Hsc70 Focus Formation at the Periphery of HSV-1 Transcription Sites Requires ICP27

The cellular chaperone protein Hsc70, along with components of the 26S proteasome and ubiquitin-conjugated proteins have been shown to be sequestered in discrete foci in the nuclei of herpes simplex virus 1 (HSV-1) infected cells. We recently reported that cellular RNA polymerase II (RNAP II) undergoes proteasomal degradation during robust HSV-1 transcription, and that the immediate early protein ICP27 interacts with the C-terminal domain and is involved in the recruitment of RNAP II to viral transcription/replication compartments.Here we show that ICP27 also interacts with Hsc70, and is required for the formation of Hsc70 nuclear foci. During infection with ICP27 mutants that are unable to recruit RNAP II to viral replication sites, viral transcript levels were greatly reduced, viral replication compartments were poorly formed and Hsc70 focus formation was curtailed. Further, a dominant negative Hsc70 mutant that cannot hydrolyze ATP, interfered with RNAP II degradation during HSV-1 infection, and an increase in ubiquitinated forms of RNAP II was observed. There was also a decrease in virus yields, indicating that proteasomal degradation of stalled RNAP II complexes during robust HSV-1 transcription and replication benefits viral gene expression.We propose that one function of the Hsc70 nuclear foci may be to serve to facilitate the process of clearing stalled RNAP II complexes from viral genomes during times of highly active transcription

Birth after caesarean study – planned vaginal birth or planned elective repeat caesarean for women at term with a single previous caesarean birth: protocol for a patient preference study and randomised trial

Background: For women who have a caesarean section in their preceding pregnancy, two care policies for birth are considered standard: planned vaginal birth and planned elective repeat caesarean. Currently available information about the benefits and harms of both forms of care are derived from retrospective and prospective cohort studies. There have been no randomised trials, and recognising the deficiencies in the literature, there have been calls for methodologically rigorous studies to assess maternal and infant health outcomes associated with both care policies. The aims of our study are to assess in women with a previous caesarean birth, who are eligible in the subsequent pregnancy for a vaginal birth, whether a policy of planned vaginal birth after caesarean compared with a policy of planned repeat caesarean affects the risk of serious complications for the woman and her infant. Methods/Design Design: Multicentred patient preference study and a randomised clinical trial. Inclusion Criteria: Women with a single prior caesarean presenting in their next pregnancy with a single, live fetus in cephalic presentation, who have reached 37 weeks gestation, and who do not have a contraindication to a planned VBAC. Trial Entry & Randomisation: Eligible women will be given an information sheet during pregnancy, and will be recruited to the study from 37 weeks gestation after an obstetrician has confirmed eligibility for a planned vaginal birth. Written informed consent will be obtained. Women who consent to the patient preference study will be allocated their preference for either planned VBAC or planned, elective repeat caesarean. Women who consent to the randomised trial will be randomly allocated to either the planned vaginal birth after caesarean or planned elective repeat caesarean group. Treatment Groups: Women in the planned vaginal birth group will await spontaneous onset of labour whilst appropriate. Women in the elective repeat caesarean group will have this scheduled for between 38 and 40 weeks. Primary Study Outcome: Serious adverse infant outcome (death or serious morbidity). Sample Size: 2314 women in the patient preference study to show a difference in adverse neonatal outcome from 1.6% to 3.6% (p = 0.05, 80% power).Jodie M Dodd, Caroline A Crowther, Janet E Hiller, Ross R Haslam and Jeffrey S Robinso

Interactive Visualization of Function Fields by Range-Space Segmentation

We present a dimension reduction and feature extraction method for the visualization and analysis of function field data. Function fields are a class of high-dimensional, multi-variate data in which data samples are one-dimensional scalar functions. Our approach focuses upon the creation of high-dimensional range-space segmentations, from which we can generate meaningful visualizations and extract separating surfaces between features. We demonstrate our approach on high-dimensional spectral imagery, and particulate pollution data from air quality simulations

A novel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic haemangioendothelioma.

Pseudomyogenic haemangioendothelioma (PHE) is an intermediate malignant vascular soft tissue tumour primarily affecting children and young adults. The molecular basis of this neoplasm is unknown. We here used chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing, RT-PCR and quantitative real-time PCR on a series of morphologically well-characterized PHEs to show that a balanced translocation, t(7;19)(q22;q13), detected as the sole cytogenetic aberration in two cases, results in fusion of the SERPINE1 and FOSB genes. This translocation has not been observed in any other bone or soft tissue tumour. Interphase FISH on sections from eight additional PHEs identified the same SERPINE1-FOSB fusion in all cases. The role of SERPINE1, which is highly expressed in vascular cells, in this gene fusion is probably to provide a strong promoter for FOSB, which was found to be expressed at higher levels in PHEs than in other soft tissue tumours. FOSB encodes a transcription factor belonging to the FOS family of proteins, which, together with members of the JUN family of transcription factors, are major components of the activating protein 1 (AP-1) complex. Further studies are needed to understand the cellular impact of the aberrant expression of the FOSB gene, but as the t(7;19) resulting in the SERPINE1-FOSB fusion seems to be pathognomonic for PHE, FISH or RT-PCR could be useful for differential diagnostic purposes. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk