Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism

Angiotensin I-converting enzyme (ACE) is recognized as one of the main effector molecules involved in blood pressure regulation. In the last few years some polymorphisms of ACE such as the insertion/deletion (I/D) polymorphism have been described, but their physiologic relevance is poorly understood. In addition, few studies investigated if the specific activity of ACE domain is related to the I/D polymorphism and if it can affect other systems. The aim of this study was to establish a biochemical and functional characterization of the I/D polymorphism and correlate this with the corresponding ACE activity. For this purpose, 119 male brazilian army recruits were genotyped and their ACE plasma activities evaluated from the C- and N-terminal catalytic domains using fluorescence resonance energy transfer (FRET) peptides, specific for the C-domain (Abz-LFK(Dnp)OH), N-domain (Abz-SDK(Dnp)P-OH) and both C- and N-domains (Abz-FRK(Dnp)P-OH). Plasma kallikrein activity was measured using Z-Phe-Arg-AMC as substrate and inhibited by selective plasma kallikrein inhibitor (PKSI). Some physiological parameters previously described related to the I/D polymorphism such as handgrip strength, blood pressure, heart rate and BMI were also evaluated. The genotype distribution was II n = 27, ID n = 64 and DD n = 28. Total plasma ACE activity of both domains in II individuals was significantly lower in comparison to ID and DD. This pattern was also observed for C- and N-domain activities. Difference between ID and DD subjects was observed only with the N-domain specific substrate. Blood pressure, heart rate, handgrip strength and BMI were similar among the genotypes. This polymorphism also affected the plasma kallikrein activity and DD group presents high activity level. Thus, our data demonstrate that the I/D ACE polymorphism affects differently both ACE domains without effects on handgrip strength. Moreover, this polymorphism influences the kallikrein-kinin system of normotensive individuals. (C) 2009 Elsevier Ltd. All rights reserved.

Middle Pleistocene sea surface temperature in the Brazil-Malvinas Confluence Zone: Paleoceanographic implications based on planktonic foraminifera

We reconstructed Middle Pleistocene surface hydrography in the western South Atlantic based on planktonic foraminiferal assemblages, modern analog technique and Globorotalia truncatulinoides isotopic ratios of core SP1251 (38 degrees 29.7`S / 53 degrees 40.7`W / 3400 m water depth). Biostratigraphic analysis suggests that sediments were deposited between 0.3 and 0.12 Ma and therefore correlate to Marine Isotopic Stage 6 or 8. Faunal assemblage-based winter and summer SST estimates suggest that the western South Atlantic at 38 degrees S was 4-6 degrees C colder than at present, within the expected range for a glacial interval. High relative abundances of subantarctic species, particularly the dominance of Neogloboquadrina pachyderma (left), support lower than present SSTs throughout the recorded period. The oxygen isotopic composition of G. truncatulinoides suggests a northward shift of the Brazil-Malvinas Confluence Zone and of the associated mid-latitude frontal system during this Middle Pleistocene cold period, and a stronger than present influence of superficial subantarctic waters and lowering in SSTs at our core site during the recorded Middle Pleistocene glacial.

A Markovian model market-Akerlof`s lemons and the asymmetry of information

In this work we study an agent based model to investigate the role of asymmetric information degrees for market evolution. This model is quite simple and may be treated analytically since the consumers evaluate the quality of a certain good taking into account only the quality of the last good purchased plus her perceptive capacity beta. As a consequence, the system evolves according to a stationary Markov chain. The value of a good offered by the firms increases along with quality according to an exponent alpha, which is a measure of the technology. It incorporates all the technological capacity of the production systems such as education, scientific development and techniques that change the productivity rates. The technological level plays an important role to explain how the asymmetry of information may affect the market evolution in this model. We observe that, for high technological levels, the market can detect adverse selection. The model allows us to compute the maximum asymmetric information degree before the market collapses. Below this critical point the market evolves during a limited period of time and then dies out completely. When beta is closer to 1 (symmetric information), the market becomes more profitable for high quality goods, although high and low quality markets coexist. The maximum asymmetric information level is a consequence of an ergodicity breakdown in the process of quality evaluation. (C) 2011 Elsevier B.V. All rights reserved.

Generic hyperbolicity of stationary solutions for a reaction-diffusion system

In this paper, we study the generic hyperbolicity of equilibria of a reaction-diffusion system with respect to nonlinear terms in the set of C(2)-functions equipped with the Whitney Topology. To accomplish this, we combine Baire`s Lemma and the usual Transversality Theorem. (C) 2010 Elsevier Ltd. All rights reserved.

Kallikrein-Kinin System Mediated Inflammation in Alzheimer`s Disease In Vivo

The Kallikrein-Kinin System (KKS) has been associated to inflammatory and immunogenic responses in the peripheral and central nervous system by the activation of two receptors, namely B1 receptor and B2 receptor. The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins. Some authors suggest a link between the KKS and the neuroinflammation in Alzheimer`s disease (AD). We have recently described an increase in bradykinin (BK) in the cerebrospinal fluid and in densities of B1 and B2 receptors in brain areas related to memory, after chronic infusion of amyloid-beta (A beta) peptide in rats, which was accompanied by memory disruption and neuronal loss. Mice lacking B1 or B2 receptors presented reduced cognitive deficits related to the learning process, after acute intracerebroventricular (i.c.v). administration of A. Nevertheless, our group showed an early disruption of cognitive function by i.c.v. chronic infusion of A beta after a learned task, in the knock-out B2 mice. This suggests a neuroprotective role for B2 receptors. In knock-out B1 mice the memory disruption was absent, implying the participation of this receptor in neurodegenerative processes. The acute or chronic infusion of A beta can lead to different responses of the brain tissue. In this way, the proper involvement of KKS on neuroinflammation in AD probably depends on the amount of A beta injected. Though, BK applied to neurons can exert inflammatory effects, whereas in glial cells, BK can have a potential protective role for neurons, by inhibiting proinflammatory cytokines. This review discusses this duality concerning the KKS and neuroinflammation in AD in vivo.

Aging and calorie restriction modulate yeast redox state, oxidized protein removal, and the ubiquitin-proteasome system

The ubiquitin-proteasome system governs the half-life of most cellular proteins. Calorie restriction (CR) extends the maximum life span of a variety of species and prevents oxidized protein accumulation. We studied the effects of CR on the ubiquitin-proteasome system and protein turnover in aging Saccharomyces cerevisiae. CR increased chronological life span as well as proteasome activity compared to control cells. The levels of protein carbonyls, a marker of protein oxidation, and those of polyubiquitinated proteins were modulated by CR. Controls, but not CR cells, exhibited a significant increase in oxidized proteins. In keeping with decreased proteasome activity, polyubiquitinated proteins were increased in young control cells compared to time-matched CR cells, but were profoundly decreased in aged control cells despite decreased proteasomal activity. This finding is related to a decreased polyubiquitination ability due to the impairment of the ubiquitin-activating enzyme in aged control cells, probably related to a more oxidative microenvironment. CR preserves the ubiquitin-proteasome system activity. Overall, we found that aging and CR modulate many aspects of protein modification and turnover. (C) 2011 Elsevier Inc. All rights reserved.

Exercise training associated with diet improves heart rate recovery and cardiac autonomic nervous system activity in obese children

The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Delta HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Delta HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Delta HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 +/- 0.2 years; body mass index (BMI) >95(th) percentile) were divided into 2 groups: D (n = 15; BMI = 31 +/- 1 kg/m(2)) and DET (n = 18; 29 +/- 1 kg/m(2)). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Delta HRR1 was defined as the difference between heart rate at peak and at 1-min post-exercise. CANSA was assessed using power spectral analysis of heart rate variability at rest. The sympathovagal balance (low frequency and high frequency ratio, LF/HF) was measured. After interventions, all obese children showed reduced body weight (P < 0.05). The D group did not improve in terms of peak VO(2), Delta HRR1 or LF/HF ratio (P > 0.05). In contrast, the DET group showed increased peak VO(2) (P = 0.01) and improved Delta HRR1 (Delta HRR1 = 37.3 +/- 2.6; P = 0.01) and LF/HF ratio (P = 0.001). The DET group demonstrated significant relationships among Delta HRR1, peak VO(2) and CANSA (P < 0.05). In conclusion, DET, in contrast to D, promoted improved Delta HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.

Evaluation of alternative technical markers for the pelvic coordinate system

In this study, we evaluated alternative technical markers for the motion analysis of the pelvic segment. Thirteen subjects walked eight times while tri-dimensional kinematics were recorded for one stride of each trial. Five marker sets were evaluated, and we compared the tilt, obliquity, and rotation angles of the pelvis segment: (1) standard: markers at the anterior and posterior superior iliac spines (ASIS and PSIS); (2) markers at the PSIS and at the hip joint centers, HJCs (estimated by a functional method and described with clusters of markers at the thighs); (3) markers at the PSIS and HJCs (estimated by a predictive method and described with clusters of markers at the thighs); (4) markers at the PSIS and HJCs (estimated by a predictive method and described with skin-mounted markers at the thighs based on the Helen-Hayes marker set); (5) markers at the PSIS and at the iliac spines. Concerning the pelvic angles, evaluation of the alternative technical marker sets evinced that all marker sets demonstrated similar precision across trials (about 1 degrees) but different accuracies (ranging from 1 degrees to 3 degrees) in comparison to the standard marker set. We suggest that all the investigated marker sets are reliable alternatives to the standard pelvic marker set. (C) 2009 Elsevier Ltd. All rights reserved.

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C) ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.

Regulating industrial forest concessions in Central Africa and South America

Tropical countries face special specific problems in implementing sustainable forest management (SFM). In many countries, questions are raised on whether tropical forests should be publicly, commonly or privately owned and managed in order to enhance sustainability. Other debates also focus on whether small-scale enterprises are better positioned than large-scale industrial concessions to reduce poverty and attain sustainable management. In countries where large tracts of forest are state-owned, concessions are viewed as a means of delivering services of public and collective interest through an association of private investment and public regulation. However, the success of an industrial concession model in countries with large forest resource endowment to achieve multiple goals such as sustainable forest management and local/regional development depends on two critical assumptions. First, forest functions and services should be managed and maintained as public goods. In many cases, additional uses - and corresponding rights - can take place alongside logging activities. Industrial concessions can be more efficient than other tenure models (such as community-based forest management and small-scale enterprises) in achieving SFM, add value to raw material and comply with growing environmental norms. This is especially the case in market-remote areas with low population density and poor infrastructure. Secondly, to achieve these different outcomes, any concession system needs to be monitored and regulated, especially in contexts dominated by asymmetrical information between regulating authorities and concessionaires. New institutional responses have recently been put forward in several countries, providing valuable materials to design a renewed policy mix which associates public and private incentives. This paper provides a survey of the experience of forest concessions in several Central African and South American countries. The concession system is examined in order to clarify the issues involved, the problems encountered, and what can be learned from the shared experience of these countries in the last decade. This paper argues that despite a sometimes patchy record, concessions can help promote SFM so long as they are packaged with a certain number of specific measures. (C) 2008 Elsevier B.V. All rights reserved.

Magnetization studies of binary and ternary Co-rich phases of the Co-Si-B system

CoB, CO(2)B, CoSi, Co(2)Si and CO(5)Si(2)B phases can be formed during heat-treatment of amorphous co-Si-B soft magnetic materials. Thus, it is important to determine their magnetic behavior as a function of applied field and temperature. In this study, polycrystalline single-phase samples of the above phases were produced via arc melting and heat-treatment under argon. The single-phase nature of the samples was confirmed via X-ray diffraction experiments. AC and DC magnetization measurements showed that Co(2)Si and CO(5)Si(2)B phases are paramagnetic. Minor amounts of either Co(2)Si or CoSi(2) in the CoSi-phase sample suggested a paramagnetic behavior of the CoSi-phase, however, it should be diamagnetic as shown in the literature. The diamagnetic behavior of the CoB phase was also confirmed. The paramagnetic behavior of CO(5)Si(2)B is for the first time reported. The magnetization results of the phase CO(2)B have a ferromagnetic signature already verified on previous NMR studies. A detailed set of magnetization measurements of this phase showed a change of the easy magnetization axis starting at 70K, with a temperature interval of about 13K at a very small field of 1 mT. As the strength of the field is increased the temperature interval is enlarged. The strength of field at which the magnetization saturates increases almost linearly as the temperature is increased above 70K. The room temperature total magnetostriction of the CO(2)B phase was determined to be 8 ppm at a field of 1T. (C) 2010 Elsevier B.V. All rights reserved.

Thermal expansion of the V(5)Si(3) and T(2) phases of the V-Si-B system investigated by high-temperature X-ray diffraction

The thermal expansion anisotropy of the V(5)Si(3) and T(2)-phase of the V-Si-B system were determined by high-temperature X-ray diffraction from 298 to 1273 K. Alloys with nominal compositions V(62.5)Si(37.5) (V5Si3 phase) and V(63)Si(12)B(25) (T(2)-phase) were prepared from high-purity materials through arc-melting followed by heat-treatment at 1873 K by 24 h, under argon atmosphere. The V(5)Si(3) phase exhibits thermal expansion anisotropy equals to 1.3, with thermal expansion coefficients along the a and c-axis equal to 9.3 x 10(-6) K(-1) and 11.7 x 10(-6) K(-1), respectively. Similarly, the thermal expansion anisotropy value of the T(2)-phase is 0.9 with thermal expansion coefficients equal to 8.8 x 10(-6) K(-1) and 8.3 x 10(-6) K(-1) along the, a and c-axis respectively. Compared to other isostructural silicides of the 5:3 type and the Ti(5)Si(3) phase, the V(5)Si(3) phase presents lower thermal expansion anisotropy. The T(2)-phase present in the V-Si-B system exhibits low thermal expansion anisotropy, as the T(2)-phase of the Mo-Si-B, Nb-Si-B and W-Si-B systems. (C) 2009 Elsevier Ltd. All rights reserved.

Selection of new glass-forming compositions in Al-La system using a combination of topological instability and thermodynamic criteria

A combination of an extension of the topological instability ""lambda criterion"" and a thermodynamic criterion were applied to the Al-La system, indicating the best range of compositions for glass formation. Alloy compositions in this range were prepared by melt-spinning and casting in an arc-melting furnace with a wedge-section copper mold. The GFA of these samples was evaluated by X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. The results indicated that the gamma* parameter of compositions with high GFA is higher, corresponding to a range in which the lambda parameter is greater than 0.1, which are compositions far from Al solid solution. A new alloy was identified with the best GFA reported so far for this system, showing a maximum thickness of 286 mu m in a wedge-section copper mold. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.

Aqueous two-phase extraction using thermoseparating copolymer: a new system for phenolic compounds removal from hemicelullosic hydrolysate

BACKGROUND: The hydrolysis of hemicellulosic material can provide liquor with high xylose concentration (which can be used as a fermentation medium) and phenolic compounds (Phs), potentially immunostimulating compounds. However, these hydrolysates must be detoxified in order to remove the Phs that can act as inhibitors in bioconversions. RESULTS: Aqueous two-phase systems composed of thermoseparating copolymers were used for rice straw hydrolysate detoxification. The hydrolysis process was able to promote chemical breakdown of 85% of the total hemicellulose content, 14% of the cellulose, and 2% of the lignin. The hydrolysate obtained contained 19.7 g L-1 of xylose and several phenolic compounds, such as vanillin, vanillic acid, ferullic acid, etc. The phenolics extraction was studied as a function of copolymer molar mass (1100 g mol(-1), 2000 g mol(-1) and 2800 g mol(-1)), their percentages (from 5% to 50%) and Phs initial concentration. Phenolic compounds extraction of around 80% was obtained under the following conditions: 20% (w/w) and 35% (w/w) copolymer 1100 g mol-1, 35% (w/w) copolymer 2000 g mol(-1) and 35% (w/w) copolymer 2800 g mol(-1) at 25 degrees C. CONCLUSIONS: The results demonstrated the viability of this method for the removal of Phs from rice straw hydrolysate, which has potential uses in bioconversion processes. (c) 2007 Society of Chemical Industry.

Crystallisation behaviour and glass-forming ability in Al-La-Ni system

The crystallisation behaviour for alloys in the Al-rich corner in the Al-La-Ni system is reported in this paper Alloys were selected based on the topological instability criterion (lambda criterion) calculated from the alloy composition and metallic radii of the alloying elements and aluminum Amorphous ribbons were produced by melt-spinning and the crystallisation reactions were analysed by X-ray diffraction and calorimetry The results showed that increasing the values of lambda from 0.072 to 0.16 resulted in the following changes in the crystallisation behaviour, as predicted by the lambda criterion (a) nanocrystallisation of alpha-Al for the alloy composition corresponding to lambda = 0 072 and (b) detection of the glass transition temperature, T(g), for the alloys with composition close to lambda approximate to 0.1 line. For compositions corresponding to both ends of the lambda approximate to 0 1 line (near the binaries lines) T(g) could be detected only in the ""intermediary"" central region, and the alloy we produced in this region was considered the best glass former for the Al-rich corner Also, except for the alloys with the highest NI content, crystallisation proceeded by two distinct exothermic peaks which are typical of nanocrystallisation transformation. These behaviours are discussed in terms of compositional (lambda parameter) and topological aspects to account for cluster formation in the amorphous phase. Crown Copyright (C) 2009 Published by Elsevier B V All rights reserved