PRL-3 activates mTORC1 in Cancer Progression

PRL-3, a metastasis-associated phosphatase, is known to exert its oncogenic functions through activation of PI3K/Akt, which is a key regulator of the rapamycin-sensitive mTOR complex 1 (mTORC1), but a coherent link between PRL-3 and activation of mTOR has not yet been formally demonstrated. We report a positive correlation between PRL-3 expression and mTOR phospho-activation in clinical tumour samples and mouse models of cancer and demonstrate that PRL-3 increased downstream signalling to the mTOR substrates, p70S6K and 4E-BP1, by increasing PI3K/Akt-mediated activation of Rheb-GTP via TSC2 suppression. We also show that PRL-3 increases mTOR translocation to lysosomes via increased mTOR binding affinity to Rag GTPases in an Akt-independent manner, demonstrating a previously undescribed mechanism of action for PRL-3. PRL-3 also enhanced matrix metalloproteinase-2 secretion and cellular invasiveness via activation of mTOR, attributes which were sensitive to rapamycin treatment. The downstream effects of PRL-3 were maintained even under conditions of environmental stress, suggesting that PRL-3 provides a strategic survival advantage to tumour cells via its effects on mTOR.

Cataract surgical outcomes, visual function and quality of life in four rural districts in Vietnam.

BACKGROUND: To evaluate cataract surgical outcomes in four rural districts of Ha Tinh Province, Vietnam. DESIGN: Cross-sectional study. PARTICIPANTS: Post-cataract surgery patients sampled randomly from facilities in four rural districts of Ha Tinh Province >3 months after surgery. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), visual function and quality of life. RESULTS: Among 412 patients, the mean age was 74.5 ± 9.4 years, 67% (276) were female, and 377 (91.5%) received intraocular lenses (IOL). Nearly two-thirds of patients had no postoperative visits after discharge. Postoperatively, more than 40% of eyes had presenting VA <6/18, while 20% remained <6/60. The mean self-reported visual function and quality of life for all patients were 68.7 ± 23.8 and 73.8 ± 21.6, respectively. Most patients (89.5%) were satisfied with surgery and the majority (94.4%) would recommend surgery to others. One-third of patients paid ≥$US50 for surgery. In multiple regression modelling, older age (P < 0.01), intraoperative complications (P < 0.01) and failure to receive an IOL (P < 0.01) were associated with postoperative VA <6/60. CONCLUSION: Satisfaction with surgery was high, and many patients were willing to pay for their operations. Poor visual outcomes were common; however, and better surgical training is needed to reduce complications and their impact on visual outcomes. More intensive postoperative follow-up may also be beneficial. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

FlexiArch-stress ribbon combination for multi-span pedestrian bridges

The potential benefits of combining the elegance of the stress ribbon concept with the robustness and speed of construction of the FlexiArch is discussed. In combination, multi-span pedestrian/cycle bridges which are innovative, highly durable and have optimal full life cycle costs can be produced with lengths of over 100 m. As the stress ribbon system is well known, the main emphasis of this paper will be on the FlexiArch. Since 1900 few arch bridges have been built, but with the development of the innovative FlexiArch this trend can be reversed as they can be installed rapidly, are cost competitive, have all the attributes of masonry arches and are very sustainable. Thus the FlexiArch represents a very attractive alternative to heavily reinforced cast in situ arches currently used in combination with stress ribbon deck systems.

Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies

Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost.