Developing and Implementing Service-Learning in Aging

This article focuses on the potential benefits of service-learning in aging to students, the university, and the community. We first discuss the concept of service-learning, clarify its parameters, and describe the types of projects that best exemplify its unique blend of service and learning. Opportunities for service-learning are examined using examples from the current Intergenerational Service-Learning Project of the National Council on Aging. The complexity of\u27 initiating and gaining acceptance of service-learning in aging projects is explored, with particular attention given to supervisory and curriculum issues. Finally, the national implications of\u27 service-learning in aging are discussed, as well as the possibilities for including service-learning approaches in some of the new federal initiatives in aging

Intergenerational School Projects: Examples and Guidelines

The residential, educational, and recreational patterns of modern American society tend to isolate the young from the old. Because there is little interaction between the age groups, each generation tends to stereotype the other. Educators must realize that these age-related stereotypes affect our interpersonal relationships, our self-images, and, consequently, our potential to live a full, rewarding life

Students as Resources to the Aging Network

In times of shrinking resources and growing needs, the aging network must increase its efforts to involve the voluntary sector in services and programs for the aged. A relatively untapped source of manpower is our nation\u27s 12,300,000 students in 3,200 colleges and universities. This article, based on the findings of a national demonstration project, examines feasible outcomes and practical limitations of service-learning as an approach for increasing the involvement of students in providing services to older persons

Intergenerational Service-Learning: Contributions to Curricula

This article reports some findings from a national demonstration project involving the National Council on the Aging (NCOA) and thirteen colleges and universities. We studied 39 courses in which students were involved in service-learning in aging. We describe and discuss (1) the range of demonstrably feasible \u27adoptions, (2) what faculty say their students learned from the experiences, and (3) faculty perceptions of personal benefits and costs associated with developing and directing these projects

Defining the chemical and molecular mechanisms of cytotoxicity Induced by the endoperoxide class of antimalarials

Artemisinin-derived endoperoxide drugs find widespread employment as frontline treatment against malaria. Although evidence of their potential to express toxicity within a clinical setting remains limited, outcomes derived from animal studies attest their ability to induce neurological and developmental toxicity in mammalian systems. Activity is further demonstrated in vitro within rapidly proliferating human cells – most notably those belonging to immortalised, cancer-derived lines – with significant cytotoxic effects being observed upon drug treatment across a range of settings. It is believed that these find their origin through a mechanism dependent upon Fe(II)-mediated reduction of the endoperoxide bridge functionality, culminating in molecular bioactivation and the subsequent formation of carbon-centred free radical species which in turn, owing to their great reactivity, impart deleterious effects upon cellular functioning. Evidence suggests that dysfunction of the mitochondrion and the formation of reactive oxygen species (ROS) are key stages in the route through which artemisinin derivatives are able to induce death. The characteristics of artesunate-stimulated impact upon mitochondrial functioning are examined. It is demonstrated that culturing of cells in the presence of galactose enhances cytotoxic potential within the HeLa line. The magnitude of this variation in sensitivity is indicative that targeting of the mitochondrion affords a route through which activity is mediated. Falls in cell viability are further preceded by declines in ATP production, providing evidence that disruption of oxidative phosphorylation occurs as an early event in the route towards death. Studies performed on mitochondrial bioenergetic function using the Seahorse XF analyser indicate that artesunate imparts dose-dependent and timedependent decreases in respiratory reserve capacity and oxidative phosphorylation coupling efficiency, whilst stimulating a switch towards glycolytic energy production. Attempts to delineate the root causes of these effects are focused upon examining the relationship between oxidative stress, Fe(II) content and mitochondrial performance. The mitochondrially-localised antioxidant tiron and the lysosomal Fe(II) chelator desferrioxamine are shown to induce substantial cytoprotective effects against artesunate within the HeLa line. Evidence derived from Seahorse XF analysis indicates strongly that these outcomes are related to the capacity of both compounds to abrogate drug impact upon the functions of the mitochondrion. It can thus be posited that mitochondrial damage has its origins in the emergence of oxidative stress, with Fe(II) content acting as key determinant in its progression. The outcomes of further examinations performed within the ρ0 HeLa line suggest an origin for ROS emergence independent of the respiratory chain. In order to test the hypothesis that artemisinin derivatives might induce direct peroxidation of the mitochondrial phospholipid cardiolipin, the impact of a cytochrome c peroxidase inhibitor TPP-IOA is examined on the response of HeLa and HL-60 cells towards artesunate treatment. Results indicate that the inhibitor has variable effects upon cardiolipin oxidation state and subsequent cell survival, leaving doubt as to the true validity of such a connection. As a further study, the cytotoxic capacities of a range of novel artemisininderived anticancer agents and wholly synthetic tetraoxane and trioxolane antimalarials are given assessment. In conclusion, it can be stated that the outcomes of the studies performed in this thesis emphasise the importance of mitochondrial liability towards the progression of artemisinininduced cell death. Further insights into the mechanistic routes through which drug administration contributes, via oxidative stress and free Fe(II) content, to the defective functioning of the organelle have been achieved

A Synthetic Biology Project – Developing a single-molecule device for screening drug–target interactions

AbstractThis review describes a European-funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug–target interactions at the single-molecule level. Production of the proteins required for the system followed the principle of previously described “bioparts” concepts (a system where a database of biological parts – promoters, genes, terminators, linking tags and cleavage sequences – is used to construct novel gene assemblies) and cassette-type assembly of gene expression systems (the concept of linking different “bioparts” to produce functional “cassettes”), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette-system. Finally, micro-engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti-malarial drugs, but we also suggest other potential uses for the device

A review of quantitative structure-activity relationship modelling approaches to predict the toxicity of mixtures

Exposure to chemicals generally occurs in the form of mixtures. However, the great majority of the toxicity data, upon which chemical safety decisions are based, relate only to single compounds. It is currently unfeasible to test a fully representative proportion of mixtures for potential harmful effects and, as such, in silico modelling provides a practical solution to inform safety assessment. Traditional methodologies for deriving estimations of mixture effects, exemplified by principles such as concentration addition (CA) and independent action (IA), are limited as regards the scope of chemical combinations to which they can reliably be applied. Development of appropriate quantitative structure-activity relationships (QSARs) has been put forward as a solution to the shortcomings present within these techniques – allowing for the potential formulation of versatile predictive tools capable of capturing the activities of a full contingent of possible mixtures. This review addresses the current state-of-the-art as regards application of QSAR towards mixture toxicity, discussing the challenges inherent in the task, whilst considering the strengths and limitations of existing approaches. Forty studies are examined within – through reference to several characteristic elements including the nature of the chemicals and endpoints modelled, the form of descriptors adopted, and the principles behind the statistical techniques employed. Recommendations are in turn provided for practices which may assist in further advancing the field, most notably with regards to ensuring confidence in the acquired predictions.publishedVersio

In Silico Identification of Chemicals Capable of Binding to the Ecdysone Receptor

The process of molting, known alternatively as ecdysis, is a feature integral in the life cycles of species across the arthropod phylum. Regulation occurs as a function of the interaction of ecdysteroid hormones with the arthropod nuclear ecdysone receptor—a process preceding the triggering of a series of downstream events constituting an endocrine signaling pathway highly conserved throughout environmentally prevalent insect, crustacean, and myriapod organisms. Inappropriate ecdysone receptor binding and activation forms the essential molecular initiating event within possible adverse outcome pathways relating abnormal molting to mortality in arthropods. Definition of the characteristics of chemicals liable to stimulate such activity has the potential to be of great utility in mitigation of hazards posed toward vulnerable species. Thus the aim of the present study was to develop a series of rule‐sets, derived from the key structural and physicochemical features associated with identified ecdysone receptor ligands, enabling construction of Konstanz Information Miner (KNIME) workflows permitting the flagging of compounds predisposed to binding at the site. Data describing the activities of 555 distinct chemicals were recovered from a variety of assays across 10 insect species, allowing for formulation of KNIME screens for potential binding activity at the molecular initiating event and adverse outcome level of biological organization. Environ Toxicol Chem 2020;39:1438–1450. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC

A Critical Review of Adverse Effects to the Kidney: Mechanisms, Data Sources and In Silico Tools to Assist Prediction

Introduction: The kidney is a major target for toxicity elicited by pharmaceuticals and environmental pollutants. Standard testing which often does not investigate underlying mechanisms has proven not to be an adequate hazard assessment approach. As such, there is an opportunity for the application of computational approaches that utilise multi-scale data based on the Adverse Outcome Pathway (AOP) paradigm, coupled with an understanding of the chemistry underpinning the molecular initiating event (MIE) to provide a deep understanding of how structural fragments of molecules relate to specific mechanisms of nephrotoxicity. Aims covered: The aim of this investigation was to review the current scientific landscape related to computational methods, including mechanistic data, AOPs, publicly available knowledge bases and current in silico models, for the assessment of pharmaceuticals and other chemicals with regard to their potential to elicit nephrotoxicity. A list of over 250 nephrotoxicants enriched with, where possible, mechanistic and AOP-derived understanding was compiled. Expert opinion: Whilst little mechanistic evidence has been translated into AOPs, this review identified a number of data sources of in vitro, in vivo and human data that may assist in the development of in silico models which in turn may shed light on the inter-relationships between nephrotoxicity mechanisms