Data_Sheet_1_Hsc70-4 aggravates PolyQ-mediated neurodegeneration by modulating NF-κB mediated immune response in Drosophila.PDF

Huntington’s disease occurs when the stretch of CAG repeats in exon 1 of the huntingtin (htt) gene crosses the permissible limit, causing the mutated protein (mHtt) to form insoluble aggregates or inclusion bodies. These aggregates are non-typically associated with various essential proteins in the cells, thus disrupting cellular homeostasis. The cells try to bring back normalcy by synthesizing evolutionary conserved cellular chaperones, and Hsp70 is one of the families of heat shock proteins that has a significant part in this, which comprises of heat-inducible and cognate forms. Here, we demonstrate that the heat shock cognate (Hsc70) isoform, Hsc70-4/HSPA8, has a distinct role in polyglutamate (PolyQ)-mediated pathogenicity, and its expression is enhanced in the polyQ conditions in Drosophila. Downregulation of hsc70-4 rescues PolyQ pathogenicity with a notable improvement in the ommatidia arrangement and near-normal restoration of optic neurons leading to improvement in phototaxis response. Reduced hsc70-4 also attenuates the augmented immune response by decreasing the expression of NF-κB and the antimicrobial peptides, along with that JNK overactivation is also restored. These lead to the rescue of the photoreceptor cells, indicating a decrease in the caspase activity, thus reverting the PolyQ pathogenicity. At the molecular level, we show the interaction between Hsc70-4, Polyglutamine aggregates, and NF-κB, which may be responsible for the dysregulation of signaling molecules in polyQ conditions. Thus, the present data provides a functional link between Hsc70-4 and NF-κB under polyQ conditions.</p

Assemble–Disassemble–Reassemble Dynamics in Copper Nanocluster-Based Superstructures

Assembling metal nanoclusters (MNCs) to form superstructures generates exciting photophysical properties distinct from those of their discrete precursors. Controlling the assembly process of MNCs and understanding the assembly–disassembly dynamics can have implications in achieving the reversible self-assembly of MNCs. The formation of self-assembled copper nanoclusters (CuNCs) as homogeneous superstructures and the underlying mechanisms governing such a process remain unexplored. Smart molecular imprinting of surface ligands can establish the forces necessary for the formation of such superstructures. Herein, we report highly luminescent, ordered superstructures of 4-phenylimidazole-2-thiol (4-PIT)-protected CuNCs with the help of l-ascorbic acid as a secondary ligand. Through a comprehensive spectroscopic analysis, we deciphered the mechanism of the self-assembly process, where the role of interligand H-bonding and C–H−π interactions was established. Notably, efficient reversibility of assembly–disassembly was demonstrated by re-establishing the interligand interactions and regenerating their photophysical and morphological signatures

Fluorescence Resonance Energy Transfer in a Supramolecular Assembly of Luminescent Silver Nanoclusters and a Cucurbit[8]uril-Based Host–Guest System

The understanding of interactions between organic chromophores and biocompatible luminescent noble metal nanoclusters (NCs) leading to an energy transfer process that has applications in light-harvesting materials is still in its nascent stage. This work describes a photoluminescent supramolecular assembly, made in two stages, employing an energy transfer process between silver (Ag) NCs as the donor and a host–guest system as the acceptor that can find potential applications in diverse fields. Initially, we explored the host–guest chemistry between a cationic guest ethidium bromide and cucurbit[8]uril host to modulate the fluorescence property of the acceptor. The host–guest interactions were characterized by using UV–vis absorption, steady-state and time-resolved spectroscopy, molecular docking, proton 1H nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and isothermal calorimetry studies. Next, we prepared a series of blue-emitting AgNCs using different templates such as proteins and peptides. We have found that these AgNCs can be employed as a donor in the energy transfer process upon mixing with the above acceptor for emission color tuning. Our in-depth studies also revealed that surface ligands could play a key role in modulating the energy transfer efficiency. Overall, by employing a noncovalent strategy, we have tried to develop Förster resonance energy transfer (FRET) pairs using blue-emitting NCs and a host–guest complex that could find potential applications in constructing advanced sustainable light-harvesting, white light-emitting, and anti-counterfeiting materials

DNA-Templated Modulation in the Photophysical Properties of a Fluorescent Molecular Rotor Auramine O by Varying the DNA Composition

This work delineates an integrative approach combining spectroscopic and computational studies to decipher the association-induced fluorescence properties of a fluorescent molecular rotor, viz., auramine O (AuO), after interacting with 20-mer duplex DNA having diverse well-matched base pairs. While exploring the scarcely explored sequence-dependent interaction mechanism of AuO and DNA, we observed that DNA could act as a conducive scaffold to the formation of AuO dimer through noncovalent interactions at lower molecular density. The photophysical properties of AuO depend on the nucleotide compositions as described from sequence-dependent shifting in the emission and absorption maxima. Furthermore, we explored such DNA base pair-dependent fluorescence spectral characteristics of AuO toward discriminating the thermodynamically most stable single nucleotide mismatch in a 20-mer sequence. Our results are interesting and could be useful in developing analogues with further enhanced emission properties toward mismatched DNA sequences