Macrophage Subset Sensitivity to Endotoxin Tolerisation by Porphyromonas gingivalis

Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14hi and CD14lo M1- and M2-like MΦs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and vitamin D3, respectively. MΦ subsets were pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14lo and CD14hi M2 regulatory MΦs and CD14lo M1 MΦs whereas CD14hi M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14hi M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity

Shape control of high degree-of-freedom variable geometry trusses

Common static trusses are constrained to permit no relative motion between truss elements. A Variable Geometry Truss (VGT), however, is a truss which contains some number of variable length links. The extensible links allow the truss to change shape in a precise, controllable manner. These changes can also be used to control the vibrational response of a truss structure or to perform robotic tasks. Many geometric configurations, both planar and spatial, are possible candidates for VGT manipulators. Here, only two geometries are discussed; the three degree-of-freedom (DOF) spatial octahedral/octahedral truss and the three DOF planar tetrahedral truss. These truss geometries are used as the fundamental element in a repeating chain of trusses. This results in a highly dexterous manipulator with perhaps 30 to 60 degrees of freedom that retains the favorable stiffness properties of a conventional truss. From a fixed base, this type of manipulator could perform shape or vibration control while extending and snaking through complex passageways or moving around obstacles to perform robotic tasks. The approach taken here is to first concentrate on fully understanding the forward and inverse kinematics of the fundamental elements and then utilizing the insight thus gained to solve the more complex problem of the kinematic chains

Experiences of integrated care for dementia from family and carer perspectives: A framework analysis of massive open online course discussion board posts

Background Integrated Care for dementia is an increasingly popular approach to supporting people with dementia, bringing services together to form a single cohesive provision for service users. This approach is still in its infancy but has the potential to improve the management of dementia, social care and to enhance the patient experience. Aims To understand views and experiences of integrated health and social care for dementia from the perspective of carers, families, healthcare professionals and researchers. Methods Crowdsourcing views and experiences from 'Bridging the Dementia Divide', a massive open online course at the University of Derby, provide a rich source of qualitative data from carers, families and healthcare professionals. We analysed 847 massive open online course discussion board posts using a Framework Analysis approach. Results Participants described how Integrated Care for dementia should be person-centred and holistic, involving a multidisciplinary team of health and social care practitioners, as well as the patient, the family and the wider community. The establishment of Integrated Care for dementia was viewed positively.N/

Active vibration mitigation of distributed parameter, smart-type structures using Pseudo-Feedback Optimal Control (PFOC)

A new, near-optimal feedback control technique is introduced that is shown to provide excellent vibration attenuation for those distributed parameter systems that are often encountered in the areas of aeroservoelasticity and large space systems. The technique relies on a novel solution methodology for the classical optimal control problem. Specifically, the quadratic regulator control problem for a flexible vibrating structure is first cast in a weak functional form that admits an approximate solution. The necessary conditions (first-order) are then solved via a time finite-element method. The procedure produces a low dimensional, algebraic parameterization of the optimal control problem that provides a rigorous basis for a discrete controller with a first-order like hold output. Simulation has shown that the algorithm can successfully control a wide variety of plant forms including multi-input/multi-output systems and systems exhibiting significant nonlinearities. In order to firmly establish the efficacy of the algorithm, a laboratory control experiment was implemented to provide planar (bending) vibration attenuation of a highly flexible beam (with a first clamped-free mode of approximately 0.5 Hz)

On the Schrödinger-Newton equation and its symmetries: a geometric view

LaTeX 29 pages; minor correctionsInternational audienceThe \SN (SN) equation is recast on purely geometrical grounds, namely in terms of Bargmann structures over (\d+1)-dimensional Newton-Cartan (NC) spacetimes. Its maximal group of invariance, which we call the SN group, is determined as the group of conformal Bargmann automorphisms that preserve the coupled Schr\"odinger and NC gravitational field equations. Canonical unitary representations of the SN group are worked out, helping us recover, in particular, a very specific occurrence of dilations with dynamical exponent z=(\d+2)/3

Using Ripple Effects Mapping to understand the longer-term impacts of delivering a dance programme for older adults on dance artists

Background: The dance workforce plays a central role in delivering arts and health programmes yet there is little exploration of how programme delivery impacts dance artists in a professional or personal capacity. This study explored the experiences of dance artists delivering Dance On, which engages inactive older people 55yrs+. Methods: Ripple Effects Mapping was used to explore the short- and long term experiences and practices of dance artists delivering a dance programme. Findings: Two ripples were developed 1) Becoming a specialist 2) Connecting with communities. These ripples highlighted the strengths of the sustained nature of the programme and emphasised the need for ongoing support from employing organisations, communities, and dance artist peers. Conclusion: This study showcases the central role dance artists play in upholding the outcomes we observe in arts and health work–their role, expertise, and commitment to programmes should be further illuminated and supported through ongoing discourse about their practice

Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets

Human-mediated biological exchange has had global social and ecological impacts. In subS-aharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation

The Green, Green Grass of Home: an archaeo-ecological approach to pastoralist settlement in central Kenya

© 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This paper considers the ecological residues of pastoralist occupation at the site of Maili Sita in Laikipia, central Kenya, drawing links with the archaeological record so as to contribute a fresh approach to the ephemeral settlement sites of mobile herding communities, a methodological aspect of African archaeology that remains problematic. Variations in the geochemical and micromorphological composition of soils along transects across the site are compared with vegetation distributions and satellite imagery to propose an occupation pattern not dissimilar to contemporary Cushitic-speaking groups further north. We argue that Maili Sita exemplifies the broad migratory and cultural exchange networks in place during the mid- to late second millennium AD, with pastoralist occupants who were both physically and culturally mobile.British Academy (2002-5 Funding) European Union - Marie Curie Initiatives (EXT grant 2007-11

Investigation of the Role of TNF-α Converting Enzyme (TACE) in the Inhibition of Cell Surface and Soluble TNF-α Production by Acute Ethanol Exposure

Toll-like receptors (TLRs) play a fundamental role in the immune system by detecting pathogen associated molecular patterns (PAMPs) to sense host infection. Ethanol at doses relevant for humans inhibits the pathogen induced cytokine response mediated through TLRs. The current study was designed to investigate the mechanisms of this effect by determining whether ethanol inhibits TLR3 and TLR4 mediated TNF-α secretion through inhibition of transcription factor activation or post-transcriptional effects. In NF-κB reporter mice, activation of NF-κB in vivo by LPS was inhibited by ethanol (LPS alone yielded 170,000±35,300 arbitrary units of light emission; LPS plus ethanol yielded 56,120±16880, p = 0.04). Inhibition of protein synthesis by cycloheximide revealed that poly I:C- or LPS-induced secreted TNF-α is synthesized de novo, not released from cellular stores. Using real time RT-PCR, we found inhibition of LPS and poly I:C induced TNF-α gene transcription by ethanol. Using an inhibitor of tumor necrosis factor alpha converting enzyme (TACE), we found that shedding caused by TACE is a prerequisite for TNF-α release after pathogen challenge. Flow cytometry was used to investigate if ethanol decreases TNF-α secretion by inhibition of TACE. In cells treated with LPS, ethanol decreased both TNF-α cell surface expression and secretion. For example, 4.69±0.60% of untreated cells were positive for cell surface TNF-α, LPS increased this to 25.18±0.85%, which was inhibited by ethanol (86.8 mM) to 14.29±0.39% and increased by a TACE inhibitor to 57.88±0.62%. In contrast, cells treated with poly I:C had decreased secretion of TNF-α but not cell surface expression. There was some evidence for inhibition of TACE by ethanol in the case of LPS, but decreased TNF-α gene expression seems to be the major mechanism of ethanol action in this system