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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ArgBP2, and its brain-specific splice variant, nArgBP2, are interactors and substrates of Abl/Arg tyrosine kinases and of the ubiquitin ligase Cbl. They are members of a family of adaptor proteins that colocalize with actin on stress fibers and at cell-adhesion sites, including neuronal synapses. We show here that their NH2-terminal region, which contains a sorbin homology domain domain, interacts with spectrin, and we identify binding proteins for their COOH-terminal SH3 domains. All these binding partners participate in the regulation of the actin cytoskeleton. These include dynamin, synaptojanin, and WAVE isoforms, as well as WAVE regulatory proteins. At least two of the ArgBP2/nArgBP2 binding partners, synaptojanin 2B and WAVE2, undergo ubiquitination and Abl-dependent tyrosine phosphorylation. ArgBP2/nArgBP2 knockdown in astrocytes produces a redistribution of focal adhesion proteins and an increase in peripheral actin ruffles, whereas nArgBP2 overexpression produces a collapse of the actin cytoskeleton. Thus, ArgBP2/nArgBP2 is a scaffold protein that control the balance between adhesion and motility by coordinating the function of multiple signaling pathways converging on the actin cytoskeleton.
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PMID:The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton. 1565 45

A series of mesostructured Cu-SiO2 composites have been synthesized with sodium metasilicate (Na2SiO3) and cuprammonia nitrate (Cu(NH3)4(NO3)2) respectively used as Si and Cu sources. The synthetic procedures were conducted at room temperature, and cetyltrimethylammonia bromide was used as a template. Under our experimental conditions, ordered mesoporous Cu-SiO2 composites could be obtained with a copper content up to 16.8 wt %. Average pore diameters (2.80-3.15 nm), wall thickness (1.30-2.20 nm), and specific surface area (1020-690 m2/g) are found to vary linearly with copper content (0-16.8 wt %). Results of thermal gravimetry-differential thermal analysis reveal the collapse temperature of the order structure starts at approximately 1250 K for mesoporous Cu-SiO2 with 16.8 wt % copper content. As indicated by the outcomes of inductively coupled plasma and X-ray photoelectron spectroscopy studies, copper is mainly incorporated inside the pore wall rather than embedded on the wall surface. Copper species strongly interact with silica, and calcination at high temperatures cannot cause phase separation between silica and copper oxide. Cu status in mesoporous Cu-SiO2 composites is similar to that in copper silicate in neighboring structures. Based on the results, a S+ I- I+ I- mechanism is proposed in which copper entities are surrounded by silicon species during synthesis of the mesostructured composite.
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PMID:Novel coassembly route to Cu-SiO2 MCM-41-like mesoporous materials. 1583 67

Red blooms of Euglena sp. in the floodplain wetland ecosystems of Barak Valley, Assam, India, were found to be induced by high concentrations of NH3-N, NO3, Fe, Mg and to some extent, PO4, Cu and Zn in their water. The trace elements were rapidly accumulated by the bloom organisms to high levels, whereby their concentrations in the water declined, leading to a collapse of the bloom, which tended to reappear as decomposition again led to the release of the nutrients. The bloom also harboured fairly high density of certain other algae and zooplankton, thereby acting as a sub-system within the wetland ecosystem. The bloom is non-toxic and is exploited as a fish food by the fish-farmers who artificially induce a bloom for augmenting the growth of surface-feeding species of fishes.
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PMID:Euglenoid blooms in the floodplain wetlands of Barak Valley, Assam, North eastern India. 1584 51

The Danube nutrient loads are affected by human impacts mainly from agriculture and wastewater discharges. Knowledge about the Danube nutrient loads and the changes of these loads over time is essential for understanding the changes within the ecosystem of the Black Sea, induced by these loads. The paper shows the long term changes of the nutrient load along the Danube estimated by measurements from different countries and institutions. The results show large differences between Dissolved Inorganic Nitrogen (DIN) and Total Phosphorus (TP). For TP, the Danube River loads show a strong decrease since 1988-1992, especially in the Middle and Lower basin. This change is probably partly connected to the dramatic economic changes in the Middle and Eastern European countries following the collapse of the communist system. The DIN load does not show a decreasing trend in the last decade. The data indicate that there may be a decreasing trend in the anthropogenic emissions, but that such a trend is counteracted by a significantly increasing trend of the Danube discharge in the last decade. The accuracy of the available data is analysed in the paper as well.
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PMID:Changes of the nutrient loads of the Danube since the late eighties: An analysis based on long term changes along the whole Danube River and its main tributaries. 1611 34

Aromatic amine dehydrogenase uses a tryptophan tryptophylquinone (TTQ) cofactor to oxidatively deaminate primary aromatic amines. In the reductive half-reaction, a proton is transferred from the substrate C1 to betaAsp-128 O-2, in a reaction that proceeds by H-tunneling. Using solution studies, kinetic crystallography, and computational simulation we show that the mechanism of oxidation of aromatic carbinolamines is similar to amine oxidation, but that carbinolamine oxidation occurs at a substantially reduced rate. This has enabled us to determine for the first time the structure of the intermediate prior to the H-transfer/reduction step. The proton-betaAsp-128 O-2 distance is approximately 3.7A, in contrast to the distance of approximately 2.7A predicted for the intermediate formed with the corresponding primary amine substrate. This difference of approximately 1.0 A is due to an unexpected conformation of the substrate moiety, which is supported by molecular dynamic simulations and reflected in the approximately 10(7)-fold slower TTQ reduction rate with phenylaminoethanol compared with that with primary amines. A water molecule is observed near TTQ C-6 and is likely derived from the collapse of the preceding carbinolamine TTQ-adduct. We suggest this water molecule is involved in consecutive proton transfers following TTQ reduction, and is ultimately repositioned near the TTQ O-7 concomitant with protein rearrangement. For all carbinolamines tested, highly stable amide-TTQ adducts are formed following proton abstraction and TTQ reduction. Slow hydrolysis of the amide occurs after, rather than prior to, TTQ oxidation and leads ultimately to a carboxylic acid product.
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PMID:New insights into the reductive half-reaction mechanism of aromatic amine dehydrogenase revealed by reaction with carbinolamine substrates. 1747 20

Acid dissociation constants of side-chain acidic groups of amino acid residues in peptides can be determined by 1H NMR, provided resonances can be resolved for carbon-bonded reporter protons located near the acidic group. We report here that the increased resolution of the band-selective homonuclear-decoupled (BASHD) TOCSY experiment greatly extends the range of application of the NMR method for determination of residue-specific, side-chain acid dissociation constants of peptides that contain multiple residues of the same amino acid. Chemical shift-pH titration curves are obtained from cross-peaks for reporter protons in BASHD-TOCSY spectra measured as a function of pH. The method is based on using sequence-dependent differences in the chemical shifts of resonances for the backbone CalphaH protons and the increased resolution in BASHD-TOCSY spectra from collapse of CalphaH multiplets to singlets in the F1 dimension to resolve resonances for the side-chain reporter protons. Application of the method is demonstrated by determination of residue-specific pKA values for each of the side-chain ammonium groups of the six lysine residues in the hexadecapeptide Ac-SRGKAKVKAKVKDQTK-NH2. Chemical shift-pH titration curves were obtained for the lysine side-chain CepsilonH2 reporter protons from their resolved CalphaH-CepsilonH2 TOCSY cross-peaks in BASHD-TOCSY spectra. Relative acidities of the six ammonium groups were also determined from the residue specific chemical shift-pH titration data by a pH-independent method, and calculation of fractional concentrations of protonation microspecies using the residue-specific pKAs is also described.
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PMID:Determination of residue-specific acid dissociation constants for peptides by band-selective homonuclear-decoupled (1)H NMR. 1767 82

The role of water in promoting the formation of protofilaments (the basic building blocks of amyloid fibrils) is investigated using fully atomic molecular dynamics simulations. Our model protofilament consists of two parallel beta-sheets of Alzheimer Amyloid-beta 16-22 peptides (Ac-K(16)-L(17)-V(18)-F(19)-F(20)-A(21)-E(22)-NH2). Each sheet presents a distinct hydrophobic and hydrophilic face and together self-assemble to a stable protofilament with a core consisting of purely hydrophobic residues (L(17), F(19), A(21)), with the two charged residues (K(16), E(22)) pointing to the solvent. Our simulations reveal a subtle interplay between a water mediated assembly and one driven by favorable energetic interactions between specific residues forming the interior of the protofilament. A dewetting transition, in which water expulsion precedes hydrophobic collapse, is observed for some, but not all molecular dynamics trajectories. In the trajectories in which no dewetting is observed, water expulsion and hydrophobic collapse occur simultaneously, with protofilament assembly driven by direct interactions between the hydrophobic side chains of the peptides (particularly between F-F residues). For those same trajectories, a small increase in the temperature of the simulation (on the order of 20 K) or a modest reduction in the peptide-water van der Waals attraction (on the order of 10%) is sufficient to induce a dewetting transition, suggesting that the existence of a dewetting transition in simulation might be sensitive to the details of the force field parametrization.
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PMID:Role of water in mediating the assembly of Alzheimer amyloid-beta Abeta16-22 protofilaments. 1866 94

The reactions of substituted benzhydryl bromides Ar(2)CHBr with primary and secondary amines in DMSO yield benzhydryl amines Ar(2)CHNRR', benzophenones Ar(2)C=O, and benzhydrols Ar(2)CHOH. Kinetic investigations at 20 degrees C revealed the rate law -d[Ar(2)CHBr]/dt = (k(1) + k(2)[HNRR'])[Ar(2)CHBr], where the amine independent term k(1) gave rise to the formation of Ar(2)C=O and Ar(2)CHOH and the amine-dependent term k(2)[HNRR'] was responsible for the formation of Ar(2)CHNRR'. Clear evidence for concomitant S(N)1 and S(N)2 processes was obtained. While the rate constants of the S(N)1 reactions correlate with Hammett's sigma(+) constants (rho = -3.22), the second-order rate constants k(2) for the S(N)2 reactions are not correlated with the electron releasing abilities of the substituents, indicating that the transition states of the S(N)2 reactions do not merge with the transition states of the S(N)1 reactions. The correlation equation log k(20 degrees C) = s(E + N), where nucleophiles are characterized by N and s and electrophiles are characterized by E (J. Am. Chem. Soc. 2001, 123, 9500-9512), was used to calculate the lifetimes of benzhydrylium ions in the presence of amines and DMSO. The change from S(N)1 to S(N)2 mechanism occurred close to the point where the calculated rate constant for the collapse of the benzhydrylium ions with the amines just reaches the vibrational limit; that is, the concerted S(N)2 mechanism was only followed when it was enforced by the lifetime of the intermediate. The nucleophile-specific parameters N and s needed for this analysis were determined by studying the kinetics of the reactions of a variety of amines with amino-substituted benzhydrylium tetrafluoroborates (Ar(2)CH(+)BF(4)(-)) of known electrophilicity E in DMSO. Analogously, the rates of the reactions of laser flash photolytically generated benzhydrylium ions Ar(2)CH(+) with DMSO in acetonitrile were employed to determine the nucleophile-specific parameters N and s of DMSO, and it is reported that DMSO is a significantly stronger O-nucleophile than water and ordinary alcohols.
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PMID:Can one predict changes from S(N)1 to S(N)2 mechanisms? 1963 6

2,3,5-Tris(glutathion-S-yl)-hydroquinone (TGHQ), a metabolite of hydroquinone, is toxic to renal proximal tubule epithelial cells. TGHQ retains the ability to redox cycle and create an oxidative stress. To assist in elucidating the contribution of reactive oxygen species (ROS) to TGHQ-induced toxicity, we determined whether the antioxidant, N-acetyl-L-cysteine (NAC), could protect human kidney proximal tubule epithelial cells (HK-2 cell line) against TGHQ-induced toxicity. NAC provided remarkable protection against TGHQ-induced toxicity to HK-2 cells. NAC almost completely inhibited TGHQ-induced cell death, mitochondrial membrane potential collapse, as well as ROS production. NAC also attenuated TGHQ-induced DNA damage and the subsequent activation of poly (ADP-ribose) polymerase and ATP depletion. Moreover, NAC significantly attenuated c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase phosphorylation induced by TGHQ. In contrast, NAC itself markedly increased extracellular regulated kinase1/2 (ERK1/2) activation, and the upstream mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor, PD-98059, only partially inhibited this activation, suggesting that NAC can directly activate ERK1/2 activity. However, although NAC is frequently utilized as a glutathione (GSH) precursor, the cytoprotection afforded by NAC in HK-2 cells was not a consequence of increased GSH levels. We speculate that NAC exerts its protective effect in part by directly scavenging ROS and in part via ERK1/2 activation.
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PMID:The cytoprotective effect of N-acetyl-L-cysteine against ROS-induced cytotoxicity is independent of its ability to enhance glutathione synthesis. 2113 14

Metal-organic frameworks (MOFs), besides being porous materials exhibit a very rich chemistry, which can be used for the synthesis of composites and/or the reactive adsorption of toxic gases. In this study, composites of MOFs (MOF-5, HKUST-1 or MIL-100(Fe)) and a graphitic compound (graphite or graphite oxide, GO) were synthesized and tested for the removal of NH(3), H(2)S and NO(2) under ambient conditions. The materials were characterized before and after exposure to the target gases by X-ray diffraction, thermogravimetric analysis, N(2) sorption measurement and FT-IR spectroscopy. The results indicate that strong chemical bonds exist between the MOF and GO as a result of the coordination between the GO oxygen groups and the MOFs' metallic centers. Depending on the structure of the MOF, such interactions induce the formation of a new pore space in the interface between the carbon layers and the MOF units, which enhances the physical adsorption capacity of the toxic gases. When unsaturated metallic sites are present in the MOFs, the target gases are also adsorbed via coordination to these centers. Further reaction with the framework leads to the formation of complexes. This is accompanied by the collapse of the MOF structure.
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PMID:Exploring the coordination chemistry of MOF-graphite oxide composites and their applications as adsorbents. 2235 54


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