Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria

Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria.     

Tuning the electrochemistry of Re2(6+) species with divergent bicyclic guanidinate ligands and by modification of axial π interactions

Four Re(2)(6+) paddlewheel compounds with equatorial bicyclic guanidinate ligands and two monodentate anions in axial positions show a large change in the metal-metal distance that depends on the bite angle of the ligands and whether there are pi interactions between the dimetal unit and the axial ligands. These processes are accompanied by significant changes in the redox behavior. The two pairs of compounds that have been synthesized are Re(2)(tbn)(4)Cl(2), 1, and Re(2)(tbn)(4)(SO(3)CF(3))(2), 2, as well as Re(2)(tbo)(4)Cl(2), 3, and Re(2)(tbo)(4)(SO(3)CF(3))(2), 4, where tbn is the anion of a bicyclic guanidinate with six- and five-membered rings (1,5,7-triazabicyclo[4.3.0]non-6-ene) and tbo is an analogous species with two five-membered rings (the anion of 1,4,6-triazabicyclo[3.3.0]oct-4-ene). For both 1 and 2 as well as for 3 and 4, the metal-metal distances are shorter for the triflate species than for the chloride analogues because of the π interactions of the Cl with the π bonds of the triply bonded Re(2)(6+) cores compounded by a small but symmetry allowed interaction between the antisymmetric combination of the filled σp orbitals of the chlorine atom and the empty σ* orbital of the metal atoms. In addition there is a significant increase in the Re-Re distance from that in the six/five tbn-membered ring to the five/five-membered tbo species. Electrochemical measurements show two redox processes for each set of compounds corresponding to the uncommon Re(2)(6+) → Re(2)(7+) and Re(2)(7+) → Re(2)(8+) processes, which are strongly affected by the bite angle of the guanidinate ligand as well as the ability of the axial ligands to interact with the π orbitals of the dirhenium unit. For 1 and 3, the first redox couples are at 0.146 and 0.487 V, respectively, while for 2 and 4 these are at 0.430 and 0.698 V, respectively.     

Phenotypic Assays for β-Amyloid in Mouse Embryonic Stem Cell-Derived Neurons

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Informal Networks and Resistance to Organizational Change: The Introduction of Quality Standards in a Transport Company

In this paper we investigate the association between resistance to the introduction of ISO quality standards in a transport company and three effects of the informal advice and trust networks in the organization. The analysis includes four prevailing explanations from the literature on organizational resistance: job satisfaction, perceived legitimacy, unit grouping and decision making authority. The network effects we propose are: (a) a contagion effect, which predicts that members with the same opinion tend to have close or equal trust and advice relations; (b) a prominence effect, which predicts that prominent actors in the trust network show less resistance than other members—and that prominent members of the advice network show more resistance than less prominent actors; (c) a role equivalence effect, which predicts that members with the same patterns of combined trust/advice relations show the same resistance. The paper presents the operationalization and measurement of the variables and the results of three analyses to test the effects. Contagion of resistance appears to be very significant in the trust network. Resistance gradually erodes in the trust network when moving from management to employees. Members who are trusted in the transport company are significantly less resistant to the introduction of the quality standards than members who are not especially trusted. This network effect is controlled for the significant effects of job satisfaction and perceived legitimacy. The role equivalence structure of the combined trust/advice network does not explain the resistance. We conclude that informal networks have important effects on resistance to the proposed changes in the transport company. The case study shows how network analysis can be used to empirically test for effects of social relations in organizations.     

Synthesis,characterization, crystal structure and toxicity evaluation of Co (II), Cu (II), Mn (II), Ni (II), Pd (II) and Pt (II) complexes with Schiff base derived from 2-chloro-5-(trifluoromethyl)aniline

A bidentate NO donor Schiff base, 2-(((2-chloro-5- (trifluoromethyl)phenyl)imino)methyl) phenol ( HL ¹ ) and its complexes [Co(L¹)₂(H₂O)₂] ( 1 ), [Cu(L¹)₂] ( 2 ), [Mn(L¹)₂(H₂O)₂] ( 3 ), [Ni(L¹)₂(H₂O)₂] ( 4 ), [Pd₂(L¹)₂(OAc)₂·1.16H₂O] ( 5 ), [Pt(L¹)₂] ( 6 ) were synthesized and characterized by different physico-chemical techniques including elemental and thermal analysis, magnetic susceptibility measurements, molar electric conductivity, IR, ¹H-NMR, ¹³C-NMR, UV–Vis, mass spectroscopies and X-ray powder diffraction (XRD). The molecular structures of ligand HL ¹ and two complexes ( 2 and 5 ) were confirmed by X-ray crystallography analysis on the monocrystal. In this complexes, the metal ions are in distorted square-planar environments. The copper (II) complex is mononuclear and crystallized in a monoclinic space group P21/c, whereas palladium (II) complex is dinuclear and crystallized in the trigonal crystal system R-3. The toxicity of the ligand and complexes was evaluated on both plant and animal cells, using the plant species Triticum aestivum L. and the crustacean Artemia franciscana Kellogg. At concentrations up to 100 μM the compounds presented very little toxicity on Artemia franciscana Kellogg. Moreover, the palladium (II) complex was devoid of any toxicity on the plant cells.     

Comparative study of the behavior of carboxymethyl cellulose-g-poly(N-isopropylacrylamide) copolymers and their equivalent physical blends

A comparative study of the behavior of carboxymethyl cellulose and poly(N-isopropylacrylamide) (PNIPAM) as graft copolymers and physical blends, in solution and in solid state was accomplished by viscometry, turbidimetry, IR spectroscopy, X-ray diffraction, thermogravimetry, and enzymatic degradation. Both in diluted and concentrated solutions, the graft copolymers exhibited a thermothickening effect, while the corresponding mixtures of the two components exhibited an Arrhenius behavior. Solid phase investigations showed morphological differences between graft copolymers and their equivalent physical blends. The enzymatic degradation behavior is essentially similar both for copolymers and blends (enzymatic degradation activity has similar values) although a slight increased enzymatic activity was noticed for the graft copolymers in comparison with the blends.     

Structure and activity of LaMn1?yCoyO3 perovskites

Substituted LaMn_1−yCo_yO₃ perovskite-type oxides (0.0 ≤ y ≤ 1.0) prepared by the citrae method, have been investigated as catalysts in the total combustion of acetylacetate. The characterization results indicate that the catalytic activity is enhanced in the substituted perovskites. The most active is the one with y = 0.5.