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61.
Maria E. Silva Serra Dina Murtinho Albertino Goth António M. D'A. Rocha Gonsalves Paulo E. Abreu Alberto A. C. C. Pais 《Chirality》2010,22(4):425-431
New chiral salen ligands were prepared by the ultrasound‐irradiated condensation of optically active (1R, 3S)‐1,2,2‐trimethyl‐1,3‐diaminocyclopentane with aromatic 1‐hydroxyaldehydes. The ultrasound‐mediated process is more convenient due to shorter reaction times, energy economy, and easier isolation of the products. The in situ formed Ti(IV)(salen) complexes, evaluated as catalysts in the enantioselective trimethylsilylcyanation of benzaldehyde, were found to be efficient for this process, originating the corresponding product in high yields (72–99%) and selectivities of up to 79%. The lowest energy transition states were determined by computational studies. These results were in qualitative agreement with the experimentally observed ones. Chirality, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
62.
Prospects of yeast systems biology for human health: integrating lipid, protein and energy metabolism 总被引:2,自引:0,他引:2
The yeast Saccharomyces cerevisiae is a widely used model organism for studying cell biology, metabolism, cell cycle and signal transduction. Many regulatory pathways are conserved between this yeast and humans, and it is therefore possible to study pathways that are involved in disease development in a model organism that is easy to manipulate and that allows for detailed molecular studies. Here, we briefly review pathways involved in lipid metabolism and its regulation, the regulatory network of general metabolic regulator Snf1 (and its human homologue AMPK) and the proteostasis network with its link to stress and cell death. All the mentioned pathways can be used as model systems for the study of homologous pathways in human cells and a failure in these pathways is directly linked to several human diseases such as the metabolic syndrome and neurodegeneration. We demonstrate how different yeast pathways are conserved in humans, and we discuss the possibilities of using the systems biology approach to study and compare the pathways of relevance with the objective to generate hypotheses and gain new insights. 相似文献
63.
The purpose of this study was to prepare sublingual tablets, containing the antiasthmatic drug ketotifen fumarate which suffers an extensive first-pass effect, using the fast-melt granulation technique. The powder mixtures containing the drug were agglomerated using a blend of polyethylene glycol 400 and 6000 as meltable hydrophilic binders. Granular mannitol or granular mannitol/sucrose mixture were used as fillers. A mechanical mixer was used to prepare the granules at 40°C. The method involved no water or organic solvents, which are used in conventional granulation, and hence no drying step was included, which saved time. Twelve formulations were prepared and characterized using official and non official tests. Three formulations showed the best results and were subjected to an ex vivo permeation study using excised chicken cheek pouches. The formulation F4I possessed the highest permeation coefficient due to the presence of the permeation enhancer (polyethylene glycol) in an amount which allowed maximum drug permeation, and was subjected to a pharmacokinetic study using rabbits as an animal model. The bioavailability of F4I was significantly higher than that of a commercially available dosage form (Zaditen® solution-Novartis Pharma-Egypt) (p > 0.05). Thus, fast-melt granulation allowed for rapid tablet disintegration and an enhanced permeation of the drug through the sublingual mucosa, resulting in increased bioavailabililty.Key words: chicken pouches, fast-melt granulation, ketotifen fumarate, permeation, sublingual tablet, Zaditen® 相似文献
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66.
Spectrin is an ubiquitous protein in metazoan cells, and its flexibility is one of the keys to maintaining cellular structure and organization. Both alpha-spectrin and beta-spectrin polypeptides consist primarily of triple coiled-coil modular repeat units, and two important factors that determine spectrin flexibility are the bending flexibility between two consecutive repeat units and the conformational flexibility of individual repeat units. Atomistic molecular dynamics (MD) simulations are used here to study double spectrin repeat units (DSRUs) from the human erythrocyte beta-spectrin (HEbeta89) and the chicken brain alpha-spectrin (CBalpha1617). From the results of MD simulations, a highly conserved Trp residue in the A-helix of most repeat units that has been suggested to be important in conferring stability to the coiled-coil structures is found not to have a significant effect on the conformational flexibility of individual repeat units. Characterization of the bending flexibility for two consecutive repeats of spectrin via atomistic simulations and coarse-grained (CG) modeling indicate that the bending flexibility is governed by the interactions between the AB-loop of the first repeat unit, the BC-loop of the second repeat unit and the linker region. Specifically, interactions between residues in these regions can lead to a strong directionality in the bending behavior of two repeat units. The biological implications of these finding are discussed. 相似文献
67.
Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability 下载免费PDF全文
Kroboth K Newton IP Kita K Dikovskaya D Zumbrunn J Waterman-Storer CM Näthke IS 《Molecular biology of the cell》2007,18(3):910-918
Most sporadic colorectal tumors carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein is involved in many processes that govern gut tissue. In addition to its involvement in the regulation of beta-catenin, APC is a cytoskeletal regulator with direct and indirect effects on microtubules. Cancer-related truncation mutations lack direct and indirect binding sites for microtubules in APC, suggesting that loss of this function contributes to defects in APC-mutant cells. In this study, we show that loss of APC results in disappearance of cellular protrusions and decreased cell migration. These changes are accompanied by a decrease in overall microtubule stability and also by a decrease in posttranslationally modified microtubules in the cell periphery particularly the migrating edge. Consistent with the ability of APC to affect cell shape, the overexpression of APC in cells can induce cellular protrusions. These data demonstrate that cell migration and microtubule stability are linked to APC status, thereby revealing a weakness in APC-deficient cells with potential therapeutic implications. 相似文献
68.
Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin 总被引:4,自引:0,他引:4
Nachmias B Lazar I Elmalech M Abed-El-Rahaman I Asshab Y Mandelboim O Perlman R Ben-Yehuda D 《Apoptosis : an international journal on programmed cell death》2007,12(7):1129-1142
Livin is a member of the Inhibitor of Apoptosis Protein family which inhibits apoptosis induced by a variety of stimuli. We
previously identified Livin and demonstrated that following apoptotic stimuli, Livin is cleaved by effector caspases to produce
a truncated form with paradoxical pro-apoptotic activity. In the present study, we reveal that while full-length Livin shows
diffuse cytoplasmic localization, truncated Livin (tLivin) is found in a peri-nuclear distribution with marked localization
to the Golgi apparatus. Using mutation analysis, we identified two domains that are crucial for the pro-apoptotic activity
of tLivin: the N-terminal region of tLivin which is exposed by cleavage, and the RING domain. We demonstrate that, of the
N-terminal sequence, only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin. However,
while the perinuclear localization of tLivin is essential, it is not sufficient for tLivin to exert its pro-apoptotic function.
Once tLivin is properly localized, an intact RING domain enables its pro-apoptotic function.
Electronic Supplementary Material Supplementary material is available in the online version of this article at . 相似文献
69.
Thorns, spines and prickles are among the rich arsenal of antiherbivore defence mechanisms that plants have evolved. Many of these thorns are aposematic, that is, marked by various types of warning coloration. This coloration was recently proposed to deter large herbivores. Yet, the mechanical defence provided by thorns against large herbivores might be only the tip of the iceberg in a much more complicated story. Here we present evidence that thorns harbour an array of pathogenic bacteria that are much more dangerous to herbivores than the painful mechanical wounding by the thorns. Pathogenic bacteria like Clostridium perfringens, the causative agent of the life-threatening gas gangrene, and others, were isolated and identified from date palm (with green-yellow-black aposematic spines) and common hawthorn (with red aposematic thorns). These thorn-inhabiting bacteria have a considerable potential role in antiherbivory, and may have uniquely contributed to the common evolution of aposematism (warning coloration) in thorny plants. 相似文献
70.
Salem Jennifer Ben Iacovoni Jason S. Calise Denis Arvanitis Dina N. Beaudry Francis 《Neurochemical research》2022,47(8):2416-2430
Neurochemical Research - Myocardial infraction (MI) is the principal risk factor for the onset of heart failure (HF). Investigations regarding the physiopathology of MI progression to HF have... 相似文献