Circadian Biology: A 2.5 Billion Year Old Clock

SummaryA recent study suggests that circadian clocks may have evolved at the time of the Great Oxidation Event 2.5 billion years ago in order to drive detoxification of reactive oxygen species

Microbial dynamics and core microbiome of red-backed salamanders (Plethodon cinereus)

Beneficial cutaneous bacteria on amphibians can protect against the lethal fungal disease chytridiomycosis, which has decimated many amphibian species. The stability of these bacterial communities likely influences health outcomes, and is investigated here for the first time. We describe the diversity of bacteria on red-backed salamanders (Plethodon cinereus) in the wild, and the stability of these communities over time in captivity using culture-independent Illumina sequencing. In the field, there was no correlation between the diversity of salamanders’ microbial communities and the diversity of their substrates’ microbial communities. Salamanders were brought into the laboratory to test for the effect of an environmental reservoir (soil) in maintaining diversity and stability and were sampled every 7 days ending at day 28. In the laboratory, the alpha diversity of salamanders in the ‘no bacterial reservoir’ treatment decreased, whereas it remained constant in the ‘bacterial reservoir treatment’. The treatment groups diverged from each other, yielding significant differences in beta-diversity. Eight OTUs defined a core community, i.e., present on \u3e90% of salamanders through time, and a majority of these taxa such as Pseudomonadaceae, are known to secrete antifungal metabolites. Alpha diversity decreased in the treatment lacking a soil reservoir, one core OTU from the phylum Verrucomicrobia dominated the community. This result suggests that the non-core community on the salamanders regulate the core community and that the non-core community is dependent on the soil reservoir. Bacterial community structure in both treatments changed when their salamander hosts were brought into the laboratory. Diversity was more constant in the bacterial reservoir treatment. Defensive function of salamanders’ cutaneous microbiota may depend on the diversity and stability of the core community

Publication bias in clinical trials

This is the protocol for a review and there is no abstract. The objectives are as follows: To summarise evidence of publication bias for trials of health care interventions.Output Type: Protoco

Organizational Learning Capability in SMEs: An Empirical Development of Innovation in the Supply Chain

Evidence that a company’s innovation performance, Knowledge Management capability, and its corporate and operational performance are inextricably linked has been the focus of numerous academic studies over recent years. Whilst a significant body of research exists focusing on learning at company level, little research exists on how supply chains learn and innovate in collaborative working environments. The aim of this paper is to determine the learning and innovation skills that emerged from a collaborative project with new developed supply chain. Its focus is on identifying how each organisation within the supply chain developed its Organisational Learning Capability (OLC) when the companies were tasked to collaborate and develop a new and innovative product. The companies had not previously worked with each other and so the project monitored the level of collaborative activity as well as innovative output from the collaboration. The results suggest that improved organistional learning capabilities led to increased levels of organisational innovation as well as improved supply chain collaboration. The paper concludes with the development of a Supply Chain Organisational Learning and Innovation Framework (SCOLIF) and the identification of a number of cultural dimensions which are considered useful for managers and engineers to consider when implementing innovation project

Vertebrate Hosts as Islands: Dynamics of Selection, Immigration, Loss, Persistence, and Potential Function of Bacteria on Salamander Skin.

Skin bacterial communities can protect amphibians from a fungal pathogen; however, little is known about how these communities are maintained. We used a neutral model of community ecology to identify bacteria that are maintained on salamanders by selection or by dispersal from a bacterial reservoir (soil) and ecological drift. We found that 75% (9/12) of bacteria that were consistent with positive selection, <1% of bacteria that were consistent with random dispersal and none of the bacteria that were consistent under negative selection had a 97% or greater match to antifungal isolates. Additionally we performed an experiment where salamanders were either provided or denied a bacterial reservoir and estimated immigration and loss (emigration and local extinction) rates of bacteria on salamanders in both treatments. Loss was strongly related to bacterial richness, suggesting competition is important for structuring the community. Bacteria closely related to antifungal isolates were more likely to persist on salamanders with or without a bacterial reservoir, suggesting they had a competitive advantage. Furthermore, over-represented and under-represented operational taxonomic units (OTUs) had similar persistence on salamanders when a bacterial reservoir was present. However, under-represented OTUs were less likely to persist in the absence of a bacterial reservoir, suggesting that the over-represented and under-represented bacteria were selected against or for on salamanders through time. Our findings from the neutral model, migration and persistence analyses show that bacteria that exhibit a high similarity to antifungal isolates persist on salamanders, which likely protect hosts against pathogens and improve fitness. This research is one of the first to apply ecological theory to investigate assembly of host associated-bacterial communities, which can provide insights for probiotic bioaugmentation as a conservation strategy against disease

The configuration and experience mapping of an accessible VR environment for effective design reviews

This paper presents a new VR interaction environment for the evaluation of digital prototypes, specifically in designer-client review sessions, and documents its implementation via experience mapping. Usability of VR controllers and basic manipulation remains a barrier for lay users, and a range of typical implementations are reviewed, highlighting the need for an easily accessible interface for this setting. The resulting interface configuration – the Control Carousel – demonstrates how the appropriate use of familiar mechanisms can increase VR accessibility. Three case studies using the Carousel in commercial design projects are described, and the subsequent interface refinements outlined. Finally, the development of an experience map describing the logistical, interactive and emotive factors affecting the Carousel’s implementation, is documented. This provides insights on how experience mapping can be used as part of a human-centred design process to ensure VR environments are attuned to the requirements of users, in this instance delivering improved collaborative reviews

Circadian clocks, glucocorticoids and the gated inflammatory response

In mammals endogenous, self sustained oscillators, known as circadian clocks, have evolved as a result of day night cycles, with a period close to 24 hours, and are involved in many physiological processes; such as sleep wake cycles, metabolic and hormonal activity. The suprachiasmatic nucleus (SCN), is the central oscillator, and is synchronised to the external environment by light, via the eye. It has been demonstrated that peripheral clocks, too, contain the circadian oscillator, with tissues such as the lung, liver, heart and kidney as well as many isolated cell types remaining rhythmic, in culture, for many days. However, these peripheral oscillators require a signal from the central oscillator in order to co-ordinate a synchronised time. Leading candidates in the relay of this information are the circulating glucocorticoid hormones corticosterone (rodents) or cortisol (man), which are known to have potent effects on the peripheral clock, both in-vivo and in-vitro. Further to this, glucocorticoids have been used for many decades to suppress the symptoms of inflammation, a by product of many human diseases.This thesis aims to address the temporal regulation of the peripheral clock by the endogenous glucocorticoid, corticosterone, using a transgenic mouse harbouring a luciferase conjugated clock reporter, and circadian reporter cell lines. It also aims to address the relative contribution of the two closely related nuclear hormone receptors, the glucocorticoid and mineralocorticoid receptors. A further aim of the work with glucocorticoid signalling was to design a flow-though culture system, in order to address the effects of the endogenous pulsatile release of glucocorticoids on the peripheral oscillator. This thesis also aims to characterise the inflammatory response in relation to its circadian characteristics; its relationship with corticosterone and the effect of inflammation on the central clock components. Finally, this thesis aims to investigate a potential input/output of the clock, a member of the family of C/EBP transcription factors, C/EBP alpha, and whether it is under endogenous circadian control and regulated by glucocorticoids.Work in this thesis has shown that glucocorticoids dynamically regulate the peripheral clock at all phases of the circadian cycle and that this regulation occurs mainly through the glucocorticoid receptor; yet the mineralocorticoid receptor does have a function in the immediate response to glucocorticoid administration. Furthermore, as a result of the initial temporal profile after corticosterone addition, on the clock protein PERIOD2, I have shown transient regulation of the clock through Caveolin-1 based signalling. There is also a significant circadian component to the inflammatory response, which appears, at least in part, to be REV-ERB alpha mediated, and the inflammatory response also has profound effects on circadian gene expression in the periphery. A functional flow-through system was designed and a working model produced, albeit with technical difficulties, to address glucocorticoid pulsing and circadian timing but much more work is needed for effects to be fully understood. C/EBP alpha appears not to be under circadian regulation nor under direct glucocorticoid regulation, at least in peripheral models used here.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The effects of yoga on shoulder and spinal actions for women with breast cancer-related lymphoedema of the arm: A randomised controlled pilot study

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abstract Background: We aimed to evaluate the effect of an 8-week yoga intervention on the shoulder and spinal actions of women with breast cancer-related arm lymphoedema. Method: A randomised controlled pilot trial. The intervention group (n = 12) completed eight weeks of daily yoga sessions while the control group (n = 11) continued with best current care including information on compression sleeves, skin care, risks of temperature variations and recommended safe use of affected arm. Lumbo-pelvic posture, range of motion (ROM) in the shoulder and spine, and strength in shoulder and pectoral major and minor, and serratus anterior were taken at baseline, week 8 and after a 4-week follow-up. Outcome assessors were blinded to allocation. Results: At week eight the intervention group had an improvement in lumbo-pelvic posture, as indicated by a reduction in pelvic obliquity compared to the control group (mean difference = −8.39°, 95 % CI: −15.64 to −1.13°, p = 0.023). A secondary finding was that strength in shoulder abduction significantly increased following the yoga intervention in both the affected (9.5 kg; CI: 0.34 to 18.66, p = 0.042) and non-affected arm (11.58 kg; CI: 0.25 to 22.91; p = 0.045). There were no significant between group changes in any ROM measures as a result of the yoga intervention. Conclusion: This pilot study demonstrates that participation in yoga may provide benefits for posture and strength in women with Breast Cancer Related Lymphoedema. The improvements may be attributed to the focus of yoga on overall postural and functional movement patterns. Further trials with longer intervention that follow this methodology are warranted. Trial registration: The Australian New Zealand Clinical Trials Registry ACTRN12611000202965. Keywords: Yoga, Arm lymphoedema, Breast cancer, Range of motion, Strength testing Abbreviations: BCRL, Breast cancer related lymphoedema; ROM, Range of motion; QOL, Quality of life; RCT, Randomised controlled trial; BIS, Bioimpedance spectroscopy; LPSI, Left posterior superior iliac spine; RPSI, Right posterior superior iliac spine; LACR, Left acromion; RACR, Right acromio

The application of generative algorithms in human-centered product development

Algorithmic design harnesses the power of computation to generate a form based on input data and rules. In the product design setting, a major advantage afforded by this approach is the ability to automate the customization of design variations in accordance with the requirements of individual users. The background knowledge, intuition, and critical judgement of the designer are still essential but are focused on different areas of the design process. Thus far, little research has been applied directly to the problem of ergonomics in generative design. In this paper, we review the relevant literature in generative design, topology optimization, and computational design in order to describe the ways in which algorithms can be incorporated into the design process from a human-factors perspective–design tailored around human anatomy and usability requirements. We then develop a model for approaching generative design development work, oriented around human factors (particular ergonomics), and describe a case study from the PRIME-VR2 research project in which an algorithmic workflow utilized user scan data and 3D-printing technology to generate bespoke versions of a standard controller device