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The synthesis of a new bifunctional compound in which two aminoacridine chromophores are linked by the bicyclic depsipeptidic backbone of des-N-tetramethylTriostin A is described. The molecule, bis-[(9-acridinyl)-D-seryl-L-alanyl-L-cysteinyl-L-valine] dilactone disulphide, structurally analogous to the antibiotic anti-tumour drug Triostin A, is shown to possess a high affinity to DNA and to act as a bis-intercalator on the basis of spectroscopic, viscosimetric and thermal-denaturation studies. This model constitutes the first attempt of a synergic association between a peptidic moiety that mimics a naturally occurring drug and aminoacridine, the two parts themselves each exhibiting a high affinity for the DNA target. ...
Aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects. [PubChem]
This thesis describes the synthesis and radiohalogenation of compounds of potential use for tumor targeting.. The first section describes the synthesis and radioiodination of DNA intercalating compounds. The compounds are derivatives of 9-aminoacridine, and the anthracyclins daunorubicin and doxorubicin. The precursor compounds were labeled with 125I (T1/2 = 60 days), which is an Auger emitting nuclide. 125I decaying in the close vicinity of DNA is known to have a much higher cell killing effect than 125I decaying in the cytoplasm and some of the labeled compounds prepared in this thesis are currently being tested for use in targeted radionuclide therapy for cancer.. The second section describes the radiobromination of closo-carboranes by subjecting the corresponding iodinated compounds to palladium-catalyzed halogen exchange using [76Br]bromide. The 76Br isotope (T1/2 = 16.2 h) is a positron emitting nuclide that is suitable for PET studies. Via the halogen exchange reaction good to excellent ...
Fig. 2. Fractional Ca2+ currents in wild-type and mutant NMDAR channels. A, MeanPf values in wild-type (wt) and mutant NR1-NR2A channels containing alanine substitutions of the DRPEER motif. Cells were bathed in 143.5 mm NaCl and 1.8 mm CaCl2. The holding potential (V) was −60 mV to the reversal potential (Jatzke et al., 2002). Pf values significantly different from those in wild type are shown asgray bars. B, Mean Ca2+ permeability ratios (PCa/PCs) in wt and mutant NR1-NR2A channels containing alanine substitutions of the DRPEER motif.PCa/PCsvalues were derived from changes in reversal potentials ongoing from a Cs+-based reference solution to a solution in which CsCl was replaced by 1.8 mm Ca2+ and 140 mm NMDG (see Materials and Methods).PCa/PCsvalues significantly different from those in wild type are shown asgray bars. C, MeanPf values in mutant channels containing oppositely charged substitutions of the DRPEER motif or of homologous positions in NR2A (see Fig. 1). Results are recorded and ...
The goal of the work presented here was to study and quantify the contribution of each cause to the measured excess-head. Chemo-osmotic and thermo-osmotic permeabilities were obtained by experiments and using theoretical models. Theoretical models are based on the reproduction of the interactions occurring between the charged surface of clay minerals and pore solution and their upscaling at the representative elementary volume macroscopic scale. Chemical osmosis phenomenon is related to anionic exclusion and the determination of the chemo osmotic efficiency requires the resolution of an electrical interactions model. A triple-layer-model which considers diffuse layers overlapping was improved during this thesis to be able to take into account the effect of multi-ionic solutions, i.e. nearest than the natural waters composition, and, thus, to constrain better the chemo-osmotic efficiency. Thermo-osmosis process is poorly characterized so that no satisfactory macroscopic expression to calculate ...
The I 9.2 cell line is a caspase-8 mutant of the wild-type Jurkat cell line A3 (see ATCC CRL-2570). Wild-type A3 cells were made neomycin resistant and treated with three cycles of exposure to the frameshifting mutagen ICR-191 to isolate clones harboring recessive mutations that were resistant to killing by Fas antibody.  Ref ICR-191 treated clones were serially diluted in 96-well plates in the presence of Fas Antibody for 3 to 5 weeks. Ref  Two of these ICR-191 treated clones have been deposited at the ATCC . They are I 9.2 (ATCC CRL-2571), a clone with a mutation in the cysteine protease caspase-8/FLICE and I 2.1 (ATCC CRL-2572), a clone with a mutation in the adaptor FADD.  
The effect of three accelerators of hemolysis-acetylphenylhydrazine, 9-aminoacridine, and phenothiazone-upon protein and lipid monolayers has been examined. These compounds, in low concentration, cause marked expansion of monolayers of plasma albumin, but have no apparent effect upon cholesterol films. It is suggested that these accelerators may affect the protein component of the erythrocyte membrane, thus enhancing the action of hemolytic agents.. ...
We investigated the effect of Helianthus tuberosus agglutinin (HTA) on neutrophil migration in vivo and in vitro. The role of resident cells in this effect was analyzed. Peritonitis was induced by injecting stimuli into rat (150-200 g) peritoneal cav
Quinacrine dihydrochloride is the dihydrochloride salt of the 9-aminoacridine derivative quinacrine with potential antineoplastic and antiparasitic activities. Quinacrine may inhibit the transcription and activity of both basal and inducible nuclear factor-kappaB (NF-kappaB), which may result in the induction of tumor suppressor p53 transcription, the restoration of p53-dependent apoptotic pathways, and tumor cell apoptosis. Continuous NF-kappaB signaling, present in many tumors and in chronic inflammatory processes, promotes the expression of antiapoptotic proteins and cytokines while downregulating the expression of proapoptotic proteins, such as p53. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus) .
TY - JOUR. T1 - Novel acridine-based compounds that exhibit an anti-pancreatic cancer activity are catalytic inhibitors of human topoisomerase II. AU - Oppegard, Lisa M.. AU - Ougolkov, Andrei V.. AU - Luchini, Doris N.. AU - Schoon, Renee A.. AU - Goodell, John R.. AU - Kaur, Harneet. AU - Billadeau, Daniel D.. AU - Ferguson, David M. AU - Hiasa, Hiroshi. PY - 2009/1/14. Y1 - 2009/1/14. N2 - We have identified a small library of novel substituted 9-aminoacridine derivatives that inhibit cell proliferation of pancreatic cancer cell lines by inducing apoptosis [Goodell, J.R. et al., 2008. J. Med. Chem. 51, 179-182.]. To further investigate their antiproliferative activities, we have assessed the antiproliferative activity of these acridine-based compounds against several pancreatic cancer cell lines. All four compounds used in this study inhibited the proliferation of pancreatic cancer cell lines in vitro. In addition, we have employed a xenograft tumor model and found that these compounds also ...
A native species of river banks and floodplains in our area, but also escaped from cultivation and widespread along railroads and roadsides, in fields and fencerows, at old homesites and vacant lots, and in other disturbed places; found in both wet and dry ground.. This sunflower was once grown commonly for its crisp tubers, produced on the rhizomes, which can be eaten raw or cooked. Fragmentary specimens lacking information on habit of underground parts are easily confused with H. annuus, but the latter has larger heads (on all but very small plants) and a tendency to relatively broader leaves.. ...
Two new epoxy steroids, 5α,8α-epidioxy-22β,23β-epoxyergosta-6-en-3β-ol (1) and 5α,8α-epidioxy-22α,23α-epoxyergosta-6-en-3β-ol (2), and ten known steroids including (24R)-5α,8α-epidioxyergosta-6-en-3β-ol (3), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (4), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3β-ol (5), β-sitosterol (6), sitost-5-en-3β-ol acetate (7), 7α-hydroxysitosterol (8), schleicheol 2 (9), (24R)-24-ethyl-5α-cholestane-3β,5α,6β-triol (10), 7α-hydroxystigmasterol (11), and stigmasterol (12) were isolated from Helianthus tuberosus grown in Laizhou salinized land of coastal zone of Bohai Sea, China. The structures of these compounds were unambiguously established by 1D, 2D NMR and mass spectroscopic techniques. The new compounds 1 and 2 exhibited weak antibacterial activity and no antifungal activity.
Diffuse scattering in decagonal phases is due to deviations from strict aperiodic and periodic order in the quasiperiodic plane and along the unique direction, respectively. Results from X-ray (synchrotron) and neutron diffraction experiments, mainly carried out with decagonal Al-Ni-Co, are presented. Most prominent are diffuse maxima, diffuse streaks, phason affected reflection profiles, and diffuse layers perpendicular to the unique axis. Disorder models in decagonal qc-structures, in particular lamellar domain-like ordering in super-space are outlined. The terms structure and phase in context with disordered structures are discussed. ...
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A large cytoplasmic membrane-bounded vesicle with an electron dense granular core, up to 150-200 nm in diameter, found in neurosecretory cells in the hypothalamus. [ISBN:01950657191, NIF_Subcellular:sao2031592629]
Variability in macroelement content in the aboveground part of Helianthus tuberosus L. at different nitrogen fertilization levels | B. Sawicka, D. Kalesa, D. Skiba | Agricultural Journals
Despite the fact that both Gouauxs (Yamashita et al., 2005; Singh et al., 2007; Piscitelli et al., 2010) and Javitchs (Shi et al., 2008; Quick et al., 2009) groups have used structural and functional approaches to clarify the debate on the LeuT substrate stoichiometry and elucidate the mechanism of LeuT transport and inhibition, these approaches have not been enough to establish a consensus. Even more surprising is the fact that the same or very similar techniques have produced very different results. Crystallography has shown mixed results. One group detected density in the proposed second binding site corresponding to a detergent molecule (Quick et al., 2009), whereas the other group modeled structural water molecules to account for the excess of electron density in the extracellular vestibule of LeuT (Yamashita et al., 2005). From a crystallographic perspective, there could be two different ways to shed light on these intriguing results. The first one would be to screen for other ...
The serotonin transporter (SERT) controls synaptic serotonin levels and is the primary target for antidepressants, including selective serotonin reuptake inhibitors (e.g. (S)-citalopram) and tricyclic antidepressants (e.g. clomipramine). In addition to a high affinity binding site, SERT possesses a low affinity allosteric site for antidepressants. Binding to the allosteric site impedes dissociation of antidepressants from the high affinity site, which may enhance antidepressant efficacy. Here we employ an induced fit docking/molecular dynamics protocol to identify the residues that may be involved in the allosteric binding in the extracellular vestibule located above the central substrate binding (S1) site. Indeed, mutagenesis of selected residues in the vestibule reduces the allosteric potency of (S)-citalopram and clomipramine. The identified site is further supported by the inhibitory effects of Zn(2+) binding in an engineered site and the covalent attachment of ...
Biomass Accumulation and Nutrient Uptake of Jerusalem Artichoke Helianthus tuberosus L.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
SNAP-25 is a Q-SNARE protein mediating exocytosis of neurosecretory vesicles including chromaffin granules. SNAP-25 K201Q mutant showed no changes compared with SNAP-25 wild-type. However, K201E, R198Q, and R198E displayed reduced release frequencies, slower release kinetics, and prolonged fusion pore duration that were correlated with reduced probability to engage in the tightly zippered state. The results show that the positively charged amino acids at the SNAP-25 C terminus promote tight SNARE complex zippering and are required for high release frequency and rapid release in individual fusion events. being the number of cells in a group. Results Transmitter release 15291-76-6 IC50 kinetics determined by amperometry To investigate the role of positively charged amino acids in the C terminal domain of SNAP-25, SNAP-25 wt and R198Q, R198E, K201Q, or K201E mutants were overexpressed in bovine chromaffin cells (Fig. 1separately and averaging the best fit parameters (see Table 3). 15291-76-6 IC50 ...
Fig. 6 Proposed substrate transport mechanism in LeuT.. (1) Under apo state conditions, LeuT preferentially assumes an outward-facing open conformation with relatively high Gibbs free energy. (2) HDX is decreased upon Na+ binding, suggesting stabilization of the protein backbone in basically the same transporter conformation as for apo state, presumably the outward-facing open. (3) According to crystal structures (5), binding of a transportable hydrophobic amino acid (for example, leucine) prompts occlusion of the extracellular vestibule. EL4 and the water-mediated salt bridge between Arg30 and Asp404 prevent water access to the substrate binding site. On the basis of HDX data, it appears that the substrate-bound, outward-facing occluded state represents the thermodynamically most favorable LeuT conformation in the transport cycle. (4) As shown for MhsT (11) and supported by the results herein, the concurrent unwinding of the intracellular halves of TMs 1 and 5 creates a solvent pathway for ...
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This study was conducted to find out the effect of adding different levels of Jerusalem Artichoke Tubers (Helianthus tuberosus L.) (JAT) powder and Sprout Germinated Barley (SGB) powder to common carp diets (Cyprinus carpio L.) on the rates parameters of Apparent Digestible Coefficient (ADC%) and Apparent Protein Digestible (APD%). 147 fish were distributed to seven treatments, 7 fish in each aquarium with three replications per treatment, for a period of 70 days. It was fed with 3% of weight of the biomass and was given twice a day. The (JAT) powder was added at the rate of 2.5, 5 and 7.5 g/kg, for the first, second, and third treatments respectively, add (SGB) powder 2.5, 5 and 7.5 g/kg for the fourth, fifth and sixth treatments respectively. ADC% Rate, third treatment which was 7.5 g/kg of JAT significantly P≤0.05 outperformed, for ADC (69.915%) on all treatments, It did not differ did not differ significantly P≤0.05 with both the fifth treatment (5 g/kg SGB) and the sixth one (7.5 g/kg ...
Some of the more frequent questions that people ask me center on obtaining seed from Jerusalem artichokes for breeding. Many crops that are propagated from tubers have a reduced capability for sexual reproduction. You will see this theme come up again and again in this blog, but the details differ from one species to another ...
Although several proteins have been implicated in secretory vesicle tethering, the identity and mechanical properties of the components forming the physical vesicle-plasma membrane link remain unknown. Here we present the first experimental measurements of nanomechanical properties of secretory vesicle-plasma membrane tethers using combined AFM force clamp and TIRF microscopy on membrane sheets from PC12 cells expressing the vesicle marker ANF-eGFP. Application of pulling forces generated tether extensions composed of multiple steps with variable length. The frequency of short (|10 nm) tether extension events was markedly higher when a fluorescent vesicle was present at the cantilever tip and increased in the presence of GTPγS, indicating that these events reflect specifically the properties of vesicle-plasma membrane tethers. The magnitude of the short tether extension events is consistent with extension lengths expected from progressive unfolding of individual helices of the exocyst complex,
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Jerusalem artichoke (Helianthus tuberosus L.) produces substantial shoots not used as food. To test its potential as a sustainable bioenergy crop, we studied the effects of synthetic fertilizer and intercropped legumes as nitrogen (N) sources on the growth, aboveground biomass dry matter yield and energy qualities of this crop. Plant height, leaf area index (LAI), SPAD-value, biomass yield, ash content and mineral element composition were determined. Mean aboveground biomass yields were not significantly affected by N source (legume intercrops and synthetic fertilizer) and ranged from 13 to 17 t ha(-1). Remarkably, plants given no fertilizer yielded equally to plants given 90 N kg ha(-1). These results confirm that Jerusalem artichoke, compared to other energy crops, have less need for N and can potentially be sustained by N fixing legumes in an intercropped system. This could reduce or eliminate production and environmental cost in cultivation of biomass feedstock for energy use ...
Among the range of materials used in bioengineering, parylene-C has been used in combination with silicon oxide and in presence of the serum proteins, in cell patterning. However, the structural properties of adsorbed serum proteins on these substrates still remain elusive. In this study, we use an optical biosensing technique to decipher the properties of fibronectin (Fn) and serum albumin adsorbed on parylene-C and silicon oxide substrates. Our results show the formation of layers with distinct structural and adhesive properties. Thin, dense layers are formed on parylene-C, whereas thicker, more diffuse layers are formed on silicon oxide. These results suggest that Fn acquires a compact structure on parylene-C and a more extended structure on silicon oxide. Nonetheless, parylene-C and silicon oxide substrates coated with Fn host cell populations that exhibit focal adhesion complexes and good cell attachment. Albumin adopts a deformed structure on parylene-C and a globular structure on silicon ...
Myeloid-derived suppressor cells (MDSC) certainly are a main element of the immune system suppressive network defined in cancer and several additional pathological conditions. tumor-free mice. Manifestation of NOX2 subunits in MDSC was managed by the STAT3 transcription element. In the lack of NOX2 activity MDSC dropped the capability to suppress T-cell reactions and quickly differentiated Read More. ...
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Practical applications: Unsaturated lactones are structural elements often found in natural products, which have medicinal value. Benzolactones derived from anacardic acid reported in this work have some structural similarity with lactones such as massoia lactone having medicinal value. Therefore with this idea in mind, the unsaturated benzolactones reported in this work will be tested for their anti pathogenic activity. 3-Propylphenol is used in combination with racemic 1-octen-3-ol and p-cresol to prepare a kairomone for tsetse fly traps. Results from this work describe the suitability of anacardic acid for synthesizing 3-propylphenol. The fact that 3-propylphenol can be synthesized from anacardic acid, a component of cashew nut shell liquid is of particular interest since most of the areas affected with tsetse flies are suitable for growing cashew plants. This means the raw materials (CNSL) for synthesis of 3-propylphenol will be obtained from within the same region where the kairomone is to ...
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