Genetic differentiation across the social transition in a socially polymorphic sweat bee, Halictus rubicundus

Eusociality is widely considered a major evolutionary transition. The socially polymorphic sweat bee Halictus rubicundus, solitary in cooler regions of its holarctic range and eusocial in warmer parts, is an excellent model organism to address this transition, and specifically the question of whether sociality is associated with a strong barrier to gene flow between phenotypically divergent populations. Mitochondrial DNA (COI) from specimens collected across the British Isles, where both solitary and social phenotypes are represented, displayed limited variation, but placed all specimens in the same European lineage; haplotype network analysis failed to differentiate solitary and social lineages. Microsatellite genetic variability was high and enabled us to quantify genetic differentiation among populations and social phenotypes across Great Britain and Ireland. Results from conceptually different analyses consistently showed greater genetic differentiation between geographically distant populations, independently of their social phenotype, suggesting that the two social forms are not reproductively isolated. A landscape genetic approach revealed significant isolation by distance (Mantel test r = 0.622, p

Use of FibreCement in House in Northern Ireland

This journal has an editorial board from Switzerland, Belgium, Germany, France, Great Britain and Ireland. The journal is distributed to architectural practices throughout Europe.

Polyomavirus enhancer activator 3 protein promotes breast cancer metastatic progression through Snail-induced epithelial-mesenchymal transition.

Polyomavirus enhancer activator 3 protein (Pea3), also known as ETV4, is a member of the Ets-transcription factor family, which promotes metastatic progression in various types of solid cancer. Pea3-driven epithelial-mesenchymal transition (EMT) has been described in lung and ovarian cancers. The mechanisms of Pea3-induced EMT, however, are largely unknown. Here we show that Pea3 overexpression promotes EMT in human breast epithelial cells through transactivation of Snail (SNAI1), an activator of EMT. Pea3 binds to the human Snail promoter through the two proximal Pea3 binding sites and enhances Snail expression. In addition, knockdown of Pea3 in invasive breast cancer cells results in down-regulation of Snail, partial reversal of EMT, and reduced invasiveness in vitro. Moreover, knockdown of Snail partially rescues the phenotype induced by Pea3 overexpression, suggesting that Snail is one of the mediators bridging Pea3 and EMT, and thereby metastatic progression of the cancer cells. In four breast cancer patient cohorts whose microarray and survival data were obtained from the Gene Expression Omnibus database, Pea3 and Snail expression are significantly correlated with each other and with overall survival of breast cancer patients. We further demonstrate that nuclear localization of Pea3 is associated with Snail expression in breast cancer cell lines and is an independent predictor of overall survival in a Chinese breast cancer patient cohort. In conclusion, our results suggest that Pea3 may be an important prognostic marker and a therapeutic target for metastatic progression of human breast cancer. © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK/T cell lymphoma revealed by gene expression profiling

We performed comprehensive genome-wide gene expression profiling (GEP) of extranodal nasal-type natural killer/T-cell lymphoma (NKTL) using formalin-fixed, paraffin-embedded tissue (n = 9) and NK cell lines (n = 5) in comparison with normal NK cells, with the objective of understanding the oncogenic pathways involved in the pathogenesis of NKTL and to identify potential therapeutic targets. Pathway and network analysis of genes differentially expressed between NKTL and normal NK cells revealed significant enrichment for cell cycle-related genes and pathways, such as PLK1, CDK1, and Aurora-A. Furthermore, our results demonstrated a pro-proliferative and anti-apoptotic phenotype in NKTL characterized by activation of Myc and nuclear factor kappa B (NF-kappa B), and deregulation of p53. In corroboration with GEP findings, a significant percentage of NKTLs (n = 33) overexpressed c-Myc (45.4%), p53 (87.9%), and NF-kappa B p50 (67.7%) on immunohistochemistry using a tissue microarray containing 33 NKTL samples. Notably, overexpression of survivin was observed in 97% of cases. Based on our findings, we propose a model of NKTL pathogenesis where deregulation of p53 together with activation of Myc and NF-kappa B, possibly driven by EBV LMP-1, results in the cumulative up-regulation of survivin. Down-regulation of survivin with Terameprocol (EM-1421, a survivin inhibitor) results in reduced cell viability and increased apoptosis in tumour cells, suggesting that targeting survivin may be a potential novel therapeutic strategy in NKTL. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Guidelines for the measurement of BCR-ABL1 transcripts in chronic myeloid leukaemia

Molecular testing for the BCR-ABL1 fusion gene by real time quantitative polymerase chain reaction (RT-qPCR) is the most sensitive routine approach for monitoring the response to therapy of patients with chronic myeloid leukaemia. In the context of tyrosine kinase inhibitor (TKI) therapy, the technique is most appropriate for patients who have achieved complete cytogenetic remission and can be used to define specific therapeutic milestones. To achieve this effectively, standardization of the laboratory procedures and the interpretation of results are essential. We present here consensus best practice guidelines for RT-qPCR testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 21 testing laboratories in the United Kingdom and Ireland in accordance with the procedures of the UK Clinical Molecular Genetics Society.

‘The ‘Complexity of Imprisonment: The Northern Ireland Experience'

This article will examine the thesis that Northern Ireland experiences a relatively low level of crime. It will explore the possible reasons why crime in the North has not witnessed a dramatic increase. In light of this, the article will highlight the difficulties surrounding the current prison system and illustrate that once again Northern Ireland is experiencing a very different criminal justice system in comparison to Great Britain. Although the prisons are now being used predominately to deal with “ordinary’ crime”, they are still part of the political process.

PARP inhibition induces BAX/BAK-independent synthetic lethality of BRCA1-deficient non-small cell lung cancer

Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11-19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A 7000 yr perspective on volcanic ash clouds affecting northern Europe

The ash cloud resulting from the 2010 eruption of Eyjafjöll caused severe disruption to air travel across Europe but as a geological event, it is not unprecedented. Analysis of peat and lake sediments from northern Europe has revealed the presence of microscopic layers of Icelandic volcanic ash (tephra). These sedimentary records, together with historical records of Holocene ash falls, demonstrate that Icelandic volcanoes have generated substantial ash clouds that reached northern Europe many times. Here we present the first comprehensive compilation of sedimentary and historical records of ash-fall events in northern Europe, spanning the last 7000 years. Within this period ten tephra layers have been identified in the Faroe Islands, 14 in Great Britain, 11 in Germany, 38 in Scandinavia and 33 in Ireland. Seven ash fall events have been historically documented prior to the Eyjafjöll 2010 event. Ash fall events appear to be more frequent in the last 1500 years, but it is unclear whether this reflects a true increase in eruption frequency or dispersal, or is an artefact of the records themselves or the way they have been generated. In the last 1,000 years, volcanic ash clouds reached Northern Europe with a mean return interval of 53 ± 8 years (the range of return intervals is between 6 and 112 years). Modelling using the ash records for the last millennium indicates that for any 10 year period there is a 17% probability of tephra fallout event in Northern Europe. These values must be considered as conservative estimates due to the nature of tephra capture and preservation in the sedimentary record.

Changes in the prevalence of badger persecution in Northern Ireland.

Animal populations generally increase after release from hunting pressure and/or cessation of illegal persecution. Implementation of full legislative protection of the Eurasian badger Meles meles in Great Britain is thought to have led to increases in badger abundance due to reduced levels of persecution. Conversely, prevalence of badger persecution in Northern Ireland was historically much higher than in Great Britain, and badger abundance remained stable over time despite similar legislative protection. We examined temporal changes in the prevalence of badger sett disturbance in Northern Ireland from 1990/1993 to 2007/2008 in relation to population status. A total of 56 (12.6%) of 445 setts surveyed during 1990/1993 had been disturbed compared to 29 (4.4%) of 653 setts during 2007/2008. This was a significant decline (-65%) in the incidence of sett disturbance over the 14–18-year period. Most notably, the incidence of digging at badger setts, indicative of local badger baiting activity, declined from 50% to 3.5% of disturbed setts. Signs of recent disturbance were significantly more frequent at disused setts suggesting that once disturbed, badgers may vacate a sett. The number of badger social groups in Northern Ireland did not differ between the two study periods, suggesting that previously high levels of badger persecution did not limit the number of badger social groups. The stability of the badger population in Northern Ireland compared to the growing population in Great Britain cannot be attributed to changes in the prevalence of persecution. Differences in the trajectories of both populations could be due to a range of factors including climate, habitat composition and structure, farming practices or food availability. More work is needed to determine how such factors influence badger population dynamics.