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Objectives: The current method for testing new drugs against tuberculosis in vivo is the enumeration of bacteria in organs by cfu assay. Owing to the slow growth rate of Mycobacterium tuberculosis (Mtb), these assays can take months to complete. Our aim was to develop a more efficient, fluorescence-based imaging assay to test new antibiotics in a mouse model using Mtb reporter strains.Methods: A commercial IVIS Kinetic® system and a custom-built laser scanning system with fluorescence molecular tomography (FMT) capability were used to detect fluorescent Mtb in living mice and lungs ex vivo. The resulting images were analysed and the fluorescence was correlated with data from cfu assays.Results: We have shown that fluorescent Mtb can be visualized in the lungs of living mice at a detection limit of ∼8 × 10⁷ cfu/lung, whilst in lungs ex vivo a detection limit of ∼2 × 10⁵ cfu/lung was found. These numbers were comparable between the two imaging systems. Ex vivo lung fluorescence correlated to numbers of bacteria in tissue, and the effect of treatment of mice with the antibiotic moxifloxacin could be visualized and quantified after only 9 days through fluorescence measurements, and was confirmed by cfu assays.Conclusions: We have developed a new and efficient method for anti-tuberculosis drug testing in vivo, based on fluorescent Mtb reporter strains. Using this method instead of, or together with, cfu assays will reduce the time required to assess the preclinical efficacy of new drugs in animal models and enhance the progress of these candidates into clinical trials against human tuberculosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Checkpoint kinase 2 (CHK2) is activated by DNA damage and can contribute to p53 stabilization, modulating growth arrest and/or apoptosis. We investigated the contribution of CHK2 to oxaliplatin-mediated toxicity in a colorectal cancer model.Experimental Approach: We evaluated the ability of CHK2 small molecule inhibitors to potentiate oxaliplatin-induced toxicity. The role of CHK2 in oxaliplatin-induced apoptosis was investigated in HCT116 cells that were wild-type (WT) or KO for CHK2. Small molecule inhibitors of CHK2 were used in combination studies with oxaliplatin in this cell model.Key Results: In oxaliplatin-treated CHK2 KO cells, accelerated apoptosis was accompanied by attenuated p53 stabilization and p21(WAF-1) up-regulation correlating with increased Bax expression, cytochrome c release and elevated caspase activity. The higher levels of apoptosis in CHK2 KO cells were restored to control (WT) levels when CHK2 was re-introduced. This 'uncoupling' of p53 stabilization and Bax up-regulation in CHK2 KO cells suggested oxaliplatin-induced apoptosis was due to a p53-independent response. Combination studies revealed that CHK2 inhibitor II or debromohymenialdisine antagonized the responses to oxaliplatin. This inhibitory effect correlated with decreases in apoptosis, p53 stabilization and DNA inter-strand cross-link formation, and was dependent on the presence (but not activity) of CHK2.Conclusions and Implications: Combinations of CHK2 inhibitors with oxaliplatin should further sensitize cells to oxaliplatin treatment. However, these inhibitors produced an antagonistic effect on the response to oxaliplatin, which was reversed on the re-introduction of CHK2. These observations may have implications for the use of oxaliplatin in colorectal cancer therapy in combination with therapies targeting CHK2. [ABSTRACT FROM AUTHOR]

This article examines the suitability of two different materials which are black graphite carbon fiber and red pre-impregnated fiberglass from which to fabricate artificial dragonfly wing frames. These wings could be of use in Biomimetic Micro Aerial Vehicles (BMAV). BMAV are a new class of unmanned micro-sized air vehicles that mimic flying biological organisms. Insects, such as dragonflies, possess corrugated and complex vein structures that are difficult to mimic. Simplified dragonfly wing frames were fabricated from these materials and then a nano-composite film was adhered to them, which mimics the membrane of an actual dragonfly. Experimental analysis of these results showed that although black graphite carbon fiber and red pre-impregnated fiberglass offer some structural advantages, red pre-impregnated fiberglass was a less preferred option due to its warpage and shrinking effects. Black graphite carbon fiber with its high load bearing capability is a more suitable choice for consideration in future BMAV applications.

Abstract Background Scotland has a policy aimed at increasing physical activity levels in the population, but evidence on how to achieve this is still developing. Studies that focus on encouraging real world participants to start physical activity in their settings are needed. The Walking for Well-being in the West study was designed to assess the effectiveness of a pedometer-based walking programme in combination with physical activity consultation. The study was multi-disciplinary and based in the community. Walking for Well-being in the West investigated whether Scottish men and women, who were not achieving the current physical activity recommendation, increased and maintained walking behaviour over a 12 month period. This paper outlines the rationale and design of this innovative and pragmatic study. Methods Participants were randomised into two groups: Group 1: Intervention (pedometer-based walking programme combined with a series of physical activity consultations); Group 2: Waiting list control for 12 weeks (followed by minimal pedometer-based intervention). Physical activity (primary outcome) was measured using pedometer step counts (7 day) and the International Physical Activity Questionnaire (long version). Psychological processes were measured using questionnaires relating to the Transtheoretical Model of Behaviour Change, mood (Positive and Negative Affect Schedule) and quality of life (Euroqol EQ-5D instrument). Physiological measures included anthropometric and metabolic outcomes. Environmental influences were assessed subjectively (Neighbourhood Quality of Life Survey) and objectively (neighbourhood audit tool and GIS mapping). The qualitative evaluation employed observation, semi-structured interviews and focus groups. A supplementary study undertook an economic evaluation. Discussion Data analysis is on-going. Walking for Well-being in the West will demonstrate if a pedometer based walking programme, in combination with physical activity consultation results in a sustainable increase in walking behaviour in this sample of Scottish adults over a 12 month period. The study will examine the complex relationships between behavioural change, health consequences and the role of the environment, in conjunction with the cost effectiveness of this approach and a detailed insight into the participants' experiences of the intervention. Trial registration Current Controlled Trials ISRCTN88907382