Iron metabolism in trypanosomatids, and its crucial role in infection.

Iron is almost ubiquitous in living organisms due to the utility of its redox chemistry. It is also dangerous as it can catalyse the formation of reactive free radicals - a classical double-edged sword. In this review, we examine the uptake and usage of iron by trypanosomatids and discuss how modulation of host iron metabolism plays an important role in the protective response. Trypanosomatids require iron for crucial processes including DNA replication, antioxidant defence, mitochondrial respiration, synthesis of the modified base J and, in African trypanosomes, the alternative oxidase. The source of iron varies between species. Bloodstream-form African trypanosomes acquire iron from their host by uptake of transferrin, and Leishmania amazonensis expresses a ZIP family cation transporter in the plasma membrane. In other trypanosomatids, iron uptake has been poorly characterized. Iron-withholding responses by the host can be a major determinant of disease outcome. Their role in trypanosomatid infections is becoming apparent. For example, the cytosolic sequestration properties of NRAMP1, confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of iron may be favourable rather than detrimental to Trypanosoma cruzi. The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention

Describing the effect of chiropractic cervical manipulation on disturbed sleeping patterns

Abstract:Purpose: To describe whether chiropractic cervical manipulation may have an effect on disturbed sleeping patterns. Method: All volunteers were required to complete the Pittsburgh Sleep Quality Index, which ultimately resulted in the recruitment of ten participants who matched the inclusion and exclusion criteria. After the selection process had been completed, the first consultation was conducted. In this consultation, an information form was given to the participants, and each was asked to sign an informed consent form. Pre-consultation education regarding the use of the FitBit was also completed. Thereafter, a full case history was taken and a full physical exam as well as a cervical spine regional exam was performed. Each participant’s FitBit data, personal comments, MLSEQ and LSEQ were used by the researcher to describe whether or not chiropractic cervical manipulation had an effect on each participant’s disturbed sleeping pattern. Each participant attended six consultations over a period two weeks. Chiropractic treatment took place at four of the six consultations. Procedure: At each consultation, the participants were required to report on any changes they had experienced from the previous consultation, whether it was related to chiropractic treatment or not. They were required to fill out the modified portion of the Leeds Sleep Evaluation Questionnaire, which was collected and compared at the end of the trial. The orthopaedic tests that presented positive on the first consult were re-tested to identify any changes or improvements. The participants were also treated with a chiropractic cervical manipulation from the second to the fifth visit. At the end of the study, the participants were required to fill out the full Leeds Sleep Evaluation Questionnaire and return the FitBit. The modified Leeds Sleep Evaluation Questionnaire, the full Leeds Sleep Evaluation Questionnaire and the FitBit data were analysed and reported on. Results: Clinically, rather limited trends or linear improvements were presented. Some participants showed an improvement on some nights of the study, but not often enough to comment on. Statistically, the results that presented were insignificant; this may be due to the small sample size and perhaps because the study did not take place over a long enough period. Conclusion: The participants did not show sufficient objective changes over the course of the study to substantiate any evidence of change. Rather limited linear trends of improvements presented for all measures of..

Biomass encounter rates limit the size scaling of feeding interactions

This is the final version. Available from the publisher via the DOI in this record.The rate that consumers encounter resources in space necessarily limits the strength of feeding interactions that shape ecosystems. To explore the link between encounters and feeding, we first compiled the largest available dataset of interactions in the marine benthos by extracting data from published studies and generating new data. These data indicate that the size‐scaling of feeding interactions varies among consumer groups using different strategies (passive or active) to encounter different resource types (mobile or static), with filter feeders exhibiting the weakest feeding interactions. Next, we used these data to develop an agent‐based model of resource biomass encounter rates, underpinned by consumer encounter strategy and resource biomass density. Our model demonstrates that passive strategies for encountering small, dispersed resources limits biomass encounter rates, necessarily limiting the strength of feeding interactions. Our model is based on generalisable assumptions, providing a framework to assess encounter‐based drivers of consumption and coexistence across systems.Leverhulme Trus

Young peoples' views of online historical archives

Digitized collections are ‘a rich source of instructional material for history teachers’ [1 p314] but it has been noted these ‘remained largely underused’. There is ‘a growing interest in both improving the user experience and in justifying the creation of digital collections to multiple stakeholders’ [2 p339]. Within the UK an estimated £130m has been invested in digitisation projects [3]. Re-cent changes to the UK National Curriculum for history have placed greater emphasis upon the importance of understanding methods of historical enquiry and the use of evidence. Therefore, the digitized collections created by this investment should be a vital classroom tool. This study set out to investigate within the UK the level of awareness of these resources and their value to young learners aged 8-16 years. There were two stages to this qualitative study. Stage one was the delivery of a workshop which introduced young learners to a range of digital archives. After this the young people were given a period of time to use the online archives and explore the difference forms of historical evidence. Stage two involved focus groups with a sample of the young people during which participants were asked to discuss their end-user experience. Key findings included enhanced personal learning experience, development of a personal connection to the past, and identification of issues related to usability and practical application in a classroom learning context

Exercise on Referral – Symposium hosted by the Physical Activity Special Interest Group of the Wolfson Research Institute for Health and Wellbeing, Durham University

THE Physical Activity Special Interest Group of the Wolfson Research Insti- tute for Health and Wellbeing (Durham University) hosted a symposium focused on exercise referral schemes (ERS), on 14 October 2016 at the College of St Hild and St Bede, Durham. Exercise referral schemes typically allow health professionals, such as general practitioners, nurses and physiotherapists to refer inactive individuals with long-term health conditions to a third party leisure provider for a supervised exercise programme, with the aim of increasing physical activity levels. The symposium was lively and thought-provoking with pres- entations divided into two core themes: ‘Emerging Evidence for ERS’ and ‘Future Developments for ERS’

On the context-dependent scaling of consumer feeding rates

This is the final version. Available from Wiley via the DOI in this record.The stability of consumer–resource systems can depend on the form of feeding interactions (i.e.functional responses). Size-based models predict interactions–and thus stability–based on con-sumer–resource size ratios. However, little is known about how interaction contexts (e.g. simpleor complex habitats) might alter scaling relationships. Addressing this, we experimentally mea-sured interactions between a large size range of aquatic predators (4–6400 mg over 1347 feedingtrials) and an invasive prey that transitions among habitats: from the water column (3D interac-tions) to simple and complex benthic substrates (2D interactions). Simple and complex substratesmediated successive reductions in capture rates–particularly around the unimodal optimum–and promoted prey population stability in model simulations. Many real consumer–resource sys-tems transition between 2D and 3D interactions, and along complexity gradients. Thus, Context-Dependent Scaling (CDS) of feeding interactions could represent an unrecognised aspect of foodwebs, and quantifying the extent of CDS might enhance predictive ecology

Challenges in Chagas Disease Drug Development.

The protozoan parasite Trypanosoma cruzi causes Chagas disease, an important public health problem throughout Latin America. Current therapeutic options are characterised by limited efficacy, long treatment regimens and frequent toxic side-effects. Advances in this area have been compromised by gaps in our knowledge of disease pathogenesis, parasite biology and drug activity. Nevertheless, several factors have come together to create a more optimistic scenario. Drug-based research has become more systematic, with increased collaborations between the academic and commercial sectors, often within the framework of not-for-profit consortia. High-throughput screening of compound libraries is being widely applied, and new technical advances are helping to streamline the drug development pipeline. In addition, drug repurposing and optimisation of current treatment regimens, informed by laboratory research, are providing a basis for new clinical trials. Here, we will provide an overview of the current status of Chagas disease drug development, highlight those areas where progress can be expected, and describe how fundamental research is helping to underpin the process

Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease has two types, the cardiac form and the digestive form; some patients have symptoms of both. How the parasite causes digestive disease is poorly understood. It is known that damage to the gut’s nervous system is an important factor, but it has been unclear exactly where and when this damage occurs during the course of an infection and also why only a subset of infected people suffer from this outcome. We studied infections in mice and found certain combinations of strains of parasites and mice that exhibited symptoms similar to human digestive Chagas patients, including a problem with peristalsis that localised specifically to the colon. Using parasites that were genetically engineered to emit both bioluminescent and fluorescent light, we tracked infections over time and were able to analyse rare infected cells deep within the muscle tissue of the wall of the colon. We found evidence of damaged neurons in the same location as these infection foci over 6 months after initial infection. Our results show that digestive Chagas disease probably develops as a result of chronic infection and inflammation, which potentially changes approaches to treatment