Background
Interleukin (IL)‐33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL‐33 release is controlled. The transcription ...factor nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) plays a key role in antioxidant response regulation.
Objective
The goal of this project was to investigate the role of cellular oxidative stress in controlling IL‐33 release in airway epithelium.
Methods
Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type‐2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2‐cyano‐3,12‐dioxooleana‐1,9‐dien‐28‐oic acid methyl ester (CDDO‐Me) was used to evaluate the role of Nrf2‐induced antioxidant molecules.
Results
Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N‐acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL‐33 release. Administration of CDDO‐Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO‐Me treatment reduced allergen‐induced ATP secretion and IL‐33 release by airway epithelial cells in vitro and protected mice from IL‐33 release and asthma‐like pathological changes in the lungs.
Conclusions
The balance between oxidative stress and antioxidant responses plays a key role in controlling IL‐33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.
Within biology, molecules are arranged in hierarchical structures that coordinate and control the many processes that allow for complex organisms to exist. Proteins and other functional ...macromolecules are often studied outside their natural nanostructural context because it remains difficult to create controlled arrangements of proteins at this size scale. Viruses are elegantly simple nanosystems that exist at the interface of living organisms and nonliving biological machines. Studied and viewed primarily as pathogens to be combatted, viruses have emerged as models of structural efficiency at the nanoscale and have spurred the development of biomimetic nanoparticle systems. Virus-like particles (VLPs) are noninfectious protein cages derived from viruses or other cage-forming systems. VLPs provide incredibly regular scaffolds for building at the nanoscale. Composed of self-assembling protein subunits, VLPs provide both a model for studying materials' assembly at the nanoscale and useful building blocks for materials design. The robustness and degree of understanding of many VLP structures allow for the ready use of these systems as versatile nanoparticle platforms for the conjugation of active molecules or as scaffolds for the structural organization of chemical processes. Lastly the prevalence of viruses in all domains of life has led to unique activities of VLPs in biological systems most notably the immune system. Here we discuss recent efforts to apply VLPs in a wide variety of applications with the aim of highlighting how the common structural elements of VLPs have led to their emergence as paradigms for the understanding and design of biological nanomaterials.
Oxide electronic materials provide a plethora of possible applications and offer ample opportunity for scientists to probe into some of the exciting and intriguing phenomena exhibited by oxide ...systems and oxide interfaces. In addition to the already diverse spectrum of properties, the nanoscale form of oxides provides a new dimension of hitherto unknown phenomena due to the increased surface-to-volume ratio. Oxide electronic materials are becoming increasingly important in a wide range of applications including transparent electronics, optoelectronics, magnetoelectronics, photonics, spintronics, thermoelectrics, piezoelectrics, power harvesting, hydrogen storage and environmental waste management. Synthesis and fabrication of these materials, as well as processing into particular device structures to suit a specific application is still a challenge. Further, characterization of these materials to understand the tunability of their properties and the novel properties that evolve due to their nanostructured nature is another facet of the challenge. The research related to the oxide electronic field is at an impressionable stage, and this has motivated us to contribute with a roadmap on 'oxide electronic materials and oxide interfaces'. This roadmap envisages the potential applications of oxide materials in cutting edge technologies and focuses on the necessary advances required to implement these materials, including both conventional and novel techniques for the synthesis, characterization, processing and fabrication of nanostructured oxides and oxide-based devices. The contents of this roadmap will highlight the functional and correlated properties of oxides in bulk, nano, thin film, multilayer and heterostructure forms, as well as the theoretical considerations behind both present and future applications in many technologically important areas as pointed out by Venkatesan. The contributions in this roadmap span several thematic groups which are represented by the following authors: novel field effect transistors and bipolar devices by Fortunato, Grundmann, Boschker, Rao, and Rogers; energy conversion and saving by Zaban, Weidenkaff, and Murakami; new opportunities of photonics by Fompeyrine, and Zuniga-Perez; multiferroic materials including novel phenomena by Ramesh, Spaldin, Mertig, Lorenz, Srinivasan, and Prellier; and concepts for topological oxide electronics by Kawasaki, Pentcheva, and Gegenwart. Finally, Miletto Granozio presents the European action 'towards oxide-based electronics' which develops an oxide electronics roadmap with emphasis on future nonvolatile memories and the required technologies. In summary, we do hope that this oxide roadmap appears as an interesting up-to-date snapshot on one of the most exciting and active areas of solid state physics, materials science, and chemistry, which even after many years of very successful development shows in short intervals novel insights and achievements. Guest editors: M S Ramachandra Rao and Michael Lorenz
A phenomenological dislocation-based approach is proposed to account for the necking phenomenon during tensile deformation of metals and alloys. The critical strain corresponding to the onset of ...tensile instability is predicted in a simple explicit form based on the Kocks-Mecking dislocation kinetics approach. The model strongly suggests that uniform elongation is controlled primarily by the rate of dislocation recovery. The role of the stain rate sensitivity in stabilizing uniform plastic flow is also elucidated. Model predictions are found to be in excellent agreement with experimental data obtained for ultrafine grained 316L steel produced by severe plastic deformation. The approach presented provides general ques for designing materials with enhanced ductility, including ultrafine grained and bulk nanostructured metals and alloys. The proposed recipe is based on microstructural control of the rate of dynamic recovery of dislocation.
Display omitted
Materials scientists increasingly draw inspiration from the study of how biological systems fabricate materials under mild synthetic conditions by using self‐assembled macromolecular templates. ...Containerlike protein architectures such as viral capsids and ferritin are examples of such biological templates. These protein cages have three distinct interfaces that can be synthetically exploited: the interior, the exterior, and the interface between subunits. The subunits that comprise the building blocks of these structures can be modified both chemically and genetically in order to impart designed functionality to different surfaces of the cage. Therefore, the cages possess a great deal of synthetic flexibility, which allows for the introduction of multifunctionality in a single cage. In addition, hierarchical assembly of the functionalized cages paves the way for development of a new class of materials with a wide range of applications from electronics to biomedicine.
Biological systems fabricate materials under mild synthetic conditions using self‐assembled macromolecular templates. Containerlike protein architectures such as viral capsids and ferritin are examples of such biological templates. Three distinct interfaces can be synthetically exploited: the interior, the exterior, and the interface between subunits (see figure). Recent studies investigating the development of some containerlike protein‐cage architectures for material synthesis are presented in this article.
Revisiting the classical topic of the strain hardening behaviour from a perspective of the analytical model based on the evolution of dislocation density with strain, we extended the capacity of the ...single internal variable model towards predicting necking instability and re-examined the grain size dependence of the flow stress. An excellent agreement is observed between the model predictions of the necking strain and stress and the results of tensile testing of nickel polycrystals with grain sizes varied from sub-micrometres to hundred micrometres. The pivotal significance of the dynamic recovery in the occurrence of necking has been analysed and emphasised in the context of the discussion on the effect of grain size on flow stress. The most interesting corollary of the analysis made is that not only the simple modelling of the dislocation density evolution, which can be traced back from the very early stage of plastic flow in materials with different grain sizes, can be used for realistic approximation of the stress-strain behaviour during homogeneous deformation under constant plastic strain rate, but also for predicting the onset of necking instability with high confidence.
PDF
