An Appraisal of Ulcerative Colitis

In writing about a subject like ulcerative colitis, it would be comforting to imagine oneself to be somewhere near the "growing edge," if not just exactly in the front line. And yet, this "growing edge" is so often disappointing, if not positively misleading, for too many of the new advances are reminiscent of the Seed which fell on stony ground:''and because it had no root it withered away."This is particularly true about researches into the aetiology and nature of ulcerative colitis. The fact that the disease is a cruel scourge of healthy young people, treatable to some extent, and yet imperfectly understood, has produced the attitude of mind that ulcerative colitis is a challenge. Although many valuable advances have resulted, it is probable that more pet theories have gained hold in this disease than in any other, and consequently there is considerable diversity of opinion regarding its nature and its treatment. Ideally, there should be a team, consisting of physician, surgeon and psychiatrist, each with something to offer in the treatment of the patient, but, in the international congress on ulcerative colitis, co-operation was curiously lacking, and the individual members seemed unable to concern themselves with approaches which were not their own

Evolving Gaits for Damage Control in a Hexapod Robot

Autonomous robots are increasingly used in remote and hazardous environments, where damage to sensory-actuator systems cannot be easily repaired. Such robots must therefore have controllers that continue to function effectively given unexpected malfunctions and damage to robot morphology. This study applies the Intelligent Trial and Error (IT&E) algorithm to adapt hexapod robot control to various leg failures and demonstrates the IT&E map-size parameter as a critical parameter in influencing IT&E adaptive task performance. We evaluate robot adaptation for multiple leg failures on two different map-sizes in simulation and validate evolved controllers on a physical hexapod robot. Results demonstrate a trade-off between adapted gait speed and adaptation duration, dependent on adaptation task complexity (leg damage incurred), where map-size is crucial for generating behavioural diversity required for adaptation

Identification and transcript analysis of a novel wallaby (Macropus eugenii) basal-like breast cancer cell line

<p>Abstract</p> <p>Background</p> <p>A wide variety of animal models have been used to study human breast cancer. Murine, feline and canine mammary tumor cell lines have been studied for several decades and have been shown to have numerous aspects in common with human breast cancer. It is clear that new comparative approaches to study cancer etiology are likely to be productive.</p> <p>Results</p> <p>A continuous line of breast carcinoma cells (WalBC) was established from a primary breast cancer that spontaneously arose in a female tammar wallaby (<it>Macropus eugenii</it>). The primary tumor was 1.5 cm³and although large, did not appear to invade the stroma and lacked vimentin expression. The WalBC cell line was cultured from the primary tumor and passaged for 22 months. WalBC cells displayed an epithelial morphology when grown on plastic, were not EGF responsive, stained strongly for cyto-keratin and negatively for vimentin. WalBC cells were shown to be non-invasive within a Matrigel invasion assay and failed to produce tumors following transplantation into nude mice. Gene expression profiling of WalBC cells was performed using a cDNA microarray of nearly 10,000 mammary gland cDNA clones and compared to normal primary mammary cells and profiles of human breast cancer. Seventy-six genes were down-regulated and sixty-six genes were up-regulated in WalBC cells when compared to primary mammary cells. WalBC cells exhibited expression of known markers of basal invasive human breast cancers as well as increased KRT17, KRT 14 and KRT 19, DSP, s100A4, NDRG-1, ANXA1, TK1 and AQP3 gene expression and decreased gene expression of TIMP3, VIM and TAGLN. New targets for breast cancer treatment were identified such as ZONAB, PACSIN3, MRP8 and SUMO1 which have human homologues.</p> <p>Conclusion</p> <p>This study demonstrates how novel models of breast cancer can provide new fundamental clues regarding cancer etiology which may lead to new human treatments and therapies.</p

Targeting NETs using dual-active DNase1 variants

Background: Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA (dsDNA) and chromatin, respectively. Methods: Here, we engineered a dual-active DNase with combined DNase1 and DNase1L3 activities and characterized the enzyme for its NET degrading potential in vitro. Furthermore, we produced a mouse model with transgenic expression of the dual-active DNase and analyzed body fluids of these animals for DNase1 and DNase 1L3 activities. We systematically substituted 20 amino acid stretches in DNase1 that were not conserved among DNase1 and DNase1L3 with homologous DNase1L3 sequences. Results: We found that the ability of DNase1L3 to degrade chromatin is embedded into three discrete areas of the enzyme's core body, not the C-terminal domain as suggested by the state-of-the-art. Further, combined transfer of the aforementioned areas of DNase1L3 to DNase1 generated a dual-active DNase1 enzyme with additional chromatin degrading activity. The dual-active DNase1 mutant was superior to native DNase1 and DNase1L3 in degrading dsDNA and chromatin, respectively. Transgenic expression of the dual-active DNase1 mutant in hepatocytes of mice lacking endogenous DNases revealed that the engineered enzyme was stable in the circulation, released into serum and filtered to the bile but not into the urine. Conclusion: Therefore, the dual-active DNase1 mutant is a promising tool for neutralization of DNA and NETs with potential therapeutic applications for interference with thromboinflammatory disease states

Where It’s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 Images in Tumors of Living Mice

Purpose: Tumor microenvironments show remarkable tumor pO_{2} heterogeneity, as seen in prior EPR pO_{2} images (EPROI). pO_{2} correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position. Procedures: To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO_{2}. Results: Quantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO_{2}, median pO_{2}, and the fraction of voxels in the biopsy volume with pO_{2} less than 3, 6, and 10 Torr. Conclusions: This validates EPROI hypoxic fractions at the molecular level and provides a new paradigm for the assessment of the relationship, in vivo, between hypoxia and hypoxia response proteins. When translated to human subjects, this will enhance understanding of human tumor pathophysiology and cancer response to therapy

Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma

\ua9 2023 The Author(s). Published by Oxford University Press on behalf of British Association of Dermatologists.Background: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. Objectives: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. Methods: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. Results: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P &lt; 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P &lt; 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. Conclusions: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence

Crop Updates 2000 - Oilseeds

This session covers seventeen papers from different authors: Introduction, Paul Carmody, Centre for Cropping Systems CANOLA AGRONOMY 2. Genotype, location and year influence the quality of canola grown across southern Australia, PingSi1, Rodney Mailer2, Nick Galwey1 and David Turner1, 1Plant Sciences, Faculty of Agriculture, The University of Western Australia, 2Agricultural Research Institute, New South Wales Agriculture 3. Development of Pioneer® Canola varieties for Australian market,Kevin Morthorpe, StephenAddenbrooke, Pioneer Hi-Bred Australia Pty Ltd 4. Canola, Erucic Acid, Markets and Agronomic Implications, Peter Nelson, The Grain Pool of Western Australia 5. The control of Capeweed in Clearfield Production System for Canola, Mike Jackson and ScottPaton, Cyanamid Agriculture Pty Ltd 6. Responsiveness of Canola to Soil Potassium Levels: How Low Do We Have To Go? Ross Brennan, Noeleen Edwards, Mike Bolland and Bill Bowden,Agriculture Western Australia 7. Adaption of Indian Mustard (Brassica juncea) in the Mediterranean Environment of South Western Australia, C.P. Gunasekera1, L.D. Martin1, G.H. Walton2 and K.H.M. Siddique2 1Muresk Institute of Agriculture, Curtin University of Technology, Northam, 2Agriculture Western Australia 8. Physiological Aspects of Drought Tolerance in Brassica napus and B.juncea, Sharon R. Niknam and David W. Turner, Plant Sciences, Faculty of Agriculture, The University of Western Australia 9. Cross resistance of chlorsulfuron-resistant wild radish to imidazolinones, Abul Hashem, Harmohinder Dhammu and David Bowran, Agriculture Western Australia 10. Canola Variety and PBR Update 2000, From The Canola Association of Western Australia 11. Development of a canola ideotype for the low rainfall areas of the western Australian wheat belt, Syed H. Zaheer, Nick W. Galwey and David W. Turner, Faculty of Agriculture, The University of Western Australia DISEASE MANAGEMENT 12. Evaluation of fungicides for the management of blackleg in canola, Ravjit Khangura and Martin J. Barbetti, Agriculture Western Australia 13. Impact-IFÒ: Intergral in the control of Blackleg, Peter Carlton, Trials Coordinator, Elders Limited 14. Forecasting aphid and virus risk in canola, Debbie Thackray, Jenny Hawkes and Roger Jones, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 15. Beet western yellow virus in canola: 1999 survey results, wild radish weed reservoir and suppression by insecticide, Roger Jones and Brenda Coutts, Agriculture Western Australia 16. Are canola crops resilient to damage by aphids and diamond back moths? Françoise Berlandier, Agriculture Western Australia ECONOMIC OUTLOOK 17. Outlook for prices and implications for rotations, Ross Kingwell1,2, Michael O’Connell1 and Simone Blennerhasset11Agriculture Western Australia 2University of Western Australi

More than just a bracelet: the use of material symbolism to communicate love

There is growing recognition of the place of love in residential care for children (Smith, 2009). This paper is a critical analysis of a range of existing research on residential child care as well as studies of material culture and of care relationships more broadly. It argues that, despite increasing regulation and surveillance, adults and children find ways to show and feel love in the context of residential care. Whilst love may be regarded as something to be avoided or indeed prohibited in an adult/child care setting these deep bonds find expression in the everyday life of the children's home. By looking at love in this embodied way, the 'realness' of material things to assert connection and recognition of love (Layne, 2000) is examined. As Gorenstein (1996, p.8) suggests 'objects...[are] the perfect vehicles for conveying themes that are not commonly accepted in a community'. The paper emphasises the recognition of these symbolic and metaphorical forms of communication in practice