Recent improvements in the development of A2B adenosine receptor agonists

Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary artery disorders and atherosclerosis

Retention and intentions to quit among Australian male\ud apprentices

Purpose: In response to both the increasing concern of the declining rates of apprentices and the limited research in this area, the purpose of this paper is to investigate the individual processes involved in apprentices’ decisions to remain in their apprenticeship.-----\ud \ud Design/methodology/approach: Specifically, five individual domains were investigated: motivation style (intrinsic and extrinsic motivation); coping style (emotion-focused and\ud problem-focused); apprentice experiences (satisfaction, work conditions, expectations, formal training and recognition); financial responsibility; and demographic factors (age, geographic location, education/training and organisational tenure). Three measures were used to assess these five domains: the work preference inventory, the brief cope and the apprentice experience questionnaire. A\ud total of 326 male participants were recruited from Victoria and Queensland.-----\ud \ud Findings: Logistic regression was performed to determine if motivation style, coping style, apprentice experiences and demographic factors could predict thoughts towards remaining in an apprenticeship. A Chi-square test was conducted to determine if financial responsibility had an impact on thoughts towards remaining in a trade. Overall results suggested that intrinsic motivation, satisfaction, working conditions and geographic location could predict apprentices’ thoughts towards staying in an apprenticeship.-----\ud \ud Research limitations/implications: The results can only be generalised to those who were currently undertaking an apprenticeship and not those who had already left. Furthermore, the outcome variable in this study was “thoughts towards quitting” and not actual quitting per se; however, social desirability effects may have influenced the responses somewhat.-----\ud \ud Originality/value: By utilising this data, educators and employers alike could now be one step closer to retaining the much-needed apprentices of Australia and it may be that other countries such as Germany, India, France, Turkey, the USA, and the UK may pool informational research resources to\ud counter the global downturn in apprentices’ availability.\ud \u

Work expectations and other factors influencing male apprentices' intentions to quit their trade\ud

This study examined the current trade shortage in Australian industry from the perspective of fewer young people entering the trades. We investigated the extent to which certain variables (relationship with their boss/supervisor; relationship with their co-workers; extrinsic motivation within the compensation subscale; the use of emotion-focused coping styles rather than problem-focused styles; and apprentices' work expectations) could predict their intention to quit or stay in the job. Of the five predictors, only two (relationship with their boss/supervisor and/or their relationship with their co-workers) were found to have the ability to significantly predict intention to quit. Comparisons between Queensland and Victorian participants led to the conclusion that an apprentice's choice to stay in or leave their trade was individually specific, and was most likely not based solely on one explicit factor, but on a range of work-related factors, which they, personally, considered important. \ud \u