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Intracellular decay of N6‐methyladenine (m6A)‐containing RNA potentially induces aberrant N6‐methyl‐2′‐adenine (6mdA) misincorporation into DNA. Biophysically, misincorporated 6mdA may destabilize the DNA duplex in a manner similar to bona fide methylated 6mdA DNA, thereby affecting DNA replication and transcription. Utilizing heavy stable isotope labeling and ultrasensitive UHPLC–MS/MS assay, we demonstrate that intracellular m6A‐RNA decay does not generate free 6mdA species, nor lead to any misincorporated DNA 6mdA in most mammalian cell lines tested, unveiling the existence of a sanitation mechanism that prevents 6mdA misincorporation. Depletion of deaminase ADAL increases the levels of free 6mdA species, concomitant with the presence of DNA‐misincorporated 6mdA resulting from intracellular RNA m6A decay, suggesting that ADAL catabolizes 6mdAMP in vivo. Furthermore, we show that the overexpression of adenylate kinase 1 (AK1) promotes 6mdA misincorporation, while AK1 knockdown diminishes 6mdA incorporation, in ADAL‐deficient cells. We conclude that ADAL together with other factors (such as MTH1) contributes to 2′‐deoxynucleotide pool sanitation in most cells but compromised sanitation (e.g., in NIH3T3 cells) and increased AK1 expression may facilitate aberrant 6mdA incorporation. This sanitation mechanism may provide a framework for the maintenance of the epigenetic 6mdA landscape. Synopsis: Intracellular decay of m6A‐containing RNA may induce aberrant N6‐methyl‐2′‐adenine (6mdA) incorporation into DNA, affecting its replication and transcription. This study unveils a 2′‐deoxynucleotide pool sanitation mechanism acting to suppress potential DNA 6mdA misincorporation.Intracellular m6A‐RNA decay does not induce any free 6mdA species, nor lead to any misincorporated DNA 6mdA in most mammalian cell lines tested.An active sanitation mechanism blocks 6mdA misincorporation.ADAL deaminase and other regulatory factors, such as MTH1, contribute to the sanitation.Compromised sanitation and increased adenylate kinase AK1 expression facilitate aberrant 6mdA incorporation. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor targeting estrogen receptors (ERs), has been implicated in the promotion of breast cancer. Perinatal exposure of BPA could induce longitudinal alteration of DNA hydroxymethylation in imprinted loci of mouse blood cells. To date, no data has been reported on the effects of BPA on DNA hydroxymethylation in breast cells. Therefore, we asked whether BPA can induce DNA hydroxymethylation change in human breast cells. Given that dysregulated epigenetic DNA hydroxymethylation is observed in various cancers, we wondered how DNA hydroxymethylation modulates cancer development, and specifically, whether and how BPA and its analogs promote breast cancer development via DNA hydroxymethylation. Objectives: We aimed to explore the interplay of the estrogenic activity of bisphenols at environmental exposure dose levels with TET dioxygenase-catalyzed DNA hydroxymethylation and to elucidate their roles in the proliferation of [ER.sup.+] breast cancer cells as stimulated by environmentally relevant bisphenols. Methods: Human MCF-7 and T47D cell lines were used as ER-dependent breast cell proliferation models, and the human MDA-MB-231 cell line was used as an ER-independent breast cell model. These cells were treated with BPA or bisphenol S (BPS) to examine BPA/BPS-related proliferation. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and enzyme-linked immunosorbent assays (ELISAs) were used to detect DNA hydroxymethylation. Crispr/Cas9 and RNA interference technologies, quantitative polymerase chain reaction (qPCR), and Western blot analyses were used to evaluate the expression and function of genes. Co-immunoprecipitation (Co-IP), bisulfite sequencing-PCR (BSP), and chromatin immunoprecipitation-qPCR (ChIP-qPCR) were used to identify the interactions of target proteins. Results: We measured higher proliferation in ER+ breast cancer cells treated with BPA or its replacement, BPS, accompanied by an ER[alpha]-dependent decrease in genomic DNA hydroxymethylation. The results of our overexpression, knockout, knockdown, and inhibition experiments suggested that TET2-catalyzed DNA hydroxymethylation played a suppressive role in BPA/BPS-stimulated cell proliferation. On the other hand, we observed that TET2 was negatively regulated by the activation of ER[alpha] (dimerized and phosphorylated), which was also induced by BPA/BPS binding. Instead of a direct interaction between TET2 and ER[alpha], data of our Co-IP, BSP, and ChIP-qPCR experiments indicated that the activated ER[alpha] increased the DNA methyltransferase (DNMT)-mediated promoter methylation of TET2, leading to an inhibition of the TET2 expression and DNA hydroxymethylation. Conclusions: We identified a new feedback circuit of ER[alpha] activation-DNMT-TET2-DNA hydroxymethylation in [ER.sup.+] breast cancer cells and uncovered a pivotal role of TET2-mediated DNA hydroxymethylation in modulating BPA/BPS-stimulated proliferation. Moreover, to our knowledge, we for the first time established a linkage among chemical exposure, DNA hydroxymethylation, and tumor-associated proliferation. These findings further clarify the estrogenic activity of BPA/BPS and its profound implications for the regulation of epigenetic DNA hydroxymethylation and cell proliferation., Introduction Bisphenol A (BPA) is a well-known environmental endocrine disruptor, causing adverse alterations in the reproductive system, liver, and mammary glands (Vandenberg et al. 2007; Michalowicz 2014; Rodgers et al. [...]

We report the design and fabrication of diamond Lamb wave spin-mechanical resonators embedded in a two-dimensional (2D) phononic crystal square lattice. The rectangular resonator features gigahertz in-plane compression modes protected by the phononic bandgap of the square lattice. A membrane-in-bulk approach is developed for the fabrication of the suspended 2D structure. This approach overcomes the limitations of fabrication approaches, which are either incompatible with the necessary high-temperature thermal annealing or unsuitable for 2D structures with the required feature size. Graded soft oxygen etching, with the etching rate decreased gradually to below 1 nm/min, is used to remove defective surface layers damaged by reactive ion etching. Combining the graded etching with other established surface treatment techniques reduces the optical linewidth of nitrogen vacancy centers in resonators with a thickness below 1 μm to as narrow as 330 MHz. [ABSTRACT FROM AUTHOR]

Resolving the genetic basis of fertility restoration for cytoplasmic male sterility (CMS) can improve the efficiency of three-line hybrid breeding. However, the genetic determinants of male fertility restoration in cotton are still largely unknown. This study comprehensively compared the full-length transcripts of CMS-D2 and CMS-D8 systems to identify potential genes linked with fertility restorer genes Rf1 or Rf2. Target comparative analysis revealed a higher percentage of differential genes in each restorer line as compared to their corresponding sterile and maintainer lines. An array of genes with specific expression in the restorer line of CMS-D2 had functional annotations related to floral development and pathway enrichments in various secondary metabolites, while specifically expressed genes in the CMS-D8 restorer line showed functional annotations related to anther development and pathway enrichment in the biosynthesis of secondary metabolites. Further analysis identified potentially key genes located in the target region of fertility restorer genes Rf1 or Rf2. In particular, Ghir_D05G032450 can be the candidate gene related to restorer gene Rf1, and Ghir_D05G035690 can be the candidate gene associated with restorer gene Rf2. Further gene expression validation with qRT-PCR confirmed the accuracy of our results. Our findings provide useful insights into decoding the potential regulatory network that retrieves pollen fertility in cotton and will help to further reveal the differences in the genetic basis of fertility restoration for two CMS systems. [ABSTRACT FROM AUTHOR]

Previous work regarding low-rank matrix recovery has concentrated on the scenarios in which the matrix is noise-free and the measurements are corrupted by noise. However, in practical application, the matrix itself is usually perturbed by random noise preceding to measurement. This paper concisely investigates this scenario and evidences that, for most measurement schemes utilized in compressed sensing, the two models are equivalent with the central distinctness that the noise associated with double noise model is larger by a factor to m n / M , where m , n are the dimensions of the matrix and M is the number of measurements. Additionally, this paper discusses the reconstruction of low-rank matrices in the setting, presents sufficient conditions based on the associating null space property to guarantee the robust recovery and obtains the number of measurements. Furthermore, for the non-Gaussian noise scenario, we further explore it and give the corresponding result. The simulation experiments conducted, on the one hand show effect of noise variance on recovery performance, on the other hand demonstrate the verifiability of the proposed model. [ABSTRACT FROM AUTHOR]