Building a flagellum in biological outer space.

Flagella, the rotary propellers on the surface of bacteria, present a paradigm for how cells build and operate complex molecular 'nanomachines'. Flagella grow at a constant rate to extend several times the length of the cell, and this is achieved by thousands of secreted structural subunits transiting through a central channel in the lengthening flagellum to incorporate into the nascent structure at the distant extending tip. A great mystery has been how flagella can assemble far outside the cell where there is no conventional energy supply to fuel their growth. Recent work published by Evans et al. [Nature (2013) 504: 287-290], has gone some way towards solving this puzzle, presenting a simple and elegant transit mechanism in which growth is powered by the subunits them selves as they link head-to-tail in a chain that is pulled through the length of the growing structure to the tip. This new mechanism answers an old question and may have resonance in other assembly processes.This is the published version of the manuscript. It was published in the journal Microbial Cell by Shared Science Publishers OG and can be found here: http://microbialcell.com/wordpress/wp-content/uploads/2014/01/2014A-Evans-Microbial-Cell.pd

c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines

It is widely accepted that the c-Fos gene has a role in proliferation and differentiation of bone cells. ATP-induced c-Fos activation is relevant to bone homeostasis, because nucleotides that are present in the environment of bone cells can contribute to autocrine/paracrine signalling. Gut hormones have previously been shown to have an effect on bone metabolism. In this study, we used the osteoblastic Saos-2 cell line transfected with a c-Fos-driven reporter stimulated with five gut hormones: glucose inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), ghrelin and obestatin, in the presence or absence of ATP. In addition, TE-85 cells were used to determine the time course of c-Fos transcript induction following stimulation with GLP-1, and GLP-2 with or without ATP, using reverse transcription qPCR. The significant results from the experiments are as follows: higher level of c-Fos induction in presence of GIP, obestatin (p = 0.019 and p = 0.011 respectively), and GIP combined with ATP (p < 0.001) using the luciferase assay; GLP-1 and GLP-2 combined with ATP (p = 0.034 and p = 0.002, respectively) and GLP-2 alone (p < 0.001) using qPCR. In conclusion, three of the gut peptides induced c-Fos, providing a potential mechanism underlying the actions of these hormones in bone which can be directed or enhanced by the presence of ATP

Risk factors for recurrent injurious falls that require hospitalization for older adults with dementia: a population based study

Background: Older adults with dementia are at an increased risk of falls, however, little is known about risk factors for recurrent injurious falls (a subsequent fall after the first fall has occurred) among this group. This study aimed to identify risk factors for recurrent injurious falls requiring hospitalization among adults aged 60+ years with dementia. Methods: This retrospective, whole-population cohort study was conducted using the Western Australian Hospital Morbidity Data System and Western Australian Death Registrations from 2001 to 2013. Survival analysis using a stratified conditional Cox model (type 1) was undertaken to identify risk factors for recurrent injurious falls requiring hospitalization. Results: There were 32,519 participants with an index hospital admission with dementia during the study period. Over 27 % (n = 8970) of the cohort experienced a total of 11,073 injurious falls requiring hospitalization during follow up with 7297 individuals experiencing a single fall, 1330 experiencing two falls and 343 experiencing three or more falls. The median follow-up time for each individual was 2.49 years. Females were at a significantly increased risk of 7 % for recurrent injurious falls resulting in hospitalization (adjusted hazard ratio 1.07, 95 % CI 1.01–1.12), compared to males. Increasing age, living in rural areas, and having an injurious fall in the year prior to the index hospital admission with dementia also increased the risk of recurrent injurious falls resulting in hospitalization. Conclusions: Screening those with dementia for injurious falls history could help to identify those most at risk of recurrent injurious falls. Improvement of heath care an

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Reassembling difference? Rethinking inclusion through/as embodied ethics

This paper considers inclusion through the lens of embodied ethics. It does so by connecting feminist writing on recognition, ethics and embodiment to recent examples of political activism as instances of recognition-based organizing. In making these connections, the paper draws on insights from Judith Butler’s recent writing on the ethics and politics of assembly in order to re-think how inclusion might be understood and practiced. The paper has three inter-related aims: (i) to emphasize the importance of a critical reconsideration of the ethics and politics of inclusion given, on the one hand, its positioning as an organizational ‘good’ and on the other, the conditions attached to it; (ii) to develop a critique of inclusion, drawing on insights from recent feminist thinking on relational ethics, and (iii) to connect this theoretical critique of inclusion, re-considered here through the lens of embodied ethics, to assembly as a form of feminist activism. Each of these aims underpins the theoretical and empirical discussion developed in the paper, specifically its focus on the relationship between embodied ethics, the interplay between theory and practice, and a politics of assembly as the basis for a critical reconsideration of inclusion

A Methodological Framework for the Evaluation of Syndromic Surveillance Systems: A Case Study of England

Background: Syndromic surveillance complements traditional public health surveillance by collecting and analysing health indicators in near real time. The rationale of syndromic surveillance is that it may detect health threats faster than traditional surveillance systems permitting more timely, and hence potentially more effective public health action. The effectiveness of syndromic surveillance largely relies on the methods used to detect aberrations. Very few studies have evaluated the performance of syndromic surveillance systems and consequently little is known about the types of events that such systems can and cannot detect. Methods: We introduce a framework for the evaluation of syndromic surveillance systems that can be used in any setting based upon the use of simulated scenarios. For a range of scenarios this allows the time and probability of to be determined and uncertainty is fully incorporated. In addition, we demonstrate how such a framework can model the benefits of increases in the number of centres reporting syndromic data and also determine the minimum size of outbreaks that can or cannot be detected. Here, we demonstrate its utility using simulations of national influenza outbreaks and localised outbreaks of cryptosporidiosis. Results: Influenza outbreaks are consistently detected with larger outbreaks being detected in a more timely manner. Small cryptosporidiosis outbreaks (<1000 symptomatic individuals) are unlikely to be detected. We also demonstrate the advantages of having multiple syndromic data streams (e.g. emergency attendance data, telephone helpline data, general practice consultation data) as different streams are able to detect different types outbreaks with different efficacy (e.g. emergency attendance data are useful for the detection of pandemic influenza but not for outbreaks of cryptosporidiosis). We also highlight that for any one disease, the utility of data streams may vary geographically, and that the detection ability of syndromic surveillance varies seasonally (e.g. an influenza outbreak starting in July is detected sooner than one starting later in the year). We argue that our framework constitutes a useful tool for public health emergency preparedness in multiple settings. Conclusions: The proposed framework allows the exhaustive evaluation of any syndromic surveillance system and constitutes a useful tool for emergency preparedness and response

Predictors of Employee Involvement in a Worksite Health Promotion Program

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67001/2/10.1177_109019819001700404.pd

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Field-study science classrooms as positive and enjoyable learning environments

We investigated differences between field-study classrooms and traditional science classrooms in terms of the learning environment and students’ attitudes to science, as well as the differential effectiveness of field-study classrooms for students differing in sex and English proficiency. A modified version of selected scales from the What Is Happening In this Class? questionnaire was used to assess the learning environment, whereas students’ attitudes were assessed with a shortened version of a scale from the Test of Science Related Attitudes. A sample of 765 grade 5 students from 17 schools responded to the learning environment and attitude scales in terms of both their traditional science classrooms and classrooms at a field-study centre in Florida. Large effect sizes supported the effectiveness of the field-studies classroom in terms of both the learning environment and student attitudes. Relative to the home school science class, the field-study class was considerably more effective for students with limited English proficiency than for native English speakers