The rational inclusion of enzyme-inspired features around the cobaloxime core reinstates its status as a leading synthetic photo-/electro-catalyst for hydrogen production.

The development of a bidirectional catalyst for oxygen reduction and water oxidation is the key to establishing sustainable energy transduction from renewable resources. We report a stable homogeneous molecular copper complex, comprising of a labile diimine-dioxime ligand framework, that enables rapid and complete 4e − /4H + electrocatalysis for both oxygen reduction (2.1(±0.01) × 10 5 s −1 ) and water oxidation (3.2(±0.01) × 10 5 s −1 ) in aqueous solution presumably via in situ formation of binuclear intermediates. Computational investigations unravel the pivotal role of the interactive flexible ligand scaffold in accommodating the copper-core in variable oxidation states and influencing the O−O bond cleavage/formation dynamics during the catalysis. This study sets up a template for designing molecular catalysts for mediating energyrelevant multielectron/multiproton reactions in both oxidizing and reducing environments.

Alzheimer's disease (AD) manifests as neuronal loss. On the premise of Grb2 overexpression in AD mouse brain and brain tissues of AD patients, our study primarily focuses on the stability of cytoskeletal proteins in the context of degenerative AD-like conditions. Two predominant molecular features of AD, extracellular accumulation of β-amyloid oligomers and intracellular elevation of amyloid precursor protein intracellular domain levels, have been used to closely inspect the series of signalling events. In their presence, multiple signalling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton, and Grb2 partially counterbalances the cytoskeletal loss. Increased Grb2-NOX4 interactions play a preventive role against cytoskeletal disassembly, in turn blocking the activity of nitrogen oxides and decreasing the expression of slingshot homolog 1 (SSH-1) protein, a potent inducer of cytoskeleton disassembly. This study unravels a unique role of Grb2 in protecting the cytoskeletal architecture in AD-like conditions and presents a potential new strategy for controlling neurodegeneration.

No abstract

Alzheimer’s Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Reportedly, two non-canonical Receptor Tyrosine Kinases (RTKs), ALK and RYK, both targets of the same micro RNA miR-1271, exhibit significant and consistent functional downregulation in post-mortem AD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor. Here we show that Grb2 and NOX4 play critical roles in reducing the severity of both the diseases. The study demonstrates that the abundance of Grb2 in degenerative conditions, in conjunction with NOX4, reverse cytoskeletal degradation by counterbalancing the network of small GTPases. PAX4, a transcription factor for both Grb2 and NOX4, emerges as the key link between the common pathways of AD and T2D. Downregulation of both ALK and RYK through miR-1271, elevates the PAX4 level by reducing its suppressor ARX via Wnt/b-Catenin signaling. For the first time, this study brings together RTKs beyond Insulin Receptor (IR) family, transcription factor PAX4 and both AD and T2D pathologies on a common regulatory platform.