Electromyometrial Imaging of Uterine Contractions in Pregnant Women.

During normal pregnancy, the uterine smooth muscle, the myometrium, begins to have weak, uncoordinated contractions at late gestation to help the cervix remodel. In labor, the myometrium has strong, coordinated contractions to deliver the fetus. Various methods have been developed to monitor uterine contraction patterns to predict labor onset.

Noninvasive electromyometrial imaging of human uterine maturation during term labor.

Electromyometrial imaging (EMMI) was recently developed to image the three-dimensional (3D) uterine electrical activation during contractions noninvasively and accurately in sheep. Herein we describe the development and application of a human EMMI system to image and evaluate 3D uterine electrical activation patterns at high spatial and temporal resolution during human term labor. We demonstrate the successful integration of the human EMMI system during subjects' clinical visits to generate noninvasively the uterine surface electrical potential maps, electrograms, and activation sequence through an inverse solution using up to 192 electrodes distributed around the abdomen surface.

A multidisciplinary Prematurity Research Cohort Study.

Background: Worldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth.

Analysis of Electrophysiological Activation of the Uterus During Human Labor Contractions.

This cohort study uses electromyometrial imaging to examine the underlying electrophysiological origins of human labor at the myometrium level.

RNA-Seq identifies genes whose proteins are upregulated during syncytia development in murine C2C12 myoblasts and human BeWo trophoblasts.

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression, quantitative protein expression, and siRNA knockdown we identified genes and their cognate proteins which are similarly upregulated in two cellular models of mammalian syncytia development (human BeWo cytotrophoblast to syncytiotrophoblast and murine C2C12 myoblast to myotube). These include DYSF, PDE4DIP, SPIRE2, NDRG1, PLEC, GPR146, HSPB8, DHCR7, and HDAC5.

Addressing Gaps in Pediatric Scientist Development: The Department Chair View of 2 AMSPDC-Sponsored Programs.

Pediatric physician-scientists are important members of the biomedical workforce who are instrumental in translating research advances into novel patient treatment strategies, yet their numbers have been declining over the past four decades. In order to increase the pipeline of pediatric physician-scientists, the Association of Medical School Pediatric Department Chairs (AMSPDC) leads the Frontiers in Science (FIS) and Pediatric Scientist Development Program (PSDP). These programs provide mentorship, networking, and funding opportunities for pediatric residents and fellows who are interested in pursuing research careers.

Electromyometrial imaging dataset of electromyograms and isochrone maps under deformation/electrical noise contaminations.

The dataset presented in this paper is related to the recent work "" [1]. The dataset including body-uterus geometry obtained from magnetic resonance imaging (MRI), uterine electrograms and isochrone maps reconstructed using Electromyometrial imaging (EMMI) under various levels of deformations and electrical noise contamination in a translational sheep model are reported. The dataset make it possible for detailed evaluation and further improvement of EMMI.

Accuracy of electromyometrial imaging of uterine contractions in clinical environment.

Clinically, uterine contractions are monitored with tocodynamometers or intrauterine pressure catheters. In the research setting, electromyography (EMG), which detects electrical activity of the uterus from a few electrodes on the abdomen, is feasible, can provide more accurate data than these other methods, and may be useful for predicting preterm birth. However, EMG lacks sufficient spatial resolution and coverage to reveal where uterine contractions originate, how they propagate, and whether preterm contractions differ between women who do and do not progress to preterm delivery.

Noninvasive high-resolution electromyometrial imaging of uterine contractions in a translational sheep model.

In current clinical practice, uterine contractions are monitored via a tocodynamometer or an intrauterine pressure catheter, both of which provide crude information about contractions. Although electrohysterography/electromyography can measure uterine electrical activity, this method lacks spatial specificity and thus cannot accurately measure the exact location of electrical initiation and location-specific propagation patterns of uterine contractions. To comprehensively evaluate three-dimensional uterine electrical activation patterns, we describe here the development of electromyometrial imaging (EMMI) to display the three-dimensional uterine contractions at high spatial and temporal resolution.

RNA-Seq identifies genes whose proteins are transformative in the differentiation of cytotrophoblast to syncytiotrophoblast, in human primary villous and BeWo trophoblasts.

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression and quantitative protein expression, we identified genes and their cognate proteins which are coordinately up- or down-regulated in two cellular models of cytotrophoblast to syncytiotrophoblast development, human primary villous and human BeWo cytotrophoblasts. These include hCGβ, TREML2, PAM, CRIP2, INHA, FLRG, SERPINF1, C17orf96, KRT17 and SAA1.

RNF4-Dependent Oncogene Activation by Protein Stabilization.

Ubiquitylation regulates signaling pathways critical for cancer development and, in many cases, targets proteins for degradation. Here, we report that ubiquitylation by RNF4 stabilizes otherwise short-lived oncogenic transcription factors, including β-catenin, Myc, c-Jun, and the Notch intracellular-domain (N-ICD) protein. RNF4 enhances the transcriptional activity of these factors, as well as Wnt- and Notch-dependent gene expression.

Isoform-specific SCF(Fbw7) ubiquitination mediates differential regulation of PGC-1α.

The E3 ubiquitin ligase and tumor suppressor SCF(Fbw7) exists as three isoforms that govern the degradation of a host of critical cell regulators, including c-Myc, cyclin E, and PGC-1α. Peroxisome proliferator activated receptor-gamma coactivator 1α (PGC-1α) is a transcriptional coactivator with broad effects on cellular energy metabolism. Cellular PGC-1α levels are tightly controlled in a dynamic state by the balance of synthesis and rapid degradation via the ubiquitin-proteasome system.

Commentary: physician-scientist attrition: stemming the tide through national networks for training and development.

Future advances in medicine depend on a reliable pipeline of physician-scientists. However, the changing demographics of physician-scientists, including the advanced age of new MD investigators, and attrition along the physician-scientist developmental pathway are cause for concern. Recently developed National Institutes of Health-funded national networks for physician-scientist training and development-such as the Advanced Research Institute in Geriatric Mental Health and the Pediatric Scientist Development Program-offer valuable approaches to supporting and retaining these trainees.

The Future of Children's Health in the Genomic Era.

The effects of genomic medicine on child health promise to be profound. Medical applications will eventually include characterizing patients' genomes to detect predictive mutations for pre-symptomatic counseling where treatment exists; to search for causes of diseases of unknown etiology, and to detect carriers for prenatal counseling; to define cancer and other disease-based genomes to design individualized therapy; and to understand our microbiomes to modify these in health and disease. Rapid advances in technology and bioinformatics have reduced the cost and the time and increased the accuracy necessary to sequence whole genomes or whole exomes.

Ubiquitin proteasome-dependent degradation of the transcriptional coactivator PGC-1{alpha} via the N-terminal pathway.

PGC-1α is a potent, inducible transcriptional coactivator that exerts control on mitochondrial biogenesis and multiple cellular energy metabolic pathways. PGC-1α levels are controlled in a highly dynamic manner reflecting regulation at both transcriptional and post-transcriptional levels. Here, we demonstrate that PGC-1α is rapidly degraded in the nucleus (t(½ 0.

Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9.

The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor involved in the metabolism of various extracellular ligands, including proteinases, that play critical roles in tumor invasion. Although several studies have shown an increased expression of LRP1 in cancer cells, its function in tumor development and progression remains largely unclear. Here, we reveal a novel mechanism by which LRP1 induces the expression of matrix metalloproteinase 2 (MMP2) and MMP9 and thereby promotes the migration and invasion of human glioblastoma U87 cells.

Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology.

Cellular proteins are in a dynamic state maintained by synthesis and degradation. The ubiquitin proteolytic pathway is responsible for the degradation of the bulk of cellular proteins including short-lived, regulatory, and misfolded/denatured proteins. Ubiquitin-mediated proteolysis involves covalent attachment of multiple ubiquitin molecules to the protein substrate and degradation of the targeted protein by the 26S proteasome.

Glucocorticoids differentially regulate degradation of MyoD and Id1 by N-terminal ubiquitination to promote muscle protein catabolism.

Accelerated protein degradation via the ubiquitin-proteasome pathway is the principal cause of skeletal muscle wasting associated with common human disease states and pharmacological treatment with glucocorticoids. Although many protein regulatory factors essential for muscle development and regeneration are degraded via the ubiquitin system, little is known about the mechanisms and regulation of this pathway that promote wasting muscle. Here, we demonstrate that, in differentiated myotubes, glucocorticoid, via the glucocorticoid receptor, selectively induces a decrease in protein abundance of MyoD, a master switch for muscle development and regeneration, but not that of its negative regulator Id1.

In vivo interactions of MyoD, Id1, and E2A proteins determined by acceptor photobleaching fluorescence resonance energy transfer.

MyoD, a skeletal muscle transcription factor, is rapidly degraded by the ubiquitin-proteasome system. MyoD interacts with ubiquitously expressed E2A or inhibitor of DNA binding (Id) proteins to activate or inhibit transcription, respectively. Furthermore, MyoD has been shown to modulate the ubiquitin-mediated degradation of Id1 and E2A proteins, E12 and E47.

Slow endocytosis of the LDL receptor-related protein 1B: implications for a novel cytoplasmic tail conformation.

The LDL receptor-related protein 1B (LRP1B) is a putative tumor suppressor homologous to LRP1. Both LRP1 and LRP1B contain cytoplasmic tails with several potential endocytosis motifs. Although the positions of these endocytic motifs are similar in both receptors, LRP1B is internalized at a 15-fold slower rate than LRP1.

E12 and E47 modulate cellular localization and proteasome-mediated degradation of MyoD and Id1.

Programs of tissue differentiation are likely controlled by factors regulating gene expression and protein degradation. In muscle, the degradation of the muscle transcription factor MyoD and its inhibitor Id1 occurs via the ubiquitin-proteasome system. E12 and E47, splice products of the E2A gene, interact with MyoD to activate transcription of the muscle program and are also degraded by the ubiquitin-proteasome system (t(1/2) = approximately 6 h).

Ubiquitin-proteasome-mediated degradation, intracellular localization, and protein synthesis of MyoD and Id1 during muscle differentiation.

Mammalian skeletal myogenesis results in the differentiation of myoblasts to mature syncytial myotubes, a process regulated by an intricate genetic network of at least three protein families: muscle regulatory factors, E proteins, and Id proteins. MyoD, a key muscle regulatory factor, and its negative regulator Id1 have both been shown to be degraded by the ubiquitin-proteasome system. Using C2C12 cells and confocal fluorescence microscopy, we showed that MyoD and Id1 co-localize within the nucleus in proliferating myoblasts.