The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65

Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B.  In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place.  We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle.  We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells.  This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light.  RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels.  Following a 50–60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity.  Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction.  Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision

Update on neutrophil function in severe inflammation

Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

The effects of acute infection and inflammation on phase II detoxifying enzymes

Thesis (M.S.)--University of Hawaii at Manoa, 2007.Includes bibliographical references (leaves 71-82).xiii, 82 leaves, bound 29 cmInfection and inflammation may alter liver metabolism causing significant changes in drug efficacy and toxicity. The expression and activity of the Cytochromes P450 in human liver are significantly down-regulated during acute infection and inflammation but little is known about Phase II metabolizing enzymes. We treated the human liver cell line HepG2 with TNF-α and IL-1β to at 0.1-1000 U/mL for 0-48 hours as a model of acute infection and inflammation. Cells were harvested at each time point and assessed for cell death (MIT assay) and levels of reactive oxygen species (ROS) and for the expression and activity of the major Phase II enzymes UDP-glucuronosyl transferase (UGT), Glutathione-S-transferase (GST) and Sulfotransferase (SULT). Since all of these enzymes have hepatic nuclear factor (HNF) recognition sequences in their genes, we assessed the effects of the cyrokines on HNF1 and HNF4 expression and nuclear translocation with immunofluorescence. UGT enzymes are not significantly affected by pro-inflammatory cytokines and SULT enzymes showed no change in activity while GST enzymes showed a significant increase in activity but returned to norma1levels by 48 hours. Higher GST activity may confer lower efficacy of drugs during acute infection and inflammation

Conflicting conceptualizations of human resource accounting

Purpose: The purpose of this paper is to examine the differing perceptions or conceptualizations that have contributed to prevailing views held by accountants on the measurement and reporting of human resources. Design/methodology/approach: The study provides an analysis of extant literature and presents a theoretical framework on the relationship between HR, intellectual capital and goodwill. Findings: The lack of traction in the progress of accounting for people is due to several factors including tension between employees and management, the demands of internal and external stakeholders, and the historic roots of accounting for labour. Research limitations/implications: The paper provides suggestions as to how the debate regarding the valuing and reporting of human resources may be rekindled. Originality/value: This study highlights the historical context for the lack of traction in the area of accounting for people, and the relatively recent development of the Intellectual Capital Statement as a partial but positive development in the area

Conflicting conceptualizations of human resource accounting

Purpose: The purpose of this paper is to examine the differing perceptions or conceptualizations that have contributed to prevailing views held by accountants on the measurement and reporting of human resources. Design/methodology/approach: The study provides an analysis of extant literature and presents a theoretical framework on the relationship between HR, intellectual capital and goodwill. Findings: The lack of traction in the progress of accounting for people is due to several factors including tension between employees and management, the demands of internal and external stakeholders, and the historic roots of accounting for labour. Research limitations/implications: The paper provides suggestions as to how the debate regarding the valuing and reporting of human resources may be rekindled. Originality/value: This study highlights the historical context for the lack of traction in the area of accounting for people, and the relatively recent development of the Intellectual Capital Statement as a partial but positive development in the area

Incumbents' Interests and Gender Quotas

The introduction of mandatory gender quotas in party lists is a reform that many countries have recently adopted or have been considering. The electoral system affects the incumbents' incentives to make such reforms, their details, and their effectiveness. We show that male incumbents can actually expect an increased incumbency advantage when gender quotas are introduced, if they are elected through single-member district majority rule. On the other hand, no expectation of male advantage can reduce the incumbents' fear of being replaced if they are elected through closed-list proportional representation. As France has both electoral systems, we validate the above argument using a formal model of constitutional design as well as an empirical analysis of the legislative elections in France, displaying the existence of male bias in the last three elections. We also show that parity may have Assembly composition effects and policy effects that vary with the electoral system