Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast

A model for replicative life span extension by calorie restriction (CR) in yeast has been proposed whereby reduced glucose in the growth medium leads to activation of the NAD(+)–dependent histone deacetylase Sir2. One mechanism proposed for this putative activation of Sir2 is that CR enhances the rate of respiration, in turn leading to altered levels of NAD(+) or NADH, and ultimately resulting in enhanced Sir2 activity. An alternative mechanism has been proposed in which CR decreases levels of the Sir2 inhibitor nicotinamide through increased expression of the gene coding for nicotinamidase, PNC1. We have previously reported that life span extension by CR is not dependent on Sir2 in the long-lived BY4742 strain background. Here we have determined the requirement for respiration and the effect of nicotinamide levels on life span extension by CR. We find that CR confers robust life span extension in respiratory-deficient cells independent of strain background, and moreover, suppresses the premature mortality associated with loss of mitochondrial DNA in the short-lived PSY316 strain. Addition of nicotinamide to the medium dramatically shortens the life span of wild type cells, due to inhibition of Sir2. However, even in cells lacking both Sir2 and the replication fork block protein Fob1, nicotinamide partially prevents life span extension by CR. These findings (1) demonstrate that respiration is not required for the longevity benefits of CR in yeast, (2) show that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and (3) suggest that CR acts through a conserved, Sir2-independent mechanism in both PSY316 and BY4742

Updating and validating quality prescribing indicators for use in Australian general practice

© 2019 La Trobe University. This study aims to update and validate quality prescribing indicators (QPIs) for Australian general practice. The study comprised two phases: (1) developing preliminary potential QPIs based on the 2006 National Prescribing Service (NPS) MedicineWise indicators, published literature, international indicators and guidelines, and through qualitative focus group discussions; and (2) validating the proposed QPIs through a two-round online survey using the Delphi technique. The Delphi panel included four GPs, four pharmacists and two clinical pharmacologists. The Delphi panel rated the potential QPIs for their validity, importance and feasibility using a 1-10 Likert scale. In round one, all proposed QPIs presented as 'prescribing rules' achieved high scores regarding validity, importance and feasibility No rule was eliminated and three new rules were introduced. Rules were reworded into 'prescribing indicators' for round two, which resulted in 35 indicators being accepted and two indicators being eliminated. The final QPIs also include seven drug-drug interactions, which received high scores in round one. In conclusion, 42 QPIs were nominated for use in Australian general practice, based on their validity, importance and feasibility. If implemented, these QPIs have the potential to assist in efforts to improve the quality and safety of medicines management

Policy Review: Addressing the Complex Challenges of Regulating Biotherapeutics

The advancing industry of biotherapeutics is providing the public with new promising and innovative drugs which may pose risks if their production, distribution, and marketing are not directly governed by legislation. Apart from international agreements, such as the Cartagena Protocol, there are no specific and direct laws or regulations governing manipulated cell-based therapeutics in Canada. The introduction of these laws and regulations in Canada will allow for the safe research and use of biotherapeutics in a proactive manner

Toward a unifying framework for evolutionary processes

The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields

Mixed Chamber Ensembles

KSU School of Music presents Mixed Chamber Ensembles.https://digitalcommons.kennesaw.edu/musicprograms/1312/thumbnail.jp

Aberrant Function of Learning and Cognitive Control Networks Underlie Inefficient Cognitive Flexibility in Anorexia Nervosa: A Cross-Sectional fMRI Study

Objectives People with Anorexia Nervosa exhibit difficulties flexibly adjusting behaviour in response to environmental changes. This has previously been attributed to problematic behavioural shifting, characterised by a decrease in fronto-striatal activity. Additionally, alterations of instrumental learning, which relies on fronto-striatal networks, may contribute to the observation of inflexible behaviour. The authors sought to investigate the neural correlates of cognitive flexibility and learning in Anorexia Nervosa. Method Thirty-two adult females with Anorexia Nervosa and thirty-two age-matched female control participants completed the Wisconsin Card Sorting Task whilst undergoing functional magnetic resonance imaging. Event-related analysis permitted the comparison of cognitive shift trials against those requiring maintenance of rule-sets and allowed assessment of trials representing learning. Results Although both groups performed similarly, we found significant interactions in the left middle frontal gyrus, precuneus and superior parietal lobule whereby blood-oxygenated-level dependent response was higher in Anorexia Nervosa patients during shifting but lower when maintaining rule-sets, as compared to healthy controls. During learning, posterior cingulate cortex activity in healthy controls decreased whilst increasing in the Anorexia Nervosa group, whereas the right precuneus exhibited the opposite pattern. Furthermore, learning was associated with lower blood-oxygenated-level dependent response in the caudate body, as compared to healthy controls. Conclusions People with Anorexia Nervosa display widespread changes in executive function. Whilst cognitive flexibility appears to be associated with aberrant functioning of the fronto-parietal control network that mediates between internally and externally directed cognition, fronto-striatal alterations, particularly within the caudate body, were associated with instrumental learning. Together, this shows how perseverative tendencies could be a substrate of multiple high-order processes that may contribute to the maintenance of Anorexia Nervosa