Evolution of the JAK-STAT pathway

The JAK-STAT pathway represents a finely tuned orchestra capable of rapidly facilitating an exquisite symphony of responses from a complex array of extracellular signals. This review explores the evolution of the JAK-STAT pathway: the origins of the individual domains from which it is constructed, the formation of individual components from these basic building blocks, the assembly of the components into a functional pathway, and the subsequent reiteration of this basic template to fulfill a variety of roles downstream of cytokine receptors.

Pathway from vocational education and associate degree to higher education: Chinese international students in Australia

Understanding factors influencing international students' decision to engage in international education is essential for education providers to better cater for students' educational expectations and enhance their attractiveness to international students. Whilst there has been extensive research on the reasons why international students undertake cross-border higher education, international students' motivations for enrolling in vocational education and associate degree programmes are still under-researched. Drawing on semi-structured interviews with 30 international students from China, this research found that pathway to higher education appears to be the most important factor motivating international students to undertake vocational education and associate degree programmes. In addition, prospect of immigration, English language proficiency, previous academic performance, agent's recommendations and relatives' and friends' advice are amongst the important factors that students take into account in their decision to choose vocational education and associate degree programmes. This research also examines why Chinese international students have chosen vocational education programmes in a dual-sector university over vocational education colleges. It found that the flexibility to articulate to higher education, international reputation of the programme, practical training and favourable location are key issues that these students draw on when making their decision to study in a dual-sector university.

The yield of essential oils in Melaleuca alternifolia (Myrtaceae) is regulated through transcript abundance of genes in the MEP pathway

Medicinal tea tree (Melaleuca alternifolia) leaves contain large amounts of an essential oil, dominated by monoterpenes. Several enzymes of the chloroplastic methylerythritol phosphate (MEP) pathway are hypothesised to act as bottlenecks to the production of monoterpenes. We investigated, whether transcript abundance of genes encoding for enzymes of the MEP pathway were correlated with foliar terpenes in M. alternifolia using a population of 48 individuals that ranged in their oil concentration from 39 -122 mg x g DM(-1). Our study shows that most genes in the MEP pathway are co-regulated and that the expression of multiple genes within the MEP pathway is correlated with oil yield. Using multiple regression analysis, variation in expression of MEP pathway genes explained 87% of variation in foliar monoterpene concentrations. The data also suggest that sesquiterpenes in M. alternifolia are synthesised, at least in part, from isopentenyl pyrophosphate originating from the plastid via the MEP pathway.

Low spatial frequency contrast sensitivity deficits in migraine are not visual pathway selective

Some people who experience migraine demonstrate reduced visual contrast sensitivity that is measurable between migraines. Contrast sensitivity loss to low spatial frequency gratings has been previously attributed to possible impairment of magnocellular pathway function. This study measured contrast sensitivity using low spatial frequency targets (0.25–4 c/deg) where the adaptation aspects of the stimuli were designed to preferentially assess either magnocellular or parvocellular pathway function (steady and pulsed pedestal technique). Twelve people with migraine with measured visual field abnormalities and 17 controls participated. Subjects were tested foveally and at 10° eccentricity. Foveally, there was no significant difference in group mean contrast sensitivity. At 10°, the migraine group demonstrated reduced contrast sensitivity for both the stimuli designed to assess magnocellular and parvocellular function (P < 0.05). The functional deficits measured in this study infer that abnormalities of the low spatial frequency sensitive channels of both pathways contribute to contrast sensitivity deficits in people with migraine.

Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells.

Plumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.

The STARS signaling pathway: a key regulator of skeletal muscle function

During the last decade, the striated muscle activator of Rho signaling (STARS), a muscle-specific protein, has been proposed to play an increasingly important role in skeletal muscle growth, metabolism, regeneration and stress adaptation. STARS influences actin dynamics and, as a consequence, regulates the myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) transcriptional program, a well-known pathway controlling skeletal muscle development and function. Muscle-specific stress conditions, such as exercise, positively regulates, while disuse and degenerative muscle diseases are associated with a downregulation of STARS and its downstream partners, suggesting a pivotal role for STARS in skeletal muscle health. This review provides a comprehensive overview of the known role and regulation of STARS and the members of its signaling pathway, RhoA, MRTF-A and SRF, in skeletal muscle.

HealthPathways: creating a pathway for health systems reform

Inefficiencies in the co-ordination and integration of primary and secondary care services in Australia, have led to increases in waiting times, unnecessary presentations to emergency departments and issues around poor discharge of patients. HealthPathways is a program developed in Canterbury, New Zealand, that builds relationships between General Practitioners and Specialists and uses information technology so that efficiency is maximised and the right patient is given the right care at the right time. Healthpathways is being implemented by a number of Medicare Locals across Australia however, little is known about the impact HealthPathways may have in Australia. This article provides a short description of HealthPathways and considers what it may offer in the Australian context and some of the barriers and facilitators to implementation. What is known about the topic? Early evidence on HealthPathways suggests that the program does seem to be strengthening relationships between GPs and secondary care specialists. In New Zealand advances in efficiency and system integration have been noted. However, there is limited evidence on the effectiveness of HealthPathways in Australia. What does this paper add? It is one of the first published papers to provide a perspective around HealthPathways and draws existing evidence and research to explore some of the barriers and facilitators to the development and implementation of HealthPathways in Australia. What are the implications for practitioners'? Early evidence suggests HealthPathways could help GPs and other practitioners' in the delivery of health services, it could also help to strengthen practitioner relationships.

Failures in communication through documents and documentation across the perioperative pathway.

AIMS AND OBJECTIVES: To explore how communication failures occur in documents and documentations across the perioperative pathway in nurses' interactions with other nurses, surgeons and anaesthetists. BACKGROUND: Documents and documentation are used to communicate vital patient and procedural information among nurses, and in nurses' interactions with surgeons and anaesthetists, across the perioperative pathway. Previous research indicates that communication failure regularly occurs in the perioperative setting. DESIGN: A qualitative study was undertaken. METHODS: The study was conducted over three hospitals in Melbourne, Australia. One hundred and twenty-five healthcare professionals from the disciplines of surgery, anaesthesia and nursing participated in the study. Data collection commenced in January 2010 and concluded in October 2010. Data were generated through 350 hours of observation, two focus groups and 20 semi-structured interviews. A detailed thematic analysis was undertaken. RESULTS: Communication failure occurred owing to a reliance on documents and documentation to transfer information at patient transition points, poor quality documents and documentation, and problematic access to information. Institutional ruling practices of professional practice, efficiency and productivity, and fiscal constraint dominated the coordination of nurses', surgeons' and anaesthetists' communication through documents and documentation. These governing practices configured communication to be incongruous with reliably meeting safety and quality objectives. CONCLUSIONS: Communication failure occurred because important information was sometimes buried in documents, insufficient, inaccurate, out-of-date or not verbally reinforced. Furthermore, busy nurses were not always able to access information they required in a timely manner. Patient safety was affected, which led to delays in treatment and at times inadequate care. RELEVANCE TO CLINICAL PRACTICE: Organisational support needs to be provided to nurses, surgeons and anaesthetists so they have sufficient time to complete, locate, and read documents and documentation. Infrastructure supporting communication technologies should be implemented to enable the rapid retrieval, entry, and dispersion of information.

The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and Mitochondrial Biogenesis without Altering Insulin Sensitivity.

Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would influence muscle DG content and insulin sensitivity. Muscle PtdEtn synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout mice, intramyocellular and membrane-associated DG was markedly increased. Importantly, however, this was not associated with insulin resistance. Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were increased in muscle-specific ECT knockout mice and were accompanied by enhanced exercise performance. These findings highlight the importance of the CDP-ethanolamine pathway in regulating muscle DG content and challenge the DG-induced insulin resistance hypothesis.

Effect of resistance exercise contraction mode and protein supplementation on members of the STARS signalling pathway

The striated muscle activator of Rho signalling (STARS) pathway is suggested to provide a link between external stress responses and transcriptional regulation in muscle. However, the sensitivity of STARS signalling to different mechanical stresses has not been investigated. In a comparative study, we examined the regulation of the STARS signalling pathway in response to unilateral resistance exercise performed as either eccentric (ECC) or concentric (CONC) contractions as well as prolonged training; with and without whey protein supplementation. Skeletal muscle STARS, myocardian-related transcription factor-A (MRTF-A) and serum response factor (SRF) mRNA and protein, as well as muscle cross-sectional area and maximal voluntary contraction, were measured. A single-bout of exercise produced increases in STARS and SRF mRNA and decreases in MRTF-A mRNA with both ECC and CONC exercise, but with an enhanced response occurring following ECC exercise. A 31% increase in STARS protein was observed exclusively after CONC exercise (P < 0.001), while pSRF protein levels increased similarly by 48% with both CONC and ECC exercise (P < 0.001). Prolonged ECC and CONC training equally stimulated muscle hypertrophy and produced increases in MRTF-A protein of 125% and 99%, respectively (P < 0.001). No changes occurred for total SRF protein. There was no effect of whey protein supplementation. These results show that resistance exercise provides an acute stimulation of the STARS pathway that is contraction mode dependent. The responses to acute exercise were more pronounced than responses to accumulated training, suggesting that STARS signalling is primarily involved in the initial phase of exercise-induced muscle adaptations.