Glucocorticoids accelerate maturation of the heme pathway in fetal liver through effects on transcription and DNA methylation

<p>Glucocorticoids are widely used in threatened preterm labor to promote maturation in many organ systems in preterm babies and have significant beneficial effects on morbidity and mortality. We performed transcriptional profiling in fetal liver in a rat model of prenatal glucocorticoid exposure and identified marked gene expression changes in heme biosynthesis, utilization, and degradation pathways in late gestation. These changes in gene expression associated with alterations in DNA methylation and with a reduction in hepatic heme concentration. There were no persistent differences in gene expression, DNA methylation, or heme concentrations at 4 weeks of age, suggesting that these are transient effects. Our findings are consistent with glucocorticoid-induced accelerated maturation of the haematopoietic system and support the hypothesis that glucocorticoids can drive changes in gene expression in association with alterations in DNA methylation.</p

The second set of pulsar discoveries by CHIME/FRB/Pulsar: 14 Rotating Radio Transients and 7 pulsars

The Canadian Hydrogen Mapping Experiment (CHIME) is a radio telescope located in British Columbia, Canada. The large field of view (FOV) of $\sim$ 200 square degrees has enabled the CHIME/FRB instrument to produce the largest FRB catalog to date. The large FOV also allows CHIME/FRB to be an exceptional pulsar and Rotating Radio Transient (RRAT) finding machine, despite saving only the metadata information of incoming Galactic events. We have developed a pipeline to search for pulsars/RRATs using DBSCAN, a clustering algorithm. Output clusters are then inspected by a human for pulsar/RRAT candidates and follow-up observations are scheduled with the more sensitive CHIME/Pulsar instrument. The CHIME/Pulsar instrument is capable of a near-daily search mode observation cadence. We have thus developed the CHIME/Pulsar Single Pulse Pipeline to automate the processing of CHIME/Pulsar search mode data. We report the discovery of 21 new Galactic sources, with 14 RRATs, 6 regular slow pulsars and 1 binary system. Owing to CHIME/Pulsar's daily observations we have obtained timing solutions for 8 of the 14 RRATs along with all the regular pulsars. This demonstrates CHIME/Pulsar's ability at finding timing solutions for transient sources

Defining a spinal microcircuit that gates myelinated afferent input: implications for tactile allodynia

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I–IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain

The cellular and synaptic architecture of the mechanosensory dorsal horn

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception

Psychological and educational interventions for managing eczema

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. 1. To assess the clinical outcomes of psychological and educational interventions in children and adults with eczema. 2. To summarise the availability and principal findings of relevant economic evaluations

The impact of web-based and face-to-face simulation on patient deterioration and patient safety : Protocol for a multi-site multi-method design

Background: There are international concerns in relation to the management of patient deterioration which has led to a body of evidence known as the 'failure to rescue' literature. Nursing staff are known to miss cues of deterioration and often fail to call for assistance. Medical Emergency Teams (Rapid Response Teams) do improve the management of acutely deteriorating patients, but first responders need the requisite skills to impact on patient safety. Methods/design: In this study we aim to address these issues in a mixed methods interventional trial with the objective of measuring and comparing the cost and clinical impact of face-to-face and web-based simulation programs on the management of patient deterioration and related patient outcomes. The education programs, known as 'FIRST2ACT', have been found to have an impact on education and will be tested in four hospitals in the State of Victoria, Australia. Nursing staff will be trained in primary (the first 8 min) responses to emergencies in two medical wards using a face-to-face approach and in two medical wards using a web-based version FIRST2ACTWeb. The impact of these interventions will be determined through quantitative and qualitative approaches, cost analyses and patient notes review (time series analyses) to measure quality of care and patient outcomes. Discussion: In this 18 month study it is hypothesised that both simulation programs will improve the detection and management of deteriorating patients but that the web-based program will have lower total costs. The study will also add to our overall understanding of the utility of simulation approaches in the preparation of nurses working in hospital wards. (ACTRN12616000468426, retrospectively registered 8.4.2016). © 2016 The Author(s)

Revisiting the influence of top-down and bottom-up pressures on Wa hia hé:ta (yellow perch Perca flavescens Mitchill, 1814) population dynamics in Kaniatarowanenneh (the Upper St. Lawrence River): Implications for collaborative research

Kaniatarowanenneh (St. Lawrence River) is the outflow of one of the world’s largest freshwater ecosystems and its ecological health has implications for resource management. The population dynamics of an ecologically and economically important fish, the Wa hia hé:ta, Mohawk for yellow perch (Perca flavescens Mitchill, 1814), are considered by including data that extends to the past century to redress temporal gaps in comparative literature. We found both a significant top-down effect from piscivorous fish as well as a significant bottom-up effect related to total phosphorus on yellow perch relative abundance in the Lake Ontario-Upper St. Lawrence system. Regarding the bottom-up effect, the current state of yellow perch reflects the population size prior to cultural eutrophication (pre-1940s/50s) likely responding to the re-oligotrophication of the system. These findings emphasize the importance of considering historical records in fish population dynamics research to incorporate shifting population baselines into fisheries management. The study also demonstrates the need for collaborative approaches that bring critical new insights and multivocality. </jats:p

CHD7 Targets Active Gene Enhancer Elements to Modulate ES Cell-Specific Gene Expression

CHD7 is one of nine members of the chromodomain helicase DNA–binding domain family of ATP–dependent chromatin remodeling enzymes found in mammalian cells. De novo mutation of CHD7 is a major cause of CHARGE syndrome, a genetic condition characterized by multiple congenital anomalies. To gain insights to the function of CHD7, we used the technique of chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP–Seq) to map CHD7 sites in mouse ES cells. We identified 10,483 sites on chromatin bound by CHD7 at high confidence. Most of the CHD7 sites show features of gene enhancer elements. Specifically, CHD7 sites are predominantly located distal to transcription start sites, contain high levels of H3K4 mono-methylation, found within open chromatin that is hypersensitive to DNase I digestion, and correlate with ES cell-specific gene expression. Moreover, CHD7 co-localizes with P300, a known enhancer-binding protein and strong predictor of enhancer activity. Correlations with 18 other factors mapped by ChIP–seq in mouse ES cells indicate that CHD7 also co-localizes with ES cell master regulators OCT4, SOX2, and NANOG. Correlations between CHD7 sites and global gene expression profiles obtained from Chd7+/+, Chd7+/−, and Chd7−/− ES cells indicate that CHD7 functions at enhancers as a transcriptional rheostat to modulate, or fine-tune the expression levels of ES–specific genes. CHD7 can modulate genes in either the positive or negative direction, although negative regulation appears to be the more direct effect of CHD7 binding. These data indicate that enhancer-binding proteins can limit gene expression and are not necessarily co-activators. Although ES cells are not likely to be affected in CHARGE syndrome, we propose that enhancer-mediated gene dysregulation contributes to disease pathogenesis and that the critical CHD7 target genes may be subject to positive or negative regulation