The Cornucopia of Intestinal Chemosensory Transduction

The chemosensory transduction mechanisms that the gastrointestinal (GI) tract uses to detect chemical and nutrient stimuli are poorly understood. The GI tract is presented with a wide variety of stimuli including potentially harmful chemicals or toxins as well as ‘normal’ stimuli including nutrients, bacteria and mechanical forces. Sensory transduction is at its simplest the conversion of these stimuli into a neural code in afferent nerves. Much of the information encoded is used by the enteric nervous system to generate local reflexes while complementary information is sent to the central nervous system via afferents or by release of hormones to affect behaviour. This review focuses on the chemosensory transduction mechanisms present in the GI tract. It examines the expression and localisation of the machinery for chemosensory transduction. It summarises the types of cells which might be involved in detecting stimuli and releasing neuroactive transmitters. Finally, it highlights the idea that chemosensory transduction mechanisms in the GI tract utilise many overlapping and complementary mechanisms for detecting and transducing stimuli into reflex action

Biomechanics of Pharyngeal Deglutitive Function Following Total Laryngectomy

Copyright © 2016 American Academy of Otolaryngology—Head and Neck Surgery Foundation. Reprinted by permission of SAGE PublicationsObjective: Post-laryngectomy surgery, pharyngeal weakness and pharyngoesophageal junction (PEJ) restriction are the underlying candidate mechanisms of dysphagia. We aimed to determine, in laryngectomees whether: 1) hypopharyngeal propulsion is reduced and/or PEJ resistance is increased; 2) endoscopic dilatation improves dysphagia; and 3) if so, whether symptomatic improvement correlate with reduction in resistance to flow across the PEJ. Methods: Swallow biomechanics were assessed in 30 total laryngectomees. Average peak contractile pressure (hPP) and hypopharyngeal intrabolus pressure (hIBP) were measured from combined high resolution manometry and video-fluoroscopic recordings of barium swallows (2, 5&10ml). Patients were stratified into severe dysphagia (Sydney Swallow Questionnaire (SSQ)>500) and mild/nil dysphagia (SSQ≤500). In 5 patients, all measurements were repeated after endoscopic dilatation. Results: Dysphagia was reported by 87%, and 57% had severe and 43% had minor/nil dysphagia. Laryngectomees had lower hPP than controls (110±14mmHg vs 170±15mmHg; p<0.05), while hIBP was higher (29±5mmHg vs 6±5mmHg; p<0.05). There were no differences in hPP between patient groups. However, hIBP was higher in severe than in mild/nil dysphagia (41±10mmHg vs 13±3mmHg; p<0.05). Pre-dilation hIBP (R2=0.97) and its decrement following dilatation (R2=0.98) were good predictors of symptomatic improvement. Conclusion: Increased PEJ resistance is the predominant determinant of dysphagia as it correlates better with dysphagia severity than peak pharyngal contractile pressure. While both baseline PEJ resistance and its decrement following dilatation are strong predictors of outcome following dilatation, the peak pharyngeal pressure is not. PEJ resistance is vital to detect as it is the only potentially reversible component of dysphagia in this context

Exposure and impact of a mass media campaign targeting sexual health amongst Scottish men who have sex with men: an outcome evaluation

Background: This paper explores the exposure and impact of a Scottish mass media campaign: Make Your Position Clear. It ran from October 2009 to July 2010, targeted gay men and other men who have sex with men (MSM), and had two key aims: to promote regular sexual health and HIV testing every 6 months, and to promote the use of appropriate condoms and water-based lubricant with each episode of anal intercourse. Methods: A cross-sectional survey (anonymous and self-report) was conducted 10 months after the campaign was launched (July 2010). Men were recruited from commercial venues. Outcome measures included use of lubricant, testing for sexually transmitted infections and HIV, and intentions to seek HIV testing within the following six months. Linear-by-linear chi-square analysis and binary logistic regressions were conducted to explore the associations between the outcome measures and campaign exposure. Results: The total sample was 822 men (62.6% response rate). Men self-identifying as HIV positive were excluded from the analysis (n = 38). Binary logistic analysis indicated that those with mid or high campaign exposure were more likely to have been tested for HIV in the previous six months when adjusted for age, area of residence and use of the “gay scene” (AOR = 1.96, 95% CI = 1.26 to 3.06, p = .003), but were not more likely to be tested for STIs (AOR = 1.37, 95% CI = 0.88 to 2.16, p = .167). When adjusted for previous HIV testing, those with mid or high campaign exposure were not more likely to indicate intention to be tested for HIV in the following six months (AOR = 1.30, 95% CI = 0.73 to 2.32, p = .367). Those with no campaign exposure were less likely than those with low exposure to have used appropriate lubricant with anal sex partners in the previous year (AOR = 0.42, 95% CI = 0.23 to 0.77, p = .005). Conclusions: The campaign had demonstrable reach. The analysis showed partial support for the role of mass media campaigns in improving sexual health outcomes. This suggests that a role for mass media campaigns remains within combination HIV prevention

Energy and force analysis of Ti-6Al-4V linear friction welds for computational modeling input and validation data

The linear friction welding (LFW) process is finding increasing use as a manufacturing technology for the production of titanium alloy Ti-6Al-4V aerospace components. Computational models give an insight into the process, however, there is limited experimental data that can be used for either modeling inputs or validation. To address this problem, a design of experiments approach was used to investigate the influence of the LFW process inputs on various outputs for experimental Ti-6Al-4V welds. The finite element analysis software DEFORM was also used in conjunction with the experimental findings to investigate the heating of the workpieces. Key findings showed that the average interface force and coefficient of friction during each phase of the process were insensitive to the rubbing velocity; the coefficient of friction was not coulombic and varied between 0.3 and 1.3 depending on the process conditions; and the interface of the workpieces reached a temperature of approximately approximately 1273 K (1000 °C) at the end of phase 1. This work has enabled a greater insight into the underlying process physics and will aid future modeling investigations.EPSRC, Boeing Company, Welding Institut

Influence of the Earth on the background and the sensitivity of the GRM and ECLAIRs instruments aboard the Chinese-French mission SVOM

SVOM (Space-based multi-band astronomical Variable Object Monitor) is a future Chinese-French satellite mission which is dedicated to Gamma-Ray Burst (GRB) studies. Its anti-solar pointing strategy makes the Earth cross the field of view of its payload every orbit. In this paper, we present the variations of the gamma-ray background of the two high energy instruments aboard SVOM, the Gamma-Ray Monitor (GRM) and ECLAIRs, as a function of the Earth position. We conclude with an estimate of the Earth influence on their sensitivity and their GRB detection capability.Comment: 24 pages, 15 figures, accepted for publication in Experimental Astronom

A random cell motility gradient downstream of FGF controls elongation of amniote embryos

Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements

Staphylococcus aureus ATP Synthase Promotes Biofilm Persistence by Influencing Innate Immunity

ABSTRACT Staphylococcus aureus is a major cause of prosthetic joint infection (PJI), which is characterized by biofilm formation. S. aureus biofilm skews the host immune response toward an anti-inflammatory profile by the increased recruitment of myeloid-derived suppressor cells (MDSCs) that attenuate macrophage proinflammatory activity, leading to chronic infection. A screen of the Nebraska Transposon Mutant Library identified several hits in the ATP synthase operon that elicited a heightened inflammatory response in macrophages and MDSCs, including atpA, which encodes the alpha subunit of ATP synthase. An atpA transposon mutant (ΔatpA) had altered growth kinetics under both planktonic and biofilm conditions, along with a diffuse biofilm architecture that was permissive for leukocyte infiltration, as observed by confocal laser scanning microscopy. Coculture of MDSCs and macrophages with ΔatpA biofilm elicited significant increases in the proinflammatory cytokines interleukin 12p70 (IL-12p70), tumor necrosis factor alpha (TNF-α), and IL-6. This was attributed to increased leukocyte survival resulting from less toxin and protease production by ΔatpA biofilm as determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The enhanced inflammatory response elicited by ΔatpA biofilm was cell lysis-dependent since it was negated by polyanethole sodium sulfanate treatment or deletion of the major autolysin, Atl. In a mouse model of PJI, ΔatpA-infected mice had decreased MDSCs concomitant with increased monocyte/macrophage infiltrates and proinflammatory cytokine production, which resulted in biofilm clearance. These studies identify S. aureus ATP synthase as an important factor in influencing the immune response during biofilm-associated infection and bacterial persistence. IMPORTANCE Medical device-associated biofilm infections are a therapeutic challenge based on their antibiotic tolerance and ability to evade immune-mediated clearance. The virulence determinants responsible for bacterial biofilm to induce a maladaptive immune response remain largely unknown. This study identified a critical role for S. aureus ATP synthase in influencing the host immune response to biofilm infection. An S. aureus ATP synthase alpha subunit mutant (ΔatpA) elicited heightened proinflammatory cytokine production by leukocytes in vitro and in vivo, which coincided with improved biofilm clearance in a mouse model of prosthetic joint infection. The ability of S. aureus ΔatpA to augment host proinflammatory responses was cell lysis-dependent, as inhibition of bacterial lysis by polyanethole sodium sulfanate or a ΔatpAΔatl biofilm did not elicit heightened cytokine production. These studies reveal a critical role for AtpA in shaping the host immune response to S. aureus biofilm

The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods

A recent workshop entitled The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods was held in Paris in December 2010, sponsored by the French National Centre for Scientific Research (CNRS) and by the journal Human Biology. This workshop was intended to foster a debate on questions related to the family names and to compare different multidisciplinary approaches involving geneticists, historians, geographers, sociologists and social anthropologists. This collective paper presents a collection of selected communications