Background:The highly flexible C-terminal region of TDP-43 is implicated in disease pathology. Results: An amyloidogenic core was identified to be critical for TDP-43 aggregation. Conclusion: Helix-to-sheet structural transformation of the amyloidogenic core initiates TDP-43 aggregation and cytoplasmic inclusion formation. Significance: This is a potential therapeutic target for mitigating the TDP-43 proteinopathies.

The fabrication of ordered microstructures is of importance to much of modern science and technology, which thus actively drives the development of various patterning technologies besides photolithography. Soft lithography, [1] encompassing many flexible methods, has become one of the most robust and versatile non-photolithographic routes to ordered microstructures. The success of soft lithography relies on the use of a poly(dimethylsiloxane) (PDMS) elastomer as a stamp, mold, or mask, which ensures the conformal contact between surfaces of the PDMS and substrates of interest and the easy release without destroying the formed microstructures. By flexibly applying different methods of soft lithography, a variety of materials (such as organic molecules, [2] proteins, [3] colloids, [4] metals, [5] and polymers [6] ) could not only be transferred from the surface of a PDMS stamp to the specific area of a substrate, but also be selectively removed from the substrate surface to the PDMS stamp surface using a lift-up process. [7] Colloidal crystals made of polymer or inorganic microspheres have attracted extensive interest due to their potential applications as sensing, [8] optical, [9] and photonic bandgap materials, [10] and for the creation of highly ordered macroporous materials [11] and high-strength ceramics.[12] Usually, specific microstructures are anticipated in colloidal crystals for their device applications, [13] e.g., chemical and biochemical sensors, and photonic chips. Based on photolithography and soft lithography technologies, a large number of solid surfaces could be patterned into nano-or micrometer-sized relief structures, [14] or areas with different properties, such as wettability, [15] charged nature, [16] or current density. [17] These patterned surfaces could be subsequently used to direct the self-assembly of microspheres for creating colloidal crystals with defined crystalline orientations, shapes, and sizes. Most of these methods are commonly based on the strategy of the confined selfassembly of microspheres, in which the patterning and formation of colloidal crystals take place simultaneously. In this communication, we report a complementary soft lithography technique to pattern the obtained colloidal crystals using a lift-up process. Because this method is based on the selective transfer of a single layer of close-packed microspheres from the crystal film to the PDMS stamp surface, it is possible to realize fine control over the microstructures of colloidal film using a layer-by-layer lift-up process. Figure 1 outlines the procedure used to pattern colloidal crystals using the lift-up soft lithography. Monodisperse silica microspheres were assembled into colloidal crystals on the silicon wafer by the evaporation of suspension (see Experimental). A PDMS stamp with patterned features was brought into conformal contact with the surface of the crystal film under a certain pressure. After the sample was heated at 100 C for 3 h and the PDMS stamp was carefully peeled away, a single layer ...