Saccharomyces cerevisiae displays a stable transcription start site landscape in multiple conditions.

One of the fundamental processes that determine cellular fate is regulation of gene transcription. Understanding these regulatory processes is therefore essential for understanding cellular responses to changes in environmental conditions. At the core promoter, the regulatory region containing the transcription start site (TSS), all inputs regulating transcription are integrated.

Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia.

Transcriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming.

CAGEr: precise TSS data retrieval and high-resolution promoterome mining for integrative analyses.

Cap analysis of gene expression (CAGE) is a high-throughput method for transcriptome analysis that provides a single base-pair resolution map of transcription start sites (TSS) and their relative usage. Despite their high resolution and functional significance, published CAGE data are still underused in promoter analysis due to the absence of tools that enable its efficient manipulation and integration with other genome data types. Here we present CAGEr, an R implementation of novel methods for the analysis of differential TSS usage and promoter dynamics, integrated with CAGE data processing and promoterome mining into a first comprehensive CAGE toolbox on a common analysis platform.

Trans-splicing and operons in metazoans: translational control in maternally regulated development and recovery from growth arrest.

Polycistronic mRNAs transcribed from operons are resolved via the trans-splicing of a spliced-leader (SL) RNA. Trans-splicing also occurs at monocistronic transcripts. The phlyogenetically sporadic appearance of trans-splicing and operons has made the driving force(s) for their evolution in metazoans unclear.

Chloral hydrate sedation for magnetic resonance imaging in newborn infants.

Background: The aim of this study was to look for clinically significant adverse effects of chloral hydrate used in a large cohort of infants sedated for magnetic resonance imaging.

Method: Case notes of infants who underwent magnetic resonance imaging (MRI) scanning from 2008 to 2010 were reviewed, with patient demographics, sedation dose, comorbidities, time to discharge, and side effects of sedation noted.

Results: Four hundred and eleven infants (median [range] postmenstrual age per weight at scan 42 [31(+4) -60] weeks per 3500 g [1060-9900 g]) were sedated with chloral hydrate (median [range] dose 50 [20-80] mg·kg(-1)).

The mystery of extreme non-coding conservation.

Regions of several dozen to several hundred base pairs of extreme conservation have been found in non-coding regions in all metazoan genomes. The distribution of these elements within and across genomes has suggested that many have roles as transcriptional regulatory elements in multi-cellular organization, differentiation and development. Currently, there is no known mechanism or function that would account for this level of conservation at the observed evolutionary distances.

Parents' experiences of information and communication in the neonatal unit about brain imaging and neurological prognosis: a qualitative study.

Aim: To explore parental information and communication needs during their baby's care in the neonatal unit with a focus on brain imaging and neurological prognosis.

Methods: Eighteen parents recruited from one neonatal unit in the United Kingdom participated in semi-structured qualitative interviews using a grounded theory approach. The topic guide focused on information received about neonatal brain imaging, diagnosis and prognosis, emotional impact and support.

Inotropes in preterm infants--evidence for and against.

There is significant uncertainty regarding the optimal circulatory management of preterm infants, with research in the field limited by the paucity of safe, reproducible biomarkers of circulatory function. This review discusses the physiology and pathophysiology of circulatory function in preterm infants, describes the mode of action and evidence for and against commonly used and recently trialled inotropic therapies and provides recommendations for managing circulatory dysfunction in the transitional period and in the context of sepsis/necrotizing enterocolitis. We recommend a pragmatic approach of assessing multiple aspects of circulatory function (blood pressure alone correlates weakly with volume of flow) in each infant, tailoring therapy on the basis of the change in function desired and frequently reassessing response to intervention.

Making enhancers from spare parts of the genome.

New studies show that novel long-range enhancers of developmental genes can emerge by exaptation of protein-coding sequences with no previous regulatory function.

The effect of preterm birth on thalamic and cortical development.

Preterm birth is a leading cause of cognitive impairment in childhood and is associated with cerebral gray and white matter abnormalities. Using multimodal image analysis, we tested the hypothesis that altered thalamic development is an important component of preterm brain injury and is associated with other macro- and microstructural alterations. T(1)- and T(2)-weighted magnetic resonance images and 15-direction diffusion tensor images were acquired from 71 preterm infants at term-equivalent age.

A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm.

Diffuse white matter injury is common in preterm infants and is a candidate substrate for later cognitive impairment. This injury pattern is associated with morphological changes in deep grey nuclei, the localization of which is uncertain. We test the hypotheses that diffuse white matter injury is associated with discrete focal tissue loss, and that this image phenotype is associated with impairment at 2years.

Magnetic resonance biomarkers of neuroprotective effects in infants with hypoxic ischemic encephalopathy.

Evaluation of infants with hypoxic ischemic encephalopathy by magnetic resonance spectroscopy and imaging is useful to direct clinical care, and may assist the evaluation of candidate neuroprotective therapies. Cerebral metabolites measured by magnetic resonance spectroscopy, and visual analysis of magnetic resonance images during the first 30 days after birth accurately predict later neurological outcome and are valid biomarkers of the key physiological processes underlying brain injury in neonatal hypoxic ischemic encephalopathy. Visual assessment of magnetic resonance images may also be a suitable surrogate outcome in studies of neuroprotective therapies but current magnetic resonance methods are relatively inefficient for use in early phase, first in human infant studies of novel neuroprotective therapies.

The association of lung disease with cerebral white matter abnormalities in preterm infants.

Objective: Preterm infants have a high incidence of neurodevelopmental impairment associated with diffuse cerebral white matter abnormalities and also a high incidence of serious respiratory disease. However, it is unclear if lung disease and brain injury are related, and previous research has been impeded by confounding effects, including prematurity and infection. Using a new approach that permits multivariate statistical analysis, we tested the hypothesis that lung disease is associated with specific white matter abnormalities, detected as reduced fractional anisotropy (FA) in diffusion tensor imaging data.

Hypoxic-ischemic encephalopathy in preterm infants: antecedent factors, brain imaging, and outcome.

Our objectives were to establish antecedent factors and patterns of brain injury and their prognostic value in preterm infants with hypoxic-ischemic encephalopathy (HIE). Essential inclusion criteria were gestation (GA) < or =36 wk, Apgar scores <5/<7 at 1/5 min, major resuscitation at birth, and a brain MRI <6 postnatal wk. At least one additional criterion was required of the following: abnormal intrapartum CTG, sentinel event, meconium, cord pH <7.