RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair

Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end resection and upsets DSB repair pathway choice. RNF169 acts as a molecular rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP analyses of AsiSI-induced DSBs unveiled that RNF169 exhibits robust accumulation at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs. Accordingly, we found that RNF169 promotes CtIP-dependent DSB resection and favors homology-mediated DSB repair, and further showed that RNF169 dose-dependently stimulates single-strand annealing repair, in part, by alleviating the 53BP1-imposed barrier to DSB end resection. Our results highlight the interplay of RNF169 with 53BP1 in fine-tuning choice of DSB repair pathways

Phototunable biomemory based on light-mediated charge trap

Phototunable biomaterial‐based resistive memory devices and understanding of their underlying switching mechanisms may pave a way toward new paradigm of smart and green electronics. Here, resistive switching behavior of photonic biomemory based on a novel structure of metal anode/carbon dots (CDs)‐silk protein/indium tin oxide is systematically investigated, with Al, Au, and Ag anodes as case studies. The charge trapping/detrapping and metal filaments formation/rupture are observed by in situ Kelvin probe force microscopy investigations and scanning electron microscopy and energy‐dispersive spectroscopy microanalysis, which demonstrates that the resistive switching behavior of Al, Au anode‐based device are related to the space‐charge‐limited‐conduction, while electrochemical metallization is the main mechanism for resistive transitions of Ag anode‐based devices. Incorporation of CDs with light‐adjustable charge trapping capacity is found to be responsible for phototunable resistive switching properties of CDs‐based resistive random access memory by performing the ultraviolet light illumination studies on as‐fabricated devices. The synergistic effect of photovoltaics and photogating can effectively enhance the internal electrical field to reduce the switching voltage. This demonstration provides a practical route for next‐generation biocompatible electronics

Spirometric Standards for Healthy Children and Adolescents of Korean Chinese in Northeast China

In China there are 1,923,842 Korean Chinese, who live mostly (92.27%) in the country's three northeast provinces. In spite of this sizeable number, no spirometric data are available at present on them. The present study investigated normal spirometric reference values for the Korean Chinese children and adolescents. Spirometry was performed in 443 healthy Korean Chinese children and adolescents aged 8-18 yr with measurements of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF) and maximum mid-expiratory flow (MMEF). Reference equations for FEV1, FVC, PEF and MMEF were derived by using multiple regression analysis. All of the measured spirometric parameters correlated positively with height and age significantly (P < 0.001). The predicted values of FVC and FEV1 were higher than values obtained by using Caucasian and other Asian equations (P < 0.001). A set of spirometric reference equations has been derived using a relatively large, healthy, non-smoking young Korean Chinese population with a wide range of ages and heights, the results of which differ from those gained from several other reference equations. These reference equations should be used for evaluation of lung function in this population

Genetic polymorphisms of CYP2A13 and its relationship to nasopharyngeal carcinoma in the Cantonese population

Nasopharyngeal carcinoma (NPC) is characterized by a high prevalence in Southern China, especially among Cantonese individuals of the Guangdong Province. Epidemiological studies have suggested that frequent exposure to high levels of nitrosamine from preserved foods such as salted fish could be a risk factor for NPC. Cytochrome P450 encompasses a family of enzymes that metabolize carcinogens and CYP2A13, a member of this family, is expressed predominantly in the respiratory tract with the highest levels in the nasal mucosa. In an effort to test whether a correlation exists between CYP2A13 genetic polymorphism and the risk of developing NPC, we sequenced all nine exons and the exon-intron junctions of the CYP2A13 gene in 45 NPC patients. We identified a total of 21 single nucleotide polymorphism (SNPs), including 7 novel SNPs. The most frequent functional variant allele was 74A-1757G-3375T-7233G with a haplotype frequency of 7.8% in the 45 NPC cases. In addition, a stop codon mutation was detected in one case. We then selected the 3 most frequent SNPs and one stop codon mutation to expand our study to a case-control analysis within the Cantonese population. A novel haplotype consisting 8 SNPs in introns, and four additional novel SNPs were identified; but no correlation between CYP2A13 genetic polymorphism and individual susceptibility to NPC was observed

Tulp1 deficiency causes early-onset retinal degeneration through affecting ciliogenesis and activating ferroptosis in zebrafish

Mutations in TUB-like protein 1 (TULP1) are associated with severe early-onset retinal degeneration in humans. However, the pathogenesis remains largely unknown. There are two homologous genes of TULP1 in zebrafish, namely tulp1a and tulp1b. Here, we generated the single knockout (tulp1a(−/−) and tulp1b(−/−)) and double knockout (tulp1-dKO) models in zebrafish. Knockout of tulp1a resulted in the mislocalization of UV cone opsins and the degeneration of UV cones specifically, while knockout of tulp1b resulted in mislocalization of rod opsins and rod-cone degeneration. In the tulp1-dKO zebrafish, mislocalization of opsins was present in all types of photoreceptors, and severe degeneration was observed at a very early age, mimicking the clinical manifestations of TULP1 patients. Photoreceptor cilium length was significantly reduced in the tulp1-dKO retinas. RNA-seq analysis showed that the expression of tektin2 (tekt2), a ciliary and flagellar microtubule structural component, was downregulated in the tulp1-dKO zebrafish. Dual-luciferase reporter assay suggested that Tulp1a and Tulp1b transcriptionally activate the promoter of tekt2. In addition, ferroptosis might be activated in the tulp1-dKO zebrafish, as suggested by the up-regulation of genes related to the ferroptosis pathway, the shrinkage of mitochondria, reduction or disappearance of mitochondria cristae, and the iron and lipid droplet deposition in the retina of tulp1-dKO zebrafish. In conclusion, our study establishes an appropriate zebrafish model for TULP1-associated retinal degeneration and proposes that loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2, which further increases the death of photoreceptors via ferroptosis. These findings offer insight into the pathogenesis and clinical treatment of early-onset retinal degeneration

Scattering Fields Control by Metamaterial Device Based on Ultra-Broadband Polarization Converters

We proposed a novel ultra-broadband meta¬material screen with controlling the electromagnetic scat¬tering fields based on the three layers wideband polariza¬tion converter (TLW-PC). The unit cell of TLW-PC was composed of a three layers substrate loaded with double metallic split-rings structure and a metal ground plane. We observed that the polarization converter primarily per¬formed ultra-broadband cross polarization conversion from 5.71 GHz to 14.91 GHz. Furthermore, a metamaterial screen, which contributed to the low scattering charac¬teristics, had been exploited with the orthogonal array based on TLW-PC. The near scattering electronic fields are controlled due to the change of phase and amplitude for incident wave. The metamaterial screen significantly exhibited low scattering characteristics from 5.81 GHz to 15.06 GHz. To demonstrate design, a metamaterial device easily implemented by the common printed circuit board method has been fabricated and measured. Experimental results agreed well with the simulated results