Monitoring Alzheimer Amyloid Peptide Aggregation by EPR

Plaques containing the aggregated β-Amyloid (Aβ) peptide in the brain are the main indicators of Alzheimer’s disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Aβ. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Aβ peptide variant containing an N-terminal cysteine (cys-Aβ) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Δ-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Aβ). Fibril formation in solutions of pure SL-Aβ and of SL-Aβ mixed with Aβ was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Aβ, one to a multimer (8–15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation

mini me swift the first mobile owl reasoner for ios

Mobile reasoners play a pivotal role in the so-called Semantic Web of Things. While several tools exist for the Android platform, iOS has been neglected so far. This is due to architectural differences and unavailability of OWL manipulation libraries, which make porting existing engines harder. This paper presents Mini-ME Swift, the first Description Logics reasoner for iOS. It implements standard (Subsumption, Satisfiability, Classification, Consistency) and non-standard (Abduction, Contraction, Covering, Difference) inferences in an OWL 2 fragment. Peculiarities are discussed and performance results are presented, comparing Mini-ME Swift with other state-of-the-art OWL reasoners

On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

Performance of two-dimensional shear wave elastography and transient elastography compared to liver biopsy for staging of liver fibrosis.

BACKGROUND Staging of liver fibrosis traditionally relied on liver histology, however transient elastography (TE) and more recently two-dimensional shear wave elastography (2D-SWE) evolved to non-invasive alternatives. Hence, we evaluated the diagnostic accuracy of 2D-SWE assessed by the Canon Aplio i800 ultrasound system using liver biopsy as reference and compared the performance to TE. METHODS In total, 108 adult patients with chronic liver disease undergoing liver biopsy, 2D-SWE and TE were enrolled prospectively at the University Hospital Zurich. Diagnostic accuracies were evaluated using the area under the receiver operating characteristic (AUROC) analysis, and optimal cutoff values by Youden's index RESULTS: Diagnostic accuracy of 2D-SWE was good for significant (≥F2; AUROC 85.2%, 95% confidence interval (95%CI):76.2-91.2%) as well as severe fibrosis (≥F3; AUROC 86.8%, 95%CI:78.1-92.4%) and excellent for cirrhosis (AUROC 95.6%, 95%CI:89.9-98.1%), compared to histology. TE performed equally well (significant fibrosis: 87.5%, 95%CI:77.7-93.3%; severe fibrosis: 89.7%, 95%CI:82.0-94.3%; cirrhosis: 96%, 95%CI:90.4-98.4%), and accuracy was not statistically different to 2D-SWE. 2D-SWE optimal cutoff values were 6.5, 9.8 and 13.1 kPa for significant fibrosis, severe fibrosis, and cirrhosis, respectively. CONCLUSIONS Performance of 2D-SWE was good to excellent and well comparable with TE, supporting the application of this 2D-SWE system in the diagnostic workup of chronic liver disease

Electrochromism: a useful probe to study algal photosynthesis.

In photosynthesis, electron transfer along the photosynthetic chain results in a vectorial transfer of protons from the stroma to the lumenal space of the thylakoids. This promotes the generation of an electrochemical proton gradient (Deltamu(H)(+)), which comprises a gradient of electric potential (DeltaPsi) and of proton concentration (DeltapH). The Deltamu(H)(+) has a central role in the photosynthetic process, providing the energy source for ATP synthesis. It is also involved in many regulatory mechanisms. The DeltapH modulates the rate of electron transfer and triggers deexcitation of excess energy within the light harvesting complexes. The DeltaPsi is required for metabolite and protein transport across the membranes. Its presence also induces a shift in the absorption spectra of some photosynthetic pigments, resulting in the so-called ElectroChromic Shift (ECS). In this review, we discuss the characteristic features of the ECS, and illustrate possible applications for the study of photosynthetic processes in vivo