In vivo assessment of muscle membrane properties in myotonic dystrophy

INTRODUCTION: Myotonia in myotonic dystrophy types 1 (DM1) and 2 (DM2) is generally attributed to reduced chloride channel conductance. We used muscle velocity recovery cycles (MVRCs) to investigate muscle membrane properties in DM1 and DM2, with comparisons with myotonia congenita (MC). METHODS: MVRCs and responses to repetitive stimulation were compared between patients with DM1 (n=18), DM2 (n=5), MC (n=18), and normal controls (n=20). RESULTS: Both DM1 and DM2 showed enhanced late supernormality after multiple conditioning stimuli, indicating delayed repolarization as in MC. Contrary to MC, however, DM1 showed reduced early supernormality after multiple conditioning stimuli, and weak DM1 patients also showed abnormally slow latency recovery after repetitive stimulation. DISCUSSION: These findings support impaired chloride conductance in both DM1 and DM2. The early supernormality changes indicate that sodium currents were reduced in DM1, while the weakness-associated slow recovery after repetitive stimulation may provide an indication of reduced Na(+) /K(+) -ATPase activation

Polypyrimidine tract-binding proteins are essential for B cell development.

Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle

Workflows for Quantitative Data Analysis in The Social Sciences

The background is given to how statistical analysis is used by quantitative social scientists. Developing statistical analyses requires substantial effort, yet there are important limitations in current practice. This has motivated the authors to create a more systematic and effective methodology with supporting tools. The approach to modelling quantitative data analysis in the social sciences is presented. Analysis scripts are treated abstractly as mathematical functions and concretely as web services. This allows individual scripts to be combined into high-level workflows. A comprehensive set of tools allows workflows to be defined, automatically validated and verified, and automatically implemented. The workflows expose opportunities for parallel execution, can define support for proper fault handling, and can be realised by non-technical users. Services, workflows and datasets can also be readily shared. The approach is illustrated with a realistic case study that analyses occupational position in relation to health

Disruptive moments as opportunities towards justice-oriented pedagogical practice in Informal Science Learning

Despite the promise of Informal Science Learning settings (ISLs) in supporting youth science engagement in ways that value their experiences and communities, in practice, such opportunities are limited. While some ISLs promote more culturally relevant approaches to science engagement, many still reflect White supremacist and patriarchal worldviews in discourse and practice. In Research Practice Partnerships, we engaged eight ISL educators from two partner sites—a community center and science center, and youth from across their six programs. Using participatory ethnography we explore how educators' pedagogical practices supported youth in codeveloping more justice-oriented ISL experiences—experiences which disrupt these dominant and oppressive norms. Our analysis pays attention, in particular, to those fraught moments when youth, in interaction with peers and educators, sought to disrupt their ISL experience in ways that centered and amplified their lives, hopes, and desires for being and learning in ISL and humanized the ISL learning community. Two kinds of pedagogical response patterns emerged that we report on in our findings: (1) collaborative critique and (2) critically being with each other towards new relationalities. We discuss how these two practices centered political and ethical dimensions of teaching and learning, fundamentally shifting power and relationalities towards new ISL possibilities. We also discuss how these practices involved leveraging specific moments to resee youths' activities in new ways, making visible how an ISL space limited opportunities for youth visibility of presence in science—a kind of pausing for justice

<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops

Black Stork Down: Military Discourses in Bird Conservation in Malta

Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

Denitrification and nitrous oxide emissions from riparian forests soils exposed to prolonged nitrogen runoff

Compared to upland forests, riparian forest soils have greater potential to remove nitrate (NO3) from agricultural run-off through denitrification. It is unclear, however, whether prolonged exposure of riparian soils to nitrogen (N) loading will affect the rate of denitrification and its end products. This research assesses the rate of denitrification and nitrous oxide (N2O) emissions from riparian forest soils exposed to prolonged nutrient run-off from plant nurseries and compares these to similar forest soils not exposed to nutrient run-off. Nursery run-off also contains high levels of phosphate (PO4). Since there are conflicting reports on the impact of PO4 on the activity of denitrifying microbes, the impact of PO4 on such activity was also investigated. Bulk and intact soil cores were collected from N-exposed and non-exposed forests to determine denitrification and N2O emission rates, whereas denitrification potential was determined using soil slurries. Compared to the non-amended treatment, denitrification rate increased 2.7- and 3.4-fold when soil cores collected from both N-exposed and non-exposed sites were amended with 30 and 60 μg NO3-N g-1 soil, respectively. Net N2O emissions were 1.5 and 1.7 times higher from the N-exposed sites compared to the non-exposed sites at 30 and 60 μg NO3-N g-1 soil amendment rates, respectively. Similarly, denitrification potential increased 17 times in response to addition of 15 μg NO3-N g-1 in soil slurries. The addition of PO4 (5 μg PO4–P g-1) to soil slurries and intact cores did not affect denitrification rates. These observations suggest that prolonged N loading did not affect the denitrification potential of the riparian forest soils; however, it did result in higher N2O emissions compared to emission rates from non-exposed forests

Barriers and opportunities for evidence-based health service planning: the example of developing a Decision Analytic Model to plan services for sexually transmitted infections in the UK

Decision Analytic Models (DAMs) are established means of evidence-synthesis to differentiate between health interventions. They have mainly been used to inform clinical decisions and health technology assessment at the national level, yet could also inform local health service planning. For this, a DAM must take into account the needs of the local population, but also the needs of those planning its services. Drawing on our experiences from stakeholder consultations, where we presented the potential utility of a DAM for planning local health services for sexually transmitted infections (STIs) in the UK, and the evidence it could use to inform decisions regarding different combinations of service provision, in terms of their costs, cost-effectiveness, and public health outcomes, we discuss the barriers perceived by stakeholders to the use of DAMs to inform service planning for local populations, including (1) a tension between individual and population perspectives; (2) reductionism; and (3) a lack of transparency regarding models, their assumptions, and the motivations of those generating models

How to increase the potential policy impact of environmental science research

This article highlights eight common issues that limit the policy impact of environmental science research. The article also discusses what environmental scientists can do to resolve these issues, including (1) optimising the directness of their study so that it examines similar processes/populations/environments/ecosystems to that of policy interest; (2) using the most powerful study design possible, to increase confidence in the identified causal mechanisms; (3) selecting a sufficient sample size, to reduce the chance of false positives/negatives and increase policy-makers’ confidence in extrapolation of the findings; (4) minimizing the risk of bias through randomization of study units to treatment and control groups (reducing the risk of selection bias), blinding of study units and investigators (reducing the risk of performance and detection bias), following-up study units from enrolment to study completion (reducing the risk of attrition bias) and prospectively registering the study on a publically-available platform (reducing the risk of reporting and publication bias); (5) proving that statistical analyses meet test assumptions by reporting the results of statistical assumption checks, ideally publishing full datasets online in an open-access format; (6) publishing the research whether statistically significant or not, policy-makers are just as interested in the negative or insignificant results as they are in the positive results; (7) making the study easy to find and use, the title and abstract of an article are of high importance in determining whether articles are examined in detail or not and used to inform policy; (8) contributing towards systematic reviews on environmental topics, to provide policy-makers with comprehensive, reproducible and updateable syntheses of all the evidence on a given topic.</p