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.

Electrical transport in single-crystalline Li(0.9)Mo(6)O(17): A two-band Luttinger liquid exhibiting Bose metal behavior

Temperature-dependent electrical resistance in quasi-one-dimensional Li(0.9)Mo(6)O(17) is described by two Luttinger liquid anomalous exponents alpha, each associated with a distinct one dimensional band. The band with alpha < 1 is argued to crossover to a higher dimension below the temperature T(M'), leading to superconductivity. Disorder and magnetic fields are shown to induce the Bose metal behavior in this bulk compound.

UNIQUENESS AND NONUNIQUENESS RESULTS FOR A CERTAIN CLASS OF ALMOST PERIODIC DISTRIBUTIONS

We consider distributions u is an element of S'(R) of the form u(t) = Sigma(n is an element of N) a(n)e(i lambda nt), where (a(n))(n is an element of N) subset of C and Lambda = (lambda n)(n is an element of N) subset of R have the following properties: (a(n))(n is an element of N) is an element of s', that is, there is a q is an element of N such that (n(-q) a(n))(n is an element of N) is an element of l(1); for the real sequence., there are n(0) is an element of N, C > 0, and alpha > 0 such that n >= n(0) double right arrow vertical bar lambda(n)vertical bar >= Cn(alpha). Let I(epsilon) subset of R be an interval of length epsilon. We prove that for given Lambda, (1) if Lambda = O(n(alpha)) with alpha < 1, then there exists epsilon > 0 such that u vertical bar I(epsilon) = 0 double right arrow u 0; (2) if Lambda = O(n) is uniformly discrete, then there exists epsilon > 0 such that u vertical bar I(epsilon) = 0 double right arrow u 0; (3) if alpha > 1 and. is uniformly discrete, then for all epsilon > 0, u vertical bar I(epsilon) = 0 double right arrow u = 0. Since distributions of the above mentioned form are very common in engineering, as in the case of the modeling of ocean waves, signal processing, and vibrations of beams, plates, and shells, those uniqueness and nonuniqueness results have important consequences for identification problems in the applied sciences. We show an identification method and close this article with a simple example to show that the recovery of geometrical imperfections in a cylindrical shell is possible from a measurement of its dynamics.

Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection

Galectin-3 is a beta-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAc beta 1-4(Fuc alpha 1-3) GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine beta 1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in nonlymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S. mansoni.

Direct Measurement of the Bose-Einstein Condensation Universality Class in NiCl(2)-4SC(NH(2))(2) at Ultralow Temperatures

In this work, we demonstrate field-induced Bose-Einstein condensation (BEC) in the organic compound NiCl(2)-4SC(NH(2))(2) using ac susceptibility measurements down to 1 mK. The Ni S=1 spins exhibit 3D XY antiferromagnetism between a lower critical field H(c1)similar to 2 T and a upper critical field H(c2)similar to 12 T. The results show a power-law temperature dependence of the phase transition line H(c1)(T)-H(c1)(0)=aT(alpha) with alpha=1.47 +/- 0.10 and H(c1)(0)=2.053 T, consistent with the 3D BEC universality class. Near H(c2), a kink was found in the phase boundary at approximately 150 mK.

On the resilience of long cycles in random graphs

In this paper we determine the local and global resilience of random graphs G(n,p) (p >> n(-1)) with respect to the property of containing a cycle of length at least (1 - alpha)n. Roughly speaking, given alpha > 0, we determine the smallest r(g) (G, alpha) with the property that almost surely every subgraph of G = G(n,p) having more than r(g) (G, alpha)vertical bar E(G)vertical bar edges contains a cycle of length at least (1 - alpha)n (global resilience). We also obtain, for alpha < 1/2, the smallest r(l) (G, alpha) such that any H subset of G having deg(H) (v) larger than r(l) (G, alpha) deg(G) (v) for all v is an element of V(G) contains a cycle of length at least (1 - alpha)n (local resilience). The results above are in fact proved in the more general setting of pseudorandom graphs.

COMPLETE ISOMORPHIC CLASSIFICATIONS OF SOME SPACES OF COMPACT OPERATORS

This paper is a continuation and a complement of our previous work on isomorphic classification of some spaces of compact operators. We improve the main result concerning extensions of the classical isomorphic classification of the Banach spaces of continuous functions on ordinals. As an application, fixing an ordinal a and denoting by X(xi), omega(alpha) <= xi < omega(alpha+1), the Banach space of all X-valued continuous functions defined in the interval of ordinals [0,xi] and equipped with the supremum, we provide complete isomorphic classifications of some Banach spaces K(X(xi),Y(eta)) of compact operators from X(xi) to Y(eta), eta >= omega. It is relatively consistent with ZFC (Zermelo-Fraenkel set theory with the axiom of choice) that these results include the following cases: 1.X* contains no copy of c(0) and has the Mazur property, and Y = c(0)(J) for every set J. 2. X = c(0)(I) and Y = l(q)(J) for any infinite sets I and J and 1 <= q < infinity. 3. X = l(p)(I) and Y = l(q)(J) for any infinite sets I and J and 1 <= q < p < infinity.

Coconut coir as biosorbent for Cr(VI) removal from laboratory wastewater

A high cost-effective treatment of sulphochromic waste is proposed employing a raw coconut coir as biosorbent for Cr(VI) removal. The ideal pH and sorption kinetic, sorption capacities, and sorption sites were the studied biosorbent parameters. After testing five different isotherm models with standard solutions, Redlich-Peterson and Toth best fitted the experimental data, obtaining a theoretical Cr(VI) sorption capacity (SC) of 6.3 mg g(-1). Acid-base potentiometric titration indicated around of 73% of sorption sites were from phenolic compounds, probably lignin. Differences between sorption sites in the coconut coir before and after Cr adsorption identified from Fourier transform infrared spectra suggested a modification of sorption sites after sulphochromic waste treatment, indicating that the sorption mechanism involves organic matter oxidation and chromium uptake. For sulphocromic waste treatment, the SC was improved to 26.8 +/- 0.2 mg g(-1), and no adsorbed Cr(VI) was reduced, remaining only Cr(III) in the final solution. The adsorbed material was calcinated to obtain Cr2O3, with a reduction of more than 60% of the original mass. (c) 2008 Elsevier B.V. All rights reserved.

Aerobic exercise training improves skeletal muscle function and Ca(2+) handling-related protein expression in sympathetic hyperactivity-induced heart failure

Bueno CR Jr, Ferreira JC, Pereira MG, Bacurau AV, Brum PC. Aerobic exercise training improves skeletal muscle function and Ca(2+) handling-related protein expression in sympathetic hyperactivity-induced heart failure. J Appl Physiol 109: 702-709, 2010. First published July 1, 2010; doi: 10.1152/japplphysiol.00281.2010.-The cellular mechanisms of positive effects associated with aerobic exercise training on overall intrinsic skeletal muscle changes in heart failure (HF) remain unclear. We investigated potential Ca(2+) abnormalities in skeletal muscles comprising different fiber compositions and investigated whether aerobic exercise training would improve muscle function in a genetic model of sympathetic hyperactivity-induced HF. A cohort of male 5-mo-old wild-type (WT) and congenic alpha(2A)/alpha(2C) adrenoceptor knockout (ARKO) mice in a C57BL/6J genetic background were randomly assigned into untrained and trained groups. Exercise training consisted of a 8-wk running session of 60 min, 5 days/wk (from 5 to 7 mo of age). After completion of the exercise training protocol, exercise tolerance was determined by graded treadmill exercise test, muscle function test by Rotarod, ambulation and resistance to inclination tests, cardiac function by echocardiography, and Ca(2+) handling-related protein expression by Western blot. alpha(2A)/alpha(2C)ARKO mice displayed decreased ventricular function, exercise intolerance, and muscle weakness paralleled by decreased expression of sarcoplasmic Ca(2+) release-related proteins [alpha(1)-, alpha(2)-, and beta(1)-subunits of dihydropyridine receptor (DHPR) and ryanodine receptor (RyR)] and Ca(2+) reuptake-related proteins [sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) 1/2 and Na(+)/Ca(2+) exchanger (NCX)] in soleus and plantaris. Aerobic exercise training significantly improved exercise tolerance and muscle function and reestablished the expression of proteins involved in sarcoplasmic Ca(2+) handling toward WT levels. We provide evidence that Ca(2+) handling-related protein expression is decreased in this HF model and that exercise training improves skeletal muscle function associated with changes in the net balance of skeletal muscle Ca(2+) handling proteins.

An Apparent Paradox: Attenuation of Phenylephrine-mediated Calcium Mobilization and Hyperreactivity to Phenylephrine in Contralateral Carotid After Balloon Injury

Balloon catheter injury promotes hyperreactivity to phenylephrine (Phe) in the contralateral carotid. Phe-induced contraction involves calcium mobilization, a process that may be sensitive to reactive oxygen species. In this study, we investigated whether increased reactivity to Phe in the contralateral carotid is due to alterations in calcium mobilization by Phe and reactive oxygen species signaling. Concentration-response curves to Phe were obtained in control and contralateral arteries 4 days after balloon injury. Tiron did not modify E(max) to Phe in control arteries but reduced this parameter in the contralateral carotid to control levels. Moreover, immunofluorescence to dihydroethydine showed increased basal oxidative stress in the contralateral artery compared with control artery. Intracellular calcium mobilization by Phe in the contralateral artery was not different from control, but Phe-induced extracellular calcium mobilization was reduced in the contralateral artery compared with that in the control. These data were confirmed by confocal microscopy using Fluo 3-AM. Tiron and SC-236 increased Phe-induced calcium influx in the contralateral artery, which was similar to controls in the same conditions. However, catalase did not modify this response. Taken together, our results suggest that superoxide anions and prostanoids from cyclooxygenase-2 alter pathways downstream of alpha(1)-adrenoceptor activation in the contralateral carotid in response to injury. This results in reduced Phe-induced calcium influx, despite hyperreactivity to Phe.

Sesquiterpenes Lactones and Flavonoids from Eremanthus argenteus (Asteraceae)

Two new sesquiterpene lactones 8 alpha-(2`,3`-dihydroxy-2`-methylbutanoyl)-15-desoxygoyazensolide and 16 alpha-(1`,2`-dihydroxy-1`-methylpropyl)-eremantholide have been identified as constituents of Eremanthus argenteus aerial parts. In addition, two known sesquiterpene lactones and three flavonoids were isolated. Their structures were established on the basis of spectroscopic and spectrometric data.

A new approach to the granulation of beta-cyclodextrin inclusion complexes

Cyclodextrins (CDs) are annular oligosaccharides containing 6-12 glucose unities joined together by alpha-1,4 bonds. They have a conical-truncated shape with a lipophilic cavity in which different molecules can be included resulting in a stable inclusion complex. The cyclodextrins have been widely applied in pharmaceutical technology with the objective of increasing the solubility, stability and bioavailability of drugs in different pharmaceutical dosage forms, such as tablets. In order to obtain beta-CD tablets, liquid dispersions of drug/beta-CD are usually submitted to different drying processes, like spray-drying, freeze-drying or slow evaporation, being this dry material added to a number of excipients. However, such drying processes can generate particulate materials showing problems of flow and compressibility, needing their conversion into granulates by means of wetting with granulation liquid followed by additional drying. In this work, the main objective was to evaluate the preparation of tablets without the need of this additional drying step. For this purpose an aqueous dispersion containing acetaminophen/beta-CD complex and cornstarch was dried using a spouted bed and the obtained granules were compressed in tablets. Acetaminophen was used as model drug due to its low water solubility and the inexpensive and widely available cornstarch was chosen as excipient. Acetaminophen powder was added into a beta-cyclodextrin solution prepared in distilled water at 70 degrees C. Stirring was kept until this dispersion cooled to room temperature. Then cornstarch was added and the resulting dispersion was dried in spouted bed equipment. This material was compressed into tablets using an Erweka Korsh EKO tablet machine. This innovative approach allowed the tablets preparation process to be carried out with fewer steps and represents a technological reliable strategy to produce beta-cyclodextrin inclusion complexes tablets. (C) 2010 Elsevier By. All rights reserved.

Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency

Our aim was to characterize HDL subspecies and fat-soluble vitamin levels in a kindred with familial apolipoprotein A-I (apoA-I) deficiency. Sequencing of the APOA1 gene revealed a nonsense mutation at codon 22, Q[22] X, with two documented homozygotes, eight heterozygotes, and two normal subjects in the kindred. Homozygotes presented markedly decreased HDL cholesterol levels, undetectable plasma apoA-1, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease. In both homozygotes, analysis of HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I, decreased amounts of small a-3 migrating apoA-II particles, and only modestly decreased normal amounts of slow a migrating apoA-IV- and apoE-containing HDL, while in the eight heterozygotes, there was loss of large alpha-1 HDL particles. There were no significant decreases in plasma fat-soluble vitamin levels noted in either homozygotes or heterozygotes compared with normal control subjects. Our data indicate that isolated apoA-I deficiency results in marked HDL deficiency with very low apoA-II alpha-3 HDL particles, modest reductions in the separate and distinct plasma apoA-IV and apoE HDL particles, tuboeruptive xanthomas, premature coronary atherosclerosis, and no evidence of fat malabsorption.

Molecular and ultrastructural studies of the fibrotic lesions of bovine focal proliferative fibrogranulomatous panniculitis (Lechiguana)

This work aimed to investigate some aspects related to the pathogenicity of Lechiguana, a bovine fibroproliferative lesion characterized by rapid collagen accumulation. Light and transmission electron microscopy and in situ hybridization studies were performed in order to elucidate the fibrogenic activity of this lesion. The characterization of fibroblastic plasticity in the lesion was done by immunohistochemical study for alpha-smooth-muscle cell actin. The ovoid-shaped cells presented positive reaction for alpha-smooth-muscle cell actin in their cytoplasm and, at the electron-microscopic level demonstrated basal lamina-like material adjacent to the external surface and collagen fibrils that corresponded to a cell population phenotypically similar to the myofibroblast. We also investigated alpha 1 collagen type I mRNA at different times of evolution of Lechiguana lesions, using isotopic and non-isotopic in situ hybridization. The results strongly suggest the involvement of a myofibroblast-like cell population that expresses mRNA for type I collagen and is probably associated with the increase of collagen deposition.

Increased mRNA expression of collagen V gene in pulmonary fibrosis of systemic sclerosis

Background Collagen V shows promise as an inducer of interstitial lung fibrosis in experimental systemic sclerosis (SSc). Materials and methods Remodelling of the pulmonary interstitium was evaluated based on the clinical data and open lung biopsies from 15 patients with SSc. Normal lung tissues obtained from eight individuals who died of traumatic injuries were used as control group. Immunofluorescence, immunohistochemistry, morphometry, tri-dimensional reconstruction and a real-time polymerase chain reaction were used to evaluate the quantity, structure and molecular chains of collagen V. The impact of these markers was tested on clinical data. Results The main difference in collagen V content between SSc patients and the control group was an increased, abnormal and distorted fibre deposition in the alveolar septa and the pre-acinar artery wall. The lungs from SSc patients presented [alpha 1(V)] and [alpha 2(V)] mRNA chain expression increased, but [alpha 2(V)] was proportionally increased compared with the control group. High levels of collagen V were inversely associated with vital capacity (r = -0.72; P = 0.002), forced vital capacity (r = -0.76; P < 0.001), forced expiratory volume in 1-s (r = -0.89; P < 0.001) and diffusing capacity for carbon monoxide (r = -0.62; P = 0.04). Conclusions Abnormal collagen V fibres are overproduced in lungs from SSc patients and may play an important role in the pathogenesis of the disease as this molecule regulates tissue collagen assembly. The aberrant histoarchitecture observed in SSc can be related to the overexpression of the [alpha 2(V)] gene of unknown origin.