Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Analysis of phosphorus use efficiency traits in Coffea genotypes reveals Coffea arabica and Coffea canephora have contrasting phosphorus uptake and utilization efficiencies

Background and Aims: Phosphate (Pi) is one of the most limiting nutrients for agricultural production in Brazilian soils due to low soil Pi concentrations and rapid fixation of fertilizer Pi by adsorption to oxidic minerals and/or precipitation by iron and aluminum ions. The objectives of this study were to quantify phosphorus (P) uptake and use efficiency in cultivars of the species Coffea arabica L. and Coffea canephora L., and group them in terms of efficiency and response to Pi availability. Methods: Plants of 21 cultivars of C. arabica and four cultivars of C. canephora were grown under contrasting soil Pi availabilities. Biomass accumulation, tissue P concentration and accumulation and efficiency indices for P use were measured. Key Results: Coffee plant growth was significantly reduced under low Pi availability, and P concentration was higher in cultivars of C. canephora. The young leaves accumulated more P than any other tissue. The cultivars of C. canephora had a higher root/shoot ratio and were significantly more efficient in P uptake, while the cultivars of C. arabica were more efficient in P utilization. Agronomic P use efficiency varied among coffee cultivars and E16 Shoa, E22 Sidamo, Iêmen and Acaiá cultivars were classified as the most efficient and responsive to Pi supply. A positive correlation between P uptake efficiency and root to shoot ratio was observed across all cultivars at low Pi supply. These data identify Coffea genotypes better adapted to low soil Pi availabilities, and the traits that contribute to improved P uptake and use efficiency. These data could be used to select current genotypes with improved P uptake or utilization efficiencies for use on soils with low Pi availability and also provide potential breeding material and targets for breeding new cultivars better adapted to the low Pi status of Brazilian soils. This could ultimately reduce the use of Pi fertilizers in tropical soils, and contribute to more sustainable coffee production.

The Immune-Pineal Axis Stress as a Modulator of Pineal Gland Function

The temporal organization of mammals presents a daily adjustment to the environmental light/dark cycle. The environmental light detected by the retina adjusts the central clock in the suprachiasmatic nuclei, which innervate the pineal gland through a polysynaptic pathway. During the night, this gland produces and releases the nocturnal hormone melatonin, which circulates throughout the whole body and adjusts several bodily functions according to the existence and duration of darkness. We have previously shown that during the time frame of an inflammatory response, pro-inflammatory cytokines, such as tumor necrosis factor-a, inhibit while anti-inflammatory mediators, such as glucocorticoids, enhance the synthesis of melatonin, interfering in the daily adjustment of the light/dark cycle. Therefore, injury disconnects the organism from environmental cycling, while recovery restores the light/dark information to the whole organism. Here, we extend these observations by evaluating the effect of a mild restraint stress, which did not induce macroscopic gastric lesions. After 2 h of restraint, there was an increase in circulating corticosterone, indicating activation of the hypothalamus-pituitary-adrenal (HPA) axis. In parallel, an increase in melatonin production was observed. Taking into account the data obtained with models of inflammation and stress, we reinforce the hypothesis that the activity of the pineal gland is modulated by the state of the immune system and the HPA axis, implicating the darkness hormone melatonin as a modulator of defense responses.

Beneficial Effects of Physical Training on the Cardio-Inflammatory Disorder Induced by Lung Ischemia/Reperfusion in Rats

Our laboratory demonstrated that training program attenuated the inflammatory responses in lung ischemia/reperfusion (IR). Considering the importance of the inflammatory responses on the cardiovascular system, we evaluate the effect of physical training on the vascular responsiveness and its underlying mechanism after lung IR. Male Wistar rats were submitted to run training and lung IR. Concentration-response curves for relaxing and contracting agents were obtained. Protein expressions of SOD-1 and p47(phox), plasma nitritre/nitrate (NO (x) (-) ) and interleukin 6 (IL-6) were evaluated. A decreased in the potency for acetylcholine and phenylephrine associated with an upregulation of the p47(phox) expression were found after Lung IR as well as an increase in IL-6 and NO (x) (-) levels. Run training attenuated the vascular dysfunction that was accompanied by reduction of the p47(phox) protein expression and IL-6 levels. Our findings show the beneficial effect of training on the vascular function that was associated with reduction in inflammatory response in lung IR.

Sialic Acid Residues Are Essential for the Anaphylactic Activity of Murine IgG1 Antibodies

Glycosylation of the Ab molecule is essential for maintaining the functional structure of Fc region and consequently for Ab-mediated effector functions, such as binding to cells or complement system activation. Alterations in the composition of the sugar moiety can dramatically influence Ab activity; however, it is not completely clear how differences in the N-linked oligosaccharide structure impact the biological function of Abs. We have described that murine IgG1 Abs can be separated according to their ability to elicit in vivo anaphylaxis in a fraction of anaphylactic and other of non-anaphylactic molecules. Furthermore, we showed that the N-linked oligosaccharide chain is essential for the structural conformation of the anaphylactic IgG1, the binding to Fc gamma RIII on mast cells, and, consequently, for the ability to mediate anaphylactic reactions. In this study, we evaluated the contribution of individual sugar residues to this biological function. Differences in the glycan composition were observed when we analyzed oligosaccharide chains from anaphylactic or non-anaphylactic IgG1, mainly the presence of more sialic acid and fucose residues in anaphylactic molecules. Interestingly, the enzymatic removal of terminal sialic acid residues in anaphylactic IgG1 resulted in loss of the ability to trigger mast cell degranulation and in vivo anaphylactic reaction, similarly to the deglycosylated IgG1 Ab. In contrast, fucose removal did not affect the anaphylactic function. Therefore, we demonstrated that the ability of murine IgG1 Abs to mediate anaphylaxis is directly dependent on the amount of sialic acid residues associated to the oligosaccharide chain attached to the Fc region of these molecules. The Journal of Immunology, 2008, 181: 8308-8314.

Fenofibrate and Pioglitazone Do Not Ameliorate the Altered Vascular Reactivity in Aorta of Isoproterenol-treated Rats

Chronic stimulation of beta-adrenoceptors with isoproterenol induces alteration of vascular reactivity and increases local proinflammatory cytokines. We investigated whether fenofibrate and pioglitazone, PPAR-alpha and -gamma agonists, respectively, improve the changes in vascular reactivity induced by isoproterenol. Wistar rats received isoproterenol (0.3 mg.kg(-1).day(-1), SC) or vehicle (CT) plus fenofibrate (alpha, 100 mg.kg(-1).day(-1), PO), pioglitazone (gamma, 2.5 mg.kg(-1).day(-1), PO), or water for 7 days. In aortas, isoproterenol treatment enhanced the maximal response (Rmax) to phenylephrine (10(-10) to 10(-4) M) compared to CT as previously demonstrated. The effects of endothelium removal (E-) or L-NAME incubation (100 mu M) on the phenylephrine response were smaller in isoproterenol-treated animals compared to CT while superoxide dismutase (SOD, 150 U/mL) significantly reduced the Rmax to phenylephrine to CT levels. Neither fenofibrate nor pioglitazone changed the effects induced by isoproterenol in aorta. E-, L-NAME, or SOD effects were similar between CT alpha and CT. However, pioglitazone per se increased Rmax to phenylephrine (CT: 59 +/- 4 versus CT gamma: 72 +/- 5 % of contraction to KCl). E- or L-NAME effects were reduced in CT gamma compared to CT, and SOD normalized the altered reactivity to phenylephrine in the CT gamma group. In conclusion, neither fenofibrate nor pioglitazone ameliorates the altered vascular reactivity present in aorta from isoproterenol-treated rats. Moreover, pioglitazone per se induced endothelial dysfunction and increased phenylephrine-induced contraction in aorta.

Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats

Objectives The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). Methods Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR R IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar-Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na(+)/H(+) exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. Results Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 +/- 3 vs. 123 +/- 5 mmHg, P < 0.01) and was similar to Y-WKY (94 +/- 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. Conclusion Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule. J Hypertens 29:520-528 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Electronic Structure and Spectro-Structural Correlations of Fe(III)Zn(II) Biomimetics for Purple Acid Phosphatases: Relevance to DNA Cleavage and Cytotoxic Activity

Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear Fe(II)M(II) center (M(II) = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear complex [(H(2)O)Fe(III)(mu-OH)Zn(II)(L-H)](CIO(4))(2) (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H(2)L-H) has recently been prepared and is found to closely mimic the coordination environment of the Fe(III)Zn(II) active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the Fe(III) center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted Fe(III)N(2)O(4) octahedron with a dominant tetragonal compression align ad along the mu-OH-Fe-O(phenolate) direction. To probe the role of the Fe-O(phenolate) bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH(3), -H, -Br, -NO(2)) in the 5-position. Tie effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic struck ral information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order -NO(2)<- Br <- H <- CH(3) when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(k(cat)/k(0)) is plotted against the Hammett parameter a. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing -NO(2) and electron-donating CH3 groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups.

A characterization theorem for t-representable n-dimensional triangular norms

n-dimensional fuzzy sets are an extension of fuzzy sets that includes interval-valued fuzzy sets and interval-valued Atanassov intuitionistic fuzzy sets. The membership values of n-dimensional fuzzy sets are n-tuples of real numbers in the unit interval [0,1], called n-dimensional intervals, ordered in increasing order. The main idea in n-dimensional fuzzy sets is to consider several uncertainty levels in the memberships degrees. Triangular norms have played an important role in fuzzy sets theory, in the narrow as in the broad sense. So it is reasonable to extend this fundamental notion for n-dimensional intervals. In interval-valued fuzzy theory, interval-valued t-norms are related with t-norms via the notion of t-representability. A characterization of t-representable interval-valued t-norms is given in term of inclusion monotonicity. In this paper we generalize the notion of t-representability for n-dimensional t-norms and provide a characterization theorem for that class of n-dimensional t-norms. © 2011 Springer-Verlag Berlin Heidelberg.

Color image magnification with interval-valued fuzzy sets

In this work we present a simple magnification algorithm for color images. It uses Interval-Valued Fuzzy Sets in such a way that every pixel has an interval membership constructed from its original intensity and its neighbourhood's one. Based on that interval membership, a block is created for each pixel, so this is a block expansion method.

Image reduction using fuzzy quantifiers

In this work we propose an image reduction algorith based on local reduction operators. We analyze the construction of weak local reduction operators by means of aggregation functions and we analyze the effect of several aggregation functions in image reduction with original and noisy images.

Desenvolvimento de regras de pronúncia para a síntese de fala em língua portuguesa

Sabe-se que a fala é a principal maneira de comunicação entre as pessoas. A Síntese de fala (geração automática da fala pelo computador) tem recebido atenção da comunidade acadêmica e profissional por várias décadas. Ela envolve a conversão de um texto de entrada em fala, usando algoritmos e algumas formas de fala codificada. O texto pode ser digitado pelo teclado ou obtido por reconhecimento de caracteres ou, ainda, obtido de um banco de dados. A síntese de fala pode ser usada em vários domínios de aplicação, tais como: auxílio para deficientes visuais, telecomunicações, multimídia, etc. Este trabalho apresenta um estudo sobre a produção da fala e da área de síntese de fala visando servir de subsídio para dissertações e pesquisas futuras, bem como para o Projeto Spoltech, um projeto de cooperação entre os Estados Unidos e o Brasil para o avanço da tecnologia da língua falada no Brasil (Português Brasileiro). Dentro deste estudo serão apresentadas as principais técnicas de síntese de fala, entre as quais destaca-se: Texto para Fala (TPF). Problemas de separação de sílabas, determinação da sílaba tônica, pronunciação das vogais “e” e “o” como um fonema aberto ou fechado, etc, são enfrentados dentro do contexto da área de síntese de fala para o português falado no Brasil. Tendo conhecimento destes problemas, o principal objetivo deste trabalho será criar regras para resolver o problema de pronunciação das vogais “e” e “o” de forma automática, visando obter produção sonora mais inteligível, por intermédio da implementação de um analisador estatístico, o qual verificará a letra anterior e posterior ao “e” ou “o” de uma palavra e, com isso, determinar a pronúncia dos mesmos para aquela seqüência de letras. As mesmas poderão tornar-se regras válidas para a solução do problema se atingirem 80% dos casos de ocorrência no dicionário com fonema “e” ou “o” aberto (limiar), sendo que elas serão lidas por um interpretador Scheme utilizado pelo programa Festival - ferramenta para a construção de sistemas de síntese de fala desenvolvida pelo Centre for Speech Technology Research (University of Edinburgh, Reino Unido), a qual utiliza TPF como método de síntese. Sabendo-se que o Festival gera os fonemas “e” e “o” como fechados se não há uma regra para inferir o contrário, serão consideradas apenas as regras encontradas para os fonemas abertos. Para possibilitar esta análise será utilizado um dicionário eletrônico de pronunciação (com 19.156 palavras), o qual possui a palavra e a sua respectiva pronúncia, conforme pode-se verificar no exemplo do Anexo 1.

Proposta de modelo de agente EDI para uso como ferramenta de apoio a sistemas de informação baseado em web

Este trabalho apresenta a proposta de uma arquitetura e o modelo de um Agente de Intercâmbio Eletrônico de Dados, Agente EDI, cuja função é, permitir a troca de dados estruturados entre Sistemas de Informações Distribuídos através da Internet. A estratégia de interação dos agentes possibilita uma maneira alternativa de tratar a recuperação, o armazenamento e a distribuição de dados, permitindo assim, o desenvolvimento de um modelo de Sistema de Informações baseado em Web, igualmente proposto neste trabalho. É apresentado também o desenvolvimento do Agente EDI proposto. O qual poderá ser utilizado por entidades que necessitam disponibilizar ou recuperar dados estruturados via Web, como por exemplo: informações de produtos, listas de preços, dados cadastrais, etc. A relevância deste trabalho está no fato de apresentar uma tecnologia simples e acessível, capaz de ser implementada sem a necessidade de altos investimentos e capaz de facilitar a implementação de Sistemas Distribuídos via Internet.