The alpha-to-beta conformational transition of Alzheimer's Abeta-(1-42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of beta conformation seeding

Current views of the role of beta-amyloid (Abeta) peptide fibrils range from regarding them as the cause of Alzheimer's pathology to having a protective function. In the last few years, it has also been suggested that soluble oligomers might be the most important toxic species. In all cases, the study of the conformational properties of Abeta peptides in soluble form constitutes a basic approach to the design of molecules with "antiamyloid" activity. We have experimentally investigated the conformational path that can lead the Abeta-(1-42) peptide from the native state, which is represented by an alpha helix embedded in the membrane, to the final state in the amyloid fibrils, which is characterized by beta-sheet structures. The conformational steps were monitored by using CD and NMR spectroscopy in media of varying polarities. This was achieved by changing the composition of water and hexafluoroisopropanol (HFIP). In the presence of HFIP, beta conformations can be observed in solutions that have very high water content (up to 99 % water; v/v). These can be turned back to alpha helices simply by adding the appropriate amount of HFIP. The transition of Abeta-(1-42) from alpha to beta conformations occurs when the amount of water is higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water content showed that, on going from very apolar to polar environments, the long N-terminal helix is essentially retained, whereas the shorter C-terminal helix is lost. The complete conformational path was investigated in detail with the aid of molecular-dynamics simulations in explicit solvent, which led to the localization of residues that might seed beta conformations. The structures obtained might help to find regions that are more affected by environmental conditions in vivo. This could in turn aid the design of molecules able to inhibit fibril deposition or revert oligomerization processes.     

Brittle detachment of a stiffener bonded to an elastic plate

The diffusion of contact stresses between an elastic bar, bonded to an elastic half-plane and loaded longitudinally, requires the integration of a singular integral equation. The solution of this equation is not available in closed form, but only by a series expansion of the contact tangential force mutually transmitted between the stiffener and the plate. Since forty years it has been realized that the expansion of the solution in terms of Chebyshev polynomials is its most convenient method of representation. The procedure can also be extended to treat the brittle detachments of the tips of the stiffener when, according to Griffith's criterion of fracture, a balance can be virtually established between the increase of strain energy due to a propagation of cracks and the surface energy created.     

A numerical procedure for predicting the performance of high pressure homogenizing valves

This paper describes a numerical procedure for the prediction of the homogenizing performance of high pressure homogenizing valves used in diary plants. The method is based on a strict interaction between a complex CFD code and a simple homogenizing simulation code developed by the authors. This latter implements a mathematical model for the evaluation of droplets break-up, that needs an accurate evaluation of few significant fluid dynamic parameters in the whole fluid dynamic domain inside the valve. Due to the relevant pressure gradients within the flow and to the possibility of cavitation, particular attention has been paid in defining the fluid model, the mesh and the parameters required for CFD simulations. Notwithstanding the quite simple model of the homogenizing process, comparatively with the complexity of phenomena involved, the first results obtained are in general agreement with the experimental data available. These results point out the potential of the procedure proposed as a starting point for further implementation of more complex effects.     

The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m². Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m² was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.     

Fabrication of layered polydimethylsiloxane/perfluoropolyether microfluidic devices with solvent compatibility and valve functionality

The development of multilayer soft lithography methodology has seen polydimethysiloxane (PDMS) as the preferred material for the fabrication of microfluidic devices. However, the functionality of these PDMS microfluidic chips is often limited by the poor chemical resistance of PDMS to certain solvents. Here, we propose the use of a photocurable perfluoropolyether (PFPE), specifically FOMBLIN^® MD40 PFPE, as a candidate material to provide a solvent-resistant buffer layer to make the device substantially impervious to chemically induced swelling. We first carried out a systematic study of the solvent resistance properties of FOMBLIN^® MD40 PFPE as compared with PDMS. The comparison presented here demonstrates the superiority of FOMBLIN^® MD40 PFPE over PDMS in this regard; moreover, the results permitted to categorize solvents in four different groups depending on their swelling ratio. We then present a step-by-step recipe for a novel fabrication process that uses multilayer lithography to construct a comprehensive solvent-resistant device with fluid and control channels integrated with a valve structure and also permitting easy establishment of outside connections.     

Nucleation and Crystallization of New Glasses from Fly Ash Originating from Thermal Power Plants

The nucleation and crystallization kinetics of new glasses obtained by melting mixtures of a Spanish carbon fly ash with glass cullet and dolomite slag at 1500°C has been evaluated by a calculation method. These glasses, whose microstructure was examined by TEM carbon replica, were susceptible to controlled crystallization in the 800°–1100°C range. The resulting glass-ceramics developed acicular and branched wollastonite crystals or a network of dendritic pyroxene mixed with anorthite feldspar (SEM and EDX analysis). The time–temperature–transformation curves (processing of the XRD data) showed the crystallization kinetics and the critical cooling rate to be in the 12°–42°C/min range.     

Cold sintering of diatomaceous earth

Diatomite, a natural silicate-based sedimentary rock, was densified by cold sintering at room temperature and 150°C under various pressures (100, 200, and 300 MPa) and using different NaOH water solutions (0–3 M). The relative density of cold sintered diatomite can be as high as 90%, a condition that can be achieved by conventional firing only at 1200–1300°C. The cold sintered materials maintain the same mineralogical composition of the starting powder (quartz, glass, and illite) and are constituted by well-deformed and flattened grains oriented orthogonally to the applied pressure. Conversely, an evident phase evolution takes place upon conventional firing with the formation of cristobalite and mullite. The bending strength of cold sintered artifacts can exceed 40 MPa and increases to ≈80 MPa after post-annealing at 800°C, such mechanical strength is much larger than that of conventionally pressed samples sintered at 800°C, which is only ≈1 MPa.     

In vivo characterization of renal auto-antigens involved in human auto-immune diseases: the case of membranous glomerulonephritis

Renal auto-immune diseases represent a major source of morbidity in humans. For many years the knowledge on mechanisms of auto-immunity involving the kidney has been uniquely based on animal models. However, these findings often could not be readily translated to humans owing to notably difference in antigen expression by human podocytes. One example is Heymann nephritis (HN), the experimental model of human membranous glomerulonephritis (MGN), which is obtained in rats by injecting antibodies against megalin, a protein that is not present in human glomeruli. Human studies could not be done in the past since sequencing required too much material exceeding what obtainable from tissue biopsies in vivo. Research is now on the way to identify auto-antigens and isolate specific auto-antibodies in humans. New technology developments based on tissue microdissection and proteomical analysis have facilitated the recent discoveries, allowing direct analysis of human tissue in vivo. Major advances on the pathogenesis of MGN, the prototype for the formation and glomerular deposition of auto-antibodies, are now in progress. Two independent groups have, in fact, demonstrated the existence of specific IgG(4) against phospholipase A2 receptor, aldose reductase and Mn-superoxide dismutase in glomerular eluates and in plasma of a prominent part of patients with MGN, suggesting a major role of these proteins as auto-antigens in human MGN. This review will focalize these aspects outlining the contribution of proteomics in most recent developments.     

Assessing regulatory emotional self-efficacy in three countries.

The Regulatory Emotional Self-Efficacy (RESE) scale was developed to assess perceived self-efficacy in managing negative (NEG) and in expressing positive (POS) affect (G. V. Caprara & M. Gerbino, 2001). In this study of young adults, the factorial structure of the RESE scale was found to be similar in Italy, the United States, and Bolivia. In addition to a factor for POS, NEG was represented by a second-order factor of 2 different negative affects: despondency-distress (DES) and anger-irritation (ANG). Overall, there was partial invariance at both metric and scalar levels across gender and countries. Discriminant and convergent validity of the RESE scale was further examined in the Italian sample. Stronger patterns of association of POS with prosocial behavior, of ANG with low aggressive behavior problems and irritability, and of DES with low anxiety/depressive problems and shyness and high self-esteem were found. (PsycINFO Database Record (c) 2010 APA, all rights reserved)