RESUMO
Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and TFIIH around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a new TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryo-EM and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.
RESUMO
Depth profiling is an essential method to investigate the physical and chemical properties of a solid electrolyte and electrolyte/electrode interface. In conventional depth profiling, various spectroscopic tools such as X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) are utilized to monitor the chemical states along with ion bombardment to etch a sample. Nevertheless, the ion bombardment during depth profiling results in an inevitable systematic error, i.e., the accumulation of mobile ions at the electrolyte/electrode interface, known as the ion pile-up phenomenon. Here, we propose a novel method using bias potential, the substrate-bias method, to prevent the ion pile-up phenomena during depth profiling of a solid electrolyte. When the positive bias potential is applied on the substrate (electrode), the number of accumulating ions at the electrolyte/electrode interface is significantly reduced. The in-depth XPS analysis with the biased electrode reveals not only the suppression of the ion pile-up phenomena but also the altered chemical states at the interfacial region between the electrolyte and electrode depending on the bias. The proposed substrate-bias method can be a good alternative scheme for an efficient yet precise depth profiling technique for a solid electrolyte.
RESUMO
Halide perovskite, renowned for its multifunctional properties, shows considerable promise for realizing self-charging power systems. In this study, a lead-free methylammonium bismuth iodide (MA3Bi2I9) perovskite is used to create a self-charging power unit (SPU). This involves constructing a hybrid piezoelectric-triboelectric nanogenerator (Hybrid-TENG) and utilizing MA3Bi2I9 for energy storage as an anode in a lithium-ion battery (LIB). Initially, MA3Bi2I9 nanorods are synthesized and composited with a polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene polymer. The dielectric and mechanical properties of composite films having perovskite loading content are investigated. The optimized Hybrid-TENG exhibits superior performance, generating a voltage of 537 V, current density of 13.2 µA cm- 2, and maximum power density of 3.04 mW cm-2, which can be attributed to the high piezoelectric coefficient of MA3Bi2I9 nanorods (≈20.6 pm V-1). A MA3Bi2I9 thin film, serving as an electrode in LIB, demonstrates a high specific capacity of 2378.9 mAh cm-3 (578.8 mAh g-1) with a capacity retention of ≈87.5% over 100 cycles, underscoring its stable performance. Furthermore, a Hybrid-TENG is employed to charge the MA3Bi2I9-based LIB, thus realizing an SPU for driving portable electronics. This study highlights the promising potential of perovskites for developing efficient nanogenerators and LIBs, paving the way for sustainable energy solutions in small-scale electronics.
RESUMO
Nucleotide excision repair (NER) reduces efficacy of treatment with platinum (Pt)-based chemotherapy by removing Pt lesions from DNA. Previous study has identified that missense mutation or loss of the NER genes Excision Repair Cross Complementation Group 1 and 2 (ERCC1 and ERCC2) leads to improved patient outcomes after treatment with Pt-based chemotherapies. Although most NER gene alterations found in patient tumors are missense mutations, the impact of mutations in the remaining nearly 20 NER genes is unknown. Towards this goal, we previously developed a machine learning strategy to predict genetic variants in an essential NER protein, Xeroderma Pigmentosum Complementation Group A (XPA), that disrupt repair. In this study, we report in-depth analyses of a subset of the predicted variants, including in vitro analyses of purified recombinant protein and cell-based assays to test Pt agent sensitivity in cells and determine mechanisms of NER dysfunction. The most NER deficient variant Y148D had reduced protein stability, weaker DNA binding, disrupted recruitment to damage, and degradation. Our findings demonstrate that tumor mutations in XPA impact cell survival after cisplatin treatment and provide valuable mechanistic insights to improve variant effect prediction. Broadly, these findings suggest XPA tumor variants should be considered when predicting chemotherapy response.
RESUMO
Development of miniaturized thin-film lithium-ion batteries (TF-LIBs) using vacuum deposition techniques is crucial for low-scale applications, but addressing low energy density remains a challenge. In this work, structures analogous to SiOx-based thin-film electrodes are designed with close resemblance to traditional LIB slurry formulations including active material, conductive agent, and binder. The thin-film is produced using mid-frequency sputtering with a single hybrid target consisting of SiOx nanoparticles, carbon nanotubes, and polytetrafluoroethylene. The thin-film SiOx/PPFC (plasma-polymerized fluorocarbon) involves a combination of SiOx and conductive carbon within the PPFC matrix. This results in enhanced electronic conductivity and superior elasticity and hardness in comparison to a conventional pure SiOx-based thin-film. The electrochemical performance of the half-cell consisting of thin-film SiOx/PPFC demonstrates remarkable cycling stability, with a capacity retention of 74.8% up to the 1000th cycle at 0.5 C. In addition, a full cell using the LiNi0.6Co0.2Mn0.2O2 thin-film as the cathode material exhibits an exceptional initial capacity of ≈120 mAh g-1 at 0.1 C and cycle performance, marked by a capacity retention of 90.8% from the first cycle to the 500th cycle at a 1 C rate. This work will be a stepping stone for the AM/CB/B composite electrodes in TF-LIBs.