Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP

Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK modul

The development and validation of measures to assess cooking skills and food skills

BACKGROUND: With the increase use of convenience food and eating outside the home environment being linked to the obesity epidemic, the need to assess and monitor individuals cooking and food skills is key to help intervene where necessary to promote the usage of these skills. Therefore, this research aimed to develop and validate a measure for cooking skills and one for food skills, that are clearly described, relatable, user-friendly, suitable for different types of studies, and applicable across all sociodemographic levels. METHODS: Two measures were developed in light of the literature and expert opinion and piloted for clarity and ease of use. Following this, four studies were undertaken across different cohorts (including a sample of students, both 'Food preparation novices' and 'Experienced food preparers', and a nationally representative sample) to assess temporal stability, psychometrics, internal consistency reliability and construct validity of both measures. Analysis included T-tests, Pearson's correlations, factor analysis, and Cronbach's alphas, with a significance level of 0.05. RESULTS: Both measures were found to have a significant level of temporal stability (P < 0.001). Factor analysis revealed three factors with eigenvalues over 1, with two items in a third factor outside the two suggested measures. The internal consistency reliability for the cooking skills confidence measure ranged from 0.78 to 0.93 across all cohorts. The food skills confidence measure's Cronbach's alpha's ranged from 0.85 to 0.94. The two measures also showed a high discriminate validity as there were significant differences (P < 0.05 for cooking skills confidence and P < 0.01 for food skills confidence) between Food preparation novices' and 'Experienced food preparers.' CONCLUSIONS: The cooking skills confidence measure and the food skills confidence measure have been shown to have a very satisfactory reliability, validity and are consistent over time. Their user-friendly applicability make both measures highly suitable for large scale cross-sectional, longitudinal and intervention studies to assess or monitor cooking and food skills levels and confidence

Age-Dependent Ocular Dominance Plasticity in Adult Mice

Background: Short monocular deprivation (4 days) induces a shift in the ocular dominance of binocular neurons in the juvenile mouse visual cortex but is ineffective in adults. Recently, it has been shown that an ocular dominance shift can still be elicited in young adults (around 90 days of age) by longer periods of deprivation (7 days). Whether the same is true also for fully mature animals is not yet known. Methodology/Principal Findings: We therefore studied the effects of different periods of monocular deprivation (4, 7, 14 days) on ocular dominance in C57Bl/6 mice of different ages (25 days, 90–100 days, 109–158 days, 208–230 days) using optical imaging of intrinsic signals. In addition, we used a virtual optomotor system to monitor visual acuity of the open eye in the same animals during deprivation. We observed that ocular dominance plasticity after 7 days of monocular deprivation was pronounced in young adult mice (90–100 days) but significantly weaker already in the next age group (109–158 days). In animals older than 208 days, ocular dominance plasticity was absent even after 14 days of monocular deprivation. Visual acuity of the open eye increased in all age groups, but this interocular plasticity also declined with age, although to a much lesser degree than the optically detected ocular dominance shift. Conclusions/Significance: These data indicate that there is an age-dependence of both ocular dominance plasticity and the enhancement of vision after monocular deprivation in mice: ocular dominance plasticity in binocular visual cortex is mos

Digital reconstruction of the inner ear of Leptictidium auderiense (Leptictida, Mammalia) and North American leptictids reveals new insight into leptictidan locomotor agility

Leptictida are basal Paleocene to Oligocene eutherians from Europe and North America comprising species with highly specialized postcranial features including elongated hind limbs. Among them, the European Leptictidium was probably a bipedal runner or jumper. Because the semicircular canals of the inner ear are involved in detecting angular acceleration of the head, their morphometry can be used as a proxy to elucidate the agility in fossil mammals. Here we provide the first insight into inner ear anatomy and morphometry of Leptictida based on high-resolution computed tomography of a new specimen of Leptictidium auderiense from the middle Eocene Messel Pit (Germany) and specimens of the North American Leptictis and Palaeictops. The general morphology of the bony labyrinth reveals several plesiomorphic mammalian features, such as a secondary crus commune. Leptictidium is derived from the leptictidan groundplan in lacking the secondary bony lamina and having proportionally larger semicircular canals than the leptictids under study. Our estimations reveal that Leptictidium was a very agile animal with agility score values (4.6 and 5.5, respectively) comparable to Macroscelidea and extant bipedal saltatory placentals. Leptictis and Palaeictops have lower agility scores (3.4 to 4.1), which correspond to the more generalized types of locomotion (e.g., terrestrial, cursorial) of most extant mammals. In contrast, the angular velocity magnitude predicted from semicircular canal angles supports a conflicting pattern of agility among leptictidans, but the significance of these differences might be challenged when more is known about intraspecific variation and the pattern of semicircular canal angles in non-primate mammals

Guidelines for management of ischaemic stroke and transient ischaemic attack 2008

This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation

The role of packaging for consumer products: understanding the move towards ‘plain’ tobacco packaging

The Australian Government intends to introduce plain tobacco packaging in 2012. We consider whether such a move appears justified by examining the wider marketing literature in order to understand the role that packaging has for consumer goods. Packaging is often called the fifth ‘p’ of the marketing mix. It is an effective marketing medium for all consumer products and helps build consumer relationships through possession and usage. Common packaging strategies to promote the product, distinguish products from competitors, communicate brand values and target specific consumer groups include innovative, special edition, value and green packaging. These strategies, combined with the visual and structural aspects of packaging design, such as colour, size and shape, influence consumer perceptions and purchase and usage behaviour. This gives packaging an important role at point-of-purchase and also post-purchase. Packaging also has a close relationship with the product, influencing perceived product attributes, and is a key representative of the brand. We conclude that plain tobacco packaging appears justified, based on the importance of packaging as a promotional tool, and will fundamentally restrict the opportunity for tobacco companies to influence consumers through package design

Cost-effectiveness of the Victorian Stroke Telemedicine program

Objective Stroke telemedicine improves the provision of reperfusion therapies in regional hospitals, yet evidence of its cost-effectiveness using patient-level data is lacking. The aim of this study was to estimate the cost per quality-adjusted life year (QALY) gained from stroke telemedicine. Methods As part of the Victorian Stroke Telemedicine (VST) program, stroke telemedicine provided to 16 hospitals in regional Victoria was evaluated using a historical-control design. Patient-level costs from a societal perspective (2018 Australian dollars (A$)) and QALYs up to 12 months after stroke were estimated using data from medical records, surveys at 3 months and 12 months after stroke and multiple imputation. Multivariable regression models and bootstrapping were used to estimate differences between periods. Results Costs and health outcomes were estimated from 1024 confirmed strokes suffered by patients arriving at hospital within 4.5 h of stroke onset (median age 76 years, 55$82 449 per person for the control period and A$82 259 in the intervention period (P = 0.986). QALYs at 12 months were estimated to be 0.43 per person for the control period and 0.5 per person in the intervention period (P = 0.02). Following 1000 iterations of bootstrapping, in comparison to the control period, the VST intervention was more effective and cost saving in 50.6$0 and A$50 000 per QALY gained) in 10.4% of iterations. Conclusion The VST program was likely to be cost saving or cost-effective. Our findings provide confidence in supporting wider implementation of telemedicine for acute stroke care in Australia.</jats:p