The Effects of Nicotine on the Regulation of Neuronal Alpha7 Nicotinic Acetylcholine Receptors and Intracellular Signalling Pathways

Nicotine, the addictive compound of tobacco products, exerts its effects in the brain by binding to neuronal acetylcholine nicotinic receptors (nAChRs). The aim of the present study was to increase the knowledge of nicotine s complex effects, the focus being on homomeric alpha7-nAChRs that are widely expressed in the brain. Nicotinic regulation of differential signalling molecules including transcriptional regulators was also studied. We found that the number of alpha7-nAChRs is increased in specific brain regions in mice, in a time-dependent manner after chronic oral nicotine administration. Our results suggest that in addition to alpha4beta2-nAChRs, the other major nAChR subtype expressed in the brain, the number of alpha7-nAChRs is affected by chronic presence of nicotine. We suggest that when studying the long-term effects of nicotine, the duration on administration is of great importance. Next, we observed that nicotine exposure induces accumulation of cAMP in cell cultures expressing nAChRs. Furthermore, nicotine-induced alpha7-nAChR upregulation was potentiated by treatments enhancing cAMP-signalling, suggesting a role for cAMP in the upregulation process. Protein kinase C (PKC) was found essential for the basal regulation of alpha7-nAChR number. The nicotine-evoked alpha7-nAChR upregulation could be further increased by PKC overexpression. Thirdly, the effects of nicotine on dopamine and cAMP regulated phosphoprotein (DARPP-32) were characterised in rat brain. The results show that DARPP-32 is regulated by both acute and long-term nicotine treatment in the striatal subdivisions. The effect of acute nicotine is dose-dependent and the three striatal regions display differential sensitivities to nicotine. Chronic nicotine is also able to regulate DARPP-32 signalling with prominent effect seen in the nucleus accumbens (NAc), suggesting a role for DARPP-32 in the mediation of long-term effects of nicotine. Finally, the regulation of transcription factors Elk-1 and FosB/deltaFosB by nicotine was investigated. We found that Elk-1 is activated by acute nicotine selectively in the NAc core and hippocampal area CA1, whereas acute nicotine does not affect FosB/deltaFosB. Long-term intermittent or continuous nicotine increases the level of total Elk-1 in the same brain regions as acute nicotine. FosB/deltaFosB is also affected by chronic nicotine. Thus, similarly to other drugs of abuse, nicotine regulates transcriptional regulators Elk-1 and FosB/deltaFosB. These results bring further support for a common mechanism underlying the development of addiction. Nicotine s positive effects on learning and memory might involve the transcription factor Elk-1 based on the changes seen in the hippocampus, the key area in cognitive functions.

Dancing and Professional Dancers in Roman Egypt

The main aim of the study is to create a many-sided view of dancing in Roman Egypt (1st - early 4th centuries AD) and especially of the dancers who earned their living by dancing as hired performers. Even though dancers and other performers played a central part in many kinds of festivities throughout the ancient world, research on ancient professional dancers is rare and tends to rest on the ancient literature, which reflects the opinions of the elite. Documentary written sources (i.e., papyri, ostraka) the core of the present study are mentioned rather superficially, easily resulting in a stereotypical view of the dancers. This study will balance the picture of professional dancers in antiquity and of ancient dancing in a more general sense. The second aim characterizes this study as basic research: to provide a corpus of written sources from Greco-Roman Egypt on dancing and to discuss pictorial sources contemporary with the texts. The study also takes into account the theoretical discussion that centres on dancing as a nonverbal communicative mode. Dancers are seen as significant conveyors of social and cultural matters. This study shows that dancers were hired to perform especially in religious contexts, where the local associations on the village level also played an important part as the employers of the performers. These performers had a better standard of living in economic terms than the average hired worker, and dancers were better paid than other performers. In the Egyptian villages and towns, where the dancers performed and lived, the dancers do not seem to have been marginal because they were professionals or because of some ethnic or social background. However, their possible marginality may have occurred for reasons related to the practicalities of their profession (e.g., the itinerant life style). The oriental background of performers was a literary topos reflecting partly the situation in the centres of the empire, especially Rome, where many performers were of other than Roman origin. The connection of dancing, prostitution and slavery reflects the essential link between dance, body and gender: dancers are equated with such professions or socio-legal statuses where the body is the focus of attention, a commodity and a source of sensual pleasure; this dimension is clearly observable in ancient literature. According to the Egyptian documentary sources, there is no watertight evidence that professional dancers would have been engaged in prostitution and very little, if any, evidence that the disapproval of the professional dancers expressed by the ancient authors was shared by the Egyptians. From the 4th century onwards the dancers almost disappear from the documentary sources, reflecting the political and religious changes in the Mediterranean east.

A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer

The oncogene MDM4, also known as MDMX or HDMX, contributes to cancer susceptibility and progression through its capacity to negatively regulate a range of genes with tumour-suppressive functions. As part of a recent genome-wide association study it was determined that the A-allele of the rs4245739 SNP (A>C), located in the 3'-UTR of MDM4, is associated with an increased risk of prostate cancer. Computational predictions revealed that the rs4245739 SNP is located within a predicted binding site for three microRNAs (miRNAs): miR-191-5p, miR-887 and miR-3669. Herein, we show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer. These miRNAs do not affect MDM4 mRNA levels, rather they inhibit its translation in C-allele-containing PC3 cells but not in LNCaP cells homozygous for the A-allele. By analysing gene expression datasets from patient cohorts, we found that MDM4 is associated with metastasis and prostate cancer progression and that targeting this gene with miR-191-5p or miR-887 decreases in PC3 cell viability. This study is the first, to our knowledge, to demonstrate regulation of the MDM4 rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4 rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.

The introduction of an Inter-professional learning unit: staff and student perspectives

Background The School of Clinical Sciences comprises a number of health disciplines including podiatry, paramedic science, pharmacy, medical imaging and radiation therapy. A new inter-professional unit was introduced in 2014, which covered key introductory learnings applicable for future health practitioners. This study examined teaching staff and student perspectives about their experience with the new unit for first year students. Methods Qualitative interviews with teaching staff (n=9) and focus group interviews with students (5 groups which ranged in size from 4-30) were conducted. Extensive notes were taken during the interviews Issues emerging from the interviews were identified and organised according to themes and subthemes. Results Four major themes were identified namely: Something new; To be or not to be that is the question; Advantages of the new unit; and Areas for improvement. Previous staff experience with inter-professional learning (IPL) had been ad-hoc, whereas the new unit brought together several disciplines in a planned and deliberate way. There was strong philosophical agreement about the value of IPL but some debate about the extent to which the unit provided IPL experience. The unit was seen as assisting students’ social and academic adjustment to university and provided opportunity for professional socialisation, exposure to macro and micro aspects of the Australian health care system and various types of communication. For podiatry students it was their first opportunity to formally meet and work with other podiatry students and moved their identity from ‘university student’ to ‘podiatry student’. Other positives included providing the opportunity for staff and students to interact at an early stage with the perceived benefit of reducing attrition. Areas for unit improvement included institutional arrangements, unit administration aspects and assessment. Conclusion The unit was seen as beneficial by staff and students however, students were more polarised in their views than staff. There was a tension between feeling apart of and learning about one's own profession and feeling apart of and learning about the roles of other health professionals in relation to patient care and the health care system.

Effects of the digital subtitling software on the subtitling process : A survey among Finnish professional television subtitlers

Tutkielma käsittelee suomalaisten televisiotekstittäjien ammatillisuutta, käännösprosessia ja digitaalisten tekstitysohjelmien vaikutuksia tekstitysprosessiin ammattitekstittäjien näkökulmasta. Suomen television digitalisoituminen on aiheuttanut mullistuksia myös tekstitysalalla kun tekstitettävä kuvamateriaali on ryhdytty toimittamaan käännöstoimistoille ja tekstittäjille digitaalisena. Teoriaosuudessa käsitellään käännös- ja tekstitystutkimusta sekä koulutusta Suomessa, ammattitaitoa ja ammatillisuutta sekä kääntämisen apukeinoja. Tekstittäminen esitellään erikoistuneena kääntämisen muotona. On kuitenkin myös huomioitava, että kääntäminen on yksi vaihe tekstitysprosessissa. Teoriaosuus päättyy suomalaisten televisiotekstittäjien arjen ja työkentän nykytilanteen käsittelyyn – tekstittäjät työskentelevät monenlaisilla työehdoilla ja laadun kriteerit saatetaan joutua arvioimaan uudelleen. Empiirisen osan alussa esitetään, että suomalaisia televisiotekstittäjiä on haastateltu yllättävän vähän, ja Jääskeläisen ajatuksiin nojaten mainitaan, että tekstittämisen alalla on vielä paljon tutkimatta – etenkin suomalaisesta tekstitysprosessista löytyy tutkittavaa. Tutkimuskohde on ammatikseen televisioon tekstityksiä tekevät kääntäjät. Suomalaiselle tekstitykseen erikoistuneelle käännöstoimistolle työskenteleville tekstittäjille lähetettiin alkutalvesta 2008 kyselylomake, jolla kartoitettiin sekä monivalintakysymyksillä että avoimilla kysymyksillä heidän ammatillisuuttaan, työmenetelmiään, käännös- ja tekstitysprosessiaan, ammattiylpeyttään ja -identiteettiään, ajanhallintaansa, sekä heidän käyttämäänsä digitaalista tekstitysohjelmaa. Tutkimuksessa kävi ilmi, että lähes kolmanneksella vastaajista on ammatistaan neutraali tai jopa negatiivinen käsitys. Näitä tekstittäjiä yhdistää se seikka, että kaikilla on alle 5 vuotta kokemusta alalta. Valtaosa vastanneista on kuitenkin ylpeitä siitä, että toimivat suomen kielen ammattilaisina. Tekstitysprosessi oli lomakkeessa jaettu esikatseluvaiheeseen, käännösvaiheeseen, ajastamisvaiheeseen ja korjauskatseluvaiheeseen. Tekstittäjät pyydettiin mm. arvioimaan tekstitysprosessinsa kokonaiskestoa. Kestoissa ilmeni suuria eroavaisuuksia, joista ainakin osa korreloi kokemuksen kanssa. Runsas puolet vastaajista on hankkinut digitaalisen tekstitysohjelmiston käyttöönsä ja osa ajastaa edelleen käännöstoimistossa muun muassa ohjelmiston kalleuden vuoksi. Digitaalisen ohjelmiston myötä tekstitysprosessiin ja työkäytänteisiin on tullut muutoksia, kun videonauhureista ja televisioista on siirrytty pelkän tietokoneen käyttöön. On mahdollista tehdä etätyötä kaukomailta käsin, kääntää ja ajastaa lomittain tai tehdä esiajastus ja kääntää sitten. Digitaalinen tekniikka on siis mahdollistanut tekstitysprosessin muuttumisen ja vaihtoehtoiset työmenetelmät, mutta kaikista menetelmistä ei välttämättä ole tekstittäjälle hyötyä. Perinteinen tekstitysprosessi (esikatselu, repliikkijakojen merkitseminen käsikirjoitukseen, kääntäminen ja repliikkien laadinta, korjaukset ja tarkastuskatselu) vaikuttaa edelleen tehokkaimmalta. Vaikka työkäytänteet eroavat toisistaan, kokonaiskäsitys on se, että digitalisoitumisen alkukangertelujen jälkeen tekstittäjien työskentely on tehostunut.

Transcriptional regulation of a pineapple polyphenol oxidase gene and its relationship to blackheart.

Two genes encoding polyphenol oxidase (PPO) were isolated from pineapple (Ananas comosus[L.] Merr. cv. Smooth Cayenne). Sequence analyses showed that both contained a single intron and encoded typical chloroplast-localized PPO proteins, the sequences of which corresponded to two pineapple PPO cDNAs, PINPPO1 and PINPPO2, recently described by Stewart et al. (2001). Southern blot analyses suggested that pineapple contained only two PPO genes. Analysis of expression of PINPPO1 promoter GUS fusion constructs showed this promoter had a low basal activity and was cold- and wound-inducible, consistent with known mRNA expression profiles. Striking homologies to gibberellin response complexes (GARC) were observed in sequences of both the PINPPO1 and PINPPO2 promoters. Transient assays in mature pineapple fruit and stable expression in transgenic tobacco showed that PINPPO1 promoter-GUS fusions were indeed gibberellin (GA) responsive. A role for the element within the putative GARCs in mediating GA-responsiveness of the PINPPO1 promoter was confirmed by mutational analysis. PINPPO2 was also shown to be GA-responsive by RT-PCR analysis. Mutant PINPPO1 promoter-GUS fusion constructs, which were no longer GA-inducible, showed a delayed response to cold induction in pineapple fruit in transient assays, suggesting a role for GA in blackheart development. This was supported by observations that exogenous GA3 treatment induced blackheart in the absence of chilling. Sequences showing homology to GARCs are also present in some PPO promoters in tomato, suggesting that GA regulates PPO expression in diverse species.

Regulation of Gonadotropin-Releasing Hormone (GnRH)-Receptor Gene Expression in Tilapia: Effect of GnRH and Dopamine

The present work was designed to study certain aspects of the endocrine regulation of gonadotropin-releasing hormone receptor (GnRH-R) in the pituitary of the teleost fish tilapia. A GnRH-R was cloned from the pituitary of hybrid tilapia (taGnRH-R) and was identified as a typical seven-transmembrane receptor. Northern blot analysis revealed a single GnRH-R transcript in the pituitary of approximately 2.3 kilobases. The taGnRH-R mRNA levels were significantly higher in females than in males. Injection of the salmon GnRH analog (sGnRHa; 5–50 μg/kg) increased the steady-state levels of taGnRH-R mRNA, with the highest response recorded at 25 μg/kg and at 36 h. At the higher dose of sGnRHa (50 μg/kg), taGnRH-R transcript appeared to be down-regulated. Exposure of tilapia pituitary cells in culture to graded doses (0.1–100 nM) of seabream (sbGnRH = GnRH I), chicken II (cGnRH II), or salmon GnRH (sGnRH = GnRH III) resulted in a significant increase in taGnRH-R mRNA levels. The highest levels of both LH release and taGnRH-R mRNA levels were recorded after exposure to cGnRH II and the lowest after exposure to sbGnRH. The dopamine-agonist quinpirole suppressed LH release and mRNA levels of taGnRH-R, indicating an inhibitory effect on GnRH-R synthesis. Collectively, these data provide evidence that GnRH in tilapia can up- regulate, whereas dopamine down-regulates, taGnRH-R mRNA levels.

Improving the outcomes of foot and ankle surgery. Professional impact of the Australasian College of Podiatric Surgeons' audit tool

Background Surgery is an example of expanded practice scope that enhances podiatry and incorporates inter-professional collaboration. By 2050 demand for foot and ankle procedures is predicted to rise nationally by 61.9%. Performance management of this increase motivated the development of an online audit tool. Developed in collaboration with the Australasian College of Podiatric Surgeons (ACPS), the ACPS audit tool provides real-time data capture and reporting. It is the first audit tool designed in Australia to support and improve the outcomes of foot and ankle surgery. Methods Audit activity in general, orthopaedic, plastic and podiatric surgery was examined using a case study design. Audit participation enablers and barriers were explored. Case study results guided a Delphi survey of international experts experienced or associated with foot and ankle surgery. Delphi survey-derived consensus informed modification of a generic data set from the Royal Australasian College of Surgeons (RACS). Based on the Delphi survey findings the ACPS online audit tool was developed and piloted. Reliability and validity of data entry and usability of this new tool was then assessed with an online survey. Results The case study found surgeon attitudes and behaviours positively impacted audit participation, and also indicated that audit data should be: (1) available in real time, (2) identify practice change, (3) applicable for safety and quality management, and; (4) useful for peer review discussion. The Delphi process established consensus on audit variables to be captured, including the modified RACS generic data set. 382 cases of foot and ankle surgery were captured across 3 months using the new tool. Data entry was found to be valid and reliable. Real-time outcome reporting and practice change identification impacted positively on safety and quality management and assisted peer review discussion. An online survey showed high levels of usability. Conclusions Surgeon contribution to audit tool development resulted in 100% audit participation. The data from the ACPS audit tool supported the ACPS submission to the Medical Services Advisory Committee to list podiatric surgery under Medicare, an outcome noted by the Federal Minister of Health.

The Statutory Defence(s) of 'peer professional opinion'

In the wake of the GFC and with ever increasing consumer-protection-related laws, clients are more aware of their rights and your obligations as a professional valuer. They also are more likely to take legal action if, as a result of their reliance on a valuation, they suffer a financial loss. In some Australian jurisdictions, in response to a claim of negligence, the professional valuer may be able to raise a professional practice defence under civil liability legislation. This article considers the nature of this statutory defence, what is required to rely upon it and in which jurisdictions it applies.

Infection control standards and credentialing

Infection control professionals (ICPs) play an integral part of developing, implementing, and evaluating infection control programs. In Australia, there is no minimum or standardized education to practice as an ICP. The Australasian College of Infection Prevention and Control, the professional body for ICPs in Australasia, sought to address the issue by developing a credentialing process.1, 2 and 3 This decision was made in recognition that self-regulation is one of the hallmarks of professionalism.4 The process of becoming credentialed as an ICP in Australia involves the submission of evidence against a range of criteria with a subsequent peer-review process...

A fuzzy logic based dynamic wave model inversion algorithm for canal regulation

A fuzzy logic based centralized control algorithm for irrigation canals is presented. Purpose of the algorithm is to control downstream discharge and water level of pools in the canal, by adjusting discharge release from the upstream end and gates settings. The algorithm is based on the dynamic wave model (Saint-Venant equations) inversion in space, wherein the momentum equation is replaced by a fuzzy rule based model, while retaining the continuity equation in its complete form. The fuzzy rule based model is developed on fuzzification of a new mathematical model for wave velocity, the derivational details of which are given. The advantages of the fuzzy control algorithm, over other conventional control algorithms, are described. It is transparent and intuitive, and no linearizations of the governing equations are involved. Timing of the algorithm and method of computation are explained. It is shown that the tuning is easy and the computations are straightforward. The algorithm provides stable, realistic and robust outputs. The disadvantage of the algorithm is reduced precision in its outputs due to the approximation inherent in the fuzzy logic. Feed back control logic is adopted to eliminate error caused by the system disturbances as well as error caused by the reduced precision in the outputs. The algorithm is tested by applying it to water level control problem in a fictitious canal with a single pool and also in a real canal with a series of pools. It is found that results obtained from the algorithm are comparable to those obtained from conventional control algorithms.

Social audit failure: Legal liability of external auditors

In this chapter, we look at the step beyond reporting, to the external audit or assurance function. The role of any audit engagement is to provide a professional opinion on a set of financial or non-financial assertions reported by an organization's management, based on an agreed evaluative framework. Any such opinion is not a guarantee that the underlying report is free from fraud or misstatement. Where an audit opinion on financial statements is incorrect, this is referred to as an audit failure. Specifically, the textbook definition of audit failure has two components: that the financial statements contain a serious error and that the auditor has failed to detect the error due to the auditor's failure during the audit process.

"Re-thinking" the influence of regulatory capture in the development of government regulation

On 30 March 2015 the Australian Federal Government launched its "Re-Think" initiative with the objective of achieving a better tax system which delivers taxes that are lower, simpler and fairer. The discussion paper released as part of the "Re:think" initiative is designed to start a national conversation on tax reform. However, inquiries into Australia's future tax system, subsequent reforms and the introduction of new taxes are nothing new. Unfortunately, recent history also demonstrates that reform initiatives arising from reviews of the Australian tax system are often deemed a failure. The most prominent of these failures in recent times is the Minerals Resource Rent Tax (MRRT), which lasted a mere 16 months before its announced repeal. Using the established theoretic framework of regulatory capture to interpret publically observable data, the purpose of this article is to explain the failure of this arguably sound tax. It concludes that the MRRT legislation itself, through the capture by the mining companies, provided internal subsidization in the form of reduced tax and minimal or no rents. In doing so, it offers an opportunity to understand and learn from past experiences to ensure that recommendations coming out of the Re:think initiative do not suffer the same fate.

Neurochemical regulation of auditory information processing studied with EEG/MEG: application to schizophrenia

Cognitive impairments of attention, memory and executive functions are a fundamental feature of the pathophysiology of schizophrenia. The neurophysiological and neurochemical changes in the auditory cortex are shown to underlie cognitive impairmentsin schizophrenia patients. Functional state of the neural substrate of auditory information processing could be objectively and non-invasively probed with auditory event-related potentials (ERPs) and event- related fields (ERFs). In the current work, we explored the neurochemical effect on the neural origins of auditory information processing in relation to schizophrenia. By means of ERPs/ERFs we aimed to determine how neural substrates of auditory information processing are modulated by antipsychotic medication in schizophrenia spectrum patients (Studies I, II) and by neuropharmacological challenges in healthy human subjects (Studies III, IV). First, with auditory ERPs we investigated the effects of olanzapine (Study I) and risperidone (Study II) in a group of patients with schizophrenia spectrum disorders. After 2 and 4 weeks of treatment, olanzapine has no significant effects on mismatch negativity(MMN) and P300, which, as it has been suggested, respectively reflect preattentive and attention-dependent information processing. After 2 weeks of treatment, risperidone has no significant effect on P300, however risperidone reduces P200 amplitude. This latter effect of risperidone on neural resources responsible for P200 generation could be partly explained through the action of dopamine. Subsequently, we used simultaneous EEG/MEG to investigate the effects of memantine (Study III) and methylphenidate (Study IV) in healthy subjects. We found that memantine modulates MMN response without changing other ERP components. This could be interpreted as being due to the possible influence of memantine through the NMDA receptors on auditory change- detection mechanism, with processing of auditory stimuli remaining otherwise unchanged. Further, we found that methylphenidate does not modulate the MMN response. This finding could indicate no association between catecholaminergic activities and electrophysiological measures of preattentive auditory discrimination processes reflected in the MMN. However, methylphenidate decreases the P200 amplitudes. This could be interpreted as a modulation of auditory information processing reflected in P200 by dopaminergic and noradrenergic systems. Taken together, our set of studies indicates a complex pattern of neurochemical influences produced by the antipsychotic drugs in the neural substrate of auditory information processing in patients with schizophrenia spectrum disorders and by the pharmacological challenges in healthy subjects studied with ERPs and ERFs.