Highlighting the effect of amyloid beta assemblies on the mechanical properties and conformational stability of cell membrane

Alzheimer disease (AD) is the most common cause of dementia, characterized by a progressive decline in cognitive function due to the abnormal aggregation and deposition of Amyloid beta (Aβ) fibrils in the brain of patients. In this context, the molecular mechanisms of protein misfolding and aggregation that are known to induce significant biophysical alterations in cells, including destabilization of plasma membranes, remain partially unclear. Physical interaction between the Aβ assemblies and the membrane leads to the disruption of the cell membrane in multiple ways including, surface carpeting, generation of transmembrane channels and detergent-like membrane dissolution. Understanding the impact of amyloidogenic protein in different stages of aggregation with the plasma membrane, plays a crucial role to fully elucidate the pathological mechanisms of AD. Within this framework, computer simulations represent a powerful tool able to shed lights on the interactions governing the structural influence of Aβ proteins on biological membrane. In this study, molecular dynamics (MD) simulations have been performed in order to characterize how POPC bilayer conformational and mechanical properties are affected by the interaction with Aβ11-42 peptide, oligomer and fibril

A higher Angiogenin expression is associated with a non-nuclear Maspin location in laryngeal carcinoma

Objectives. In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC). Methods. Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes. Results. On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression 655.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression 655.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041). Conclusion. Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC

The triggering of MHD instabilities through photospheric footpoint motions

The results of 3D numerical simulations modelling the twisting of a coronal loop due to photospheric vortex motions are presented. The simulations are carried out using an initial purely axial field and an initial equilibrium configuration with twist, . The non-linear and resistive evolutions of the instability are followed. The magnetic field is twisted by the boundary motions into a loop which initially has boundary layers near the photospheric boundaries as has been suggested by previous work. The boundary motions increase the twist in the loop until it becomes unstable. For both cases the boundary twisting triggers the kink instability. In both cases a helical current structure wraps itself around the kinked central current. This current scales linearly with grid resolution indicating current sheet formation. For the cases studied 35-40% of the free magnetic energy is released. This is sufficient to explain the energy released in a compact loop flare

Simulated Time Lags of Hinode/XRT and SDO/AIA Lightcurves as an Indication of Loop Heating Scenario

The precise nature of the heating mechanism in coronal loops is still a matter of enormous research. We present the results from a 1D hydrodynamic loop simulation of a coronal loop which was run using different parameters such as loops length (50, 200 and 500 Mm), maximum temperature reached (3MK and 10 MK0, and abundances. For each scenario the model outputs were used to calculate the corresponding lightcurves as seen by XRT/Be-thin and various EUV AIA channels. The lag time between the peak of these lightcurves was computed and tested using cross-correlation and plotted as a function of loop length

The Dynamics of the Innovation System for Functional Foods in South Brazil

 This study aims at identifying the dynamics of the innovation system for functional foods (FF) in Rio Grande do Sul, Brazil. Functional food is any healthy food claimed to have a health-promoting or disease-preventing property beyond the basic function of supplying nutrients. Health has been named as the most significant trend and innovation driver in the global food and drinks market. Brazil is one of the leading countries in food production and consumption, and the market for functional foods have been growing 10% per year, three times more than the market for conventional foods. Although this food category is considered mature in some developed markets (such as in Japan, in the Nordic countries and in the U.S), it is still unknown for many consumers, especially those located in developing countries. On the other hand, functional foods has been attracting the attention of multinationals and local food industries, since innovation can significantly impact on their competitive advantages. Therefore, in this study, first we are going to investigate consumers’ motivations, attitudes and intention to buy functional foods, since the market demands a better understanding of this trend. A survey with 450 consumers was conducted and provided quantitative insights. Secondly, we identified the availability of functional food products in the local retail market, through observation techniques. Our aim was to confront consumers’ needs with local food companies’ market supply. In a further stage, we are going to analyse the functioning of this innovation system, describing the agents involved in this context and their relations through in-depth interviews with local representatives (stakeholders). Innovation system is here understood as the set of distinct institutions which jointly and individually contribute to the development and diffusion of new technologies and which provides the framework within which governments form and implement policies to influence the innovation process. As such "it is a system of interconnected institutions to create, store and transfer the knowledge, skills and artefacts which define new technologies." (Metcalfe, 1995). Hence, we are investigating issues such as: Are local food companies ready to innovate in such a competitive and dynamic scenario? How can this system respond to consumers’ demands? Are there conditions for an innovative food network in South Brazil? Our contributions help to shed light into these questions. Preliminary results indicate that the innovation system for functional foods in Rio Grande do Sul is incipient, but it is developing fast. Stronger governance and co-ordination strategies are needed. There are few local functional food products in the market, but those are attractive to consumers and indicate promising opportunities. The survey shows that interviewed consumers presented positive attitudes towards functional foods and enough purchasing power to buy it. Nutritionists and other health professionals have high credibility and could help inform consumers about the benefits of particular categories of functional foods. Food industry itself is not regarded as the most trustworthy source. Finally, this study shows that the understanding of Brazilian consumers is fundamental to help food companies define their strategies. To map the most accepted categories of functional foods is also important, aiming to avoid the "tentative and error" approach

Numerical Investigation of a Coronal Mass Ejection from an Anemone Active Region: Reconnection and Deflection of the 2005 August 22 Eruption

We present a numerical investigation of the coronal evolution of a coronal mass ejection (CME) on 2005 August 22 using a 3-D thermodynamics magnetohydrodynamic model, the SWMF. The source region of the eruption was anemone active region (AR) 10798, which emerged inside a coronal hole. We validate our modeled corona by producing synthetic extreme ultraviolet (EUV) images, which we compare to EIT images. We initiate the CME with an out-of-equilibrium flux rope with an orientation and chirality chosen in agreement with observations of a H-alpha filament. During the eruption, one footpoint of the flux rope reconnects with streamer magnetic field lines and with open field lines from the adjacent coronal hole. It yields an eruption which has a mix of closed and open twisted field lines due to interchange reconnection and only one footpoint line-tied to the source region. Even with the large-scale reconnection, we find no evidence of strong rotation of the CME as it propagates. We study the CME deflection and find that the effect of the Lorentz force is a deflection of the CME by about 3 deg/Rsun towards the East during the first 30 minutes of the propagation. We also produce coronagraphic and EUV images of the CME, which we compare with real images, identifying a dimming region associated with the reconnection process. We discuss the implication of our results for the arrival at Earth of CMEs originating from the limb and for models to explain the presence of open field lines in magnetic clouds.Comment: 14 pages, 8 Figures, accepted to Astrophysical Journa

Understanding functional group and assembly dynamics in temperature responsive systems leads to design principles for enzyme responsive assemblies

Understanding the molecular rules behind the dynamics of supramolecular assemblies is fundamentally important for the rational design of responsive assemblies with tunable properties. Herein, we report that the dynamics of temperature-sensitive supramolecular assemblies is not only affected by the dehydration of oligoethylene glycol (OEG) motifs, but also by the thermally-promoted molecular motions. These counteracting features set up a dynamics transition point (DTP) that can be modulated with subtle variations in a small hydrophobic patch on the hydrophilic face of the amphiphilic assembly. Understanding the structural factors that control the dynamics of the assemblies leads to rational design of enzyme-responsive assemblies with tunable temperature responsive profiles

Coupling of Coronal and Heliospheric Magnetohydrodynamic Models: Solution Comparisons and Verification

Two well-established magnetohydrodynamic (MHD) codes are coupled to model the solar corona and the inner heliosphere. The corona is simulated using the MHD algorithm outside a sphere (MAS) model. The Lyon–Fedder–Mobarry (LFM) model is used in the heliosphere. The interface between the models is placed in a spherical shell above the critical point and allows both models to work in either a rotating or an inertial frame. Numerical tests are presented examining the coupled model solutions from 20 to 50 solar radii. The heliospheric simulations are run with both LFM and the MAS extension into the heliosphere, and use the same polytropic coronal MAS solutions as the inner boundary condition. The coronal simulations are performed for idealized magnetic configurations, with an out-of-equilibrium flux rope inserted into an axisymmetric background, with and without including the solar rotation. The temporal evolution at the inner boundary of the LFM and MAS solutions is shown to be nearly identical, as are the steady-state background solutions, prior to the insertion of the flux rope. However, after the coronal mass ejection has propagated through the significant portion of the simulation domain, the heliospheric solutions diverge. Additional simulations with different resolution are then performed and show that the MAS heliospheric solutions approach those of LFM when run with progressively higher resolution. Following these detailed tests, a more realistic simulation driven by the thermodynamic coronal MAS is presented, which includes solar rotation and an azimuthally asymmetric background and extends to the Earth’s orbit