A β-amino acid modified heptapeptide containing a designed recognition element disrupts fibrillization of the amyloid β-peptide

We study the complex formation of a peptide betaAbetaAKLVFF, previously developed by our group, with Abeta(1–42) in aqueous solution. Circular dichroism spectroscopy is used to probe the interactions between betaAbetaAKLVFF and Abeta(1–42), and to study the secondary structure of the species in solution. Thioflavin T fluorescence spectroscopy shows that the population of fibers is higher in betaAbetaAKLVFF/Abeta(1–42) mixtures compared to pure Abeta(1–42) solutions. TEM and cryo-TEM demonstrate that co-incubation of betaAbetaAKLVFF with Abeta(1–42) causes the formation of extended dense networks of branched fibrils, very different from the straight fibrils observed for Abeta(1–42) alone. Neurotoxicity assays show that although betaAbetaAKLVFF alters the fibrillization of Abeta(1–42), it does not decrease the neurotoxicity, which suggests that toxic oligomeric Abeta(1–42) species are still present in the betaAbetaAKLVFF/Abeta(1–42) mixtures. Our results show that our designed peptide binds to Abeta(1–42) and changes the amyloid fibril morphology. This is shown to not necessarily translate into reduced toxicity.

Application of interpolymer complexation to coat solid and soft surfaces

Water-soluble polymers are often capable of forming interpolymer complexes in solutions and at interfaces, which offers an excellent opportunity for surface modification. The complex formation may be driven by H-bonding between poly(carboxylic acids) and non-ionic polymers or by electrostatic attraction between oppositely-charged polyelectrolytes. In the present communication the following applications of interpolymer complexation in coating technologies will be considered: (1) Complexation between poly(acrylic acid) and non-ionic polymers via H-bonding was used to coat glass surfaces. It was realised using layer-by-layer deposition of IPC on glass surfaces with subsequent cross-linking of dry multilayers by thermal treatment. Depending on the glass surface functionality this complexation resulted in detachable and non-detachable hydrogel films; (2) Electrostatic layer-by-layer self-assembly between glycol chitosan and bovine serum albumin (BSA) was used to coat magnetic nanoparticles. It was demonstrated that the native structure of BSA remains unaffected by the self-assembling process.

Rigid ferrocenophane and its metal complexes with transition and alkaline-earth metal ions

The rigid [6]ferrocenophane, L-1, was synthesised by condensation of 1,1'-ferrocene dicarbaldehyde with trans-1,2-diaminocyclohexane in high dilution at r.t. followed by reduction. When other experimental conditions were employed, the [6,6,6]ferrocenephane (L-2) was also obtained. Both compounds were characterised by single crystal X-ray crystallography. The protonation of L-1 and its metal complexation were evaluated by the effect on the electron-transfer process of the ferrocene (fc) unit of L-1 using cyclic voltammetry (CV) and square wave voltammetry (SWV) in anhydrous CH3CN solution and in 0.1 M (Bu4NPF6)-Bu-n as the supporting electrolyte. The electrochemical process of L-1 between 300 and 900 mV is complicated by amine oxidation. On the other hand, an anodic shift from the fc/fc(+) wave of L-1 of 249, 225, 81 and 61 mV was observed by formation of Zn2+, Ni2+, Pd2+ and Cu2+ complexes, respectively. Whereas Mg2+ and Ca2+ only have with L-1 weak interactions and they promote the acid-base equilibrium of L-1. This reveals that L-1 is an interesting molecular redox sensor for detection of Zn2+ and Ni2+, although the kinetics of the Zn2+ complex formation is much faster than that of the Ni2+ one. The X-ray crystal structure of [(PdLCl2)-Cl-1] was determined and showed a square-planar environment with Pd(II) and Fe(II) centres separated by 3.781(1) angstrom. The experimental anodic shifts were elucidated by DFT calculations on the [(MLCl2)-Cl-1] series and they are related to the nature of the HOMO of these complexes and a four-electron, two-orbital interaction.

Optimizing layer-by-layer deposition of interpolymer complexes on solid substrates using Biacore

The layer-by-layer deposition of polymers onto surfaces allows the fabrication of multilayered materials for a wide range of applications, from drug delivery to biosensors. This work describes the analysis of complex formation between poly(acrylic acid) and methylcellulose in aqueous solutions using Biacore, a surface plasmon resonance analytical technique, traditionally used to examine biological interactions. This technique characterized the layer-by-layer deposition of these polymers on the surface of a Biacore sensor chip. The results were subsequently used to optimize the experimental conditions for sequential layer deposition on glass slides. The role of the solution pH and poly(acrylic acid) molecular weight on the formation of interpolymer multilayered coatings was researched, and showed that the optimal deposition of the polymer complexes was achieved at pHs ≤2.5 with a poly(acrylic acid) molecular weight of 450 kDa.

A Monte Carlo study of solutions of oppositely charged polyelectrolytes

The formation of complexes appearing in solutions containing oppositely charged polyelectrolytes has been investigated by Monte Carlo simulations using two different models. The polyions are described as flexible chains of 20 connected charged hard spheres immersed in a homogenous dielectric background representing water. The small ions are either explicitly included or their effect described by using a screened Coulomb potential. The simulated solutions contained 10 positively charged polyions with 0, 2, or 5 negatively charged polyions and the respective counterions. Two different linear charge densities were considered, and structure factors, radial distribution functions, and polyion extensions were determined. A redistribution of positively charged polyions involving strong complexes formed between the oppositely charged polyions appeared as the number of negatively charged polyions was increased. The nature of the complexes was found to depend on the linear charge density of the chains. The simplified model involving the screened Coulomb potential gave qualitatively similar results as the model with explicit small ions. Finally, owing to the complex formation, the sampling in configurational space is nontrivial, and the efficiency of different trial moves was examined.

Hsc70 is a novel interactor of NF-kappaB p65 in living hippocampal neurons

Signaling via NF-κB in neurons depends on complex formation with interactors such as dynein/dynactin motor complex and can be triggered by synaptic activation. However, so far a detailed interaction map for the neuronal NF-κB is missing. In this study we used mass spectrometry to identify novel interactors of NF-κB p65 within the brain. Hsc70 was identified as a novel neuronal interactor of NF-κB p65. In HEK293 cells, a direct physical interaction was shown by co-immunoprecipitation and verified via in situ proximity ligation in healthy rat neurons. Pharmacological blockade of Hsc70 by deoxyspergualin (DSG) strongly decreased nuclear translocation of NF-κB p65 and transcriptional activity shown by reporter gene assays in neurons after stimulation with glutamate. In addition, knock down of Hsc70 via siRNA significantly reduced neuronal NF-κB activity. Taken together these data provide evidence for Hsc70 as a novel neuronal interactor of NF-κB p65.

Microbiological profile of untreated subjects with localized aggressive periodontitis

Aim The microbial profile of localized aggressive periodontitis (LAgP) has not yet been determined. Therefore, the aim of this study was to evaluate the subgingival microbial composition of LAgP. Material and Methods One hundred and twenty subjects with LAgP (n=15), generalized aggressive periodontitis (GAgP, n=25), chronic periodontitis (ChP, n=30) or periodontal health (PH, n=50) underwent clinical and microbiological assessment. Nine subgingival plaque samples were collected from each subject and analysed for their content of 38 bacterial species using checkerboard DNA-DNA hybridization. Results Red complex and some orange complex species are the most numerous and prevalent periodontal pathogens in LAgP. The proportions of Aggregatibacter actinomycetemcomitans were elevated in shallow and intermediate pockets of LAgP subjects in comparison with those with GAgP or ChP, but not in deep sites. This species also showed a negative correlation with age and with the proportions of red complex pathogens. The host-compatible Actinomyces species were reduced in LAgP. Conclusion A. actinomycetemcomitans seems to be associated with the onset of LAgP, and Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Campylobacter gracilis, Eubacterium nodatum and Prevotella intermedia play an important role in disease progression. Successful treatment of LAgP would involve a reduction in these pathogens and an increase in the Actinomyces species.

Insulin temporal sensitivity and its signaling pathway in the rat pineal gland

Aims: In our previous work, we reported that the insulin potentiating effect on melatonin synthesis is regulated by a post-transcriptional mechanism. However, the major proteins of the insulin signaling pathway (ISP) and the possible pathway component recruited on the potentiating effect of insulin had not been characterized. A second question raised was whether windows of sensitivity to insulin exist in the pineal gland due to insulin rhythmic secretion pattern. Main methods: Melatonin content from norepinephrine(NE)-synchronized pineal gland cultures was quantified by high performance liquid chromatography with electrochemical detection and arylalkylamine-N-acetyltransferase (AANAT) activity was assayed by radiometry. Immunoblotting and immunoprecipitation techniques were performed to establish the ISP proteins expression and the formation of 14-3-3: AANAT complex, respectively. Key findings: The temporal insulin susceptibility protocol revealed two periods of insulin potentiating effect, one at the beginning and another one at the end of the in vitro induced ""night"". In some Timed-insulin Stimulation (TSs), insulin also promoted a reduction on melatonin synthesis, showing its dual action in cultured pineal glands. The major ISP components, such as IR beta, IGF-1R, IRS-1, IRS-2 and PI3K(p85), as well tyrosine phosphorylation of pp85 were characterized within pineal glands. Insulin is not involved in the 14-3-3:AANAT complex formation. The blockage of PI3K by LY 294002 reduced melatonin synthesis and AANAT activity. Significance: The present study demonstrated windows of differential insulin sensitivity, a functional ISP and the PI3K-dependent insulin potentiating effect on NE-mediated melatonin synthesis, supporting the hypothesis of a crosstalk between noradrenergic and insulin pathways in the rat pineal gland. (C) 2010 Elsevier Inc. All rights reserved.

Fibrinogen stability under surfactant interaction

Differential scanning calorimetry (DSC), circular dichroism (CD), difference spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering (SAXS) measurements have been performed in the present work to provide a quantitatively comprehensive physicochemical description of the complexation between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate, and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium perfluorooctanoate acts as a structure stabilizer at low molar concentration and as a destabilizer at high molar concentration. Fibrinogen`s secondary structure is affected by all three studied surfactants (decrease in alpha-helix and an increase in beta-sheet content) to a different extent. DSC and UV-vis revealed the existence of intermediate states in the thermal unfolding process of fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a paired-dimer structure in solution. Such a structure is unaltered by sodium octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with the fibrinogen affects the protein conformation leading to a complex formation. Taken together, all results evidence that both surfactant hydrophobicity and tail length mediate the fibrinogen stability upon interaction. (C) 2011 Elsevier Inc. All rights reserved.

Conformational Properties of Angiotensin II and Its Active and Inactive TOAC-Labeled Analogs in the Presence of Micelles. Electron Paramagnetic Resonance, Fluorescence, and Circular Dichroism Studies

The interaction between angiotensin II (AII, DRVYIHPF) and its analogs carrying 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) and detergents-negatively charged sodium dodecyl sulfate (SDS) and zwitterionic N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS)-was examined by means of EPR, CD, and fluorescence. EPR spectra of partially active TOAC(1)-AII and inactive TOAC(3)-AII in aqueous solution indicated fast tumbling, the freedom of motion being greater at the N-terminus. Line broadening occurred upon interaction with micelles. Below SDS critical micelle concentration, broader lines indicated complex formation with tighter molecular packing than in micelles. Small changes in hyperfine splittings evinced TOAC location at the micelle-water interface. The interaction with anionic micelles was more effective than with zwitterionic micelles. Peptide-micelle interaction caused fluorescence increase. The TOAC-promoted intramolecular fluorescence quenching was more, pronounced for TOAC(3)-AII because of the proximity between the nitroxide and Tyr(4). CD spectra showed that although both AII and TOAC(1)-AII presented flexible conformations in water, TOAC(3)-AII displayed conformational restriction because of the TOAC-imposed bend (Schreier et al., Biopolymers 2004, 74, 389). In HPS, conformational changes were observed for the labeled peptides at neutral and basic pH. In SDS, all peptides underwent pH-dependent conformational changes. Although the spectra suggested similar folds for All and TOAC(1)-AII, different conformations were acquired by TOAC(3)-AII. The membrane environment has been hypothesized to shift conformational equilibria so as to stabilize the receptor-bound conformation of ligands. The fact that TOAC(3)-AII is unable to acquire conformations similar to those of native AII and partially active TOAC(1)-AII is probably the explanation for its lack of biological activity. (C) 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 525-537, 2009.

Improvement of the oral praziquantel anthelmintic effect by cyclodextrin complexation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dynamics and Heterogeneity of Pb(II) Binding by SiO2 Nanoparticles in an Aqueous Dispersion

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Natal como destino turístico : um estudo das imagens (re)veladas pela mídia, pelos turistas e suas implicações educacionais e culturais

This thesis is a result of a research on Natal/RN as a tourist destination. We understand that cities are chosen as tourist destinations beyond its cartographic localization, from other dimensions of meanings that, in its set, constitute images. These images are, probably, very different of the images constructed by native and resident populations, who possess relations of identity with the place. The knowledge of the meanings that others attribute to this city as tourist destination, bring us near to the symbolic bonds established by individuals or social groups on the act of their choices, as well as bring us near to the interaction process city-tourists where the expectations are confirmed or not. The images divulgated by the media also participate of the complex formation of the tourist image that is being constructed and available for the different public, in different social contexts. The tourism constitutes a symbolic asset of the modern society, being considered by the studious, as one of the most expressive phenomena of the modernity, for involving each year displacement and the interaction of thousand of people of different cultures in the entire world. All this people s mobilization points to practical social related to personal motivations, to the entailed desired to the idea to travel and to exceed borders. It is already consensus that tourism is a phenomenon of economic growth, generating jobs, income, professional, qualification, bringing improvements for the host cities. Since 1995, in Brazil, the tourism as a sector of the economy, passed to be considered one of the national priorities, and in this perspective, the national politics of the tourism invested in infrastructure of Brazilian cities with high tourist potential, objecting to increase the flows of Brazilian and foreign tourists. Owing to this fact, the country still invests in programs of tourist marketing, mainly divulging the images of the natural beauties of Brazil abroad. And for Brazilians, the campaigns appeal to rescue the feeling to be Brazilian, associating the idea to travel and know its country. Natal city possesses an excellent positioning in the tourist marketing, being predominantly divulgated in national and international level, for its naturalistic singularity, where the images of its natural enchantments as warm water beaches, white dunes, warm weather, constant breeze and an always blue sky are shown as the favorite scene on this city. From what was viewed above that the choice of a tourist destination articulates from a determined imaginary of a place, already constructed or in process of construction, we consider the knowledge of this imaginary a basic learning for the population of the city and especially, for educators, in the formation of professionals in this area and for tourism managers, elaborators of public politics. Based on this estimative, we developed this research that had as a general objective to identify the images that illustrate Natal city as a tourist destination - our objective of study, particularly the meanings and senses attributed by the tourist marketing (hotel s folders) and by the tourists that visited the city during this study. The discussions and reflections that had guided this research had been given from the theoretical link between imaginary and social representation, also considering some interfaces between the fields of communication and symbol. From the studied authors, Baczko (1985) clarifies that the study of social imaginary is directed for the mechanisms and structures of the social life, especially for the intervention accomplishes and efficient of the representations and symbols in the practical collectives, as well as in its direction and orientation . Following this same thought, Moscovici (1978) says that the social representation are produced in communicational and symbolic contexts, and these representations once that already constituted circulate socially as almost tangible entities. Based on this fundament and on the analyze of Barthes (1990), particularly in the approach given to the reading of photographic image, we could observe on hotel s folders that each page evidences senses and meanings of functionality of internal and external spaces, pointing to the way of leisure offered by the keepers of city which is the hotels. About, the leisure that they offer, it is directed to young public, giving meaning to the young myth of personalized leisure tourism on children, young and adults images. The image about security that hotels offer and the singular image of Natal city as a paradise place, provide an idealization of pleasure through the sun, dunes, and beaches and also due to the hospitability of the natives who are assigned as educated . For the tourist that participated on this research, Natal city is tied only by the imaginary of leisure and nature which constitute the emotional link of the relation media-city-tourist. And with such force and fullness of directions the city discloses without tensions and contradictions as a place protected by a mythical and sacred aura. The study also demonstrates us that the potiguar culture remains (almost) forgotten, due to the silenced in this imaginary. In this perspective, we highlight that this culture silence is very close related to the disvalue of education in its general meaning. We defend that the imaginary apprehended constitutes a new reading and a new looking and understanding the tourist reality that comes historically consolidating in this city. In this direction, we glimpse that this study and its future dismemberments can collaborate with the process of rescue the cultural values of the potiguar people, in the way that the meaning of tourist may be redefined, and the tourist image of the city can be also disclosed for its identities particularities of its culture

Structural and functional evidence that a B chromosome in the characid fish Astyanax scabripinnis is an isochromosome

Astyanax scabripinnis possesses a widespread polymorphism for metacentric B chromosomes as large as the largest chromosome pair in the A complement. on the basis of C-banding pattern, it was hypothesized that these B chromosomes are isochromosomes that have arisen by means of centromere misdivision and chromatid nondisjunction. In the present paper we test this hypothesis by analysing (i) the localization of a repetitive DNA sequence on both B chromosome arms, and (ii) synaptonemal complex formation, in order to test the functional homology of both arms. Genomic DNA digested with KpnI and analysed by gel electrophoresis showed fragments in a ladder-like pattern typical of tandemly repetitive DNA. These fragments were cloned and their tandem organization in the genome was confirmed. A 51-bp long consensus sequence, which was AT-rich (59%) and contained a variable region and two imperfect reverse sequences, was obtained. Fluorescence in situ hybridization (FISH) localized this repetitive DNA into noncentromeric constitutive heterochromatin which encompasses the terminal region of some acrocentric chromosomes, the NOR region, and interstitial polymorphic heterochromatin in chromosome 24. Most remarkably, tandem repeats were almost symmetrically placed in the two arms of the B chromosome, with the exception of two additional small clusters proximally located on the slightly longer arm. Synaptonemal complex (SC) analysis showed 26 completely paired SCs in males with 1B. The ring configuration of the B univalent persisting until metaphase I suggests that the two arms formed chiasmata. All these data provided strong support for the hypothesis that the B chromosome is an isochromosome.

A ousadia como horizonte: religando vida e ideias na formação em enfermagem

A proposal of formation in health/nursing built on classic science, on reducing thought and flexnerian paradigm is insufficient to comprehend and intervening with an amplified way on health needs of population, given that it is produced by fragmentation of knowledge, rationalization of thought, mechanizing and biological attitudes. It is necessary that formation in health/nursing allows the construction of effectiveness of principles and guidelines of Unique System of Health (Sistema Único de Saúde - SUS). In this context of emergency of a complex formation in health/nursing, life trajectories and formation of the nurses: Abigail Moura, Francisca Valda and Raimunda Germano are examples of transgressor and successful experiences which allow inquietude, changing and transforming formation patterns and self-formation. The present study is built from the comprehension of method as strategy , defended by Morin and complexity sciences. Has as objects building biographies of formation of these three nurses who express a formation model more totalizing and humanitarian, analyzing and discussing starting from the three biographic fragments guiding principles for the current process of formation in health/nursing. From the biographies, the courage and humbleness emerge as landmarking principles of their experiences. Humbleness neither as self-depreciation nor humiliation but as consciousness of our uncompleted and unfinished essence, acceptance of boundaries and potential and reduction of intellectual vanity. Courage, for its part, is the human pulsing, uncertain for nature, which brings us to act, to face and persevere on moments of fear and difficulties. A formation in health and nursing based on courage and humbleness allows the subjects to be taken away from indifference, arrogance, inertia, pragmatism: bets on ethic and political subjects capable of minimizing unequal, inhumane and excluding processes. Na intellectual and Professional attitude which politizes the thought and science is what must be expected from a complex formation in health field, in latu mode on nursing, in particular