Hypothesis: Entrapment of lipoprotein particles in the brain causes Alzheimer’s disease

We present for consideration a hypothesis that impaired movement of lipoprotein particles in the extracellular space in the brain in ageing is central to and causes all the key pathophysiological features of Alzheimer’s disease (AD). The role of lipoprotein particles is to transport cholesterol from glial cells, where it is synthesised, to neurons, which require cholesterol for synaptic plasticity. The lipoprotein particles have a cholesterol-containing hydrophobic core, in which amyloid-β (Aβ) can be solubilised. The core is surrounded by a hydrophilic surface containing apolipoprotein E (APOE) which, as neurons bear receptors for APOE, determines the destination of the particles. The problem arises because the extracellular space is a narrow cleft, barely wider than the lipoprotein particles themselves, which they have to navigate in order to perform their crucial cholesterol-transporting function. We explain how lipoprotein particles could become trapped in the ageing extracellular matrix and that this primary abnormality results in reduced delivery of cholesterol to neurons leading to impaired synaptic plasticity, crucial for learning and memory. It can also explain extracellular Aβ accumulation, to which a microglial response generates a neurotoxic reaction, and intraneuronal tau aggregation, each of which exacerbate the problem. All these players have been known for many years to be important in Alzheimer’s pathogenesis but a single unifying mechanism to explain how they are linked has been lacking. This proposed mechanism, with entrapment of lipoproteins particles as key to the development of AD, can explain the failure of so many clinical trials and points out new directions to be taken

Recombinant production of the therapeutic peptide lunasin

<p>Abstract</p> <p>Background</p> <p>Lunasin is a chemopreventive peptide produced in a number of plant species. It comprises a helical region with homology to a region of chromatin binding proteins, an Arg-Gly-Asp cell adhesion motif and eight aspartic acid residues. <it>In vitro </it>studies indicate that lunasin suppresses chemical and oncogene driven transformation of mammalian cells. We have explored efficient recombinant production of lunasin by exploiting the <it>Clostridium thermocellum </it>CipB cellulose binding domain (CBD) as a fusion partner protein.</p> <p>Results</p> <p>We used a pET28 vector to express a CBD-lunasin fusion with a hexahistidine tag and Tobacco Etch Virus protease site, to allow protease-mediated release of native lunasin. Autoinduction in <it>E. coli </it>BL21 (DE3) Star cells achieved expression of 3.35 g/L of CBD-lunasin fusion protein. The final yield of lunasin was 210 mg/L corresponding to 32% of the theoretical yield. Purification by cellulose binding and nickel affinity chromatography were tested with the latter proving more satisfactory.</p> <p>The effects of CBD-lunasin expression on growth and morphology of the <it>E. coli </it>cells were examined by light and electron microscopy revealing an altered morphology in a proportion of cells. Cell division appeared to be inhibited in these cells resulting in elongated, non-septated cells.</p> <p>Conclusions</p> <p>The use of CBD as a fusion partner gave high protein yields by autoinduction, with lunasin release by TEV protease cleavage. With some optimisation this approach could provide a potentially valuable route for production of this therapeutic peptide. Over-expression in the host cells manifest as a cell division defect in a population of the cells, presumably mimicking some aspect of the chemopreventive function observed in mammalian cells.</p

Bridging the gap - An evaluation of the Lighthouse integrated victim witness care program

The final project report for the Lighthouse integrated victim witness care program evaluation

Care farming and green care in Salford

This report presents a University of Salford (UoS) investigation into the potential for care farming in Salford as part of the University’s teaching, research and enterprise activities. The work has critically engaged with the notion of care farming with a view to better understand how this approach can contribute to helping communities with diverse needs in terms of physical and mental health as well as wider determinants of health such as social inclusion and employability. Through the establishment of, and engagement with a network of key local stakeholders, the work developed a model that has explored the potential of a care farm. What has emerged is a first step towards the design and establishment of an urban care farm that that could serve as a centre for learning and research as well as integrate existing activities as part of a green and blue network identified through the stakeholder engagement work. This report provides a direction for future work on care farming in Salford in general, and in terms of the University’s teaching and learning activities in particular

Can smoking initiation contexts predict how adult Aboriginal smokers assess their smoking risks? A cross-sectional study using the 'Smoking Risk Assessment Target'

Objectives: Smoking prevalence is slow to reduce among Indigenous Australians of reproductive age. We analysed the relationships between age of smoking initiation, recalled initiation influences and self-assessment of smoking risks in Aboriginal smokers. Design, setting and participants: A community-based cross-sectional survey of Aboriginal smokers aged 18–45 years (N=121; 58 men) was undertaken, using single-item measures. The Smoking Risk Assessment Target (SRAT) as the primary outcome measure enabled self-assessment of smoking risks from 12 options, recategorised into 3 groups. Participants recalled influences on their smoking initiation. Multinomial logistic regression modelling included age, gender, strength of urges to smoke, age at initiation (regular uptake) and statistically significant initiation influences on χ2 tests (‘to be cool’, alcohol and cannabis). Results: Frequent initiation influences included friends (74%; SD 0.44), family (57%; SD 0.5) and alcohol (40%; SD 0.49). 54% (n=65) of smokers had the highest risk perception on the SRAT, selected by those who cared about the smoking risks and intended to quit soon. On multivariate analyses, compared with the highest level of SRAT, male gender, lower age of uptake and strong urges to smoke were significantly associated with the lowest level of SRAT, selected by those who refuted risks or thought they could not quit. Lower age of uptake and alcohol were associated with mid-level of SRAT, selected by those who cared about smoking risks, but did not consider quitting as a priority. Conclusions: Characteristics of smoking initiation in youth may have far-reaching associations with how smoking risks are assessed by adults of reproductive age, and their intentions to quit smoking. Becoming a regular smoker at under the age of 16 years, and influences of alcohol on smoking uptake, were inversely associated with high-level assessment of smoking risks and intention to quit in regional Aboriginal smokers. The SRAT may help tailor approaches to Indigenous smoking cessation

Decision-making without a brain: how an amoeboid organism solves the two-armed bandit

Several recent studies hint at shared patterns in decision-making between taxonomically distant organisms, yet few studies demonstrate and dissect mechanisms of decision-making in simpler organisms. We examine decision-making in the unicellular slime mould Physarum polycephalum using a classical decision problem adapted from human and animal decision-making studies: the two-armed bandit problem. This problem has previously only been used to study organisms with brains, yet here we demonstrate that a brainless unicellular organism compares the relative qualities of multiple options, integrates over repeated samplings to perform well in random environments, and combines information on reward frequency and magnitude in order to make correct and adaptive decisions. We extend our inquiry by using Bayesian model selection to determine the most likely algorithm used by the cell when making decisions. We deduce that this algorithm centres around a tendency to exploit environments in proportion to their reward experienced through past sampling. The algorithm is intermediate in computational complexity between simple, reactionary heuristics and calculation-intensive optimal performance algorithms, yet it has very good relative performance. Our study provides insight into ancestral mechanisms of decision-making and suggests that fundamental principles of decision-making, information processing and even cognition are shared among diverse biological systems

The botanical biofiltration of VOCs with active airflow: is removal efficiency related to chemical properties?

© 2019 Elsevier Ltd Botanical biofiltration using active green walls is showing increasing promise as a viable method for the filtration of volatile organic compounds (VOCs) from ambient air; however there is a high level of heterogeneity reported amongst VOC removal efficiencies, and the reasons for these observations have yet to be explained. Comparisons of removal efficiencies amongst studies is also difficult due to the use of many different VOCs, and systems that have been tested under different conditions. The current work describes a procedure to determine whether some of these differences may be related to the chemical properties of the VOCs themselves. This work used an active green wall system to test the single pass removal efficiency (SPRE) of nine different VOCs (acetone, benzene, cyclohexane, ethanol, ethyl acetate, hexane, isopentane, isopropanol and toluene) and explored which chemical properties were meaningful predictor variables of their biofiltration efficiencies. Ethanol was removed most efficiently (average SPRE of 96.34% ± 1.61), while benzene was least efficiently removed (average SPRE of 19.76% ± 2.93). Multiple stepwise linear regression was used to determine that the dipole moment and molecular mass were significant predictors of VOC SPRE, in combination accounting for 54.6% of the variability in SPREs amongst VOCs. The octanol water partition coefficient, proton affinity, Henry's law constant and vapour pressure were not significant predictors of SPRE. The most influential predictor variable was the dipole moment, alone accounting for 49.8% of the SPRE variability. The model thus allows for an estimation of VOC removal efficiency based on a VOC's chemical properties, and supports the idea that system optimisation could be achieved through methods that promote both VOC partitioning into the biofilter's aqueous phase, and substrate development to enhance adsorption.

Measuring the development of deep learning

The Higher Education Funding Council for England (HEFCE) in addressing teaching, learningand assessment (circular 26/95) list three key features, one of which is "[the] opportunity for andassessment of: development of ...values, motivation, or attitudes to learning."It has been reported (Fyfe, 1996) that the develop of attitudes to learning varies according towhether the programme of study is "Arts" or "Science" based. As students progress through Artsprogrammes they develop a deeper approach to learning whereas students following Scienceprogrammes develop a surface approach. In his report Fife makes no reference tointerdisciplinary programmes such as those related to the study of the environment which areinterdisciplinary.This study sets identify an appropriate method for recording students' approach to learning, toestablish base line data for four environmental orientated undergraduate programmes and toinvestigate the influence of a period of work-based learning on the development of attitudes tolearning

Pulsed electromagnetic energy treatment offers no clinical benefit in reducing the pain of knee osteoarthritis: a systematic review

Background The rehabilitation of knee osteoarthritis often includes electrotherapeutic modalities as well as advice and exercise. One commonly used modality is pulsed electromagnetic field therapy (PEMF). PEMF uses electro magnetically generated fields to promote tissue repair and healing rates. Its equivocal benefit over placebo treatment has been previously suggested however recently a number of randomised controlled trials have been published that have allowed a systematic review to be conducted. Methods A systematic review of the literature from 1966 to 2005 was undertaken. Relevant computerised bibliographic databases were searched and papers reviewed independently by two reviewers for quality using validated criteria for assessment. The key outcomes of pain and functional disability were analysed with weighted and standardised mean differences being calculated. Results Five randomised controlled trials comparing PEMF with placebo were identified. The weighted mean differences of the five papers for improvement in pain and function, were small and their 95% confidence intervals included the null. Conclusion This systematic review provides further evidence that PEMF has little value in the management of knee osteoarthritis. There appears to be clear evidence for the recommendation that PEMF does not significantly reduce the pain of knee osteoarthritis