AR mRNA stability is increased with AR-antagonist resistance Via 3’ UTR variants

Advanced prostate cancer is often treated with AR-antagonists which target the androgen receptor (AR) on which the growth of the tumour depends. Prostate cancer often develops AR-antagonist resistance via a plethora of mechanisms, many of which are as yet unknown, but it is thought that AR upregulation or AR ligand binding site mutations, may be responsible. Here we describe the production of cell lines based on LNCaP and VCaP, with acquired resistance to the clinically relevant AR-antagonists, bicalutamide and enzalutamide.In these resistant cells, we observed, via RNA-seq, that new variants in the 3’UTR of the AR mRNA were detectable and that the levels were increased both with AR-antagonist treatment and with hormonal starvation. Around 20% of AR transcripts showed a 3kb deletion within the 6.7kb 3’UTR sequence. Actinomycin D and luciferase fusion studies indicated that this shorter mRNA variant was inherently more stable in anti-androgen resistant cell lines.Of additional interest was that the AR UTR variant could be detected in the sera of prostate cancer patients in a cohort of serum samples collected from patients of Gleason grades 6-10, with an increasing level correlated to increasing grade.We hypothesise that the shorter AR UTR variant is a survival adaptation to low hormone levels and/or AR-antagonist treatment in these cells, where a more stable mRNA may allow higher levels of AR expression under these conditions

The Impact of Utah 4-H on Positive Youth Development

4-H is the largest youth development program in the United States. Utah 4-H conducts programs guided by the principles of positive youth development to help youth across the state lead a successful life. This article discusses the impact of Utah 4-H on the wellbeing of youth

A Review of Clinical Disease Scoring Systems for Cicatricial Diseases of the Conjunctiva

Cicatricial conjunctival diseases (CCDs), are a diverse group of ocular surface diseases characterized by chronic scarring of the conjunctiva. These diseases can cause significant ocular morbidity. They are life-long once acquired and can be debilitating, painful diseases leading to visual loss. A recent international consensus of ocular surface disease experts have placed emphasis on the need of validated clinical disease scoring systems for CCDs, important for the objective evaluation of disease severity, outcomes of therapies, and longitudinal monitoring of disease. This review aims to describe the various published clinical disease scoring systems available for CCDs and evaluates the benefits and limitations of each system. It can be used as a guide for clinicians managing patients with CCDs and for researchers evaluating potential therapies in clinical trials

Bone Health Improvement Protocol

Introduction. Metabolic bone disease is a malady that causessignificant morbidity and mortality to a patient who has sustaineda fragility fracture. There is currently no protocol toprevent secondary fragility fracture at our institution. The objectiveof this study was to create an appropriate protocol forimplementing clinical pathways for physicians to diagnose andtreat osteoporosis and fragility fractures by educating patients. Methods. A multidisciplinary team created an appropriateprotocol that could be implemented in an inpatient setting.A thorough literature review was conducted to evaluatepotential barriers and efficacious methods of protocol design. Results. A bone health improvement protocol was developed.Any patient over the age of 50 who sustains a fracture from lowenergy trauma, such as a fall from standing or less, should beconsidered to place into this protocol. These patients receivededucation on metabolic bone disease, a prescription for highdose vitamin D therapy, and laboratory testing to determinethe etiology of their metabolic bone disease. Continuity of careof these patients with their primary care provider was providedfor further management of their metabolic bone disease andevaluation of their disease after discharged from the hospital. Conclusion. Comprehensive secondary prevention should consistof osteoporosis assessment and treatment together with afall risk assessment. With this protocol, secondary fragility fracturespotentially could be prevented. KS J Med 2017;10(3):62-66

Moving from crime and punishment to success and reward: Transitioning from technical to educational research

Copyright © 2019: Sarah Dart, Kim Blackmore, Keith Willey, Anne Gardner, Smitha Jose, Raj Sharma, Sloan Trad, Lesley Jolly:. Many engineering academics interested in quality teaching and learning dabble with educational research. Some go further leaving their technical research field behind to embark head-long into what for many is an initially bewildering and conceptually challenging domain. Often peers perceive this transition as a crime (giving up on real engineering) liable to be punished with reduced access to funding and institutional recognition for one's research. The Australasian Association for Engineering Education (AAEE) has been sponsoring a Winter School in Engineering Education Research Methods since 2011, to help engineering academics change their transition story from one of crime and punishment to success and reward. While helpful, this transition is not a simple matter of learning new techniques but of altering one's perspective and habits of thinking and behaviour. Many participants find this both challenging and at least initially, a lonely pursuit. In this paper, participants in the 2018 school ask the question "what enables and hinders the transition to educational research"

An assertion language for constraint logic programs

In an advanced program development environment, such as that discussed in the introduction of this book, several tools may coexist which handle both the program and information on the program in different ways. Also, these tools may interact among themselves and with the user. Thus, the different tools and the user need some way to communicate. It is our design principie that such communication be performed in terms of assertions. Assertions are syntactic objects which allow expressing properties of programs. Several assertion languages have been used in the past in different contexts, mainly related to program debugging. In this chapter we propose a general language of assertions which is used in different tools for validation and debugging of constraint logic programs in the context of the DiSCiPl project. The assertion language proposed is parametric w.r.t. the particular constraint domain and properties of interest being used in each different tool. The language proposed is quite general in that it poses few restrictions on the kind of properties which may be expressed. We believe the assertion language we propose is of practical relevance and appropriate for the different uses required in the tools considered

Effect of mycorrhizal inoculation and soluble phosphorus fertilizer on growth and phosphorus uptake of pearl millet

Six mycorrhizal fungi were tested as inoculants for pearl millet (Pennisetum americanum Leeke) grown in pots maintained in a greenhouse. VAM fungi varied in their ability to stimulate plant growth and phosphorus uptake. Inoculation withGigaspora margarita, G. calospora andGlomus fasciculatum increased shoot drymatter 1.3 fold over uninoculated control. In another pot trial, inoculation withGigaspora calospora andGlomus fasciculatum resulted in dry matter and phosphorus uptake equivalent to that produced by adding phosphorus at 8 kg/ha. The influence of inoculatingGigaspora calospora on pearl millet at different levels of phosphorus fertilizer (0 to 60 kg P/ha) as triple superphosphate in sterile and unsterile alfisol soil was also studied. In sterile soil, mycorrhizal inoculation increased dry matter and phosphorus uptake at levels less than 20 kg/ha. At higher P levels the mycorrhizal effect was decreased. These studies performed in sterilized soil suggest that inoculation of pearl millet with efficient VAM fungi could be extremely useful in P deficient soils. However, its practical utility depends on screening and isolation of fungal strains which perform efficiently in natural (unsterilized) field conditions

Sports review: A content analysis of the International Review for the Sociology of Sport, the Journal of Sport and Social Issues and the Sociology of Sport Journal across 25 years

The International Review for the Sociology of Sport, the Journal of Sport and Social Issues and Sociology of Sport Journal have individually and collectively been subject to a systematic content analysis. By focusing on substantive research papers published in these three journals over a 25-year time period it is possible to identify the topics that have featured within the sociology of sport. The purpose of the study was to identify the dominant themes, sports, countries, methodological frameworks and theoretical perspectives that have appeared in the research papers published in these three journals. Using the terms, identified by the author(s), that appear in the paper’s title, abstract and/or listed as a key word, subject term or geographical term, a baseline is established to reflect on the development of the sub-discipline as represented by the content of these three journals. It is suggested that the findings illustrate what many of the more experienced practitioners in the field may have felt subjectively. On the basis of this systematic, empirical study it is now possible to identify those areas have received extensive coverage and those which are under-researched within the sociology of sport. The findings are used to inform a discussion of the role of academic journals and the recent contributions made by Michael Silk, David Andrews, Michael Atkinson and Dominic Malcolm on the past, present and future of the ‘sociology of sport’