Single Cell Multimodal Analyses Reveal Epigenomic and Transcriptomic Basis for Birth Defects in Maternal Diabetes.

Maternal diabetes mellitus is among the most frequent environmental contributors to congenital birth defects, including heart defects and craniofacial anomalies, yet the cell types affected and mechanisms of disruption are largely unknown. Using multi-modal single cell analyses, here we show that maternal diabetes affects the epigenomic landscape of specific subsets of cardiac and craniofacial progenitors during embryogenesis. A previously unrecognized cardiac progenitor subpopulation expressing the homeodomain-containing protein ALX3 showed prominent chromatin accessibility changes and acquired a more posterior identity.

Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C.

The spatial organization of the genome contributes to its function and regulation in many contexts, including transcription, replication, recombination, and repair. Understanding the exact causality between genome topology and function is therefore crucial and increasingly the subject of intensive research. Chromosome conformation capture technologies (3C) allow inferring the 3D structure of chromatin by measuring the frequency of interactions between any region of the genome.

Transcription Factor GATA4 Regulates Cell Type-Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitors.

Background: GATA4 (GATA-binding protein 4), a zinc finger-containing, DNA-binding transcription factor, is essential for normal cardiac development and homeostasis in mice and humans, and mutations in this gene have been reported in human heart defects. Defects in alternative splicing are associated with many heart diseases, yet relatively little is known about how cell type- or cell state-specific alternative splicing is achieved in the heart. Here, we show that GATA4 regulates cell type-specific splicing through direct interaction with RNA and the spliceosome in human induced pluripotent stem cell-derived cardiac progenitors.

Inversion of a topological domain leads to restricted changes in its gene expression and affects interdomain communication.

The interplay between the topological organization of the genome and the regulation of gene expression remains unclear. Depletion of molecular factors (e.g.

A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary.

cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated.

Context-Specific Transcription Factor Functions Regulate Epigenomic and Transcriptional Dynamics during Cardiac Reprogramming.

Ectopic expression of combinations of transcription factors (TFs) can drive direct lineage conversion, thereby reprogramming a somatic cell's identity. To determine the molecular mechanisms by which Gata4, Mef2c, and Tbx5 (GMT) induce conversion from a cardiac fibroblast toward an induced cardiomyocyte, we performed comprehensive transcriptomic, DNA-occupancy, and epigenomic interrogation throughout the reprogramming process. Integration of these datasets identified new TFs involved in cardiac reprogramming and revealed context-specific roles for GMT, including the ability of Mef2c and Tbx5 to independently promote chromatin remodeling at previously inaccessible sites.

The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist.

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD.

The Ftx Noncoding Locus Controls X Chromosome Inactivation Independently of Its RNA Products.

Accumulation of the Xist long noncoding RNA (lncRNA) on one X chromosome is the trigger for X chromosome inactivation (XCI) in female mammals. Xist expression, which needs to be tightly controlled, involves a cis-acting region, the X-inactivation center (Xic), containing many lncRNA genes that evolved concomitantly to Xist from protein-coding ancestors through pseudogeneization and loss of coding potential. Here, we uncover an essential role for the Xic-linked noncoding gene Ftx in the regulation of Xist expression.

Accessing Reliable Health Information on the Web: A Review of the HON Approach.

Accessing online health content of high quality and reliability presents challenges. Laypersons cannot easily differentiate trustworthy content from misinformed or manipulated content. This article describes complementary approaches for members of the general public and health professionals to find trustworthy content with as little bias as possible.

On Contributing to the Progress of Medical Informatics as Publisher.

May 1st, 2017, will mark Dieter Bergemann's 80th birthday. As Chief Executive Officer and Owner of Schattauer Publishers from 1983 to 2016, the biomedical and health informatics community owes him a great debt of gratitude. The past and present editors of Methods of Information in Medicine, the IMIA Yearbook of Medical Informatics, and Applied Clinical Informatics want to honour and thank Dieter Bergemann by providing a brief biography that emphasizes his contributions, by reviewing his critical role as an exceptionally supportive publisher for Schattauer's three biomedical and health informatics periodicals, and by sharing some personal anecdotes.

Health On the Net's 20 Years of Transparent and Reliable Health Information.

The Health On the Net Foundation (HON) was born in 1996, during the beginning of the World Wide Web, from a collective decision by health specialists, led by the late Jean-Raoul Scherrer, who anticipated the need for online trustworthy health information. Because the Internet is a free space that everyone shares, a search for quality information is like a shot in the dark: neither will reliably hit their target. Thus, HON was created to promote deployment of useful and reliable online health information, and to enable its appropriate and efficient use.

Discussion of "Computational Electrocardiography: Revisiting Holter ECG Monitoring".

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Computational Electrocardiography: Revisiting Holter ECG Monitoring" written by Thomas M. Deserno and Nikolaus Marx. It is introduced by an editorial.

The Renewed Promise of Medical Informatics.

The promise of the field of Medical Informatics has been great and its impact has been significant. In 1999, the Yearbook editors of the International Medical Informatics Association (IMIA) - also the authors of the present paper - sought to assess this impact by selecting a number of seminal papers in the field, and asking experts to comment on these articles. In particular, it was requested whether and how the expectations, represented by these papers, had been fulfilled since their publication several decades earlier.

Cis- and trans-regulation in X inactivation.

Female mammalian cells compensate dosage of X-linked gene expression through the inactivation of one of their two X chromosomes. X chromosome inactivation (XCI) in eutherians is dependent on the non-coding RNA Xist that is up-regulated from the future inactive X chromosome, coating it and recruiting factors involved in silencing and altering its chromatin state. Xist lies within the X-inactivation center (Xic), a region on the X that is required for XCI, and is regulated in cis by elements on the X chromosome and in trans by diffusible factors.

Commentaries on the IMIA Award of Excellence Lecture by Reinhold Haux.

The IMIA Yearbook editorial team asked five internationally renowned biomedical informaticians to respond to Prof. Haux's editorial. This paper summarizes their thoughts and responses.

History of medical informatics in europe - a short review by different approach.

The panel intended to collect data, opinions and views for a systematic and multiaxial approach for a comprehensive presentation of "History of Medical Informatics", treating both general (global) characteristics, but emphasizing the particular features for Europe. The topic was not only a subject of large interest but also of great importance in preparing a detailed material for celebration of forty years of medical informatics in Europe. The panel comprised a list of topics, trying to cover all major aspects to be discussed.

Clinical outcome after traumatic spinal fractures in patients with ankylosing spinal disorders compared with control patients.

Background Context: The clinical outcome of patients with ankylosing spinal disorders (ASDs) sustaining a spinal fracture has been described to be worse compared with the general trauma population.

Purpose: To investigate clinical outcome (neurologic deficits, complications, and mortality) after spinal injury in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) compared with control patients.

Study Design: Retrospective cohort study.

A network model of the molecular organization of chromatin in Drosophila.

Chromatin governs gene regulation and genome maintenance, yet a substantial fraction of the chromatin proteome is still unexplored. Moreover, a global model of the chromatin protein network is lacking. By screening >100 candidates we identify 42 Drosophila proteins that were not previously associated with chromatin, which all display specific genomic binding patterns.

The birth and evolution of a discipline devoted to information in biomedicine and health care. As reflected in its longest running journal.

Background: The journal Methods of Information in Medicine, founded in 1962, has now completed its 50th volume. Its publications during the last five decades reflect the formation of a discipline that deals with information in biomedicine and health care.

Objectives: To report about 1) the journal's origin, 2) the individuals who have significantly contributed to it, 3) trends in the journal's aims and scope, 4) influential papers and 5) major topics published in Methods over the years.

People and ideas in medical informatics - a half century review.

OBJECTIVE. Reviewing the onset and the rapid changes to make realistic predictions on the future of medical informatics. METHODS.

Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.

The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process is not genetically regulated. However, the mechanisms and chromatin modifications controlling replication timing are still unclear.

The insulator protein SU(HW) fine-tunes nuclear lamina interactions of the Drosophila genome.

Specific interactions of the genome with the nuclear lamina (NL) are thought to assist chromosome folding inside the nucleus and to contribute to the regulation of gene expression. High-resolution mapping has recently identified hundreds of large, sharply defined lamina-associated domains (LADs) in the human genome, and suggested that the insulator protein CTCF may help to demarcate these domains. Here, we report the detailed structure of LADs in Drosophila cells, and investigate the putative roles of five insulator proteins in LAD organization.

Systemic and local factors are involved in the evolution of erosions in hand osteoarthritis.

Objective: In order to gain insight in the pathogenesis of erosive hand osteoarthritis (OA), the evolution of erosions in hand OA and risk factors involved were investigated.

Methods: The 6-year evolution in radiographic Verbruggen-Veys anatomical phase was assessed in interphalangeal joints of 236 patients with hand OA (mean age 59 years, 83% women) from the GARP (for 'Genetics ARthrosis and Progression') sibling pair study. Erosive evolution comprised phase transitions from non-erosive to erosive phases and from active erosions to remodelling.