Pomegranate seed polyphenol-based nanosheets as an efficient inhibitor of amyloid fibril assembly and cytotoxicity of HEWL.

Poor water solubility and low bioavailability are considered as two main factors restricting therapeutic applications of natural polyphenols in relation to various disorders including amyloid-related diseases. Among various strategies developed to overcome these limitations, nanonization has attracted considerable attention. Herein, we compared the potency of bulk and nano forms of the polyphenolic fraction of pomegranate seed (PFPS) for modulating Hen Egg White Lysozyme (HEWL) amyloid fibril formation. Prepared PFPS nanosheets using direct oxidative pyrolysis were characterized by employing a range of spectroscopic and microscopic techniques. We found that the nano form can inhibit the assembly process and disintegrate preformed fibrils of HEWL much more effective than the bulk form of PFPS. Moreover, MTT-based cell viability and hemolysis assays showed the capacity of both bulk and nano forms of PFPS in attenuating HEWL amyloid fibril-induced toxicity, where the nano form was more effective. On the basis of thioflavin T results, a delay in the initiation of amyloid fibril assembly of HEWL appears to be the mechanism of action of PFPS nanosheets. We suggest that the improved efficiency of PFPS nanosheets in modulating the HEWL fibrillation process may be attributed to their increased surface area in accord with the surface-assistance model. Our results may present polyphenol-based nanosheets as a powerful approach for drug design against amyloid-related diseases.

A study on the interaction of the amyloid fibrils of α-synuclein and hen egg white lysozyme with biological membranes.

Alpha-synuclein (α-syn) aggregation and mitochondrial dysfunction are considered as two of the main factors associated with Parkinson's disease (PD). In the present investigation, the effectiveness of the amyloid fibrils obtained from α-syn with those of hen egg white lysozyme (HEWL), as disease-related and-unrelated proteins, to damage rat brain and rat liver mitochondria have been investigated. This was extended by looking at SH-SY5Y human neuroblastoma cells and erythrocytes, thereby investigating the significance of structural characteristics of amyloid fibrils related to their interactions with biomembranes obtained from various sources. Results presented clearly demonstrate substantial differences in the response of tested biomembranes to toxicity induced by α-syn/HEWL amyloid fibrils, highlighting a structure-function relationship. We found that fibrillar aggregates of α-syn, but not HEWL, caused a significant increase in mitochondrial ROS, loss of membrane potential, and mitochondrial swelling, in a dose-dependent manner. Toxicity was found to be more pronounced in brain mitochondria, as compared to liver mitochondria. For SH-SY5Y cells and erythrocytes, however, both α-syn and HEWL amyloid fibrils showed the capacity to induce toxicity. Taken together, these results may suggest selective toxicity of α-syn amyloid fibrils to mitochondria mediated likely by their direct interaction with the outer mitochondrial membrane, indicating a correlation between specific structural characteristics of α-syn fibrils and an organelle strongly implicated in PD pathology.

Improving Thermal Conductivity Coefficient in Oriented Strand Lumber (OSL) Using Sepiolite.

An issue in engineered wood products, like oriented strand lumber (OSL), is the low thermal conductivity coefficient of raw material, preventing the fast transfer of heat into the core of composite mats. The aim of this paper is to investigate the effect of sepiolite at nanoscale with aspect ratio of 1:15, in mixture with urea-formaldehyde resin (UF), and its effect on thermal conductivity coefficient of the final panel. Sepiolite was mixed with UF resin for 20 min prior to being sprayed onto wood strips in a rotary drum. Ten percent of sepiolite was mixed with the resin, based on the dry weight of UF resin. OSL panels with two resin contents, namely 8% and 10%, were manufactured. Temperature was measured at the core section of the mat at 5-second intervals, using a digital thermometer. The thermal conductivity coefficient of OSL specimens was calculated based on Fourier's Law for heat conduction. With regard to the fact that an improved thermal conductivity would ultimately be translated into a more effective polymerization of the resin, hardness of the panel was measured, at different depths of penetration of the Janka ball, to find out how the improved conductivity affected the hardness of the produced composite panels. The measurement of core temperature in OSL panels revealed that sepiolite-treated panels with 10% resin content had a higher core temperature in comparison to the ones containing 8% resin. Furthermore, it was revealed that the addition of sepiolite increased thermal conductivity in OSL panels made with 8% and 10% resin contents, by 36% and 40%, respectively. The addition of sepiolite significantly increased hardness values in all penetration depths. Hardness increased as sepiolite content increased. Considering the fact that the amount of sepiolite content was very low, and therefore it could not physically impact hardness increase, the significant increase in hardness values was attributed to the improvement in the thermal conductivity of panels and subsequent, more complete, curing of resin.

Mechanical and Physical Properties of Oriented Strand Lumber (OSL): The Effect of Fortification Level of Nanowollastonite on UF Resin.

The aim of this work is to investigate the effect of the fortification level of nanowollastonite on urea-formaldehyde resin (UF) and its effect on mechanical and physical properties of oriented strand lumbers (OSL). Two resin contents are applied, namely, 8% and 10%. Nanowollastonite is mixed with the resin at two levels (10% and 20%). It is found that the fortification of UF resin with 10% nanowollastonite can be considered as an optimum level. When nanowollastonite content is higher (that is, 20%), higher volume of UF resin is left over from the process of sticking the strips together, and therefore is absorbed by wollastonite nanofibers. The mechanism involved in the fortification of UF resin with nanowollastonite, which results in an improvement of thickness swelling values, can be attributed to the following two main factors: (i) nanowollastonite compounds making active bonds with the cellulose hydroxyl groups, putting them out of reach for bonding with the water molecules and (ii) high thermal conductivity coefficient of wollastonite improving the transfer of heat to different layers of the OSL mat, facilitating better and more complete resin curing. Since nanowollastonite contributes to making bonds between the wood strips, which consequently improves physical and mechanical properties, its use can be safely recommended in the OSL production process to improve the physical and mechanical properties of the panel.

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils.

A growing body of evidence indicates that membrane permeabilization, including internal membranes such as mitochondria, is a common feature and primary mechanism of amyloid aggregate-induced toxicity in neurodegenerative diseases. However, most reports describing the mechanisms of membrane disruption are based on phospholipid model systems, and studies directly targeting events occurring at the level of biological membranes are rare. Described here is a model for studying the mechanisms of amyloid toxicity at the membrane level. For mitochondrial isolation, density gradient medium is used to obtain preparations with minimal myelin contamination. After mitochondrial membrane integrity confirmation, the interaction of amyloid fibrils arising from α-synuclein, bovine insulin, and hen egg white lysozyme (HEWL) with rat brain mitochondria, as an in vitro biological model, is investigated. The results demonstrate that treatment of brain mitochondria with fibrillar assemblies can cause different degrees of membrane permeabilization and ROS content enhancement. This indicates structure-dependent interactions between amyloid fibrils and mitochondrial membrane. It is suggested that biophysical properties of amyloid fibrils and their specific binding to mitochondrial membranes may provide explanations for some of these observations.

Optimal network topology for responsive collective behavior.

Animals, humans, and multi-robot systems operate in dynamic environments, where the ability to respond to changing circumstances is paramount. An effective collective response requires suitable information transfer among agents and thus critically depends on the interaction network. To investigate the influence of the network topology on collective response, we consider an archetypal model of distributed decision-making and study the capacity of the system to follow a driving signal for varying topologies and system sizes. Experiments with a swarm of robots reveal a nontrivial relationship between frequency of the driving signal and optimal network topology. The emergent collective response to slow-changing perturbations increases with the degree of the interaction network, but the opposite is true for the response to fast-changing ones. These results have far-reaching implications for the design and understanding of distributed systems: a dynamic rewiring of the interaction network is essential to effective collective operations at different time scales.

Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei.

There are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01-0.40mg/mL) were determined. The results show that for HFBII concentrations of 0.04mg/mL and upwards the protein significantly reduced the presence of ABTS(+) radicals in the medium, the IC50 value found to be 0.13mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry.