Degeneration of dopaminergic neurons in the substantia nigra causes the motor symptoms of Parkinson’s disease. The mechanisms underlying this age-dependent and region-selective neurodegeneration remain unclear. Here we identify Cav2.3 channels as regulators of nigral neuronal viability. Cav2.3 transcripts were more abundant than other voltage-gated Ca2+ channels in mouse nigral neurons and upregulated during aging. Plasmalemmal Cav2.3 protein was higher than in dopaminergic neurons of the ventral tegmental area, which do not degenerate in Parkinson’s disease. Cav2.3 knockout reduced activity-associated nigral somatic Ca2+ signals and Ca2+-dependent after-hyperpolarizations, and afforded full protection from degeneration in vivo in a neurotoxin Parkinson’s mouse model. Cav2.3 deficiency upregulated transcripts for NCS-1, a Ca2+-binding protein implicated in neuroprotection. Conversely, NCS-1 knockout exacerbated nigral neurodegeneration and downregulated Cav2.3. Moreover, NCS-1 levels were reduced in a human iPSC-model of familial Parkinson’s. Thus, Cav2.3 and NCS-1 may constitute potential therapeutic targets for combatting Ca2+-dependent neurodegeneration in Parkinson’s disease.
Ternary spinel CuCo2O4 nanostructure clenches great potential as high-performance electrode material for next-generation energy storage systems because of its higher electrical conductivity and electrochemical activity. Carbon free and binder free 3D flower-like CuCo2O4 structure are grown on nickel foam (NF) via a facile hydrothermal synthesis method followed by annealing. The obtained CuCo2O4/NF is directly used as electrode for lithium ion batteries (LIBs) and supercapacitors (SCs) application. The electrochemical study of 3D flower-like CuCo2O4 as an electrode for LIB and SC shows highly mesoporous unique architecture plays important role in achieving high capacity/capacitance with superior cycle life. The high surface area and mesoporous nature not only offer sufficient reaction sites, but also can accelerate the liquid electrolyte to penetrate electrode and the ions to reach the reacting sites. In outcome, it exhibits highest capacity of 1160 mA h g−1 after 200 cycles when used as an anode for LIB and specific capacitance of 1002 F g−1 after 3000 cycles. The superior electrochemical of synthesized material is attributed to direct contact of electrode active material with good intrinsic electrical conductivity to the underneath conductive NF substrate builds up an express path for fast ion and electron transfer.
The present work demonstrates the chemical fixation of CO2 for the synthesis of organic carbonates using mesoporous hollow marigold CuCo2O4 spinel microspheres as a catalyst prepared using the solvothermal method.
Vimentin is an intermediate filament protein, predominantly expressed in cells of mesenchymal origin, although its aberrant expression is seen in many carcinomas during epithelial mesenchymal transition. In cancer, vimentin expression is associated with the transition from a more differentiated epithelial phenotype to a dedifferentiated state. In view of the perceived role of keratins (Ks) as regulators of differentiation in epithelia, it was important to understand whether vimentin modulates differentiation through the reprogramming of keratins, in transformed cells. To address this, vimentin was stably downregulated in oral cancer derived cells. Further, global keratin profiling was performed after high salt keratin extraction. K5/K14 pair was found to be significantly downregulated, both at protein and mRNA levels upon vimentin downregulation. The previous study from our laboratory has shown a role of the K5/K14 pair in proliferation and differentiation of squamous epithelial cells. Vimentin depleted cells showed an increase in the differentiation state, marked by an increase in the levels of differentiation specific markers K1, involucrin, filaggrin and loricrin while its proliferation status remained unchanged. Rescue experiments with the K5/K14 pair overexpressed in vimentin knockdown background resulted in decreased differentiation state. ΔNp63 emerged as one of the indirect targets of vimentin, through which it modulates the expression levels of K5/K14. Further, immunohistochemistry showed a significant correlation between high vimentin-K14 expression and recurrence/poor survival in oral cancer patients. Thus, in conclusion, vimentin regulates the differentiation switch via modulation of K5/K14 expression. Moreover, vimentin-K14 together may prove to be the novel markers for the prognostication of human oral cancer.
Ni–Fe-based
electrode materials are promising candidates
for the oxygen evolution reaction (OER). The synergy between Fe and
Ni atoms is crucial in modulating the electronic structure of the
active site to enhance electrochemical performance. Herein, a simple
chemical immersion technique was used to grow Ni–Fe oxalate
nanowires directly on a porous nickel foam substrate. The as-prepared
Ni–Fe oxalate electrode exhibited an excellent electrochemical
performance of the OER with ultralow overpotentials of 210 and 230
mV to reach 50 and 100 mA cm–2 current densities,
respectively, in a 1 M KOH aqueous solution. The excellent OER performance
of this Ni–Fe oxalate electrode can be attributed to its bimetallic
composition and nanowire structure, which leads to an efficient ionic
diffusion, high electronic conductivity, and fast electron transfer.
The overall analysis indicates a suitable approach for designing electrocatalysts
applicable in energy conversion.
The development of nanostructured architectures using low-cost first-row transition metals with high electrocatalytic activity to replace noble-metal-based electrocatalysts has recently gained considerable attention in the field of clean and sustainable...
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