Charlesrichards2821

s of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.Dendrite pathology is frequently observed in various neurodegenerative diseases (NDs). Although previous studies identified several pathogenic mediators of dendrite defects that act through loss of function in NDs, the underlying pathogenic mechanisms remain largely unexplored. Here, our search for additional pathogenic contributors to dendrite defects in NDs identifies Relish/NF-κB as a novel gain-of-toxicity-based mediator of dendrite defects in animal models for polyglutamine (polyQ) diseases and amyotrophic lateral sclerosis (ALS). In a Drosophila model for polyQ diseases, polyQ-induced dendrite defects require Dredd/Caspase-8-mediated endoproteolytic cleavage of Relish to generate the N-terminal fragment, Rel68, and subsequent Charon-mediated nuclear localization of Rel68. Rel68 alone induced neuronal toxicity causing dendrite and behavioral defects, and we identify two novel transcriptional targets, Tup and Pros, that mediate Rel68-induced neuronal toxicity. Finally, we show that Rel68-induced toxicity also contributes to dendrite and behavioral defects in a Drosophila model for ALS. Collectively, our data propose disinhibition of latent toxicity of Relish/NF-κB as a novel pathogenic mechanism underlying dendrite pathology in NDs.The signaling protein Sonic Hedgehog (SHH) is crucial for the development and function of many vertebrate tissues. It remains largely unclear, however, what defines the range and specificity of pathway activation. The adrenal gland represents a useful model to address this question, where the SHH pathway is activated in a very specific subset of cells lying near the SHH-producing cells, even though there is an abundance of lipoproteins that would allow SHH to travel and signal long-range. We determine that, whereas adrenal cells can secrete SHH on lipoproteins, this form of SHH is inactive due to the presence of cosecreted inhibitors, potentially explaining the absence of long-range signaling. Instead, we find that SHH-producing cells signal at short range via membrane-bound SHH, only to receiving cells with primary cilia. Finally, our data from NCI-H295R adrenocortical carcinoma cells suggest that adrenocortical tumors may evade these regulatory control mechanisms by acquiring the ability to activate SHH target genes in response to TGF-β.Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid overabundance stress. How cells form MDCs is unclear. Here, we show that MDCs are dynamic structures that form and stably persist at sites of contact between the ER and mitochondria. MDC biogenesis requires the ER-mitochondria encounter structure (ERMES) and the conserved GTPase Gem1, factors previously implicated in lipid exchange and membrane tethering at ER-mitochondria contacts. Interestingly, common genetic suppressors of abnormalities displayed by ERMES mutants exhibit distinct abilities to rescue MDC formation in ERMES-depleted strains and are incapable of rescuing MDC formation in cells lacking Gem1. Thus, the function of ERMES and Gem1 in MDC biogenesis may extend beyond their conventional role in maintaining mitochondrial phospholipid homeostasis. Overall, this study identifies an important function for ER-mitochondria contacts in the biogenesis of MDCs.This paper investigates the control of effective magnetic anisotropy in Permalloy linear chain arrays, achieved by tuning the symmetry arrangement of the ellipsoidal nanomagnets and the film thickness. When the ellipsoidal nanomagnets are coupled along their easy axis, stronger effective magnetic anisotropy is achieved compared to when the nanomagnets are coupled along their hard axis. A clear transition from a single domain state to a combination of complex flux closure states such as a vortex or double vortices is observed at different applied field angles when the film thickness is varied in the range from 20 nm to 100 nm. Tunable microwave absorption spectra, obtained by ferromagnetic resonance spectroscopy, established the complex interplay between the shape anisotropy and magnetostatic interactions, which becomes more intriguing at different film thicknesses and applied field angles. The micromagnetic simulations are in good agreement with the experimental results. Our results demonstrate possible ways of manipulating the effective magnetic anisotropy in arrays of nanomagnets for magnonic and microwave applications.Metal chalcogenide nanoparticles offer vast control over their optoelectronic properties via size, shape, composition, and morphology which has led to their use across fields including optoelectronics, energy storage, and catalysis. While cadmium and lead-based nanocrystals are prevalent in applications, concerns over their toxicity have motivated researchers to explore alternate classes of nanomaterials based on environmentally benign metals such as zinc and tin. The goal of this research is to identify material systems that offer comparable performance to existing metal chalcogenide systems from abundant, recyclable, and environmentally benign materials. With band gaps that span the visible through the infrared, II-V direct band gap semiconductors such as tetragonal zinc phosphide (α-Zn3P2) are promising candidates for optoelectronics. To date, syntheses of α-Zn3P2 nanoparticles have been hindered because of the toxicity of zinc and phosphorus precursors, surface oxidation, and defect states leading to carrier trapping and low photoluminescence quantum yield. This work reports a colloidal synthesis of quantum confined α-Zn3P2 nanoparticles from common phosphorus precursor tris(trimethylsilyl)phosphine and environmentally benign zinc carboxylates. Shelling of the nanoparticles with zinc sulfide is shown as a method of preventing oxidation and improving the optical properties of the nanoparticles. These results show a route to stabilizing α-Zn3P2 nanoparticles for optoelectronic device applications.Here, a strategy for the preparation of adjustable imidazolium-type ionic liquid (IL)-based carbon quantum dots (CQDs) was reported. The effect of chemical structure, including carbon chain length of the N-substitution and the type of anion, on the amphiphilicity of CQDs was systematically investigated. It was found that the hydrophobicity of CQDs can be increased with the increase of carbon chain length for substitution at the N3 position. Moreover, the amphiphilicity of CQDs was also switched by changing the hydrophilic anions to hydrophobic anions. Due to adjustable amphiphilicity, the hydrophilic and hydrophobic CQDs were used for the preparation of fluorescent hydrogels and organogels, respectively. The fluorescent CQD-doped gels showed light- and force-dual stimuli responsiveness, which provides more secure information encryption than traditional single encryption inks.Two-phase nanocomposites have gained significant research interest because of their multifunctionalities, tunable geometries and potential device applications. Different from the previously demonstrated oxide-oxide 2-phase nanocomposites, coupling nitrides with metals shows high potential for building alternative hybrid plasmonic metamaterials towards chemical sensing, tunable plasmonics, and nonlinear optics. Unique advantages, including distinct atomic interface, excellent crystalline quality, large-scale surface coverage and durable solid-state platform, address the high demand for new hybrid metamaterial designs for versatile optical material needs. This review summarizes the recent progress on nitride-metal nanocomposites, specifically targeting bottom-up self-assembled nanocomposite thin films. Various morphologies including vertically aligned nanocomposites (VANs), self-organized nanoinclusions, and nanoholes fabricated by additional chemical treatments are introduced. Starting from thin film nucleation and growth, the prerequisites of successful strain coupling and the underlying growth mechanisms are discussed. These findings facilitate a better control of tunable nanostructures and optical functionalities. Future research directions are proposed, including morphological control of the secondary phase to enhance its homogeneity, coupling nitrides with magnetic phase for the magneto-optical effect and growing all-ceramic nanocomposites to extend functionalities and anisotropy.Monoelemental two-dimensional (2D) group-VA materials have received increasing interest due to their great potential in optoelectronic applications. Despite numerous efforts have been made for their syntheses, the development of effective and better controllable synthetic approaches for the preparation of monoelemental 2D group-VA materials is still in its infancy. In this work, we report a soft-template approach for the synthesis of multilayered antimonene and bismuthene nanosheets in colloidal solutions. We show that the prepared antimonene and bismuthene nanosheets possess a well-defined rhombohedral crystal structure with impressive stability. We elucidate a formation pathway for the 2D nanosheets with small-angle X-ray diffraction (XRD) analysis. We demonstrate that SbCl3 dissolves in alkyl phosphonic acids to form a lamellar structure initially, which is apt for the formation of the final 2D morphology. The present study introduces a general route to synthesizing monoelemental 2D group-VA materials in colloidal solutions and gives a deeper insight into their growth mechanism.Zinc phosphide (Zn3P2) nanowires constitute prospective building blocks for next generation solar cells due to the combination of suitable optoelectronic properties and an abundance of the constituting elements in the Earth's crust. The generation of periodic superstructures along the nanowire axis could provide an additional mechanism to tune their functional properties. Here we present the vapour-liquid-solid growth of zinc phosphide superlattices driven by periodic heterotwins. This uncommon planar defect involves the exchange of Zn by In at the twinning boundary. We find that the zigzag superlattice formation is driven by reduction of the total surface energy of the liquid droplet. The chemical variation across the heterotwin does not affect the homogeneity of the optical properties, as measured by cathodoluminescence. The basic understanding provided here brings new propsects on the use of II-V semiconductors in nanowire technology.Helix is an important secondary structure in proteins and polypeptides, which, however, has rarely been recognized in amino acids or their simple derivatives. In this work, we firstly unveil the generic existence of supramolecular helical secondary structures in solid-state N-protected amino acids. Throughout searching in Cambridge Structural Database followed by screening, ∼10% N-protected amino acids were evidenced to form H-bonded helical structures, thus covering 15 coded amino acids and diverse types of protecting groups. Helical structures were typically classified as 21 and 31 symmetry, and specific double-strand helical structures were discovered. Computational studies on the calculated electronic circular dichroism spectra show well-defined correlation to experimental results, indicative of the supramolecular secondary structures that possess feature Cotton effects similar to naturally occurring α-helices in proteins. Such feature Cotton effects could be transferred to protecting groups, which is of vital significance to the emerging chiroptical materials.