentagens de inibição da peroxidação do ácido linoleico variaram entre os 72%, observada para o ácido p-coumárico, e os 82 %, verificada para o ácido protocatecuico. A eficiência de inibição da peroxidação por parte dos antioxidantes fenólicos em estudo foi comparada com a obtida utilizando um antioxidante de referência, o trolox. A eficiência de inibição obtida para todos os antioxidantes fenólicos estudados foi muito superior à observada para o trolox. Os resultados obtidos nesta dissertação permitem concluir que a utilização de ácidos fenólicos constitui uma boa alternativa para a estabilização de matrizes lipídicas, particularmente em combustíveis como o Biodiesel.
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BACKGROUND:: Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. METHODS:: In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. RESULTS:: Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. CONCLUSIONS:: Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. (Inflamm Bowel Dis 2010).
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Gastrin-releasing peptide receptors (GRPrs) are overexpressed on a variety of human cancers, providing the opportunity for peptide receptor targeting via radiolabeled bombesin-based peptides. As part of our ongoing investigations into the development of improved GRPr antagonists, this study aimed at verifying whether and how N-terminal modulations improve the affinity and pharmacokinetics of radiolabeled GRPr antagonists. METHODS: The potent GRPr antagonist MJ9, Pip-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (Pip, 4-amino-1-carboxymethyl-piperidine), was conjugated to 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA), and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and radiolabeled with (68)Ga and (64)Cu. The GRPr affinity of the corresponding metalloconjugates was determined using (125)I-Tyr(4)-BN as a radioligand. The labeling efficiency of (68)Ga(3+) was compared between NODAGA-MJ9 and NOTA-MJ9 in acetate buffer, at room temperature and at 95°C. The (68)Ga and (64)Cu conjugates were further evaluated in vivo in PC3 tumor xenografts by biodistribution and PET imaging studies. RESULTS: The half maximum inhibitory concentrations of all the metalloconjugates are in the high picomolar-low nanomolar range, and these are the most affine-radiolabeled GRPr antagonists we have studied so far in our laboratory. NODAGA-MJ9 incorporates (68)Ga(3+) nearly quantitatively (>98%) at room temperature within 10 min and at much lower peptide concentrations (1.4 × 10(-6) M) than NOTA-MJ9, for which the labeling yield was approximately 45% under the same conditions and increased to 75% at 95°C for 5 min. Biodistribution studies showed high and specific tumor uptake, with a maximum of 23.3 ± 2.0 percentage injected activity per gram of tissue (%IA/g) for (68)Ga-NOTA-MJ9 and 16.7 ± 2.0 %IA/g for (68)Ga-NODAGA-MJ9 at 1 h after injection. The acquisition of PET images with the (64)Cu-MJ9 conjugates at later time points clearly showed the efficient clearance of the accumulated activity from the background already at 4 h after injection, whereas tumor uptake still remained high. The high pancreas uptake for all radiotracers at 1 h after injection was rapidly washed out, resulting in an increased tumor-to-pancreas ratio at later time points. CONCLUSION: We have developed 2 GRPr antagonistic radioligands, which are improved in terms of binding affinity and overall biodistribution profile. Their promising in vivo pharmacokinetic performance may contribute to the improvement of the diagnostic imaging of tumors overexpressing GRPr.
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Alpha-ketoglutarate-dependent (R)-dichlorprop dioxygenase (RdpA) and alpha-ketoglutarate-dependent (S)-dichlorprop dioxygenase (SdpA), which are involved in the degradation of phenoxyalkanoic acid herbicides in Sphingomonas herbicidovorans MH, were expressed and purified as His6-tagged fusion proteins from Escherichia coli BL21(DE3)(pLysS). RdpA and SdpA belong to subgroup II of the alpha-ketoglutarate-dependent dioxygenases and share the specific motif HXDX(24)TX(131)HX(10)R. Amino acids His-111, Asp-113, and His-270 and amino acids His-102, Asp-104, and His 257 comprise the 2-His-1-carboxylate facial triads and were predicted to be involved in iron binding in RdpA and SdpA, respectively. RdpA exclusively transformed the (R) enantiomers of mecoprop [2-(4-chloro-2-methylphenoxy)propanoic acid] and dichlorprop [2-(2,4-dichlorophenoxy)propanoic acid], whereas SdpA was specific for the (S) enantiomers. The apparent Km values were 99 microM for (R)-mecoprop, 164 microM for (R)-dichlorprop, and 3 microM for alpha-ketoglutarate for RdpA and 132 microM for (S)-mecoprop, 495 microM for (S)-dichlorprop, and 20 microM for alpha-ketoglutarate for SdpA. Both enzymes had high apparent Km values for oxygen; these values were 159 microM for SdpA and >230 microM for RdpA, whose activity was linearly dependent on oxygen at the concentration range measured. Both enzymes had narrow cosubstrate specificity; only 2-oxoadipate was able to replace alpha-ketoglutarate, and the rates were substantially diminished. Ferrous iron was necessary for activity of the enzymes, and other divalent cations could not replace it. Although the results of growth experiments suggest that strain MH harbors a specific 2,4-dichlorophenoxyacetic acid-converting enzyme, tfdA-, tfdAalpha-, or cadAB-like genes were not discovered in a screening analysis in which heterologous hybridization and PCR were used.
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Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of antigenic peptides with murine MHC class I molecules on living cells. Photoreactive derivatives were prepared by N-terminal amidation with iodo, 4-azido salicylic acid of the Kd restricted Plasmodium berghei circumsporozoite (P.b. CS) peptide 253-260 (YIPSAEKI) and the Db-restricted Adenovirus 5 early region 1A (Ad5 E1A) peptide 234-243 (SGPSNTPPEI). As assessed in functional competition experiments, both peptide derivatives retained the specific binding activity of the parental peptides for Kd or Dd, respectively. The P.b. CS photoprobe specifically labeled Kd molecules on P815 (H-2d) cells, but failed to label RMA (H-2b) cells. Conversely, the Ad5 E1A photoprobe specifically labeled Db molecules on RMA cells, but failed to label P815 cells. When the two photoprobes were tested on a panel of Con A-activated spleen cells expressing 10 different H-2 haplotypes, significant photoaffinity labeling was observed only on H-2d cells with the P.b. CS photoprobe and on H-2b cells with the Ad5 E1A photoprobe. Labeling of cell-associated Kd or Db molecules with the photoprobes was specifically inhibited by antigenic peptides known to be presented by the same class I molecule. Photoaffinity labeling of Kd with the P.b. CS photoprobe was used to study the dynamics of peptide binding on living P815 cells. Binding increased steadily with the incubation period (up to 8 h) at 37 degrees C and at ambient temperature, but was greatly reduced (greater than 95%) at 0 to 4 degrees C or in the presence of ATP synthesis inhibitors. The magnitude of the labeling was twofold higher at room temperature than at 37 degrees C. In contrast, binding to isolated Kd molecules in solution rapidly reached maximal binding, particularly at 37 degrees C. Dissociation of the photoprobe from either cell-associated or soluble Kd molecules was similar, with a half time of approximately 1 h at 37 degrees C, whereas the complexes were long-lived at 4 degrees C in both instances.
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Using a direct binding assay based on photoaffinity labeling, we studied the interaction of T cell receptor (TCR) with a Kd-bound photoreactive peptide derivative on living cells. The Kd-restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) was reacted NH2-terminally with biotin and at the TCR contact residue Lys259 with photoreactive iodo, 4-azido salicylic acid (IASA) to make biotin-YIPSAEK(IASA)I. Cytotoxic T lymphocyte (CTL) clones derived from mice immunized with this derivative recognized this conjugate, but not a related one lacking the IASA group nor the parental PbCS peptide. The clones were Kd restricted. Recognition experiments with variant conjugates, lacking substituents from IASA, revealed a diverse fine specificity pattern and indicated that this group interacted directly with the TCR. The TCR of four clones could be photoaffinity labeled by biotin-YIPSAEK(125IASA)I. This labeling was dependent on the conjugates binding to the Kd molecule and was selective for the TCR alpha (2 clones) or beta chain (1 clone), or was common for both chains (1 clone). TCR sequence analysis showed a preferential usage of J alpha TA28 containing alpha chains that were paired with V beta 1 expressing beta chains. The TCR that were photoaffinity labeled at the alpha chain expressed these J alpha and V beta segments. The tryptophan encoded by the J alpha TA28 segment is rarely found in other J alpha segments. Moreover, we show that the IASA group interacts preferentially with tryptophan in aqueous solution. We thus propose that for these CTL clones, labeling of the alpha chain occurs via the J alpha-encoded tryptophan residue.
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Plants produce a range of biopolymers for purposes such as maintenance of structural integrity, carbon storage, and defense against pathogens and desiccation. Several of these natural polymers are used by humans as food and materials, and increasingly as an energy carrier. In this review, we focus on plant biopolymers that are used as materials in bulk applications, such as plastics and elastomers, in the context of depleting resources and climate change, and consider technical and scientific bottlenecks in the production of novel or improved materials in transgenic or alternative crop plants. The biopolymers discussed are natural rubber and several polymers that are not naturally produced in plants, such as polyhydroxyalkanoates, fibrous proteins and poly-amino acids. In addition, monomers or precursors for the chemical synthesis of biopolymers, such as 4-hydroxybenzoate, itaconic acid, fructose and sorbitol, are discussed briefly
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While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs) offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES) and neural stem cells (NSC). One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+)SSEA1(+) cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+) cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(-) cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner.
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In Brazilian agriculture, urea is the most commonly used nitrogen (N) source, in spite of having the disadvantage of losing considerable amounts of N by ammonia-N volatilization. The objectives of this study were to evaluate: N lossby ammonia volatilization from: [urea coated with copper sulfate and boric acid], [urea coated with zeolite], [urea+ammonium sulfate], [urea coated with copper sulfate and boric acid+ammonium sulfate], [common urea] and [ammonium nitrate]; and the effect of these N source son the maize yield in terms of amount and quality. The treatments were applied to the surface of a soil under no-tillage maize, in two growing seasons. The first season (2009/2010) was after a maize crop (maize straw left on the soil surface) and the second cycle (2012/2011) after a soybean crop. Due to the weather conditions during the experiments, the volatilization of ammonia-N was highest in the first four days after application of the N sources. Of all urea sources, under volatilization-favorable conditions, the loss of ammonia from urea coated with copper sulfate and boric acid was lowest, while under high rainfall, the losses from the different urea sources was similar, i.e., an adequate rainfall was favorablet o reduce volatilization. The ammonia volatilization losses were greatest in the first four days after application. Maize grain yield differed due to N application and in the treatments, but this was only observed with cultivation of maize crop residues in 2009/2010. The combination of ammonium+urea coated with copper sulfate and boric acid optimized grain yield compared to the other urea treatments. The crude protein concentration in maize was not influenced by the technologies of urea coating.
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The objective of this study was to establish cell suspension culture and plant regeneration via somatic embryogenesis of a Brazilian plantain, cultivar Terra Maranhão, AAB. Immature male flowers were used as explant source for generating highly embryogenic cultures 45 days after inoculation, which were used for establishment of cell suspension culture and multiplication of secondary somatic embryos. Five semisolid culture media were tested for differentiation, maturation, somatic embryos germination and for plant regeneration. An average of 558 plants per one milliliter of 5% SCV (settled cell volume) were regenerated in the MS medium, with 11.4 µM indolacetic acid and 2.2 µM 6-benzylaminopurine. Regenerated plants showed a normal development, and no visible somaclonal variation was observed in vitro. It is possible to regenerate plants from cell suspensions of plantain banana cultivar Terra using MS medium supplemented with 11.4 µM of IAA and 2.2 µM of BAP.
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The objective of this work was to determine the contents of methylxanthines, caffeine and theobromine, and phenolic compounds, chlorogenic and caffeic acids, in 51 mate progenies (half-sib families) and estimate the heritability of genetic parameters. Mate progenies were from five Brazilian municipalities: Pinhão, Ivaí, Barão de Cotegipe, Quedas do Iguaçu, and Cascavel. The progenies were grown in the Ivaí locality. The contents of the compounds were obtained by high performance liquid chromatography (HPLC). The estimation of genetic parameters by the restricted maximum likelihood (REML) and the prediction of genotypic values via best linear unbiased prediction (BLUP) were obtained by the Selegen - REML/BLUP software. Caffeine (0.248-1.663%) and theobromine (0.106-0.807%) contents were significantly different (p<0.05) depending on the region of origin, with high individual heritability (ĥ²>0.5). The two different progeny groups determined for chlorogenic (1.365-2.281%) and caffeic (0.027-0.037%) acid contents were not significantly different (p<0.05) depending on the locality of origin. Individual heritability values were low to medium for chlorogenic (ĥ²<0.4) and caffeic acid (ĥ²<0.3). The content of the compounds and the values of genetic parameters could support breeding programs for mate.