Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

Human melanoblasts in culture: Expression of BRN2 and synergistic regulation by fibroblast growth factor-2, stem cell factor, and endothelin-3

The BRN2 transcription factor (POU3F2, N-Oct-3) has been implicated in development of the melanocytic lineage and in melanoma. Using a low calcium medium supplemented with stem cell factor, fibroblast growth factor-2, endothelin-3 and cholera toxin, we have established and partially characterised human melanocyte precursor cells, which are unpigmented, contain immature melanosomes and lack L-dihydroxyphenylalanine reactivity. Melanoblast cultures expressed high levels of BRN2 compared to melanocytes, which decreased to a level similar to that of melanocytes when cultured in medium that contained phorbol ester but lacked endothelin-3, stem cell factor and fibroblast growth factor-2. This decrease in BRN2 accompanied a positive L-dihydroxyphenylalanine reaction and induction of melanosome maturation consistent with melanoblast differentiation seen during development. Culture of primary melanocytes in low calcium medium supplemented with stem cell factor, fibroblast growth factor-2 and endothelin-3 caused an increase in BRN2 protein levels with a concomitant change to a melanoblast-like morphology. Synergism between any two of these growth factors was required for BRN2 protein induction, whereas all three factors were required to alter melanocyte morphology and for maximal BRN2 protein expression. These finding implicate BRN2 as an early marker of melanoblasts that may contribute to the hierarchy of melanocytic gene control.

The regulation of complementary health: sacrificing integrity?

In response to the increasing use of complementary and alternative medicine (CAM), governments are exploring ways to ensure patients' safety and respond to complaints. One solution is to establish registration boards and procedures based on the model of existing health practitioner Acts. Registration will require defined minimum standards for competence, which will have to be based on scientific evidence. As scientific evidence accumulates, these modalities are likely to lose their identities as alternative and become assimilated into Western medicine.

A reduced load approximation accounting for link interactions in a loss network

This paper is concerned with evaluating the performance of loss networks. Accurate determination of loss network performance can assist in the design and dimen- sioning of telecommunications networks. However, exact determination can be difficult and generally cannot be done in reasonable time. For these reasons there is much interest in developing fast and accurate approximations. We develop a reduced load approximation that improves on the famous Erlang fixed point approximation (EFPA) in a variety of circumstances. We illustrate our results with reference to a range of networks for which the EFPA may be expected to perform badly.

Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

Neural reflex regulation of arterial pressure in pathophysiological conditions : interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex

The maintenance of arterial pressure at levels adequate to perfuse the tissues is a basic requirement for the constancy of the internal environment and survival. The objective of the present review was to provide information about the basic reflex mechanisms that are responsible for the moment-to-moment regulation of the cardiovascular system. We demonstrate that this control is largely provided by the action of arterial and non-arterial reflexes that detect and correct changes in arterial pressure (baroreflex), blood volume or chemical composition (mechano- and chemosensitive cardiopulmonary reflexes), and changes in blood-gas composition (chemoreceptor reflex). The importance of the integration of these cardiovascular reflexes is well understood and it is clear that processing mainly occurs in the nucleus tractus solitarii, although the mechanism is poorly understood. There are several indications that the interactions of baroreflex, chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system control the activity of autonomic preganglionic neurons through parallel afferent and efferent pathways to achieve cardiovascular homeostasis. It is surprising that so little appears in the literature about the integration of these neural reflexes in cardiovascular function. Thus, our purpose was to review the interplay between peripheral neural reflex mechanisms of arterial blood pressure and blood volume regulation in physiological and pathophysiological states. Special emphasis is placed on the experimental model of arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable.

Hedge accounting no mercado acionário brasileiro : efeitos na qualidade da informação contábil e disclosure

Este trabalho investiga, no mercado acionário brasileiro, o efeito da contabilidade de hedge na qualidade das informações contábeis divulgadas, no disclosure dos instrumentos financeiros derivativos e na assimetria de informação. Para medir a qualidade da informação contábil, foram utilizadas as métricas de relevância da informação contábil e informatividade dos lucros contábeis. Para a execução deste trabalho, foi constituída uma amostra geral com empresas brasileiras, não financeiras, listadas na Bolsa de Valores de São Paulo, compreendendo as 150 empresas com maior valor de mercado em 01/01/2014. A partir da amostra geral, foram constituídas amostras para a aplicação dos modelos de value relevance, informativeness, disclosure e assimetria de informação. A amostra para relevância contou com 758 observações firmas-anos, para o período de 2008 a 2013. A amostra para informatividade contou com 701 observações firmas-anos, para o período de 2008 a 2013. A amostra para disclosure contou com 100 observações firmas-anos, para o período de 2011 a 2012. A amostra para assimetria de informação contou com 100 observações firmas-anos, para o período de 2011 a 2012. Para as análises dos dados, utilizou-se regressões com errospadrão robustos com abordagem POLS e Efeitos Fixos, aplicadas sobre dados em painel. Complementarmente, para as análises do efeito do hedge accounting sobre o disclosure e assimetria de informação, foi aplicado o método de Propensity Score Matching. As evidências encontradas para a influência da contabilidade de hedge na relevância da informação contábil apontaram uma relação positiva e significante na interação com o LL. Na análise da informatividade dos lucros contábeis, a pesquisa evidenciou uma relação negativa e estatisticamente significante do lucro quando interagido com a variável dummy de hedge accounting. Quanto às evidências encontradas para a influência do hedge accounting sobre o disclosure dos derivativos, verificou-se uma relação positiva e estatisticamente significante da dummy de hedge accounting com o indicador de evidenciação dos derivativos. Em relação às evidências para a assimetria de informação, embora os coeficientes se mostrassem no sentido esperado, os mesmos não foram estatisticamente significativos. Adicionalmente, incorporamse às análises econométricas uma análise descritiva, na amostra geral, da utilização do hedge accounting no Brasil, para o ano de 2013. Dentre as 150 empresas da amostra, 49 empresas utilizaram hedge accounting, onde 41 empresas adotam apenas 1 tipo de hedge. O hedge de fluxo de caixa é o tipo de hedge mais adotado pelas empresas, sendo utilizado por 42 companhias.

Organizational and accounting change within the context of the environmental agenda: evidence from Portugal

Purpose – The purpose of this paper is to explore the process of organizational change undergone by a large Portuguese business group within the context of the environmental agenda and the role of accounting as a mechanism for change. Design/methodology/approach – The paper reports the results of a case study conducted between 2006 and 2009. Information was obtained from semi-structured interviews and secondary sources. Organizational changes were analyzed using Laughlin’s model in order to identify which category reflected most of the changes introduced to address environmental matters. Findings – This paper offers evidence that change is not a homogeneous phenomenon. Additionally, it confirms previous studies’ findings which found that accounting did not play a significant role in the process of organizational change within the context of the environmental agenda. Originality/value – This paper seeks to complement the research in this area by integrating observations from a case study into an existing model of levels of organizational change according to how a Portuguese business group incorporated environmental issues into its processes, policies and corporate culture.

Accounting and the “Doctor-Manager Relationship”

The adoption of the “new public management” in the hospital sector brought about greater presence and power to professional managers in hospitals, thus increasing the risk of conflict in the doctor-manager relationship. Aiming to enrich the discussion on the factors that could be the bases for this conflict and considering the role of accounting, the study presented here corresponds, basically, to what we call “content analysis” of qualitative studies. The results demonstrate that the Portuguese doctors as the sample studied accept, in essence, the principles of enterprise management and recognize the use of accounting information in the scope of their functions as long as they are called to participate as legitimate actors, and authorities respect their desires to preserve a practice which they consider of quality.

The Main Determinants of the Use of the Cost Accounting System in Portuguese Local Government

This paper explores the main determinants of the use of the cost accounting system (CAS) in Portuguese local government (PLG). Regression analysis is used to study the fit of a model of accounting changes in PLG, focused on cost accounting systems oriented to activities and outputs. Based on survey data gathered from PLG, we have found that the use of information in decision-making and external reporting is still a mirage. We obtain evidence about the influence of the internal organizational context (especially the lack of support and difficulties in the CAS implementation) in the use for internal purposes, while the institutional environment (like external pressures to implement the CAS) appears to be more deterministic of the external use. Results strengthen the function of external reporting to legitimate the organization’s activities to external stakeholders. On the other hand, some control variables (like political competition, usefulness and experience) also evidence some explanatory power in the model. Some mixed results were found that appeal to further research in the future. Our empirical results contribute to understand the importance of interconnecting the contingency and institutional approaches to gain a clear picture of cost accounting changes in the public sector.

The international harmonization process of public accounting in Portugal: the perspective of different stakeholders

This paper investigates the reform of public accounting in Portugal through the IPSAS adoption highlighting the perception of different stakeholders. Two competing theories (NPM and the institutional theory) are used to understand public accounting changes within the Portuguese context. In general, different stakeholders agree with the favorable moment and the context of the reform. The context of financial crises and the great external pressures to cut public deficits and to improve the quality of financial information seem to be the most important factors to stimulate changes in public accounting. In addition, stakeholders recommend the use of different strategies to ensure success.

The internationally standardized process of public accounting: the perspective of different stakeholders in Portugal

New Public Management (NPM) led to great pressures for to introduce and adapt businesslike accounting in the public sector (Hood, 1995; Lapsley, 2008; Lapsley et al., 2009), specially the transition from cash basis to accrual-based accounting. In consequence, since the last 20 years we assist to a movement towards internationally standardized of public sector accounting that led to the publication of 32 International Public Sector Accounting Standards (IPSAS) for all public sector entities from national central governments to local governments (IFAC, 2008). These standards are accrual-basis and they emphasize the balance sheet approach, the fair value measurement and the revenue-expense approach (Hints, 2007). The main innovations are associated with the use of the balance sheet approach and the fair value measurement because, traditionally, public accounting systems are mainly focused on the revenue-expense approach and on historical cost valuation (Oulasvirta, 2014).