Accurate identification of 8-oxoguanine in RNA with single-nucleotide resolution using ligase-dependent qPCR.

8-oxoguanine (oG), a prevalent oxidative modification in RNA induced by reactive oxygen species (ROS), plays a pivotal role in regulating RNA functions. Accurate detection and quantification of oG modifications is critical to understanding their biological significance and potential as disease biomarkers, but effective detection methods remain limited. Here, we have developed a highly specific T3 DNA ligase-dependent qPCR assay that exploits the enzyme's ability to discriminate oG from guanine (G) with single-nucleotide resolution.

Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism is unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans and rats. These vesicles accumulate in diabetic wounds and are enriched with microRNAs (miRNAs) (e.

ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation.

Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [ (diabetes)] and leptin [ (obese)] are not identical, and the cause remains unclear. Here, we show that , but not , mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1 mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development.

Identification of circular RNAs as regulators and noninvasive biomarkers for placenta accreta spectrum.

In Brief: Placenta accreta spectrum (PAS) has an urgent need for reliable prenatal biomarkers. This study profiled the circular RNAs (circRNAs) in PAS placenta and maternal blood and identified two circRNAs can regulate trophoblast cells invasion and serve as noninvasive prenatal biomarkers for PAS prediction.

Abstract: PAS is one of the most alarming obstetric diseases with high mortality rates.

Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules.

Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin-proteasome system and the autophagy-lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear.

The Maternal Microbiome Programs the mA Epitranscriptome of the Mouse Fetal Brain and Intestine.

The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (mA) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA mA modification of the host, it remains unclear whether the maternal microbiome affects mA epitranscriptome of the fetus so as to impact fetal development.

Arginine methylation of METTL14 promotes RNA N-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells.

RNA N-methyladenosine (mA), the most abundant internal modification of mRNAs, plays key roles in human development and health. Post-translational methylation of proteins is often critical for the dynamic regulation of enzymatic activity. However, the role of methylation of the core methyltransferase METTL3/METTL14 in mA regulation remains elusive.

Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation.

Backgrounds: Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE.

N-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2.

A dynamic epigenome is critical for appropriate gene expression in development and health. Central to this is the intricate process of transcription, which integrates cellular signaling with chromatin changes, transcriptional machinery and modifications to messenger RNA, such as N-methyladenosine (mA), which is co-transcriptionally incorporated. The integration of these aspects of the dynamic epigenome, however, is not well understood mechanistically.

The RNA N-methyladenosine modification landscape of human fetal tissues.

A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N-methyladenosine (mA), a widespread RNA modification that is implicated in many biological processes. Here, to explore the global landscape of mA in human tissues, we generated 21 whole-transcriptome mA methylomes across major fetal tissues using mA sequencing. These data reveal dynamic mA methylation, identify large numbers of tissue differential mA modifications and indicate that mA is positively correlated with gene expression homeostasis.

CVm6A: A Visualization and Exploration Database for m⁶As in Cell Lines.

N6-methyladenosine (m⁶A) has been identified in various biological processes and plays important regulatory functions in diverse cells. However, there is still no visualization database for exploring global m⁶A patterns across cell lines. Here we collected all available MeRIP-Seq and m⁶A-CLIP-Seq datasets from public databases and identified 340,950 and 179,201 m⁶A peaks dependent on 23 human and eight mouse cell lines respectively.

Exosome Release Is Regulated by mTORC1.

Exosomes are small membrane-bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1).

Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies.

Background: Autism spectrum disorder (ASD) is a common severe pervasive neurodevelopmental disorder of undetermined etiology. Environmental exposures, especially pregnancy complications, have been increasingly recognized as a potential risk factor for ASD. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) specifically draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue.

Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA of Stem Cells.

Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC).

Gcn5 determines the fate of germline stem cells through degradation of Cyclin A.

The fluctuating CDK-CYCLIN complex plays a general role in cell-cycle control. Many types of stem cells use unique features of the cell cycle to facilitate asymmetric division. However, the manner in which these features are established remains poorly understood.

Quantity versus quality: the sperm war.

The evolution of sperm traits manifests itself prolifically across species, and postcopulatory sexual selection (PSS), as executed by the female, accompanies this process. The adaptive significance of some sperm traits (for example, the shape and number of sperms) is well understood. However, the evolution of germ size has not been fully exploited.

Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans.

Processing of pre-mRNA into mRNA is an important regulatory mechanism in eukaryotes that is mediated by the spliceosome, a huge and dynamic ribonucleoprotein complex. Splicing defects are implicated in a spectrum of human disease, but the underlying mechanistic links remain largely unresolved. Using a genome-wide association approach, we have recently identified single nucleotide polymorphisms in humans that associate with nonobstructive azoospermia (NOA), a common cause of male infertility.

[Identification of C(2)M interacting proteins by yeast two-hybrid screening].

The synaptonemal complex (SC) is a huge structure which assembles between the homologous chromosomes during meiotic prophase I. Drosophila germ cell-specific nucleoprotein C(2)M clustering at chromosomes can induce SC formation. To further study the molecular function and mechanism of C(2)M in meiosis, we constructed a bait vector for C(2)M and used the yeast two-hybrid system to identify C(2)M interacting proteins.

A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30.

Mitochondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone (S3) that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2.

The niche-dependent feedback loop generates a BMP activity gradient to determine the germline stem cell fate.

Stem cells interact with surrounding stromal cells (or niche) via signaling pathways to precisely balance stem cell self-renewal and differentiation. However, little is known about how niche signals are transduced dynamically and differentially to stem cells and their intermediate progeny and how the fate switch of stem cell to differentiating cell is initiated. The Drosophila ovarian germline stem cells (GSCs) have provided a heuristic model for studying the stem cell and niche interaction.

The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response.

In the Drosophila ovary, germline stem cells (GSCs) are maintained primarily by bone morphogenetic protein (BMP) ligands produced by the stromal cells of the niche. This signaling represses GSC differentiation by blocking the transcription of the differentiation factor Bam. Remarkably, bam transcription begins only one cell diameter away from the GSC in the daughter cystoblasts (CBs).

Cis-regulatory elements affecting the Nanos gene promoter in the germline stem cells.

Drosophila Nanos gene plays an important role in stem cell maintenance and body patterning. With the purpose of understanding the cis-regulatory machinery involved in the transcription of the nanos gene in the germline stem cells, we examined its promoter fragment from +97 to -708 relative to the transcription start site and identified enhancer elements located between position -108 and +97. Experiments with transgenic flies revealed that the minimal promoter (from -108 to +20) is sufficient in the germline stem cells for the GFP expression in transgenic Drosophila.

Effete-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila.

Increasing evidence supports the idea that the regulation of stem cells requires both extrinsic and intrinsic mechanisms. However, much less is known about how intrinsic signals regulate the fate of stem cells. Studies on germline stem cells (GSCs) in the Drosophila ovary have provided novel insights into the regulatory mechanisms of stem cell maintenance.

The bantam microRNA is associated with drosophila fragile X mental retardation protein and regulates the fate of germline stem cells.

Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP). We have previously demonstrated that dFmr1, the Drosophila ortholog of the fragile X mental retardation 1 gene, plays a role in the proper maintenance of germline stem cells in Drosophila ovary; however, the molecular mechanism behind this remains elusive. In this study, we used an immunoprecipitation assay to reveal that specific microRNAs (miRNAs), particularly the bantam miRNA (bantam), are physically associated with dFmrp in ovary.