Computational selection of inhibitors of Abeta aggregation and neuronal toxicity.

Alzheimer's disease (AD) is characterized by the cerebral accumulation of misfolded and aggregated amyloid-beta protein (Abeta). Disease symptoms can be alleviated, in vitro and in vivo, by 'beta-sheet breaker' pentapeptides that reduce plaque load. However the peptide nature of these compounds, made them biologically unstable and unable to penetrate membranes with high efficiency. The main goal of this study was to use computational methods to identify small molecule mimetics with better drug-like properties. For this purpose, the docked conformations of the active peptides were used to identify compounds with similar activities. A series of related beta-sheet breaker peptides were docked to solid state NMR structures of a fibrillar form of Abeta. The lowest energy conformations of the active peptides were used to design three dimensional (3D)-pharmacophores, suitable for screening the NCI database with Unity. Small molecular weight compounds with physicochemical features and a conformation similar to the active peptides were selected, ranked by docking and biochemical parameters. Of 16 diverse compounds selected for experimental screening, 2 prevented and reversed Abeta aggregation at 2-3microM concentration, as measured by Thioflavin T (ThT) fluorescence and ELISA assays. They also prevented the toxic effects of aggregated Abeta on neuroblastoma cells. Their low molecular weight and aqueous solubility makes them promising lead compounds for treating AD.

Calcium carbonate, biogenic opal, and organic carbon content and d15N ratios of sediments from the Bering Sea

Millennial-scale paleoceanographic changes in the Bering Sea during the last 71 kyrs were reconstructed using geochemical and isotope proxies (biogenic opal, CaCO3, and total organic carbon (TOC), nitrogen and carbon isotopes of sedimentary organic matters) and microfossil (radiolaria and foraminifera) data from two cores (PC23A and PC24A) which were collected from the northern continental slope area at intermediate water depths. Biogenic opal and TOC contents were generally high with high sedimentation rates during the last deglaciation. Laminated sediment depositions during the Early-Holocene (EH) and Bølling-Allerød (BA) were closely related with the increased primary productivity recorded by high biogenic opal and TOC contents and high d15N values. Enhanced surface-water productivity was attributed to increased nutrient supply from strengthened Bering Slope Current (BSC) and from increased amount of glacial melt-water, resulting in high C/N ratios and low d13C values, and high proportion of Rhizoplegma boreale during the last deglaciation. In contrast, low surface-water productivity during the last glacial period was due to depleted nutrient supply caused by strong stratification and to restricted phytoplankton bloom by extensive sea ice distribution under cold climates. Extensive formation of sea ice produces more oxygen-rich intermediate-water, leading to oxic bottom-water conditions due to active ventilation, which favored good preservation of oxic benthic foraminifera species. Remarkable CaCO3 peaks coeval with high biogenic opal and TOC contents in both cores during MIS 3 to MIS 4 are most likely correlated with Dansgaard-Oeschger (D-O) events. High d15N and d13Corg values during D-O interstadials support increased surface-water productivity resulting from nutrients supplied mainly by intensified BSC. During the EH, BA and D-O interstadials, dominant benthic foraminifera species indicate dysoxic bottom-water conditions as a result of increased surface-water productivity and weak ventilation of intermediate-water with mitigated sea ice development caused by strengthening of the Alaskan Stream. It is of note that the bottom-water conditions and formation of intermediate-water in the Bering Sea during the last glacial period are related to the variation of dissolved oxygen concentration of the bottom-water in the northeastern Pacific and to strong ventilation of intermediate-water in the northwestern Pacific. Thus, the millennial-scale paleoceanographic events in the Bering Sea during the D-O interstadials are closely associated with the intermediate-water ventilation, ultimately leading to weakening of North Pacific Intermediate Water.

Using molecular markers to assess the effect of introgression on quantitative attributes of common bean in the Andean gene pool

Progress in bean breeding programs requires the exploitation of genetic variation that is present among races or through introgression across gene pools of Phaseolus vulgaris L. Of the two major common bean gene pools, the Andean gene pool seems to have a narrow genetic base, with about 10% of the accessions in the CIAT core collection presenting evidence of introgression. The objective of this study was to quantify the degree of spontaneous introgression in a sample of common bean landraces from the Andean gene pool. The effects of introgression on morphological, economic and nutritional attributes were also investigated. Homogeneity analysis was performed on molecular marker data from 426 Andean-type accessions from the primary centres of origin of the CIAT common bean core collection and two check varieties. Quantitative attribute diversity for 15 traits was studied based on the groups found from the cluster analysis of marker prevalence indices computed for each accession. The two-group summary consisted of one group of 58 accessions (14%) with low prevalence indices and another group of 370 accessions (86%) with high prevalence indices. The smaller group occupied the outlying area of points displayed from homogeneity analysis, yet their geographic origin was widely distributed over the Andean region. This group was regarded as introgressed, since its accessions displayed traits that are associated with the Middle American gene pool: high resistance to Andean disease isolates but low resistance to Middle American disease isolates, low seed weight and high scores for all nutrient elements. Genotypes generated by spontaneous introgression can be helpful for breeders to overcome the difficulties in transferring traits between gene pools.

Screening Anal Dysplasia in HIV-Infected Patients: Is There an Agreement Between Anal Pap Smear and High-Resolution Anoscopy-Guided Biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system (""without dysplasia"" and ""with dysplasia of any grade""). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

The Kinin System in Patients with Systemic Lupus Erythematosus Exhibiting Mucocutaneous Lesions: A Clinical Study

In the present study, we evaluated the kinin system components in the plasma of patients with systemic lupus erythematosus exhibiting mucocutaneous lesions. Fifteen women with active cutaneous lupus (P) and 15 normal healthy women (C) were studied. Low molecular (LKg) and high molecular (HKg) weight kininogen were determined by ELISA (expressed mu g Bk/ml). The activities of tissue kallikrein (TKal), plasma kallikrein (PKal) and kininase II were assayed by their action on selective substrates. Statistical analysis was performed using the Mann-Whitney test. The patients presented increased plasma levels of LKg (P = 2.98, C = 0.79) and HKg (P = 1.78, C = 0.5) associated with the increased activity of PKal (P = 2.50, C = 1.63 U/ml), TKal (P = 1.87, C = 1.30 mu M pNa/ml) and kininase II (P = 1.50, C = 0.51 mu M Hys-Leu/ml), when compared to the values observed in the control group (P < 0.0001 for each comparison). Thus, the increased concentration of all parameters of the kinin system in these patients indicate an overactivity of the kinin system in the acute phase of lupus, corroborating with the participation of these mediators in lupus pathogenesis.

Improving the prediction of plant species distribution and community composition by adding edaphic to topo-climatic variables

Questions Soil properties have been widely shown to influence plant growth and distribution. However, the degree to which edaphic variables can improve models based on topo-climatic variables is still unclear. In this study, we tested the roles of seven edaphic variables, namely (1) pH; (2) the content of nitrogen and of (3) phosphorus; (4) silt; (5) sand; (6) clay and (7) carbon-to-nitrogen ratio, as predictors of species distribution models in an edaphically heterogeneous landscape. We also tested how the respective influence of these variables in the models is linked to different ecological and functional species characteristics. Location The Western Alps, Switzerland. Methods With four different modelling techniques, we built models for 115 plant species using topo-climatic variables alone and then topo-climatic variables plus each of the seven edaphic variables, one at a time. We evaluated the contribution of each edaphic variable by assessing the change in predictive power of the model. In a second step, we evaluated the importance of the two edaphic variables that yielded the largest increase in predictive power in one final set of models for each species. Third, we explored the change in predictive power and the importance of variables across plant functional groups. Finally, we assessed the influence of the edaphic predictors on the prediction of community composition by stacking the models for all species and comparing the predicted communities with the observed community. Results Among the set of edaphic variables studied, pH and nitrogen content showed the highest contributions to improvement of the predictive power of the models, as well as the predictions of community composition. When considering all topo-climatic and edaphic variables together, pH was the second most important variable after degree-days. The changes in model results caused by edaphic predictors were dependent on species characteristics. The predictions for the species that have a low specific leaf area, and acidophilic preferences, tolerating low soil pH and high humus content, showed the largest improvement by the addition of pH and nitrogen in the model. Conclusions pH was an important predictor variable for explaining species distribution and community composition of the mountain plants considered in our study. pH allowed more precise predictions for acidophilic species. This variable should not be neglected in the construction of species distribution models in areas with contrasting edaphic conditions.

Benthos of Spanish lakes and reservoirs

A summary of the results from the study of benthos of lakes and reservoirs in Spain is provided, with a list of the species found to date. Spanish natural lakes are smaller than European lakes; the largest is Lake Sanabria, of glacial origin, which is 3 Km long and half a kilorneter wide. Many are very small and situated in the mountains; more than 200 hundred have been recorded in Spain, but only in Lake Sanabria and Lake Banyoles have the benthos been studied. Lake Sanabria is a cold oligotrophic, monomictic lake with oxygen always present in the deepest zones. Its fauna is similar to that of other central European lakes, with Mici.opsectra c.orztractu (a chironomid) as the dominan1 species. Lake Banyoles is a karstic, monomictic and multibasin lake; despite the low primary productivity, due to the abundante of sulphate in the water, the allochthonous inflow of organic matter and the inflow of water from bottom springs, the profunda1 environinent is very stressing for benthic fauna. Very low oxygen concentrations and high sulphide content in the water and sediments dueto meromixis mean that only the larva of the dipteran Chaohoi.lcs flai7icans was present in one of the 5 basins of the lake. In other basins, when oxygen is available (no meromixis), the fauna is similar to that of tlie inineralized lakes of the Aegean region and some lakes in central Italia. On the other hand, preliminary data from the Pyrenean lakes and from Sierra Nevada ponds reveal no differences with northern cold lakes. Tlie largest lakes in Spain are the reservoirs. There are nearly 1000 and data are available on 100 of them, including the kargest. In addition to oxygen and sulphide content in the bottom waters, water level fluctuation and high sedimentation rates are disturbance factors that prevented the organization of the community. Allochthonous inputs of organic matter are also an important factor both in the reservoirs and also in the small, oligotrophic lakes like Banyoles and Sanabria. As a result the meiofaunal loop is very important in many of the Spanish water bodies . For this reason the natural lakes and reservoirs of Spain are dominated by Oligochaeta, small crustaceans and the microcarnivore chironomids (such as Procladi~ls, Cladopelma and Mi(,rnc.hil-onnmus) that feed on these meoifaunal elements. The phytophagous chironomids, like Chironomus, are only abundan1 in the shallow areas of mesotrophic and eutrophic reservoirs. This situation makes it difficult to apply the typological system of SAETHER which predicts with some confidence only the benthic communities of Spanish natural lakes above 1500 m in the Pyrenees or the ponds above 2000 m in Sierra Nevada mountains. Higher temperatures (which originate a longer stratification period), the presence of sulphate in the waters of the eastern part of Spain and high inputs of sediments and allochthonous organic matter seem to be the factors that originated the differences between the benthic profunda1 faunas of Spanish lakes and reservoirs and those of the temperate lakes of north and central Europe.

Imobilização e caracterização de lacase e seu uso na biodegradação de efluentes de indústrias papeleiras

Laccase from Aspergillus sp was immobilized on glutaraldehyde-activated chitosan beads. A comparative study between free and immobilized laccase was conducted and the potential of the resulting immobilized derivative in the biodegradation of pulp and paper mill effluent was evaluated. The immobilized laccase is more resistant to various denaturing conditions, which allows for the reduction of 65% of the phenols (total and low molecular weight) and loss of 60% of total color in the effluent. These results show the potential of the immobilized laccase in the biodegradation of phenols, the chemical agents responsible for the high toxicity of the effluent generated in cellulose pulp industries.

Chemical quality parameters and bioactive compound content of brazilian berries

There is a growing consumer demand for higher healthy foods such as berries which are a rich source of phenolic compounds. The current work evaluated blackberry cultivars: Cherokee, Tupy and Xavante; raspberry cultivars: Heritage, Fallgold and Black; and the hybrid Boysenberry. All berries were grown under homogenous subtropical conditions in Brazil. Black raspberry, Cherokee and Tupy blackberry cultivars showed the highest ratio between soluble solid contents and titratable acidity, and Fallgold and Heritage raspberry showed the highest titratable acidity. Total phenolic content ranged from 2.03 to 5.33 g kg–1 fresh weight and total anthocyanin content registered values from 0.41 to 1.81 g kg–1 fresh weight. The most common phenolic acids were gallic, p-coumaric and ellagic, and for anthocyanins: cyanidin-3-glucoside and malvinidin-3-glucoside. Antioxidant capacity ranged from 14.13 to 21.51 mol equivalent trolox kg–1 fresh weight. Black raspberry, all blackberry cultivars and the Boysenberry hybrid are appropriate to be consumed fresh, while Fallgold and Heritage raspberries are recommended to the food industry. Due to their phenolic richness and antioxidant properties, these fruits are of great interest to the fresh fruit market and to pharmaceutical industries. These results could help breeders and growers when planning the cultivar selection according to their foreseeable destination.

Vacuum-ultraviolet photochemically initiated modification of polystyrene surfaces: morphological changes and mechanistic investigations

Vacuum-ultraviolet (VUV) irradiation (kexc: 172 ± 12 nm) of polystyrene films in the presence of oxygen produced not only oxidatively functionalized surfaces, but generated also morphological changes. Whereas OH- and C=O-functionalized surfaces might be used for e.g. secondary functionalization, enhanced aggregation or printing, processes leading to morphological changes open new possibilities of microstructurization. Series of experiments made under different experimental conditions brought evidence of two different reaction pathways: introduction of OH- and C=O-groups at the polystyrene pathways is mainly due to the reaction of reactive oxygen species (hydroxyl radicals, atomic oxygen, ozone) produced in the gas phase between the VUV-radiation source and the substrate. However, oxidative fragmentation leading to morphological changes, oxidation products of low molecular weight and eventually to mineralization of the organic substrate is initiated by electronic excitation of the polymer leading to C–C-bond homolysis and to a complex oxidation manifold after trapping of the C-centred radicals by molecular oxygen. The pathways of oxidative functionalization or fragmentation could be differentiated by FTIR-ATR analysis of irradiated polystyrene surfaces before and after washing with acetonitrile and microscopic fluorescence analysis of the surfaces secondarily functionalized with the N,N,N-tridodecyl-triaza-triangulenium (TATA) cation. Ozonization of the polystyrene leads to oxidative functionalization of the polymer surface but cannot initiate the fragmentation of the polymer backbone. Oxidative fragmentation is initiated by electronic excitation of the polymer (contact-mode AFM analysis), and evidence of the generation of intermediate C-centred radicals is given e.g. by experiments in the absence of oxygen leading to cross-linking (solubility effects, optical microscopy, friction-mode AFM) and disproportionation (fluorescence).

Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action.

Histological evaluation of chitosan-based biomaterials used for the correction of critical size defects in rat`s calvaria

Chitosan, a biopolymer obtained from chitin, and its derivates, such as chitosan hydrochloride, has been reported as wound healing accelerators and as possible bone substitutes for tissue engineering, and therefore these Substances could be relevant in dentistry and periodontology. The purpose of this investigation was to make a histological evaluation of chitosan and chitosan hydrochloride biomaterials (gels) used in the correction of critical size bone defects made in rat`s calvaria. Bone defects of 8 mm in diameter were surgically created in the calviria of 50 Holtzman (Rattus norvegicus) rats and filled with blood clot (control), low molecular weight chitosan, high molecular weight chitosan, low molecular weight chitosan hydrochloride, and high molecular weight chitosan hydrochloride, numbering 10 animals, divided into two experimental periods (15 and 60 days), for each biomaterial. The histological evaluation was made based on the morphology of the new-formed tissues in defect`s region, and the results indicated that there was no statistical difference between the groups when the new bone formation in the entire defect`s area were compared (p > 0.05) and, except in the control groups, assorted degrees of inflammation Could be Seen. In Conclusion, chitosan and chitosan hydrochloride biomaterials used in this study were not able to promote new bone formation in critical size defects made in rat`s calvaria. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 107-114, 2016

Histological evaluation of chitosan-based biomaterials used for the correction of critical size defects in rat's calvaria

Chitosan, a biopolymer obtained from chitin, and its derivates, such as chitosan hydrochloride, has been reported as wound healing accelerators and as possible bone substitutes for tissue engineering, and therefore these Substances could be relevant in dentistry and periodontology. The purpose of this investigation was to make a histological evaluation of chitosan and chitosan hydrochloride biomaterials (gels) used in the correction of critical size bone defects made in rat's calvaria. Bone defects of 8 mm in diameter were surgically created in the calviria of 50 Holtzman (Rattus norvegicus) rats and filled with blood clot (control), low molecular weight chitosan, high molecular weight chitosan, low molecular weight chitosan hydrochloride, and high molecular weight chitosan hydrochloride, numbering 10 animals, divided into two experimental periods (15 and 60 days), for each biomaterial. The histological evaluation was made based on the morphology of the new-formed tissues in defect's region, and the results indicated that there was no statistical difference between the groups when the new bone formation in the entire defect's area were compared (p > 0.05) and, except in the control groups, assorted degrees of inflammation Could be Seen. In Conclusion, chitosan and chitosan hydrochloride biomaterials used in this study were not able to promote new bone formation in critical size defects made in rat's calvaria. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 107-114, 2016

Desenvolvimento e aplicação de biomateriais à base de quitosana para reconstrução óssea: avaliação radiográfica e histológica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação do uso da casca do fruto e das folhas de Caesalpinia ferrea Martius como suplemento nutricional de Fe, Mn e Zn

As plantas medicinais podem ser usadas como fontes alternativas de nutrientes minerais na dieta alimentar. Elementos como ferro, manganês e zinco apresentam biodisponibilidade variável em função de suas formas químicas (espécies) presentes em um alimento. Este trabalho tem como objetivo avaliar o teor e a biodisponibilidade de ferro, manganês e zinco em extratos da casca do fruto e das folhas de Caesalpinia ferrea Martius por Espectrometria de Absorção Atômica com Chama (FAAS). Os agentes extratores testados foram as soluções de NaOH 0,05 mol. L^-1, tampão Tris-HCl 0,05 mol.L^-1 (pH= 8), tampão Tris-HCl 0,05 mol.L^-1 (pH = 8) em dodecil sulfato de sódio (SDS) 1% (m/v), HCl 0,05 mol.L^-1 e água quente (60 ºC). A casca do fruto e as folhas de Caesalpinia ferrea Martius apresentaram níveis altos de ferro e manganês quando comparados aos de outras plantas medicinais. Os elementos estudados mostraram predominante associação com compostos de alta e baixa massa molecular, espécies solúveis e insolúveis em água. Dentre os elementos analisados, o ferro apresentou melhor biodisponibilidade na casca do fruto e nas folhas. Manganês e zinco se mostraram mais biodisponível nas folhas. A casca do fruto e as folhas de Caesalpinia ferrea Martius podem ser uma fonte alternativa de ferro, manganês e zinco na dieta alimentar.