Review : alternative splicing (AS) of genes as an approach for generating protein complexity

Prior to the completion of the human genome project, the human genome was thought to have a greater number of genes as it seemed structurally and functionally more complex than other simpler organisms. This along with the belief of “one gene, one protein”, were demonstrated to be incorrect. The inequality in the ratio of gene to protein formation gave rise to the theory of alternative splicing (AS). AS is a mechanism by which one gene gives rise to multiple protein products. Numerous databases and online bioinformatic tools are available for the detection and analysis of AS. Bioinformatics provides an important approach to study mRNA and protein diversity by various tools such as expressed sequence tag (EST) sequences obtained from completely processed mRNA. Microarrays and deep sequencing approaches also aid in the detection of splicing events. Initially it was postulated that AS occurred only in about 5%; of all genes but was later found to be more abundant. Using bioinformatic approaches, the level of AS in human genes was found to be fairly high with 35-59%; of genes having at least one AS form. Our ability to determine and predict AS is important as disorders in splicing patterns may lead to abnormal splice variants resulting in genetic diseases. In addition, the diversity of proteins produced by AS poses a challenge for successful drug discovery and therefore a greater understanding of AS would be beneficial.

Unpacking ‘lessons learned’ : investigating failures and considering alternative solutions

One of the most common ways to share project knowledge is to capture the positive and negative aspects of projects in the form of lessons learned (LL). If effectively used, this process can assist project managers in reusing project knowledge and preventing future projects from repeating mistakes. Nevertheless, the process of capturing, storing, reviewing and reusing LL often remains suboptimal. Despite the potential for rich knowledge capture, lessons are often documented as simple, line-item statements devoid of context. Findings from an empirical investigation across four cases revealed a range of reasons related to the perceived quality, process and visibility of LL that lead to their limited use and application. Drawn from the cross-case analysis, this paper investigates an integrated approach to LL involving the use of a collaborative Web-based tool, which is easily accessible, intelligible and user-friendly, allowing more effective sharing of project knowledge and overcoming existing problems with LL.

Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer

We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance

Alternative modes of entrepreneurial opportunity exploitation

While entrepreneurship research has taken firm formation to be the predominant mode of opportunity exploitation, entrepreneurship can take place through many other types of organizational arrangements. In the present article, we consider one such alternative arrangement, namely the formation of inter-organizational projects (IOPs). We propose a multi-level contingency model that suggests that uncertainty both at the level of the firm and at the level of the environment makes the exploitation of opportunities through IOPs more likely. The model is tested by telephone survey data collected amongst a panel of 1725 SMEs and longitudinal industry data. Our findings provide strong support for the industry-level part of the model, but interestingly, only partial support for the firm level part of the model. This indicates that the effects of uncertainty need to be dissected into different levels of analysis to understand the conditions under which alternative modes of opportunity exploitation can be a prominent entrepreneurial alternative to new firm formation.

Patients perceptions of emergency department services : better specialised staff, convenient and available services

Many factors are identified as contributing to the high demand for emergency department (ED) care. Similarly, there have been many initiatives taken to minimise the impact that is placed on EDs. Many of these, however, do not consider the patient's opinions and motivations. The aim of this cross-sectional study was to understand patients’ perspectives and reasons behind their decision to present to EDs. 911 surveys were collected from patients presenting to eight QLD EDs in 2011. Based on the Principal Component Analysis technique, a six-item scale entitled "Best services at emergency departments" was extracted (α = 0.729) measuring patients' opinions and perspectives. Further, the independent t-tests were conducted between various groups of ED users. The results suggest that multiple users more likely viewed EDs as the best place for their conditions than the first-time users (Median 10.73 v 11.56, p<0.001). Moreover, patients who made the decision to present by themselves had a more favourable perception of the ED services than those for whom the decision was made or others were involved (Median 11.38 v 10.80, p=0.003). Method of arrival did not affect the respondents’ perception of ED (11.13 v 11.00, p=0.65). The results of this research indicate that patients’ perception of ED as the best and most appropriate place for attention to their medical conditions plays an important role in their decision to present and keep returning to ED. Understanding patients’ reasons and decisions enhances the success of planning and implementing alternative services to manage the demand for ED services.

Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine

Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agents. Oral domperidone is not approved in the US, but is used in many countries to treat nausea and vomiting, gastroparesis, and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion: The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound’s propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants or before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.

Small business prosperity and wellbeing : an alternative measure for success among small business owners

This study investigated the influences of business prosperity on small business owners’ wellbeing with gender as a moderator. A sample of 687 Australian small business owners from the Household, Income and Labour Dynamics in Australia Survey (HILDA) from 2008 to 2010 was utilised. Findings suggest that procedural utility contributed to small business owners’ wellbeing over economic utility. Procedural utility was significantly related to small business owners’ wellbeing for males and females. However, economic utility contributed only to male small business owners’ wellbeing. In order to increase the understanding of these findings it is suggested that more theoretical work regarding gender differences in procedural and economic utility should be carried out.

Using GPS technology to (re)-examine operational definitions of 'neighbourhood' in place-based health research

BACKGROUND Inconsistencies in research findings on the impact of the built environment on walking across the life course may be methodologically driven. Commonly used methods to define 'neighbourhood', from which built environment variables are measured, may not accurately represent the spatial extent to which the behaviour in question occurs. This paper aims to provide new methods for spatially defining 'neighbourhood' based on how people use their surrounding environment. RESULTS Informed by Global Positioning Systems (GPS) tracking data, several alternative neighbourhood delineation techniques were examined (i.e., variable width, convex hull and standard deviation buffers). Compared with traditionally used buffers (i.e., circular and polygon network), differences were found in built environment characteristics within the newly created 'neighbourhoods'. Model fit statistics indicated that exposure measures derived from alternative buffering techniques provided a better fit when examining the relationship between land-use and walking for transport or leisure. CONCLUSIONS This research identifies how changes in the spatial extent from which built environment measures are derived may influence walking behaviour. Buffer size and orientation influences the relationship between built environment measures and walking for leisure in older adults. The use of GPS data proved suitable for re-examining operational definitions of neighbourhood.

A review of first aid treatments for burn injuries

Throughout history there have been many different and sometimes bizarre treatments prescribed for burns. Unfortunately many of these treatments still persist today, although they often do not have sufficient evidence to support their use. This paper reviews common first aid and pre-hospital treatments for burns (water--cold or warm, ice, oils, powders and natural plant therapies), possible mechanisms whereby they might work and the literature which supports their use. From the published work to date, the current recommendations for the first aid treatment of burn injuries should be to use cold running tap water (between 2 and 15 degrees C) on the burn, not ice or alternative plant therapies.

Cyanoacrylate glue as an alternative mounting medium for resin-embedded semithin sections

Commercially available generic Superglue (cyanoacrylate glue) can be used as an alternative mounting medium for stained resin-embedded semithin sections. It is colourless and contains a volatile, quick-setting solvent that produces permanent mounts of semithin sections for immediate inspection under the light microscope. Here, we compare the use of cyanoacrylate glue for mounting semithin sections with classical dibutyl phthalate xylene (DPX) in terms of practical usefulness, effectiveness and the quality of the final microscopic image.

Variations in acculturation and Australian physical education teacher education students' receptiveness to an alternative pedagogical approach to games teaching

Background The development of intelligent, thinking performers as a central theme in Physical Education curriculum documents worldwide has highlighted the need for an evolution of teaching styles from the dominant reproductive approach. This has prompted an Australian university to change the content and delivery of a games unit within their Physical Education Teacher Education (PETE) course and adopt a productive student centred approach that is compatible with current curriculum directives. The significance of prospective physical educators’ biographies on their receptiveness to this pedagogical innovation was studied to help recognise and understand potential differences and subsequently guide programme development to help improve the impact of teacher education. Purpose To investigate whether past school and sporting experiences are powerful influences on Australian PETE recruits’ initial perspectives about effective physical education teaching practice and their receptiveness to an alternative pedagogical approach. Participants and Setting 49 first year pre-service PETE students (53% male; 47% female; mean age 18.88 ± 1.57 years) undertaking a compulsory unit on games teaching at an Australian university volunteered to take part in the study and were grouped according to their highest level of representation in games, either school/club (n=13), regional (n=20), or state/national (n=16). Students experienced the constraints-led approach as learners and teachers during an 8-week games unit informed by nonlinear pedagogy and underpinned by motor learning theory. Data collection and Analysis Prior to the commencement of the unit participants completed part A of a two part mixed response questionnaire aimed at gathering data about their physical education and sporting background. The data were summarised using descriptive statistics. Pre and post intervention, participants completed part B responding, via Likert Scale with their opinion of the importance of each sub-component of the traditional reproductive style for an effective games teaching session. This resulted in a traditional reproductive games teaching belief score. For each sub-component, participants were invited to respond in more detail to justify their opinions. A one-way between groups analysis of variance (ANOVA), Tukey’s HSD Post Hoc Test and a two - tailed, paired samples t test were used to analyse the quantitative data. Content analysis was used to analyse the qualitative data. Findings The traditional, reproductive approach was the most frequently reported teaching approach used by the physical education teachers and sports coaches of participants in all groups. Prior to the commencement of the alternate games unit, participants in each representative level group held very strong custodial traditional reproductive games teaching beliefs. After experiencing the alternative games unit there were statistically significant differences in the traditional reproductive games teaching belief mean scores for each group, This combined with participants’ qualitative responses indicated a receptiveness to the alternative pedagogy. Conclusions The results of this present study show that, contrary to previous research undertaken in North America, in Australia, it is possible for PETE educators to change beliefs in order to overcome the constraint of acculturation and provide PETE students with the knowledge, understanding and belief in an alternate approach to teaching games in physical education compatible with curriculum documents.

Where are all the female participants in sports and exercise medicine research?

The aim of this study is to estimate the ratio of male and female participants in Sports and Exercise Medicine research. Original research articles published in three major Sports and Exercise Medicine journals (Medicine and Science in Sport and Exercise, British Journal of Sports Medicine and American Journal of Sports Medicine) over a three year period were examined. Each article was screened to determine the following: total number of participants, the number of female participants and the number of male participants. The percentage of females and males per article in each of the journals was also calculated. Cross tabulations and Chi square analysis were used to compare the gender representation of participants within each of the journals. Data were extracted from 1, 382 articles involving a total of 6, 076, 705 participants. 2, 366, 998 (39%) participants were female and 3, 709, 707 (61%) male. The average percentage of female participants per article across the journals ranged from 35-37%. Females were significantly under-represented across all of the journals (X2 =23566, df=2, p<0.00001). There were no significant differences between the three journals. In conclusion, Sports and Exercise Medicine practitioners should be cognisant of sexual dimorphism and gender disparity in the current literature.

Gelatine methacrylamide-based hydrogels : an alternative three-dimensional cancer cell culture system

Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of the extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized and established as in vitro and in vivo spheroid-based models for ovarian cancer, reflecting the advanced disease stage of patients, with accumulation of multicellular spheroids in the tumour fluid (ascites). Polymer concentration (2.5-7% w/v) strongly influenced hydrogel stiffness (0.5±0.2kPa to 9.0±1.8kPa) but had little effect on solute diffusion. The diffusion coefficient of 70kDa fluorescein isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3 times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA) and stiffness (3.4kPa) allowed spheroid formation and high proliferation and metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM degradability reduced spheroid formation and proliferation rates. The incorporation of the ECM components laminin-411 and hyaluronic acid further stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre-cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer animal model was proven and led to tumour development and metastasis. These tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not the integrin antagonist ATN-161. While paclitaxel and its combination with ATN-161 resulted in a treatment response of 33-37.8%, ATN-161 alone had no effect on tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA combines relevant natural cues with tunable properties, providing an alternative, bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.