Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation.

DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored.

Event-Triggered Bounded Consensus Tracking for Second-Order Nonlinear Multi-Agent Systems with Uncertainties.

This paper is concerned with event-triggered bounded consensus tracking for a class of second-order nonlinear multi-agent systems with uncertainties (MASs). Remarkably, the considered MASs allow multiple uncertainties, including unknown control coefficients, parameterized unknown nonlinearities, uncertain external disturbances, and the leader's control input being unknown. In this context, a new estimate-based adaptive control protocol with a triggering mechanism is proposed.

Performance Optimization for a Class of Petri Nets.

Petri nets (PNs) are widely used to model flexible manufacturing systems (FMSs). This paper deals with the performance optimization of FMSs modeled by Petri nets that aim to maximize the system's performance under a given budget by optimizing both quantities and types of resources, such as sensors and devices. Such an optimization problem is challenging since it is nonlinear; hence, a globally optimal solution is hard to achieve.

Dynamics of DNA hydroxymethylation and methylation during mouse embryonic and germline development.

In mammals, DNA 5-hydroxymethylcytosine (5hmC) is involved in methylation reprogramming during early embryonic development. Yet, to what extent 5hmC participates in genome-wide methylation reprogramming remains largely unknown. Here, we characterize the 5hmC landscapes in mouse early embryos and germ cells with parental allele specificity.

Predictive values of carotid high-resolution magnetic resonance imaging for large embolus shedding in carotid artery stenting.

Background: Embolus shedding is one of the important complications in carotid artery stenting (CAS). Carotid high-resolution magnetic resonance imaging (HR-MRI) is often used to directly reflect important biological characteristics, such as plaque size and composition, as well as the structure of the carotid artery wall. The aim of this study was to investigate the predictive values of carotid HR-MRI for large embolus shedding in CAS.

Fixed-Time Leader-Following Consensus Tracking Control for Nonliear Multi-Agent Systems under Jointly Connected Graph.

This paper researches the fixed-time leader-following consensus problem for nonlinear multi-agent systems (MASs) affected by unknown disturbances under the jointly connected graph. In order to achieve control goal, this paper designs a fixed-time consensus protocol, which can offset the unknown disturbances and the nonlinear item under the jointly connected graph, simultaneously. In this paper, the states of multiple followers can converge to the state of the leader within a fixed time regardless of the initial conditions rather than just converging to a small neighborhood near the leader state.

Chemical Pretreatment Activated a Plastic State Amenable to Direct Lineage Reprogramming.

Somatic cells can be chemically reprogrammed into a pluripotent stem cell (CiPSC) state, mediated by an extraembryonic endoderm- (XEN-) like state. We found that the chemical cocktail applied in CiPSC generation initially activated a plastic state in mouse fibroblasts before transitioning into XEN-like cells. The plastic state was characterized by broadly activated expression of development-associated transcription factors (TFs), such as , , , and , with a more accessible chromatin state indicating an enhanced capability of cell fate conversion.

Obesity modulates cell-cell interactions during ovarian folliculogenesis.

Obesity is known to affect female reproduction, as evidenced by obese patients suffering from subfertility and abnormal oogenesis. However, the underlying mechanisms by which obesity impairs folliculogenesis are poorly documented. Here, we performed comprehensive single-cell transcriptome analysis in both regular diet (RD) and obese mouse models to systematically uncover how obesity affects ovarian follicle cells and their interactions.

Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing.

Developing female human germ cells undergo genome-wide epigenetic reprogramming, but de novo DNA methylation dynamics and their interplay with chromatin states and transcriptional activation in developing oocytes is poorly understood. Here, we developed a single-cell multi-omics sequencing method, scChaRM-seq, that enables simultaneous profiling of the DNA methylome, transcriptome, and chromatin accessibility in single human oocytes and ovarian somatic cells. We observed a global increase in DNA methylation during human oocyte growth that correlates with chromatin accessibility, whereas increases of DNA methylation at specific features were associated with active transcription.

Impact of Insurance Status on Diagnostic Stage in Hodgkin's Lymphoma in the United States: Implications for Detection and Outcomes.

Introduction and objective Hodgkin's lymphoma (HL) is a form of cancer originating from white blood cells that presents upon diagnosis with well-characterized symptoms (palpable lymph nodes, fever, night sweats, weight loss). HL is currently one of the most treatable cancers, with a successful treatment rate of 75% worldwide. The objective of this study is to evaluate the association between insurance status and the stage of diagnosis of HL in the United States from the years 2007 to 2016.

Unveiling the heterogeneity of NKT cells in the liver through single cell RNA sequencing.

CD1d-dependent type I NKT cells, which are activated by lipid antigen, are known to play important roles in innate and adaptive immunity, as are a portion of type II NKT cells. However, the heterogeneity of NKT cells, especially NKT-like cells, remains largely unknown. Here, we report the profiling of NKT (NK1.

Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation.

Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state.

Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis.

Recently developed DNA base editing methods enable the direct generation of desired point mutations in genomic DNA without generating any double-strand breaks, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target mutations in genomic DNA, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA. For example, the cytosine deaminase APOBEC1-which is used in cytosine base editors (CBEs)-targets both DNA and RNA, and the adenine deaminase TadA-which is used in adenine base editors (ABEs)-induces site-specific inosine formation on RNA.

Integrative single-cell analysis of transcriptome, DNA methylome and chromatin accessibility in mouse oocytes.

Oocyte growth is a key step in forming mature eggs that are ready to be fertilized. The states and modifications of chromatin represent critical sources of information for this process. However, the dynamics and interrelations of these chromatin characteristics remain elusive.

Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem cells.

In response to myeloablative stresses, HSCs are rapidly activated to replenish myeloid progenitors, while maintaining full potential of self-renewal to ensure life-long hematopoiesis. However, the key factors that orchestrate HSC activities during physiological stresses remain largely unknown. Here we report that Med23 controls the myeloid potential of activated HSCs.

The sequence preference of DNA methylation variation in mammalians.

Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic modifications in mammalian DNA. The CpG methylation level shows a bimodal distribution but the bimodality can be overestimated due to the heterogeneity of per-base depth. Here, we developed an algorithm to eliminate the effect of per-base depth inhomogeneity on the bimodality and obtained a random CpG methylation distribution.

DNA Methylation Landscape Reflects the Spatial Organization of Chromatin in Different Cells.

The relationship between DNA methylation and chromatin structure is still largely unknown. By analyzing a large set of published sequencing data, we observed a long-range power law correlation of DNA methylation with cell class-specific scaling exponents in the range of tens of kilobases. We showed that such cell class-specific scaling exponents are caused by different patchiness of DNA methylation in different cells.

The effects of cytosine methylation on general transcription factors.

DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development.

DNA Structural Correlation in Short and Long Ranges.

Recent single-molecule measurements have revealed the DNA allostery in protein/DNA binding. MD simulations showed that this allosteric effect is associated with the deformation properties of DNA. In this study, we used MD simulations to further investigate the mechanism of DNA structural correlation, its dependence on DNA sequence, and the chemical modification of the bases.

Trehalose facilitates DNA melting: a single-molecule optical tweezers study.

Using optical tweezers, here we show that the overstretching transition force of double-stranded DNA (dsDNA) is lowered significantly by the addition of the disaccharide trehalose as well as certain polyol osmolytes. This effect is found to depend linearly on the logarithm of the trehalose concentration. We propose an entropic driving mechanism for the experimentally observed destabilization of dsDNA that is rooted in the higher affinity of the DNA bases for trehalose than for water, which promotes base exposure and DNA melting.

Dynamics of spontaneous flipping of a mismatched base in DNA duplex.

DNA base flipping is a fundamental theme in DNA biophysics. The dynamics for a B-DNA base to spontaneously flip out of the double helix has significant implications in various DNA-protein interactions but are still poorly understood. The spontaneous base-flipping rate obtained previously via the imino proton exchange assay is most likely the rate of base wobbling instead of flipping.

Modeling spatial correlation of DNA deformation: DNA allostery in protein binding.

We report a study of DNA deformations using a coarse-grained mechanical model and quantitatively interpret the allosteric effects in protein-DNA binding affinity. A recent single-molecule study (Kim et al. Science 2013, 339, 816) showed that when a DNA molecule is deformed by specific binding of a protein, the binding affinity of a second protein separated from the first protein is altered.

Probing allostery through DNA.

Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs.