Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling

Beyond ‘witnessing’: children’s experiences of coercive control in domestic violence and abuse

Children’s experiences and voices are underrepresented in academic literature and professional practice around domestic violence and abuse. The project ‘Understanding Agency and Resistance Strategies’ addresses this absence, through direct engagement with children. We present an analysis from interviews with 21 children in the United Kingdom (12 girls and 9 boys, aged 8-18 years), about their experiences of domestic violence and abuse, and their responses to this violence. These interviews were analysed using interpretive interactionism. Three themes from this analysis are presented: a) ‘Children’s experiences of abusive control’, which explores children’s awareness of controlling behaviour by the adult perpetrator, their experience of that control, and its impact on them; b) ‘Constraint’, which explores how children experience the constraint associated with coercive control in situations of domestic violence, and c) ‘Children as agents’ which explores children’s strategies for managing controlling behaviour in their home and in family relationships. The paper argues that, in situations where violence and abuse occurs between adult intimate partners, children are significantly impacted, and can be reasonably described as victims of abusive control. Recognising children as direct victims of domestic violence and abuse would produce significant changes in the way professionals respond to them, by 1) recognising children’s experience of the impact of domestic violence and abuse; 2) recognising children’s agency, undermining the perception of them as passive ‘witnesses’ or ‘collateral damage’ in adult abusive encounters; and 3) strengthening professional responses to them as direct victims, not as passive witnesses to violence

Road Edge Extraction Using a Plan-View Image Transformation

A new technique to extract road edges in the road-following algorithm for autonomous road vehicle navi-gation is described. It is based on finding road edges on a subsampled plan-view of a portion of the road ahead of the vehicle. The method is illustrated in the real-time identification of road edges using a fast vertical edge de-tector and link operator applied to the transformed plan view. Location of both road edges at 20 frames per sec-ond is demonstrated. Research on autonomous navigation of robot vehicles has been increasing in the last few years 1'2>3. Part of this research consists of identifying the road from a digitised image received by a camera positioned on the robot ve-hicle. The problem of identifying roads to drive an autonomou

Improved Laboratory Transition Probabilities for Neutral Chromium and Re-determination of the Chromium Abundance for the Sun and Three Stars

Branching fraction measurements from Fourier transform spectra in conjunction with published radiative lifetimes are used to determine transition probabilities for 263 lines of neutral chromium. These laboratory values are employed to derive a new photospheric abundance for the Sun: log $\epsilon$(Cr I)$_{\odot}$ = 5.64$\pm$0.01 ($\sigma = 0.07$). These Cr I solar abundances do not exhibit any trends with line strength nor with excitation energy and there were no obvious indications of departures from LTE. In addition, oscillator strengths for singly-ionized chromium recently reported by the FERRUM Project are used to determine: log $\epsilon$(Cr II)$_{\odot}$ = 5.77$\pm$0.03 ($\sigma = 0.13$). Transition probability data are also applied to the spectra of three stars: HD 75732 (metal-rich dwarf), HD 140283 (metal-poor subgiant), and CS 22892-052 (metal-poor giant). In all of the selected stars, Cr I is found to be underabundant with respect to Cr II. The possible causes for this abundance discrepancy and apparent ionization imbalance are discussed.Comment: 44 pages, 6 figure

Urological referral of asymptomatic men in general practice in England

The Prostate Cancer Risk Management Programme (PCRMP) launched in November 2002 provides guidelines for general practitioners (GPs) on age-specific prostate-specific antigen (PSA) cutoff levels in asymptomatic men. The impact of the PCRMP on GP referrals is unknown. This study investigates whether there was a change in the proportion of asymptomatic men with raised PSA levels (⩾3 ng ml−1) who were referred to urologists since the launch of the guidelines. Sixty-nine general practices in four areas of England and the main pathology laboratory in each area, which had participated in our previous research, were asked to provide data. Forty-eight practices (70%) provided retrospective data on urological referrals in men who had a PSA test taken in the periods 1 December 2001 to 31 May 2002 (pre-launch) and 1 December 2003 to 31 May 2004 (post-launch). Data on referrals were completed for 709 (79%) out of 898 and 1040 (90%) out of 1157 raised records pre- and post-launch, respectively. The percentage of men with raised PSA levels who were asymptomatic was similar in both time periods (19–20%) and the proportion referred to urologists according to the PCRMP guidelines did not increase significantly over time (24% pre-launch and 29% post-launch, P=0.42). The referral rate was lower than expected if the guidelines had been followed. The influence of the guidelines seems to have been low. At the time of data collection, 56% (112 out of 200) of GP partners reported that they were aware of receiving the PCRMP pack. To ensure future, effective implementation of guidelines requires evaluation

Compound heterozygous RMND1 gene variants associated with chronic kidney disease, dilated cardiomyopathy and neurological involvement: a case report

Background Nuclear gene mutations are being increasingly recognised as causes of mitochondrial disease. The nuclear gene RMND1 has recently been implicated in mitochondrial disease, but the spectrum of pathogenic variants and associated phenotype for this gene, has not been fully elucidated. Case presentation An 11-month-old boy presented with renal impairment associated with a truncal ataxia, bilateral sensorineural hearing loss, hypotonia, delayed visual maturation and global developmental delay. Over a 9-year period, he progressed to chronic kidney disease stage V and developed a dilated cardiomyopathy. Abnormalities in renal and muscle biopsy as well as cytochrome c oxidase activity prompted genetic testing. After exclusion of mitochondrial DNA defects, nuclear genetic studies identified compound heterozygous RMND1 (c.713A>G, p. Asn238Ser and c.565C>T, p.Gln189*) variants. Conclusion We report RMND1 gene variants associated with end stage renal failure, dilated cardiomyopathy, deafness and neurological involvement due to mitochondrial disease. This case expands current knowledge of mitochondrial disease secondary to mutation of the RMND1 gene by further delineating renal manifestations including histopathology. To our knowledge dilated cardiomyopathy has not been reported with renal failure in mitochondrial disease due to mutations of RMND1. The presence of this complication was important in this case as it precluded renal transplantation

T2 Mapping from Super-Resolution-Reconstructed Clinical Fast Spin Echo Magnetic Resonance Acquisitions

Relaxometry studies in preterm and at-term newborns have provided insight into brain microstructure, thus opening new avenues for studying normal brain development and supporting diagnosis in equivocal neurological situations. However, such quantitative techniques require long acquisition times and therefore cannot be straightforwardly translated to in utero brain developmental studies. In clinical fetal brain magnetic resonance imaging routine, 2D low-resolution T2-weighted fast spin echo sequences are used to minimize the effects of unpredictable fetal motion during acquisition. As super-resolution techniques make it possible to reconstruct a 3D high-resolution volume of the fetal brain from clinical low-resolution images, their combination with quantitative acquisition schemes could provide fast and accurate T2 measurements. In this context, the present work demonstrates the feasibility of using super-resolution reconstruction from conventional T2-weighted fast spin echo sequences for 3D isotropic T2 mapping. A quantitative magnetic resonance phantom was imaged using a clinical T2-weighted fast spin echo sequence at variable echo time to allow for super-resolution reconstruction at every echo time and subsequent T2 mapping of samples whose relaxometric properties are close to those of fetal brain tissue. We demonstrate that this approach is highly repeatable, accurate and robust when using six echo times (total acquisition time under 9 minutes) as compared to gold-standard single-echo spin echo sequences (several hours for one single 2D slice)

Rotation and activity in the solar-metallicity open cluster NGC2516

We report new measures of radial velocities and rotation rates (v sin i) for 51 F and early-G stars in the open cluster NGC2516, and combine these with previously published data. From high signal-to-noise spectra of two stars, we show that NGC2516 has a relative iron abundance with respect to the Pleiades of delta([Fe/H])= +0.04 +/- 0.07 at the canonical reddening of E(B - V) = 0.12, in contrast to previous photometric studies that placed the cluster 0.2 to 0.4 dex below solar. We construct a color-magnitude diagram based on radial velocity members, and explore the sensitivity of photometric determinations of the metallicity and distance to assumed values of the reddening. For a metal abundance near solar, the Hipparcos distance to NGC2516 is probably underestimated. Finally, we show that the distribution of rotation rates and X-ray emission does not differ greatly from that of the Pleiades, when allowance is made for the somewhat older age of NGC2516.Comment: Accepted for publication in the Astrophysical Journal. 35 pages including 7 figure

Sources and Sinks of Greenhouse Gases from European Grasslands and Mitigation Options: The ‘GreenGrass’ Project

Adapting the management of grasslands may be used to enhance carbon sequestration into soil, but could also increase N2O and CH4 emissions. In support of the European post-Kyoto policy, the European \u27GreenGrass\u27 project (EC FP5, EVK2-CT2001-00105) has three main objectives: i) to reduce the large uncertainties concerning the estimates of CO2, N2O and CH4 fluxes to and from grassland plots under different climatic conditions and assess their global warming potential, ii) to measure net greenhouse gas (GHG) fluxes for different management which reflect potential mitigation options, iii) to construct a model of the controlling processes to quantify the net fluxes and to evaluate mitigation scenarios by up-scaling to a European level