The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans

The recognition of carbohydrate moieties by cells of the innate immune system is emerging as an essential element in antifungal immunity, but despite the number and diversity of lectins expressed by innate immune cells, few carbohydrate receptors have been characterized. Mincle, a C-type lectin, is expressed predominantly on macrophages, and is here shown to play a role in macrophage responses to the yeast Candida albicans. After exposure to the yeast in vitro, Mincle localized to the phagocytic cup, but it was not essential for phagocytosis. In the absence of Mincle, production of TNF-_ by macrophages was reduced, both in vivo and in vitro. In addition, mice lacking Mincle showed a significantly increased susceptibility to systemic candidiasis. Thus, Mincle plays a novel and nonredundant role in the induction of inflammatory signaling in response to C. albicans infection.

A role for the phagosome in cytokine secretion

Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor α (TNFα) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNFα and expands the membrane for phagocytosis.

Nerves of steel? Stress, work performance and elite athletes

There is a notable shortage of empirical research directed at measuring the magnitude and direction of stress effects on performance in a controlled environment. One reason for this is the inherent difficulties in identifying and isolating direct performance measures for individuals. Additionally, most traditional work environments contain a multitude of exogenous factors impacting individual performance, but controlling for all such factors is generally unfeasible (omitted variable bias). Moreover, instead of asking individuals about their self-reported stress levels, we observe workers’ behaviour in situations that can be classified as stressful. For this reason, we have stepped outside the traditional workplace in an attempt to gain greater controllability of these factors using the sports environment as our experimental space. We empirically investigate the relationship between stress and performance, in an extreme pressure situation (football penalty kicks) in a winner take all sporting environment (FIFA World Cup and UEFA European Cup competitions). Specifically, we examine all the penalty shootouts between 1976 and 2008 covering in total 16 events. The results indicate that extreme stressors can have a positive or negative impact on individuals’ performance. On the other hand, more commonly experienced stressors do not affect professionals’ performances.

Revision total hip replacement using the cement-in-cement technique for the acetabular component : technique and results for 60 hips

The technique of femoral cement-in-cement revision is well established, but there are no previous series reporting its use on the acetabular side at the time of revision total hip arthroplasty. We describe the surgical technique and report the outcome of 60 consecutive cement-in-cement revisions of the acetabular component at a mean follow-up of 8.5 years (range 5-12 years). All had a radiologically and clinically well fixed acetabular cement mantle at the time of revision. 29 patients died. No case was lost to follow-up. The 2 most common indications for acetabular revision were recurrent dislocation (77%) and to compliment a femoral revision (20%). There were 2 cases of aseptic cup loosening (3.3%) requiring re-revision. No other hip was clinically or radiologically loose (96.7%) at latest follow-up. One case was re-revised for infection, 4 for recurrent dislocation and 1 for disarticulation of a constrained component. At 5 years, the Kaplan-Meier survival rate was 100% for aseptic loosening and 92.2% (95% CI; 84.8-99.6%) with revision for all causes as the endpoint. These results support the use of the cement-in-cement revision technique in appropriate cases on the acetabular side. Theoretical advantages include preservation of bone stock, reduced operating time, reduced risk of complications and durable fixation.

GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.

Twitter as a technology for audiencing and fandom : the #Eurovision phenomenon

Amongst the most prominent uses of Twitter at present is its role in the discussion of widely televised events: Twitter’s own statistics for 2011, for example, list major entertainment spectacles (the MTV Music Awards, the BET Awards) and sports matches (the UEFA Champions League final, the FIFA Women’s World Cup final) amongst the events generating the most tweets per second during the year (Twitter, 2011). User activities during such televised events constitute a specific, unique category of Twitter use, which differs clearly from the other major events which generate a high rate of tweets per second (such as crises and breaking news, from the Japanese earthquake and tsunami to the death of Steve Jobs), as preliminary research has shown. During such major media events, by contrast, Twitter is used most predominantly as a technology of fandom instead: it serves in the first place as a backchannel to television and other streaming audiovisual media, enabling users offer their own running commentary on the universally shared media text of the event broadcast as it unfolds live. Centrally, this communion of fans around the shared text is facilitated by the use of Twitter hashtags – unifying textual markers which are now often promoted to prospective audiences by the broadcasters well in advance of the live event itself. This paper examines the use of Twitter as a technology for the expression of shared fandom in the context of a major, internationally televised annual media event: the Eurovision Song Contest. It constitutes a highly publicised, highly choreographed media spectacle whose eventual outcomes are unknown ahead of time and attracts a diverse international audience. Our analysis draws on comprehensive datasets for the ‘official’ event hashtags, #eurovision, #esc, and #sbseurovision. Using innovative methods which combine qualitative and quantitative approaches to the analysis of Twitter datasets containing several hundreds of thousands, we examine overall patterns of participation to discover how audiences express their fandom throughout the event. Minute-by-minute tracking of Twitter activity during the live broadcasts enables us to identify the most resonant moments during each event; we also examine the networks of interaction between participants to detect thematically or geographically determined clusters of interaction, and to identify the most visible and influential participants in each network. Such analysis is able to provide a unique insight into the use of Twitter as a technology for fandom and for what in cultural studies research is called ‘audiencing’: the public performance of belonging to the distributed audience for a shared media event. Our work thus contributes to the examination of fandom practices led by Henry Jenkins (2006) and other scholars, and points to Twitter as an important new medium facilitating the connection and communion of such fans.

Self-directed student work groups using blended learning

This paper provides a description of an innovative teaching approach designed to facilitate student work groups using a blended learning approach that incorporates both traditional face-to-face teaching methods and an online student work group facility. The teaching approach is designed to accommodate a large introductory human resource management subject positioned within an undergraduate business degree.

The Cambridge companion to creative writing [Edited book]

Creative writing has become a highly professionalised academic discipline, with popular courses and prestigious degree programmes worldwide. This book is a must for all students and teachers of creative writing, indeed for anyone who aspires to be a published writer. It engages with a complex art in an accessible manner, addressing concepts important to the rapidly growing field of creative writing, while maintaining a strong craft emphasis, analysing exemplary models of writing and providing related writing exercises. Written by professional writers and teachers of writing, the chapters deal with specific genres or forms – ranging from the novel to new media – or with significant topics that explore the cutting edge state of creative writing internationally (including creative writing and science, contemporary publishing and new workshop approaches).

Life writing

Two hundred years ago life writing was already highly popular in the form of autobiography, memoir, biography, journals, essays and diaries. It now commands a huge share of the publishing market, as there is an enormous demand from readers for narratives based directly on 'real lives'. There is a lot of common ground between the two main forms - autobiography/memoir and biography: both require skilled storytelling [rather than listing facts and events], research and imagination. The quality of the writing itself is crucial to the impact on the reader. A person can have an existing, worthy life but unfortunately write about it (or be written about) in a dull way. And how a person is remembered and valued can be a factor of life writing about or by them. This chapter will define and contextualise life writing, look at specific detailed examples, and offer guidance on how to write effectively.