Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Nebuliser therapy in the intensive care unit

The relationship between identity, lived experience, sexual practices and the language through which these are conveyed has been widely debated in sexuality literature. For example, ‘coming out’ has famously been conceptualised as a ‘speech act’ (Sedgwick 1990) and as a collective narrative (Plummer 1995), while a growing concern for individuals’ diverse identifications in relations to their sexual and gender practices has produced interesting research focusing on linguistic practices among LGBT-identified individuals (Leap 1995; Kulick 2000; Cameron and Kulick 2006; Farqhar 2000). While an explicit focus on language remains marginal to literature on sexualities (Kulick 2000), issue of language use and translation are seldom explicitly addressed in the growing literature on intersectionality. Yet intersectional perspectives ‘reject the separability of analytical and identity categories’ (McCall 2005:1771), and therefore have an implicit stake in the ‘vernacular’ language of the researched, in the ‘scientific’ language of the researcher and in the relationship of continuity between the two. Drawing on literature within gay and lesbian/queer studies and cross-cultural studies, this chapter revisits debates on sexuality, language and intersectionality. I argue for the importance of giving careful consideration to the language we choose to use as researchers to collectively define the people whose experiences we try to capture. I also propose that language itself can be investigated as a productive way to foreground how individual and collective identifications are discursively constructed, and to unpack the diversity of lived experience. I address intersectional complexity as a methodological issue, where methodology is understood not only as the methods and practicalities of doing research, but more broadly as ‘a coherent set of ideas about the philosophy, methods and data that underlie the research process and the production of knowledge’ (McCall 2005:1774). My points are illustrated with examples drawn from my ethnographic study on ‘lesbian’ identity in urban Russia, interspersed with insights from existing literature. In particular, I aim to show that an explicit focus on language can be a productive way to explore the intersections between the global, the national and the local in cross-cultural research on sexuality, while also addressing issues of positionality and accountability to the communities researched

Cumulative Low Back Load at Work as a Risk Factor of Low Back Pain: A Prospective Cohort Study

Purpose Much research has been performed on physical exposures during work (e.g. lifting, trunk flexion or body vibrations) as risk factors for low back pain (LBP), however results are inconsistent. Information on the effect of doses (e.g. spinal force or low back moments) on LBP may be more reliable but is lacking yet. The aim of the present study was to investigate the prospective relationship of cumulative low back loads (CLBL) with LBP and to compare the association of this mechanical load measure to exposure measures used previously. Methods The current study was part of the Study on Musculoskeletal disorders, Absenteeism and Health (SMASH) study in which 1,745 workers completed questionnaires. Physical load at the workplace was assessed by video-observations and force measurements. These measures were used to calculate CLBL. Furthermore, a 3-year follow-up was conducted to assess the occurrence of LBP. Logistic regressions were performed to assess associations of CLBL and physical risk factors established earlier (i.e. lifting and working in a flexed posture) with LBP. Furthermore, CLBL and the risk factors combined were assessed as predictors in logistic regression analyses to assess the association with LBP. Results Results showed that CLBL is a significant risk factor for LBP (OR: 2.06 (1.32-3.20)). Furthermore, CLBL had a more consistent association with LBP than two of the three risk factors reported earlier. Conclusions From these results it can be concluded that CLBL is a risk factor for the occurrence of LBP, having a more consistent association with LBP compared to most risk factors reported earlier. © 2012 The Author(s)

Effect of D222G Mutation in the Hemagglutinin Protein on Receptor Binding, Pathogenesis and Transmissibility of the 2009 Pandemic H1N1 Influenza Virus

Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known molecular determinants of virulence associated with previous pandemic and highly pathogenic avian influenza viruses. The frequency of the amino acid substitution D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not mild human cases represents the first molecular marker associated with enhanced disease. To assess the relative contribution of this substitution in virus pathogenesis, transmission, and tropism, we introduced D222G by reverse genetics in the wild-type HA of the 2009 H1N1 virus, A/California/04/09 (CA/04). A dose-dependent glycan array analysis with the D222G virus showed a modest reduction in the binding avidity to human-like (α2-6 sialylated glycan) receptors and an increase in the binding to avian-like (α2-3 sialylated glycan) receptors in comparison with wild-type virus. In the ferret pathogenesis model, the D222G mutant virus was found to be similar to wild-type CA/04 virus with respect to lethargy, weight loss and replication efficiency in the upper and lower respiratory tract. Moreover, based on viral detection, the respiratory droplet transmission properties of these two viruses were found to be similar. The D222G virus failed to productively infect mice inoculated by the ocular route, but exhibited greater viral replication and weight loss than wild-type CA/04 virus in mice inoculated by the intranasal route. In a more relevant human cell model, D222G virus replicated with delayed kinetics compared with wild-type virus but to higher titer in human bronchial epithelial cells. These findings suggest that although the D222G mutation does not influence virus transmission, it may be considered a molecular marker for enhanced replication in certain cell types.Centers for Disease Control and Prevention (U.S.)United States. National Institutes of Health (merit award R37 GM057073-13)Singapore-MIT Alliance for Research and Technolog

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts

Background: HLA-haploidentical hematopoietic stem cell transplantation (HSCT) is suitable for patients lacking related or unrelated HLA-matched donors. Herein, we investigated whether plerixafor (MZ), as an adjunct to G-CSF, facilitated the collection of mega-doses of hematopoietic stem cells (HSC) for TCR-αβ/CD19-depleted haploidentical HSCT, and how this agent affects the cellular graft composition. Methods: Ninety healthy donors were evaluated. Single-dose MZ was given to 30 ‘poor mobilizers’ (PM) failing to attain ≥40 CD34+ HSCs/μL after 4 daily G-CSF doses and/or with predicted apheresis yields ≤12.0x106 CD34+ cells/kg recipient’s body weight. Results: MZ significantly increased CD34+ counts in PM. Naïve/memory T and B cells, as well as natural killer (NK) cells, myeloid/plasmacytoid dendritic cells (DCs), were unchanged compared with baseline. MZ did not further promote the G-CSF-induced mobilization of CD16+ monocytes and the down-regulation of IFN-γ production by T cells. HSC grafts harvested after G-CSF + MZ were enriched in myeloid and plasmacytoid DCs, but contained low numbers of pro-inflammatory 6-sulfo-LacNAc+ (Slan)-DCs. Finally, children transplanted with G-CSF + MZ-mobilized grafts received greater numbers of monocytes, myeloid and plasmacytoid DCs, but lower numbers of NK cells, NK-like T cells and Slan-DCs. Conclusions: MZ facilitates the collection of mega-doses of CD34+ HSCs for haploidentical HSCT, while affecting graft composition

Introduction to semantic e-Science in biomedicine

The Semantic Web technologies provide enhanced capabilities that allow data and the meaning of the data to be shared and reused across application, enterprise, and community boundaries, better enabling integrative research and more effective knowledge discovery. This special issue is intended to give an introduction of the state-of-the-art of Semantic Web technologies and describe how such technologies would be used to build the e-Science infrastructure for biomedical communities. Six papers have been selected and included, featuring different approaches and experiences in a variety of biomedical domains

Yes, I Am Ready Now: Differential Effects of Paced versus Unpaced Mating on Anxiety and Central Oxytocin Release in Female Rats

Sexual activity and partner intimacy results in several positive consequences in the context of stress-coping, both in males and females, such as reduced state anxiety in male rats after successful mating. However, in female rats, mating is a rewarding experience only when the estrous female is able to control sexual interactions, i.e., under paced-mating conditions. Here, we demonstrate that sex-steroid priming required for female mating is anxiolytic; subsequent sexual activity under paced mating conditions did not disrupt this anxiolytic priming effect, whereas mating under unpaced conditions increased anxiety-related behavior. In primed females, the release of the neuropeptide oxytocin (OT) within the hypothalamic paraventricular nucleus was found to be elevated and to further increase during paced, but not unpaced mating. Central administration of an OT receptor antagonist partly prevented priming/mating-induced anxiolysis indicating the involvement of brain OT in the anxiolysis triggered by priming and/or sexual activity

Measurement of Trilinear Gauge Couplings in e+e−e^+ e^- Collisions at 161 GeV and 172 GeV

Trilinear gauge boson couplings are measured using data taken by DELPHI at 161~GeV and 172~GeV. Values for $WWV$ couplings ($V=Z, \gamma$) are determined from a study of the reactions \eeWW\ and \eeWev, using differential distributions from the $WW$ final state in which one $W$ decays hadronically and the other leptonically, and total cross-section data from other channels. Limits are also derived on neutral $ZV\gamma$ couplings from an analysis of the reaction \eegi

Akutna primjena nikotina ne poboljšava kognitivne funkcije

Chronic smokers often claim that smoking improves their cognitive abilities, such as concentration. However, scientific evidence to support this claim is scarce. Previous studies gave inconclusive results, and some of them had significant methodological flaws. Therefore, the aim of this study was to test whether smoking a single cigarette affects performance across several cognitive domains. It included a group of 22 occasional smokers aged 19–29 years. Attention, working memory, and visuospatial reasoning were assessed using a within-subjects design with a control setting. There were two separate testing sessions two days apart. Half the group started with experimental and the other half with control setting. In the experimental setting, the participants completed the first block of tasks, smoked one cigarette (with a nicotine yield of 0.5 mg), and then completed the second block of tasks. In the control setting, the procedure was the same, except that the participants had a glass of water instead of a cigarette. Repeated measures ANOVA showed no significant effects of cigarette smoking on either reaction time rates or accuracy on any of the three cognitive domains. These results suggest that, at least among young, occasional smokers, smoking does not affect cognition and the claims of its improvement are probably a result of some sort of cognitive bias.Kronični pušači često tvrde da im pušenje, između ostaloga, pozitivno utječe na kognitivne sposobnosti (npr. pomaže im u održavanju koncentracije). Je li doista tako još uvijek nemamo jednoznačan odgovor, budući da su prethodne studije ne samo dale nekonzistentne rezultate nego su bile i metodološki manjkave. Stoga je cilj ovoga istraživanja bio utvrditi utječe li konzumacija jedne cigarete na izvedbu zadataka u nekoliko različitih kognitivnih domena. U istraživanju je sudjelovala skupina povremenih pušača u dobi od 19 do 29 godina. Pomoću računalnog programa E-Prime prezentirani su zadaci koji mjere pažnju, radno pamćenje i obradu vidno-prostornih informacija. Korišten je prije-poslije nacrt, uz kontrolni i eksperimentalni uvjet. Sudionici su iste zadatke rješavali četiri puta: prije i poslije tretmana u kontrolnom uvjetu te prije i poslije tretmana u eksperimentalnom uvjetu. U kontrolnom uvjetu tretman se sastojao od čaše vode koju su sudionici morali popiti, a u eksperimentalnom uvjetu od pušenja jedne cigarete koja otpušta 0,5 mg nikotina. Stanka između kontrolnoga i eksperimentalnoga testiranja bila je dva dana. Redoslijed uvjeta bio je rotiran. Niti u jednom zadatku nije utvrđen značajan utjecaj pušenja ni na vrijeme reakcije ni na točnost rješavanja. Ovi su nalazi u skladu s hipotezom da su samoiskazi o pozitivnom utjecaju pušenja na kognitivnu učinkovitost posljedica neutemeljenih subjektivnih dojmova