Conformational analysis of LYS(11-36), a peptide derived from the beta-sheet region of T4 lysozyme, in TFE and SDS

The solution conformation of a peptide LYS(11-36), which corresponds to the beta-sheet region in T4 lysozyme, has been examined in aqueous solution, TFE, and SDS micelles by CD and H-1 NMR spectroscopy. Secondary structure predictions suggest some beta-sheet and turn character in aqueous solution but predict a helical conformation in a more hydrophobic environment. The predictions were supported by the CD and NMR studies which showed the peptide to be relatively unstructured in aqueous solution, although there was some evidence of a beta-turn conformer which was maintained in 200 mM SDS and, to a lesser extent, in 50% TFE. The peptide was significantly helical in the presence of either 50% TFE or 200 mM SDS. TFE and SDS titrations showed that the peptide could form helical, sheet, or extended structure depending on the TFE or SDS concentration. The studies indicate that peptide environment is the determining factor in secondary structure adopted by LYS(11-36).

A semi-empirical approach to optimise the quantity of drying aids required to spray dry sugar-rich foods

A semi-empirical linear equation has been developed to optimise the amount of maltodextrin additive (DE 6) required to successfully spray dry a sugar-rich product on the basis of its composition. Based on spray drying experiments, drying index values for individual sugars (sucrose, glucose, frutose) and citric acid were determined, and us;ng these index values an equation for model mixtures of these components was established. This equation has been tested with two sugar-rich natural products, pineapple juice and honey. The relationship was found to be valid for these products.

The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel

Background: Versutoxin (delta-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. delta-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; delta-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of delta ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of delta-ACTX-Hv1, determined using NMR spectroscopy, comprises a core beta region containing a triple-stranded antiparallel beta sheet, a thumb-like extension protruding from the beta region and a C-terminal 3(10) helix that is appended to the beta domain by virtue of a disulphide bond. The beta region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with mu-agatoxin-l, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, delta-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. Conclusions: delta-ACTX-Hv1 shows no structural homology with either sea anemone or alpha-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that delta-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and alpha-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.

Vascularized Bone Grafts for Upper Limb Reconstruction: Defects at the Distal Radius, Wrist, and Hand

Vascularized bone grafts have been successfully applied for the reconstruction of bone defects at the forearm, distal radius, carpus, and hand. Vascularized bone grafts are most commonly used in revision cases in which other approaches have failed. Vascularized bone grafts can be obtained from a variety of donor sites, including the fibula, the iliac crest, the distal radius (corticocancellous segments and vascularized periosteum), the metacarpals and metatarsals, and the medial femoral condyle (corticoperiosteal flaps). Their vascularity is preserved as either pedicled autografts or free flaps to carry the optimum biological potential to enhance union. The grafts can also be transferred as composite tissue flaps to reconstruct compound tissue defects. Selection of the most appropriate donor flap site is multifactorial. Considerations include size matching between donor and defect, the structural characteristics of the graft, the mechanical demands of the defect, proximity to the donor area, the need for an anastomosis, the duration of the procedure, and the donor site morbidity. This article focuses on defects of the distal radius, the wrist, and the hand. (J Hand Surg 2010;35A:1710-1718. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)

TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C > T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C > A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C > A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.

Anisotropic Reversible Aggregation of Latex Nanoparticles Suspended in a Lyotropic Nematic Liquid Crystal: Effect of Gradients of Biaxial Order

We studied the anisotropic aggregation of spherical latex particles dispersed in a lyotropic liquid crystal presenting three nematic phases; calamitic, biaxial, and discotic. We observed that in the nematic calamitic phase aggregates of latex particles are formed, which become larger and anisotropic in the vicinity of the transition to the discotic phase, due to a coalescence process. Such aggregates are weakly anisotropic and up to 50 mu m long and tend to align parallel to the director field. At the transition to the discotic phase, the aggregates dissociated and re-formed when the system was brought back to the calamitic phase. This shows that the aggregation is due to attractive and repulsive forces generated by the particular structure of the nematic phase. The surface-induced positional order was investigated by surface force apparatus experiments with the lyotropic system confined between mica surfaces, revealing the existence of a presmectic wetting layer around the surfaces and oscillating forces of increasing amplitude as the confinement thickness was decreased. We discuss the possible mechanisms responsible for the reversible aggregation of latex particles, and we propose that capillary condensation of the N(C) phase, induced by the confinement between the particles, could reduce or remove the gradient of order parameter, driving the transition of aggregates from solidlike to liquidlike and gaslike.

Salt-Induced Cardiac Hypertrophy and Interstitial Fibrosis Are Due to a Blood Pressure-Independent Mechanism in Wistar Rats

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg.kg(-1).d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg.kg(-1).d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding. J. Nutr. 140: 1742-1751, 2010.

Sleep-related changes in hemodynamic and autonomic regulation in human hypertension

Objectives The present study investigates the hemodynamic and autonomic regulation during sleep-awake transitions and across different sleep cycles in patients with essential hypertension. Methods Nineteen individuals free of sleep apnea (10 normotensive and nine hypertensive matched for age, sex, and body mass index) underwent a standard polysomnography, with simultaneous electrocardiography and beat-to-beat blood pressure monitoring (Portapres). All measurements were determined while awake (before and after sleep), as well as in the beginning and at end of the sleep cycle (first/last cycle of nonrapid and rapid eye movement stages). Results Systolic blood pressure was higher in hypertensives and exhibited a similar reduction to the normotensives ones in initial nonrapid eye movement sleep. This reduction was because of different mechanisms: a significant fall in cardiac output in normotensives, whereas in hypertensives was also dependent of a decrease in peripheral vascular resistance. Hypertensive patients presented lower heart rate variation and attenuated baroreflex sensitivity during sleep but not immediately before and after sleep. Spectral analysis suggested a higher sympathetic activity in the sleep stages in hypertension. Additionally, a progressive sympathetic predominance (final rapid eye movement> initial rapid eye movement and awake period postsleep> awake period presleep) was observed in both groups. Conclusion Hypertension is associated with depressed baroreflex sensitivity and increased sympathetic activation during sleep. The greater sympathetic predominance at the end of night (preceding the morning surge of sympathetic activity) could be implicated in the occurrence of cardiovascular events. J Hypertens 27: 1655-1663 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Concurreny based transition refinement for the verification of distributed algorithms

We suggest a new notion of behaviour preserving transition refinement based on partial order semantics. This notion is called transition refinement. We introduced transition refinement for elementary (low-level) Petri Nets earlier. For modelling and verifying complex distributed algorithms, high-level (Algebraic) Petri nets are usually used. In this paper, we define transition refinement for Algebraic Petri Nets. This notion is more powerful than transition refinement for elementary Petri nets because it corresponds to the simultaneous refinement of several transitions in an elementary Petri net. Transition refinement is particularly suitable for refinement steps that increase the degree of distribution of an algorithm, e.g. when synchronous communication is replaced by asynchronous message passing. We study how to prove that a replacement of a transition is a transition refinement.

Increased Serum IL-1 beta Level in Alzheimer`s Disease and Mild Cognitive Impairment

Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer`s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1 beta (IL-1 beta) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults ( 58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1 beta levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI ( all subtypes) had a significant increase in serum IL-1 beta levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1 beta levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI ( p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1 beta, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1 beta level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD. Copyright (C) 2009 S. Karger AG, Basel

Diagnosis of Mild Cognitive Impairment Revisited after One Year Preliminary Results of a Prospective Study

Background/Aims: The diagnostic stability of mild cognitive impairment (MCI) on short-term follow- up is a key issue in the characterization of this clinical syndrome. We aim to determine the cognitive outcome after 1 year of follow- up in a cohort of older adults. Methods: Baseline clinical and neuropsychological assessments were carried out in older subjects recruited at a tertiary memory clinic. The subjects were reassessed after 1 year of follow- up with the same clinical and neuropsychological protocol. Results: A total of 115 older adults, including MCI (n = 54) and controls (n = 61), underwent baseline and follow- up evaluation. Ten subjects classified as MCI at baseline (23%) resumed normal cognitive function and 13 controls (21%) progressed to MCI upon follow-up (chi(2) = 0.015, d.f. = 1, p = 0.90). The subjects diagnosed as having MCI on both assessments were older (p = 0.002) and had a worse global cognitive performance according to the Cambridge Cognitive Test (p = 0.014). Conclusion: The subjects who maintain the MCI status are older and have a worse baseline cognitive performance as well as multiple cognitive deficits. Copyright (C) 2009 S. Karger AG, Basel

Student characteristics and academic success: An econometric study of the performance of "equity groups"

Like previous volumes in the Educational Innovation in Economics and Business Series, this book is genuinely international in terms of its coverage. With contributions from nine different countries and three continents, it reflects a global interest in, and commitment to, innovation in business education, with a view to enhancing the learning experience of both undergraduates and postgraduates. It should prove of value to anyone engaged directly in business education, defined broadly to embrace management, finance, marketing, economics, informational studies, and ethics, or who has responsibility for fostering the professional development of business educators. The contributions have been selected with the objective of encouraging and inspiring others as well as illustrating developments in the sphere of business education. This volume brings together a collection of articles describing different aspects of the developments taking place in today’s workplace and how they affect business education. It describes strategies for breaking boundaries for global learning. These target specific techniques regarding teams and collaborative learning, transitions from academic settings to the workplace, the role of IT in the learning process, and program-level innovation strategies. This volume addresses issues faced by professionals in higher and further education and also those involved in corporate training centers and industry.

Tunicamycin inhibition of N-glycosylation of alpha-glucosidase from Aspergillus niveus: partial influence on biochemical properties

Treatment of Aspergillus niveus with 30 mu g tunicamycin/ml did not interfere with alpha-glucosidase production, secretion, or its catalytic properties. Fully- and under-glycosylated forms of the enzyme had similar molecular masses, similar to 56 kDa. Moreover, the absence of N-glycans did not affect either pH optimum (6.0) or temperature optimum (65A degrees C). The K(m) and V(max) values of under- and fully-glycosylated forms of alpha-glucosidase were similar when assessed for hydrolysis of starch (similar to 0.6 mg/ml, similar to 350 mu mol glucose per min per ml), maltose (similar to 0.54 mu mol, similar to 330 mu mol glucose per min per ml) and p-nitrophenyl-alpha-d-glucopyranoside (similar to 0.54 mu mol, similar to 8.28 mu mol p-nitrophenol per min per ml). However, the under-glycosylated form was sensitive to high temperatures probably because, in addition to stabilizing the protein conformation, glycosylation may also prevent unfolded or partially folded proteins from aggregating. Binding assays clearly showed that the under-glycosylated protein did not bind to concanavalin A but has conserve its jacalin-binding property, suggesting that only O-glycans might be intact on the tunicamycin treated form of the enzyme.

Amino acids and their transporters in the retina

This review provides an overview of the distributions, properties and roles of amino acid transport systems in normal and pathological retinal tissues and discusses the roles of specific identified transporters in the mammalian retina. The retina is used in this context as a vehicle for describing neuronal and glial properties. which are in semi, but not all cases comparable to those found elsewhere an the brain. Where significant departures are noted, these are discussed in the context of functional specialisations of the retina and its relationship to adjacent supporting tissues such as the retinal pigment epithelium. Specific examples are given where immunocytochemical labelling for amino acid transporters may yield inaccurate results, possibly because of activity-dependent conformation changes of epitopes in these proteins which render the epitopes more or less accessible to antibodies. (C) 2001 Elsevier Science Ltd. All rights reserved.

Solid-state NMR structure determination of melittin in a lipid environment

Solid-state C-13 NMR spectroscopy was used to investigate the three-dimensional structure of melittin as lyophilized powder and in ditetradecylphosphatidylcholine (DTPC) membranes. The distance between specifically labeled carbons in analogs [1-C-13]Gly3-[2-C-13]Ala4, [1-C-13]Gly3-[2-C-13]Leu6, [1-C-13]Leu13-[2-C-13]Ala15, [2-C-13]Leu13-[1-C-13]Ala15, and [1-C-13]Leu13-[2-C-13]Leu16 was measured by rotational resonance. As expected, the internuclear distances measured in [1-C-13]Gly3-[2-C-13]Ala4 and [1-C-13]Gly3-[2-C-13]Leu6 were consistent with alpha -helical structure in the N-terminus irrespective of environment. The Internuclear distances measured in [1-C-13]Leu13-[2-C-13]Ala15, [2-C-13]Leu13-[1-C-13]Ala15, and [1-C-13]Leu13-[2-C-13]Leu16 revealed, via molecular modeling, some dependence upon environment for conformation in the region of the bend in helical structure induced by Pro14. A slightly larger interhelical angle between the N- and C-terminal helices was indicated for peptide in dry or hydrated gel state DTPC (139 degrees -145 degrees) than in lyophilized powder (121 degrees -139 degrees) or crystals (129 degrees). The angle, however, is not as great as deduced for melittin in aligned bilayers of DTPC in the liquid-crystalline state (similar to 160 degrees) (R. Smith, F. Separovic, T. J. Milne, A. Whittaker, F. M. Bennett, B. A. Cornell, and A. Makriyannis, 1994, J. Mol, Biol 241:456-466). The study illustrates the utility of rotational resonance in determining local structure within peptide-lipid complexes.