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Molecular Framework (molecular + framework)
Selected AbstractsMolecular framework for response to imatinib mesylate in systemic sclerosis,ARTHRITIS & RHEUMATISM, Issue 2 2009Lorinda Chung Systemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases platelet-derived growth factor receptor (PDGFR) and Abl are hypothesized to contribute to the fibrosis and vasculopathy of the skin and internal organs. Herein we describe 2 patients with early diffuse cutaneous SSc (dcSSc) who experienced reductions in cutaneous sclerosis in response to therapy with the tyrosine kinase inhibitor imatinib mesylate. Immunohistochemical analyses of skin biopsy specimens demonstrated reductions of phosphorylated PDGFR, and Abl with imatinib therapy. By gene expression profiling, an imatinib-responsive signature specific to dcSSc was identified (P < 10,8). The response of these patients and the findings of the analyses suggest that PDGFR, and Abl play critical, synergistic roles in the pathogenesis of SSc, and that imatinib targets a gene expression program that is frequently dysregulated in dcSSc. [source] Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brainGLIA, Issue 4 2009Ariane Sharif Abstract Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron,glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of erbB signaling in human astrocytes. We showed that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand-dependent activation of different erbB receptor heterodimeric complexes in these two populations of astrocytes translated into different morphological and proliferative responses. Although morphological plasticity was more pronounced in hypothalamic astrocytes than in cortical astrocytes, the former showed a lower mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene knockdown revealed that erbB4 constitutively restrains basal proliferative activity in hypothalamic astrocytes. We further show that treatment of human astrocytes with a protein kinase C activator results in rapid tyrosine phosphorylation of erbB receptors that involves cleavage of endogenous membrane bound erbB ligands by metalloproteinases. Together, these results indicate that erbB signaling in primary human brain astrocytes is functional, region-specific, and can be activated in a paracrine and/or autocrine manner. In addition, by revealing that some aspects of astroglial erbB signaling are different between human and rodents, our results provide a molecular framework to explore the potential involvement of astroglial erbB signaling deregulation in human brain disorders. © 2008 Wiley-Liss, Inc. [source] Wave functions derived from experiment.JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 4 2003Abstract The constrained Hartree,Fock method using experimental X-ray diffraction data is extended and applied to the case of noncentrosymmetric molecular crystals. A new way to estimate the errors in derived properties as a derivative with respect to added Gaussian noise is also described. Three molecular crystals are examined: ammonia [NH3], urea [CO(NH2)2], and alloxan [(CO)4(NH)2]. The energetic and electrical properties of these molecules in the crystalline state are presented. In all cases, an enhancement of the dipole moment is observed upon application of the experimental constraint. It is found that the phases of the structure factors are robustly determined by the constrained Hartree,Fock model, even in the presence of simulated noise. Plots of the electron density, electrostatic potential, and the electron localization function for the molecules in the crystal are displayed. In general, relative to the Hartree,Fock model, there is a depletion of charge around hydrogen atoms and lone pair regions, and a build-up of charge within the molecular framework near nuclei, directed along the bonds. The electron localization function plots reveal an increase in the pair density between vicinal hydrogen atoms. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 470,483, 2003 [source] New insights into the nature of Warthin's tumourJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2009Iain David O'Neill Warthin's tumour is considered heterogeneous as to its pathogenesis with some data supporting a polyclonal origin for the epithelium, implying a non-neoplastic nature. After inconsistent reports, current information from molecular studies suggests that a recurrent t(11;19) and associated CRTC1-MAML2 fusion oncogene characterizes a subset of Warthin's tumours and supports a clonal origin in such cases. CRTC1-MAML2 is also a frequent feature of mucoepidermoid carcinoma. These findings, and the recent reports of Warthin's tumour and co-existent mucoepidermoid carcinoma with common CRTC1-MAML2 expression, provide a morphological and molecular framework for future studies as a basis for a fresh appraisal of the pathogenesis of Warthin's tumour. The underlying molecular basis and the pivotal studies defining such events are discussed. [source] Foldon-guided self-assembly of ultra-stable protein fibersPROTEIN SCIENCE, Issue 9 2008Anshul Bhardwaj Abstract A common objective in protein engineering is the enhancement of the thermodynamic properties of recombinant proteins for possible applications in nanobiotechnology. The performance of proteins can be improved by the rational design of chimeras that contain structural elements with the desired properties, thus resulting in a more effective exploitation of protein folds designed by nature. In this paper, we report the design and characterization of an ultra-stable self-refolding protein fiber, which rapidly reassembles in solution after denaturation induced by harsh chemical treatment or high temperature. This engineered protein fiber was constructed on the molecular framework of bacteriophage P22 tail needle gp26, by fusing its helical core to the foldon domain of phage T4 fibritin. Using protein engineering, we rationally permuted the foldon upstream and downstream from the gp26 helical core and characterized gp26-foldon chimeras by biophysical analysis. Our data demonstrate that one specific protein chimera containing the foldon immediately downstream from the gp26 helical core, gp26(1-140)-F, displays the highest thermodynamic and structural stability and refolds spontaneously in solution following denaturation. The gp26-foldon chimeric fiber remains stable in 6.0 M guanidine hydrochloride, or at 80°C, rapidly refolds after denaturation, and has both N and C termini accessible for chemical/biological modification, thereby representing an ideal platform for the design of self-assembling nanoblocks. [source] Hydrogen bonding and ,,, interactions in 1-benzofuran-2,3-dicarboxylic acid and its 1:1 cocrystals with pyridine, phenazine and 1,4-phenylenediamineACTA CRYSTALLOGRAPHICA SECTION C, Issue 12 2009Hatem M. Titi The structure of 1-benzofuran-2,3-dicarboxylic acid (BFDC), C10H6O5, (I), exhibits an intramolecular hydrogen bond between one ,COOH group and the other, while the second carboxyl function is involved in intermolecular hydrogen bonding to neighbouring species. The latter results in the formation of flat one-dimensional hydrogen-bonded chains in the crystal structure, which are ,,, stacked along the normal to the plane of the molecular framework, forming a layered structure. 1:1 Cocrystallization of BFDC with pyridine, phenazine and 1,4-phenylenediamine is associated with H-atom transfer from BFDC to the base and charge-assisted hydrogen bonding between the BFDC, monoanion and the corresponding ammonium species, while preserving, in all cases, the intramolecular hydrogen bond between the carboxyl and carboxylate functions. The pyridinium 2-carboxylato-1-benzofuran-3-carboxylic acid, C5H6N+·C10H5O5,, (II), and phenazinium 3-carboxylato-1-benzofuran-2-carboxylic acid, C12H9N2+·C10H5O5,, (III), adducts form discrete hydrogen-bonded ion-pair entities. In the corresponding crystal structures, the two components are arranged in either segregated or mixed ,,, stacks, respectively. On the other hand, the structure of 4-aminoanilinium 2-carboxylato-1-benzofuran-3-carboxylic acid, C6H9N2+·C10H5O5,, (IV), exhibits an intermolecular hydrogen-bonding network with three-dimensional connectivity. Moreover, this fourth structure exhibits induction of supramolecular chirality by the extended hydrogen bonding, leading to a helical arrangement of the interacting moieties around 21 screw axes. The significance of this study is that it presents the first crystallographic characterization of pure BFDC, and manifestation of its cocrystallization with a variety of weakly basic amine molecules. It confirms the tendency of BFDC to preserve its intramolecular hydrogen bond and to prefer a monoanionic form in supramolecular association with other components. The aromaticity of the flat benzofuran residue plays an important role in directing either homo- or heteromolecular ,,, stacking in the first three structures, while the occurrence of a chiral architecture directed by multiple hydrogen bonding is the dominant feature in the fourth. [source] Synthesis and antimicrobial activities of sulfonohydrazide-substituted 8-hydroxyquinoline derivative and its oxinatesAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 5 2010Ritu B. Dixit Abstract Looking at the pharmacological importance of 8-hydroxyquinolines and sulfonamides, in the present study, a novel bi-dentate ligand 4-amino- N,-[(8-hydroxyquinoline-5-yl)methyl] benzenesulfonohydrazide (AHQMBSH) having above both moieties within a single molecular framework was synthesized by the reaction of N -acetamidobenzene sulfonohydrazide with 5-chloromethyl-8-hydroxyquinoline hydrochloride. Its metal(II) oxinates were also prepared with Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) salts. All the above compounds were investigated by physicochemical analyses, thermogravimetric analysis and spectroscopic techniques. Antimicrobial activities for the above prepared compounds were carried out using the agar-plate method against various strains of bacteria (Staphylococcus aureus, Bacillus subtillis, Pseudomonas aerugionsa, Escherichia coli) and fungi (Aspergillus niger and Aspergillus flavous). The results show a significant increase in antimicrobial and antifungal activities of AHQMBSH compared with the parent 8-hydroxyquinoline and sulfonamides. Copyright © 2010 John Wiley & Sons, Ltd. [source] Insight into the free-radical-scavenging mechanism of hydroxyl-substituent Schiff bases in the free-radical-induced hemolysis of erythrocytesCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2007You-Zhi Tang Abstract This work aimed to explore the mechanism by which hydroxyl-substituent Schiff bases scavenge free-radicals. Thus, four Schiff bases, that is benzylidene aniline (BAN), 2-(phenyliminomethyl)phenol (BAH), 4-benzimidoylphenol (PBH) and 2-benzimidoylphenol (OBH), were applied to protect human erythrocytes against 2,2,-azobis(2-amidinopropane hydrochloride) (AAPH)-induced hemolysis. The results revealed that the OH attached to the ortho -position of methylene in Schiff base scavenges 1.46 radicals per molecule, the OH attached to the para -position of the N atom scavenges 2.94 radicals and the OH attached to the ortho -position of the N atom scavenges 3.63 radicals. In addition, four Schiff bases were used together with some familiar antioxidants, such as 6-hydroxyl-2,5,7,8-tetramethyl chroman-2-carboxylic acid (Trolox), L -ascorbic acid (VC), ,-tocopherol (TOH) and L -ascorbyl-6-laurate (VC-12) in AAPH-induced hemolysis of erythrocytes. It was found that, except for BAN+VC-12, BAH,+,VC-12, OBH,+,VC-12 and PBH+TOH, all the other combinations protected erythrocytes more perfectly than when used individually. This result demonstrated that a promotive protection existed between Schiff base and other antioxidants and this improved their ability to scavenge free-radicals. Finally, IC50 values of the aforementioned Schiff bases together with 2-((o -hydroxylphenylimino) methyl)phenol (OSAP) and 2-((p -hydroxylphenylimino)methyl)phenol (PSAP) were determined by reaction with two radical species, that is, 2,2,-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical (ABTS+·) and 2,2,-diphenyl-1-picrylhydrazyl (DPPH). The results implied that the molecular framework of a Schiff base and an OH attached to the ortho -position of methylene were apt to reduce radicals, but the OH attached to the aniline ring in a Schiff base was prone to scavenge radicals directly. Copyright © 2006 John Wiley & Sons, Ltd. [source] Fluorophores as Optical Sensors for Local Forces,CHEMPHYSCHEM, Issue 12 2009Stefan Marawske Abstract The main aim of this study is to investigate correlations between the impact of an external mechanical force on the molecular framework of fluorophores and the resultant changes in their fluorescence properties. Taking into account previous theoretical studies, we designed a suitable custom-tailored oligoparaphenylenevinylene derivative (OPV5) with a twisted molecular backbone. Thin foils made of PVC doped with 100 nM OPV were prepared. By applying uniaxial force, the foils were stretched and three major optical effects were observed simultaneously. First, the fluorescence anisotropy increased, which indicates a reorientation of the fluorophores within the matrix. Second, the fluorescence lifetime decreased by approximately 2.5,% (25 ps). Finally, we observed an increase in the emission energy of about 0.2,% (corresponding to a blue-shift of 1.2 nm). In addition, analogous measurements with Rhodamine 123 as an inert reference dye showed only minor effects, which can be attributed to matrix effects due to refractive index changes. To relate the observed spectroscopic changes to the underlying changes in molecular properties, quantum-chemical calculations were also performed. Semiempirical methods had to be used because of the size of the OPV5 chromophore. Two conformers of OPV5 (C2 and Cisymmetry) were considered and both gave very similar results. Both the observed blue-shift of fluorescence and the reduced lifetime of OPV5 under tensile stress are consistent with the results of the semiempirical calculations. Our study proves the feasibility of fluorescence-based local force probes for polymers under tension. Improved optical sensors of this type should in principle be able to monitor local mechanical stress in transparent samples down to the single-molecule level, which harbors promising applications in polymer science and nanotechnology. [source] | ||||||||||||||||