Uncovering the Mechanism of Aggregation of Human Transthyretin.

The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, we designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy

Dyslipidaemia and Undernutrition in Children from Impoverished Areas of Maceió, State of Alagoas, Brazil

Chronic undernutrition causes reduced growth and endocrine adaptations in order to maintain basic life processes. In the present study, the biochemical profiles of chronically undernourished children were determined in order to test the hypothesis that chronic undernutrition also causes changes in lipid profile in pre-school children. The study population comprised 80 children aged between 12 and 71 months, including 60 with moderate undernutrition [height-for-age Z (HAZ) scores ≤ −2 and > −3] and 20 with severe undernutrition (HAZ scores ≤ −3). Socioeconomic, demographic and environmental data were obtained by application of a questionnaire, and anthropometric measurements and information relating to sex, age and feeding habits were collected by a trained nutritionist. Blood samples were analysed for haemoglobin, vitamin A, insulin-like growth factor 1 (IGF-1) and serum lipids, while cortisol was assayed in the saliva. Faecal samples were submitted to parasitological investigation. Analysis of variance and χ2 methods were employed in order to select the variables that participated in the multivariate logistic regression analysis. The study population was socioeconomically homogeneous, while the lack of a treated water supply was clearly associated with the degree of malnutrition. Most children were parasitised and anaemia was significantly more prevalent among the severely undernourished. Levels of IGF-1 decreased significantly with increasing severity of undernutrition. Lipid analysis revealed that almost all of the children had dyslipidemia, while low levels of high-density lipoprotein were associated with the degree of undernutrition. It is concluded that chronic malnutrition causes endocrine changes that give rise to alterations in the metabolic profile of pre-school children

Association between malnutrition in children living in favelas, maternal nutritional status, and environmental factors

OBJECTIVE: To investigate the association of malnutrition in children living in substandard settlements (slums) of Maceió, AL, Brazil, with maternal nutritional status and environmental conditions. METHODS: Cross-sectional study involving a probability sample of 2,075 mothers (18 to 45 years) and their children (4 months to 6 years), living in the slums of the city of Maceió. First, we conducted a cluster analysis with the purpose of choosing the settlements and the administrative region of the city of Maceió with the lowest human development index. After this analysis, the 7th Administrative Region was designated for the study, including its 23 substandard settlements. Socioeconomic, demographic, anthropometric, and maternal and child health data were collected by means of household survey. The statistical analysis included the odds ratio of a child to be malnourished, and the univariate regression was used to check which maternal variables were associated with this malnutrition. RESULTS: Chronic malnutrition (-2 standard deviations/height for age) was found in 8.6% of children and was associated with mother's age and educational level, type of residence, number of rooms, flooring, water supply, and low birth weight (< 2,500 g) in children aged < 24 months. We also found an association between child malnutrition and maternal height. Such association was not observed regarding body mass index. CONCLUSIONS: The high prevalence of malnutrition observed in these settlements was related to social and environmental conditions and short maternal height, who had weight deficit or weight excess.OBJETIVO: Investigar a associação da desnutrição em crianças residentes em assentamentos subnormais (favelas) de Maceió (AL) com o estado nutricional materno e as condições socioambientais. MÉTODOS: Estudo transversal, envolvendo amostra probabilística de 2.075 mães (18 a 45 anos) e respectivos filhos (4 meses a 6 anos), moradoras nas favelas da cidade de Maceió (AL). Para escolha dos assentamentos, procedeu-se primeiramente a uma análise de clusters para eleger a região administrativa da cidade de Maceió com menor índice de desenvolvimento humano. Após essa análise, a 7ª Região Administrativa foi a designada para o estudo, com seus 23 assentamentos subnormais. Os dados socioeconômicos, demográficos, antropométricos e de saúde materno-infantil foram coletados através de inquérito domiciliar. A estatística analisou a razão de chances de uma criança ser desnutrida, e a regressão univariada foi usada para verificar quais variáveis maternas estariam associadas a essa desnutrição. RESULTADOS: A desnutrição crônica (-2 desvios padrão/altura por idade) esteve presente em 8,6% das crianças e associou-se com idade e escolaridade materna, tipo de residência, número de cômodos, revestimento de piso, origem da água e baixo peso ao nascer (< 2.500 g) em crianças com idade < 24 meses. Encontrou-se também associação entre desnutrição infantil e baixa estatura materna, que não foi observada para índice de massa corporal. CONCLUSÕES: A alta prevalência de desnutrição infantil observada nesses assentamentos esteve relacionada às condições socioambientais e à baixa estatura das mães, que apresentaram déficit ou excesso de peso.Secretaria Estadual de Saúde de AlagoasUniversidade Federal de Alagoas Faculdade de NutriçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de FisiologiaUNIFESP, Depto. de FisiologiaSciEL

One step forward: contrasting the effects of Toe clipping and PIT tagging on frog survival and recapture probability

Amphibians have been declining worldwide and the comprehension of the threats that they face could be improved by using mark-recapture models to estimate vital rates of natural populations. Recently, the consequences of marking amphibians have been under discussion and the effects of toe clipping on survival are debatable, although it is still the most common technique for individually identifying amphibians. The passive integrated transponder (PIT tag) is an alternative technique, but comparisons among marking techniques in free-ranging populations are still lacking. We compared these two marking techniques using mark-recapture models to estimate apparent survival and recapture probability of a neotropical population of the blacksmith tree frog, Hypsiboas faber. We tested the effects of marking technique and number of toe pads removed while controlling for sex. Survival was similar among groups, although slightly decreased from individuals with one toe pad removed, to individuals with two and three toe pads removed, and finally to PIT-tagged individuals. No sex differences were detected. Recapture probability slightly increased with the number of toe pads removed and was the lowest for PIT-tagged individuals. Sex was an important predictor for recapture probability, with males being nearly five times more likely to be recaptured. Potential negative effects of both techniques may include reduced locomotion and high stress levels. We recommend the use of covariates in models to better understand the effects of marking techniques on frogs. Accounting for the effect of the technique on the results should be considered, because most techniques may reduce survival. Based on our results, but also on logistical and cost issues associated with PIT tagging, we suggest the use of toe clipping with anurans like the blacksmith tree frog4814801490CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP140684/2009-3; 309229/2009-0229611-02008/54472-2FADA-UNIFESP; INCTTOX; UNICAM

Charge redistribution at Pd surfaces: ab initio grounds for tight-binding interatomic potentials

A simplified tight-binding description of the electronic structure is often necessary for complex studies of surfaces of transition metal compounds. This requires a self-consistent parametrization of the charge redistribution, which is not obvious for late transition series elements (such as Pd, Cu, Au), for which not only d but also s-p electrons have to be taken into account. We show here, with the help of an ab initio FP-LMTO approach, that for these elements the electronic charge is unchanged from bulk to the surface, not only per site but also per orbital. This implies different level shifts for each orbital in order to achieve this orbital neutrality rule. Our results invalidate any neutrality rule which would allow charge redistribution between orbitals to ensure a common rigid shift for all of them. Moreover, in the case of Pd, the power law which governs the variation of band energy with respect to coordination number, is found to differ significantly from the usual tight-binding square root.Comment: 6 pages, 2 figures, Latex; Phys.Rev. B 56 (1997

Desnutrição e práticas pré-escolares de leitura e escrita

O presente artigo procura dar conta de alguns dos resultados de uma pesquisa realizada com um grupo de treze crianças de três a cinco anos em uma instituição de educação infantil que atende crianças com desnutrição primária. Um dos objetivos do estudo foi verificar que relações e práticas de leitura e escrita se desenvolvem entre esse grupo de crianças e seu professor na pré-escola. Os dados obtidos corroboram estudos que apontam a necessidade de revisar os pressupostos das políticas educacionais de que as crianças de camadas populares trazem para a instituição de ensino problemas de aprendizagem devido a atrasos no desenvolvimento linguístico e cognitivo em decorrência da ausência de práticas de leitura e escrita em seu universo sociocultural

Fingerprinting of propolis by easy ambient sonic-spray ionization mass spectrometry

Chemical profiles of a representative set of 49 propolis ethanolic extracts collected worldwide (North and South America, Europe, Asia and Oceania) were obtained via easy ambient sonic-spray ionization mass spectrometry (EASI-MS). This simple and easily implemented fingerprinting technique analyses directly (without any pre-separation or sample manipulation) a tiny droplet of the ethanolic extract placed on a inert surface under ambient conditions. Data acquisition took about a minute per sample with no substantial sample carry-over. Extraction of propolis with ethanol by using an ultrasonic bath method gave EASI-MS data similar to the traditional maceration method, reducing total analysis time for the crude propolis resin from a week to just ca 1 h. Principal component analysis of the EASI-MS data is shown to group samples according to the plant sources of their resins, which characterizes their geographical origin. © 2009 Elsevier B.V. All rights reserved

The chemical composition and antioxidant activity of mandac¸aia (melipona quadrifasciata) geopropolis varies more due to region than month of collection.

Stingless bees are responsible for pollinating up to 90% of Brazilian flora, so their study is of commercial and ecological importance. Stingless bees mix plant resins with wax and soil, forming geopropolis. Studies of the variability in composition and activity due to species, place and season of collection are lacking

Electrospray Ionization Mass Spectrometry Fingerprinting Of Propolis.

Crude ethanolic extracts of propolis, a natural resin, have been directly analysed using electrospray ionization mass (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) in the negative ion mode. European, North American and African samples have been analyzed, but emphasis has been given to Brazilian propolis which displays diverse and region-dependent chemical composition. ESI-MS provides characteristic fingerprint mass spectra, with propolis samples being divided into well-defined groups directly related to their geographical origins. Chemometric multivariate analysis statistically demonstrates the reliability of the ESI-MS fingerprinting method for propolis. On-line ESI-MS/MS tandem mass spectrometry of characteristic [M - H](-) ion markers provides an additional dimension of fingerprinting selectivity, while structurally characterizing the ESI-MS marker components of propolis. By comparison with standards, eight such markers have been identified: para-coumaric acid, 3-methoxy-4-hydroxycinnamaldehyde, 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran, 3-prenyl-4-hydroxycinnamic acid, chrysin, pinocembrin, 3,5-diprenyl-4-hydroxycinnamic acid and dicaffeoylquinic acid. The negative mode ESI-MS fingerprinting method is capable of discerning distinct composition patterns to typify, to screen the sample origin and to reveal characteristic details of the more polar and acidic chemical components of propolis samples from different regions of the world.129739-4