Characterization of DNA methylation reader proteins in .

In plants, cytosine DNA methylation (mC) is largely associated with transcriptional repression of transposable elements, but it can also be found in the body of expressed genes, referred to as gene body methylation (gbM). gbM is correlated with ubiquitously expressed genes; however, its function, or absence thereof, is highly debated. The different outputs that mC can have raise questions as to how it is interpreted-or read-differently in these sequence and genomic contexts.

The Building Respectful Integrated Doula Support as a Gateway for Enhanced Maternal Health Outcomes and Experiences Conceptual Framework for Integrating Doula Support in the Pregnancy Continuum.

Doulas, non-clinical companions trained to provide emotional, informational, and physical support throughout the pregnancy continuum, have emerged as cost-effective interventions to enhance maternal health. This article aims to review existing definitions, roles, outcomes, and theoretic frameworks surrounding doula support, culminating in the development of the Building Respectful Integrated Doula Support as a Gateway for Enhanced Maternal Health Outcomes and Experiences (BRIDGE) conceptual framework. The BRIDGE conceptual framework provides a comprehensive understanding of doula support and its potential to improve maternal health outcomes, underscoring the importance of integrating doula support into standard maternal health care practices.

Establishment of single-cell transcriptional states during seed germination.

Germination involves highly dynamic transcriptional programs as the cells of seeds reactivate and express the functions necessary for establishment in the environment. Individual cell types have distinct roles within the embryo, so must therefore have cell type-specific gene expression and gene regulatory networks. We can better understand how the functions of different cell types are established and contribute to the embryo by determining how cell type-specific transcription begins and changes through germination.

Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species.

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates.

Approaches for the Analysis and Interpretation of Whole-Genome Bisulfite Sequencing Data.

DNA methylation is a covalent modification of DNA that plays important roles in processes such as the regulation of gene expression, transcription factor binding, and suppression of transposable elements. The use of whole-genome bisulfite sequencing (WGBS) enables the genome-wide identification and quantification of DNA methylation patterns at single-base resolution and is the gold standard for the analysis of DNA methylation. However, the computational analysis of WGBS data can be particularly challenging, as many computationally intensive steps are required.

Generation of Whole-Genome Bisulfite Sequencing Libraries for Comprehensive DNA Methylome Analysis.

Whole-genome bisulfite sequencing (WGBS) enables the detection of DNA methylation at a single base-pair resolution. The treatment of DNA with sodium bisulfite allows the discrimination of methylated and unmethylated cytosines, but the power of this technology can be limited by the input amounts of DNA and the length of DNA fragments due to DNA damage caused by the desulfonation process. Here, we describe a WGBS library preparation protocol that minimizes the loss and damage of DNA, generating high-quality libraries amplified with fewer polymerase chain reaction (PCR) cycles, and hence data with fewer PCR duplicates, from lower amounts of input material.

Benchmarking medical laboratory performance on a global scale.

Background And Aims: Laboratory performance as a relative concept needs repetitive benchmarking for continuous improvement of laboratory procedures and medical processes. Benchmarking as such establishes reference levels as a basis for improvements efforts for healthcare institutions along the diagnosis cycle, with the patient at its center. But while this concept seems to be generally acknowledged in laboratory medicine, a lack of practical implementation hinders progress at a global level.

Comparing Gender Congruency in Nonsurgical versus Postsurgical Top Surgery Patients: A Prospective Survey Study.

Background: Gender dysphoria can result in reduced quality of life. Treatments include hormone replacement therapy (HRT) and gender-affirming surgery. Our study compared congruency, satisfaction, and discrimination in patients who underwent top surgery and HRT versus HRT alone.

Sanglifehrin A mitigates multiorgan fibrosis by targeting the collagen chaperone cyclophilin B.

Pathological deposition and crosslinking of collagen type I by activated myofibroblasts drives progressive tissue fibrosis. Therapies that inhibit collagen synthesis have potential as antifibrotic agents. We identify the collagen chaperone cyclophilin B as a major cellular target of the natural product sanglifehrin A (SfA) using photoaffinity labeling and chemical proteomics.

CRISPRi-based circuits to control gene expression in plants.

The construction of synthetic gene circuits in plants has been limited by a lack of orthogonal and modular parts. Here, we implement a CRISPR (clustered regularly interspaced short palindromic repeats) interference (CRISPRi)-based reversible gene circuit platform in plants. We create a toolkit of engineered repressible promoters of different strengths and construct NOT and NOR gates in Arabidopsis thaliana protoplasts.

A modular dCas9-based recruitment platform for combinatorial epigenome editing.

Targeted epigenome editing tools allow precise manipulation and investigation of genome modifications, however they often display high context dependency and variable efficacy between target genes and cell types. While systems that simultaneously recruit multiple distinct 'effector' chromatin regulators can improve efficacy, they generally lack control over effector composition and spatial organisation. To overcome this we have created a modular combinatorial epigenome editing platform, called SSSavi.

Automated virtual reality cognitive therapy versus virtual reality mental relaxation therapy for the treatment of persistent persecutory delusions in patients with psychosis (THRIVE): a parallel-group, single-blind, randomised controlled trial in England with mediation analyses.

Background: Persecutory delusions are a major psychiatric problem that often do not respond sufficiently to standard pharmacological or psychological treatments. We developed a new brief automated virtual reality (VR) cognitive treatment that has the potential to be used easily in clinical services. We aimed to compare VR cognitive therapy with an alternative VR therapy (mental relaxation), with an emphasis on understanding potential mechanisms of action.

Transient naive reprogramming corrects hiPS cells functionally and epigenetically.

Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function. These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown.

Exploring the identity of individual plant cells in space and time.

In recent years, single-cell genomics, coupled to imaging techniques, have become the state-of-the-art approach for characterising biological systems. In plant sciences, a variety of tissues and species have been profiled, providing an enormous quantity of data on cell identity at an unprecedented resolution, but what biological insights can be gained from such data sets? Using recently published studies in plant sciences, we will highlight how single-cell technologies have enabled a better comprehension of tissue organisation, cell fate dynamics in development or in response to various stimuli, as well as identifying key transcriptional regulators of cell identity. We discuss the limitations and technical hurdles to overcome, as well as future directions, and the promising use of single-cell omics to understand, predict, and manipulate plant development and physiology.

Collaborative Training as a Conduit to Build Knowledge in Black Birth Workers.

Background: Black women have worse birthing outcomes in part due to perceived racism. Therefore, mistrust between Black birthing people and their obstetric providers is profound. Black birthing people may use doulas to support and advocate throughout their pregnancy.

Multiplexed single-cell 3D spatial gene expression analysis in plant tissue using PHYTOMap.

Retrieving the complex responses of individual cells in the native three-dimensional tissue context is crucial for a complete understanding of tissue functions. Here, we present PHYTOMap (plant hybridization-based targeted observation of gene expression map), a multiplexed fluorescence in situ hybridization method that enables single-cell and spatial analysis of gene expression in whole-mount plant tissue in a transgene-free manner and at low cost. We applied PHYTOMap to simultaneously analyse 28 cell-type marker genes in Arabidopsis roots and successfully identified major cell types, demonstrating that our method can substantially accelerate the spatial mapping of marker genes defined in single-cell RNA-sequencing datasets in complex plant tissue.

Spontaneous Rupture of the Extensor Pollicis Longus Tendon: A Systematic Review.

Background: Extensor pollicis longus (EPL) rupture and tenosynovitis of the third dorsal compartment is often described in association with a history of rheumatoid arthritis or in the setting of a distal radius fracture. However, the literature suggests multiple other potential factors that may lead to a seemingly spontaneous rupture.

Methods: We performed a systematic review following guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Embryonic Stem Cell-Derived Neurons as a Model System for Epigenome Maturation during Development.

DNA methylation in neurons is directly linked to neuronal genome regulation and maturation. Unlike other tissues, vertebrate neurons accumulate high levels of atypical DNA methylation in the CH sequence context (mCH) during early postnatal brain development. Here, we investigate to what extent neurons derived in vitro from both mouse and human pluripotent stem cells recapitulate in vivo DNA methylation patterns.

Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential.

Current approaches to staging chronic liver diseases have limited utility for predicting liver cancer risk. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and pre-malignant livers using two distinct mouse models. Downstream analyses unraveled a previously uncharacterized disease-associated hepatocyte (daHep) transcriptional state.

Sanglifehrin A mitigates multi-organ fibrosis in vivo by inducing secretion of the collagen chaperone cyclophilin B.

Pathological deposition and crosslinking of collagen type I by activated myofibroblasts drives progressive tissue fibrosis. Therapies that inhibit collagen synthesis by myofibroblasts have clinical potential as anti-fibrotic agents. Lysine hydroxylation by the prolyl-3-hydroxylase complex, comprised of cartilage associated protein, prolyl 3-hydroxylase 1, and cyclophilin B, is essential for collagen type I crosslinking and formation of stable fibers.

Systematic evaluation of chromatin immunoprecipitation sequencing to study histone occupancy in dormancy transitions of grapevine buds.

The regulation of DNA accessibility by histone modification has emerged as a paradigm of developmental and environmental programming. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a versatile tool to investigate in vivo protein-DNA interaction and has enabled advances in mechanistic understanding of physiologies. The technique has been successfully demonstrated in several plant species and tissues; however, it has remained challenging in woody tissues, in particular complex structures such as perennating buds.