Development of a cell population migration assay

Cellular migration is central to many physiological and pathological processes, from wound healing and the immune response to cancer cell invasion. Many in-vitro assays have been developed to study these processes and can be classified by the nature of the assay, for example migration of single cells or entire populations, as well as migration on a planar surface or through a 3D structure. This work concerns the development of an assay to study the migration of whole populations of cells across a deformable planar substratum, which may be coated in adsorbed adhesion molecules. The technique detailed below was developed from the Teflon fence assay

Comparative growth and management of white and red clovers

peer-reviewedThe aim of this paper is to provide the underpinning scientific basis for the optimum management of white and red clovers. Critical morphological and canopy characteristics which influence the yield and persistence of white and red clover in swards, and how management factors (choice of cultivar, defoliation and nitrogen (N) fertilizer) modify these are considered. Canopy development is vitally important as it determines the extent to which a) light is intercepted for photosynthesis needed for growth and b) the base of the sward is deprived of the red component in daylight, inhibiting branching of stolons and crowns in white and red clover, respectively. The role of cultivar, defoliation and N fertilizer in determining yield and persistence of the two legumes, mainly in mixtures with grass, are discussed principally in terms of morphological development and exploitation of light. It is concluded that optimum management for grass/white clover places emphasis on building up stolons and maximising contribution of clover leaf area to the upper layers of the mixed canopy and, while red clover is more competitive to grass than white clover, that benefit is lost when a grass/red clover sward is grazed

Leaf appearance of annual clovers responds to photoperiod atemergence

Leaf appearance rate and time to canopy expansion of four annual clover species (arrowleaf, balansa,gland and Persian) were quantified in field and controlled environment studies. Crops sown in autumn,which experienced shortening daylengths at emergence, had a slower rate of leaf production and con-sequently took a longer time to initiate branching, than spring-sown crops. When autumn-sown ‘Bolta’balansa clover emerged on the shortest day in winter (21 June), the rate of leaf appearance was lengthenedby 4◦C d/leaf/h. When the same species emerged after the shortest day, into an increasing photoperiod,the phyllochron was shortened by 5◦C d/leaf/h. This influence of photoperiod on the phyllochron conse-quently altered the time to axillary leaf production (branching). Throughout all sowing dates, phyllochronwas the fastest for ‘Prima’ gland (33–91◦C d/leaf) and slowest for ‘Cefalu’ arrowleaf (53–116◦C d/leaf)clovers. ‘Bolta’ balansa was 44–82◦C d/leaf and ‘Mihi’ Persian 61–93◦C d/leaf. The response of phyllochronto photoperiod suggests these annual clovers should be sown in late summer or early autumn to initiateaxillary leaf production as soon as possible to ensure maximize dry matter for early spring

Thrombospondin 1 is a key mediator of transforming growth factor β-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanism

BACKGROUND: The mechanism underlying the ability of fibroblasts to contract a collagen gel matrix is largely unknown. Fibroblasts from scarred (lesional) areas of patients with the fibrotic disease scleroderma show enhanced ability to contract collagen relative to healthy fibroblasts. Thrombospondin 1 (TSP1), an activator of latent transforming growth factor (TGF)β, is overexpressed by scleroderma fibroblasts. In this report we investigate whether activation of latent TGFβ by TSP1 plays a key role in matrix contraction by normal and scleroderma fibroblasts. METHODS: We use the fibroblast populated collagen lattices (FPCL) model of matrix contraction to show that interfering with TSP1/TGFβ binding and knockdown of TSP1 expression suppressed the contractile ability of normal and scleroderma fibroblasts basally and in response to TGFβ. Previously, we have shown that ras/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) mediates matrix contraction basally and in response to TGFβ. RESULTS: During mechanical stimulation in the FPCL system, using a multistation tensioning-culture force monitor (mst-CFM), TSP1 expression and p-ERK activation in fibroblasts are enhanced. Inhibiting TSP1 activity reduced the elevated activation of MEK/ERK and expression of key fibrogenic proteins. TSP1 also blocked platelet-derived growth factor (PDGF)-induced contractile activity and MEK/ERK activation. CONCLUSIONS: TSP1 is a key mediator of matrix contraction of normal and systemic sclerosis fibroblasts, via MEK/ERK

Pairing correlations and transitions in nuclear systems

We discuss several pairing-related phenomena in nuclear systems, ranging from superfluidity in neutron stars to the gradual breaking of pairs in finite nuclei. We describe recent experimental evidence that points to a relation between pairing and phase transitions (or transformations) in finite nuclear systems. A simple pairing interaction model is used in order to study and classify an eventual pairing phase transition in finite fermionic systems such as nuclei. We show that systems with as few as 10-16 fermions can exhibit clear features reminiscent of a phase transition.Comment: Proceedings of COMEX1, Sorbonne, Paris, june 10-13 2003. To appear in Nuclear Physics

P Cygni Profiles of Molecular Lines Toward Arp 220 Nuclei

We report ~100 pc (0farcs3) resolution observations of (sub)millimeter HCO+ and CO lines in the ultraluminous infrared galaxy Arp 220. The lines peak at two merger nuclei, with HCO+ being more spatially concentrated than CO. Asymmetric line profiles with blueshifted absorption and redshifted emission are discovered in HCO+(3-2) and (4-3) toward the two nuclei and in CO(3-2) toward one nucleus. We suggest that these P Cygni profiles are due to ~100 km s–1 outward motion of molecular gas from the nuclei. This gas is most likely outflowing from the inner regions of the two nuclear disks rotating around individual nuclei, clearing the shroud around the luminosity sources there

A Diagnosis of Irritable Bowel Syndrome Using Rome IV Criteria and Limited Investigations is Durable in Secondary Care

Background & Aims Irritable bowel syndrome (IBS) is a positive diagnosis, made using symptom-based criteria and limited, judicious, investigation. However, this may lead to uncertainty on the part of clinicians regarding potential for a missed diagnosis of organic gastrointestinal disease. Few studies have examined durability of a diagnosis of IBS, and none have used the current gold standard to diagnose IBS, the Rome IV criteria. Methods We collected complete symptom data from 373 well-characterized adults meeting Rome IV criteria for IBS referred to a single UK clinic between September 2016 and March 2020. All patients underwent relatively standardized work-up to exclude relevant organic disease before diagnosis. We followed these individuals up to December 2022, assessing rates of rereferral, reinvestigation, and missed organic gastrointestinal disease. Results During a mean follow-up of 4.2 years per patient (total follow-up in all patients, 1565 years), 62 (16.6%) patients were rereferred. Of these, 35 (56.5%) were rereferred for IBS and 27 (43.5%) for other gastrointestinal symptoms. Among the 35 rereferred with IBS this was caused by a change in symptoms in only 5 (14.3%). Reinvestigation was undertaken in 21 (60.0%) of 35 rereferred with IBS and 22 (81.5%) of 27 rereferred with other symptoms (P = .12). Only 4 (9.3% of those reinvestigated and 1.1% of the entire cohort) new cases of relevant organic disease, which may have been responsible for IBS symptoms at baseline, were identified (1 case of chronic calcific pancreatitis among those rereferred with IBS and 1 case each of inflammatory bowel disease–unclassified, moderate bile acid diarrhea, and small bowel obstruction among those rereferred with other gastrointestinal symptoms). Conclusions Despite rereferral for gastrointestinal symptoms among 1 in 6 patients overall, with almost 10% rereferred with ongoing IBS symptoms, and substantial reinvestigation rates, missed organic gastrointestinal disease occurred in only 1%. A diagnosis of Rome IV IBS after limited investigation is safe and durable

Novel symptom clusters predict disease impact and healthcare utilisation in inflammatory bowel disease: Prospective longitudinal follow-up study

Background Predicting adverse disease outcomes and high-volume users of healthcare amongst patients with inflammatory bowel disease (IBD) is difficult. Aims The aim of this study is to use latent class analysis to create novel clusters of patients and to assess whether these predict outcomes during 6.5 years of longitudinal follow-up. Methods Baseline demographic features, disease activity indices, anxiety, depression, and somatoform symptom-reporting scores were recorded for 692 adults. Faecal calprotectin (FC) was analysed at baseline in 348 (50.3%) patients (<250 mcg/g defined biochemical remission). Using baseline gastrointestinal and psychological symptoms, latent class analysis identified specific patient clusters. Rates of glucocorticosteroid prescription or flare, escalation, hospitalisation, or intestinal resection were compared between clusters using multivariate Cox regression. Results A three-cluster model was the optimum solution; 132 (19.1%) patients had below-average gastrointestinal and psychological symptoms (cluster 1), 352 (50.9%) had average levels of gastrointestinal and psychological symptoms (cluster 2), and 208 (30.1%) had the highest levels of both gastrointestinal and psychological symptoms (cluster 3). Compared with cluster 1, cluster 3 had significantly increased risk of flare or glucocorticosteroid prescription (hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.46–3.10), escalation (HR: 1.92; 95% CI: 1.34–2.76), a composite of escalation, hospitalisation, or intestinal resection (HR: 2.05; 95% CI: 1.45–2.88), or any of the endpoints of interest (HR: 2.06; 95% CI: 1.45–2.93). Healthcare utilisation was highest in cluster 3. Conclusions Novel model-based clusters identify patients with IBD at higher risk of adverse disease outcomes who are high-volume users of healthcare

The politics of innovation: why innovations need a godfather

Innovation is closely linked to the development of technology. Hence it is often assumed that when an innovation fails it is the technology that is at fault. While this may be true in many instances, there are occasions when it is not the technology that is at fault, rather, it is managerial and organisational aspects that cause problems and lead to failure. Studies have shown that individuals who take on specific roles can play an important part in avoiding these problems. These roles include the technological gatekeeper, the product champion and the sponsor/coach. In addition to these roles, this paper argues that there is another, namely that of godfather. With this role a highly respected, senior figure within an organisation provides support that is critical in ensuring the project overcomes the hurdles that lie in the path of any major new development. The nature of the godfather role is explored through three case studies. These provide examples of the role and show how it can facilitate the innovation process

‘Engage the World’: examining conflicts of engagement in public museums

Public engagement has become a central theme in the mission statements of many cultural institutions, and in scholarly research into museums and heritage. Engagement has emerged as the go-to-it-word for generating, improving or repairing relations between museums and society at large. But engagement is frequently an unexamined term that might embed assumptions and ignore power relationships. This article describes and examines the implications of conflicting and misleading uses of ‘engagement’ in relation to institutional dealings with contested questions about culture and heritage. It considers the development of an exhibition on the Dead Sea Scrolls by the Royal Ontario Museum, Toronto in 2009 within the new institutional goal to ‘Engage the World’. The chapter analyses the motivations, processes and decisions deployed by management and staff to ‘Engage the World’, and the degree to which the museum was able to re-think its strategies of public engagement, especially in relation to subjects,issues and publics that were more controversial in nature