RESUMO
Poly(ADP-ribosylation) (PARylation) is a post-translational modification mediated by a subset of ADP-ribosyl transferases (ARTs). Although PARylation-inhibition based therapies are considered as an avenue to combat debilitating diseases such as cancer and myopathies, the role of this modification in physiological processes such as cell differentiation remains unclear. Here, we show that Tankyrase1 (TNKS1), a PARylating ART, plays a major role in myogenesis, a vital process known to drive muscle fiber formation and regeneration. Although all bona fide PARPs are expressed in muscle cells, experiments using siRNA-mediated knockdown or pharmacological inhibition show that TNKS1 is the enzyme responsible of catalyzing PARylation during myogenesis. Via this activity, TNKS1 controls the turnover of mRNAs encoding myogenic regulatory factors such as nucleophosmin (NPM) and myogenin. TNKS1 mediates these effects by targeting RNA-binding proteins such as Human Antigen R (HuR). HuR harbors a conserved TNKS-binding motif (TBM), the mutation of which not only prevents the association of HuR with TNKS1 and its PARylation, but also precludes HuR from regulating the turnover of NPM and myogenin mRNAs as well as from promoting myogenesis. Therefore, our data uncover a new role for TNKS1 as a key modulator of RBP-mediated post-transcriptional events required for vital processes such as myogenesis.
Assuntos
Desenvolvimento Muscular , Fibras Musculares Esqueléticas , Miogenina , RNA Mensageiro , Tanquirases , Tanquirases/metabolismo , Tanquirases/genética , Humanos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Desenvolvimento Muscular/genética , Animais , Fibras Musculares Esqueléticas/metabolismo , Camundongos , Miogenina/genética , Miogenina/metabolismo , Nucleofosmina , Proteína Semelhante a ELAV 1/metabolismo , Proteína Semelhante a ELAV 1/genética , Estabilidade de RNA/genética , Poli ADP Ribosilação/genética , Linhagem Celular , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Diferenciação Celular/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Células HEK293RESUMO
Hydrogen gas evolution using an impure or saline water feed is a promising strategy to reduce overall energy consumption and investment costs for on-site, large-scale production using renewable energy sources. The chlorine evolution reaction is one of the biggest concerns in hydrogen evolution with impure water feeds. The "alkaline design criterion" in impure water electrolysis was examined here because water oxidation catalysts can exhibit a larger kinetic overpotential without interfering chlorine chemistry under alkaline conditions. Here, we demonstrated that relatively inexpensive thin-film composite (TFC) membranes, currently used for high-pressure reverse osmosis (RO) desalination applications, can have much higher rejection of Cl- (total crossover of 2.9 ± 0.9 mmol) than an anion-exchange membrane (AEM) (51.8 ± 2.3 mmol) with electrolytes of 0.5 M KOH for the anolyte and 0.5 M NaCl for the catholyte with a constant current (100 mA/cm2 for 20 h). The membrane resistances, which were similar for the TFC membrane and the AEM based on electrochemical impedance spectroscopy (EIS) and Ohm's law methods, could be further reduced by increasing the electrolyte concentration or removal of the structural polyester supporting layer (TFC-no PET). TFC membranes could enable pressurized gas production, as this membrane was demonstrated to be mechanically stable with no change in permeate flux at 35 bar. These results show that TFC membranes provide a novel pathway for producing green hydrogen with a saline water feed at elevated pressures compared to systems using AEMs or porous diaphragms.
Assuntos
Cloro , Hidrogênio , Metacrilatos , Osmose , Membranas Artificiais , Águas Salinas , CloretosRESUMO
HuR (ElavL1) is one of the main post-transcriptional regulators that determines cell fate. Although the role of HuR in apoptosis is well established, the post-translational modifications that govern this function remain elusive. In this study, we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is instrumental in the pro-apoptotic function of HuR. During apoptosis, a substantial reduction in HuR PARylation is observed. This results in the cytoplasmic accumulation and the cleavage of HuR, both of which are essential events for apoptosis. These effects are mediated by a pADP-ribose-binding motif within the HuR-HNS region (HuR PAR-binding site). Under normal conditions, the association of the HuR PAR-binding site with pADP-ribose is responsible for the nuclear retention of HuR. Mutations within this motif prevent the binding of HuR to its import factor TRN2, leading to its cytoplasmic accumulation and cleavage. Collectively, our findings underscore the role of PARylation in controlling the pro-apoptotic function of HuR, offering insight into the mechanism by which PARP1/2 enzymes regulate cell fate and adaptation to various assaults.
Assuntos
Processamento de Proteína Pós-Traducional , Ribose , Mutação , Diferenciação Celular , Domínios ProteicosRESUMO
The integration of distributed renewable energy technologies (such as building-integrated photovoltaics (BIPV)) into buildings, especially in space-constrained urban areas, offers sustainable energy and helps offset fossil-fuel-related carbon emissions. However, the intermittent nature of these distributed renewable energy sources can negatively impact the larger power grids. Efficient onsite energy storage solutions capable of providing energy continuously can address this challenge. Traditional large-scale energy storage methods like pumped hydro and compressed air energy have limitations due to geography and the need for significant space to be economically viable. In contrast, electrochemical storage methods like batteries offer more space-efficient options, making them well suited for urban contexts. This literature review aims to explore potential substitutes for batteries in the context of solar energy. This review article presents insights and case studies on the integration of electrochemical energy harvesting and storage into buildings. The seamless integration can provide a space-efficient source of renewable energy for new buildings or existing structures that often have limited physical space for retrofitting. This work offers a comprehensive examination of existing research by reviewing the strengths and drawbacks of various technologies for electrochemical energy harvesting and storage, identifying those with the potential to integrate into building skins, and highlighting areas for future research and development.