Toll-like receptor 4 and CD14 polymorphisms in ankylosing spondylitis: Evidence of a weak association in finns

Objective To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS). Methods A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed. Results In the Finnish study the CD74-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses. Conclusion CD14 and TLR4 showed an association with AS in the Finns only.

Prediction of a large-gap quantum-spin-Hall insulator: Diamond-like GaBi bilayer

A quantum-spin-Hall (QSH) state was achieved experimentally, albeit at a low critical temperature because of the narrow band gap of the bulk material. Twodimensional topological insulators are critically important for realizing novel topological applications. Using density functional theory (DFT), we demonstrated that hydrogenated GaBi bilayers (HGaBi) form a stable topological insulator with a large nontrivial band gap of 0.320 eV, based on the state-of-the-art hybrid functional method, which is implementable for achieving QSH states at room temperature. The nontrivial topological property of the HGaBi lattice can also be confirmed from the appearance of gapless edge states in the nanoribbon structure. Our results provide a versatile platform for hosting nontrivial topological states usable for important nanoelectronic device applications.

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI.

"Like a monkey with a miniature cymbal": Cultural practices of repetition in visual social media

Looping media are recurring components of online content, from gifs to Vine videos, in addition to the conceptual repetition of memes and related practices. This paper analyses practices around looping visual media as examples of vernacular creativity, social media literacies, and internet culture, especially for irreverent and playful purposes. Focusing on the LGBTQ digital cultural context as a pilot study, this research examines multi-platform uses of looping media, including personal narratives through Vine videos and animated gifs on Tumblr. In addition to textual analysis of LGBTQ looping visual social media content, the study will further explore the platform context as part of the experience of looped media. The research will address how these factors may also contribute to practices of irreverence and play, both within the specific case of LGBTQ culture and internet culture more generally.

The acceptability, usability and short-term outcomes of Get Real: A web-based program for psychotic-like experiences (PLEs)

Background Psychotic-like experiences (PLEs) are subclinical delusional ideas and perceptual disturbances that have been associated with a range of adverse mental health outcomes. This study reports a qualitative and quantitative analysis of the acceptability, usability and short term outcomes of Get Real, a web program for PLEs in young people. Methods Participants were twelve respondents to an online survey, who reported at least one PLE in the previous 3 months, and were currently distressed. Ratings of the program were collected after participants trialled it for a month. Individual semi-structured interviews then elicited qualitative feedback, which was analyzed using Consensual Qualitative Research (CQR) methodology. PLEs and distress were reassessed at 3 months post-baseline. Results User ratings supported the program's acceptability, usability and perceived utility. Significant reductions in the number, frequency and severity of PLE-related distress were found at 3 months follow-up. The CQR analysis identified four qualitative domains: initial and current understandings of PLEs, responses to the program, and context of its use. Initial understanding involved emotional reactions, avoidance or minimization, limited coping skills and non-psychotic attributions. After using the program, participants saw PLEs as normal and common, had greater self-awareness and understanding of stress, and reported increased capacity to cope and accept experiences. Positive responses to the program focused on its normalization of PLEs, usefulness of its strategies, self-monitoring of mood, and information putting PLEs into perspective. Some respondents wanted more specific and individualized information, thought the program would be more useful for other audiences, or doubted its effectiveness. The program was mostly used in low-stress situations. Conclusions The current study provided initial support for the acceptability, utility and positive short-term outcomes of Get Real. The program now requires efficacy testing in randomized controlled trials.

Subtypes of psychotic-like experiences are differentially associated with suicidal ideation, plans and attempts in young adults

Psychotic-like experiences (PLEs) have been associated with increased risk of suicidality, but it is unclear whether the level of risk varies with different types of PLE. A cross-sectional online survey was completed by 1610 university students. Respondents completed the Community Assessment of Psychic Experiences-15 (CAPE-P15) assessing PLEs on three subscales: Perceptual Abnormalities (PA), Persecutory Ideation (PI) and Bizarre Experiences (BE). Lifetime suicidal ideation, plans and attempts, cannabis, ecstasy and methamphetamine use and family history of mental disorder were also assessed. Multinomal logistic regression was used to examine unique determinants of lifetime suicidality, defined as any history of (i) suicidal ideation or plans and (ii) any attempt, relative to no lifetime history of suicidality. A lifetime history of PA and PI provided significant unique contributions to the prediction of suicide risk, after control for other significant predictors. BE were not associated with any suicide variable demonstrating the variation in risk of suicidality with different types of PLEs. Perceptual abnormalities and persecutory ideation as measured by the CAPE-P15 are the PLEs associated with a higher risk of lifetime suicidality.

Current CAPE-15: A measure of recent psychotic-like experiences and associated distress

Aim Psychotic-like experiences (PLEs) are common in young people and are associated with both distress and adverse outcomes. The Community Assessment of Psychic Experiences-Positive Scale (CAPE-P) provides a 20-item measure of lifetime PLEs. A 15-item revision of this scale was recently published (CAPE-P15). Although the CAPE-P has been used to assess PLEs in the last 12 months, there is no version of the CAPE for assessing more recent PLEs (e.g. 3 months). This study aimed to determine the reliability and validity of the current CAPE-P15 and assess its relationship with current distress. Method A cross-sectional online survey of 489 university students (17–25 years) assessed lifetime and current substance use, current distress, and lifetime and 3-month PLEs on the CAPE-P15. Results Confirmatory factor analysis indicated that the current CAPE-P15 retained the same three-factor structure as the lifetime version consisting of persecutory ideation, bizarre experiences and perceptual abnormalities. The total score of the current version was lower than the lifetime version, but the two were strongly correlated (r = .64). The current version was highly predictive of generalized distress (r = .52) and indices that combined symptom frequency with associated distress did not confer greater predictive power than frequency alone. Conclusion This study provided preliminary data that the current CAPE-P15 provides a valid and reliable measure of current PLEs. The current CAPE-P15 is likely to have substantial practical utility if it is later shown to be sensitive to change, especially in prevention and early intervention for mental disorders in young people.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Mice lacking the serotonin Htr2B receptor gene present an antipsychotic-sensitive schizophrenic-like phenotype

Impulsivity and hyperactivity share common ground with numerous mental disorders, including schizophrenia. Recently, a population-specific serotonin 2B (5-HT2B) receptor stop codon (ie, HTR2B Q20*) was reported to segregate with severely impulsive individuals, whereas 5-HT2B mutant (Htr2B−/−) mice also showed high impulsivity. Interestingly, in the same cohort, early-onset schizophrenia was more prevalent in HTR2B Q*20 carriers. However, the putative role of 5-HT2B receptor in the neurobiology of schizophrenia has never been investigated. We assessed the effects of the genetic and the pharmacological ablation of 5-HT2B receptors in mice subjected to a comprehensive series of behavioral test screenings for schizophrenic-like symptoms and investigated relevant dopaminergic and glutamatergic neurochemical alterations in the cortex and the striatum. Domains related to the positive, negative, and cognitive symptom clusters of schizophrenia were affected in Htr2B−/− mice, as shown by deficits in sensorimotor gating, in selective attention, in social interactions, and in learning and memory processes. In addition, Htr2B−/− mice presented with enhanced locomotor response to the psychostimulants dizocilpine and amphetamine, and with robust alterations in sleep architecture. Moreover, ablation of 5-HT2B receptors induced a region-selective decrease of dopamine and glutamate concentrations in the dorsal striatum. Importantly, selected schizophrenic-like phenotypes and endophenotypes were rescued by chronic haloperidol treatment. We report herein that 5-HT2B receptor deficiency confers a wide spectrum of antipsychotic-sensitive schizophrenic-like behavioral and psychopharmacological phenotypes in mice and provide first evidence for a role of 5-HT2B receptors in the neurobiology of psychotic disorders

New directions: Air pollution challenges for developing megacities like Delhi

Most major cities around the world experience periods of elevated air pollution levels, which exceed international health-based air quality standards (Kumar et al., 2013). Although it is a global problem, some of the highest air pollution levels are found in rapidly expanding cities in India and China. The sources, emissions, transformations and broad effects of meteorology on air pollution are reasonably well accounted in air quality control strategies in many developed cities; however these key factors remain poorly constrained in the growing cities of countries with emerging economies. We focus here on Delhi, one of the largest global population centres, which faces particular air pollution challenges, now and in the future.

Prolonged consumption of sucrose in a binge-like manner, alters the morphology of medium spiny neurons in the nucleus accumbens shell

The modern diet has become highly sweetened, resulting in unprecedented levels of sugar consumption, particularly among adolescents. While chronic long-term sugar intake is known to contribute to the development of metabolic disorders including obesity and type II diabetes, little is known regarding the direct consequences of long-term, binge-like sugar consumption on the brain. Because sugar can cause the release of dopamine in the nucleus accumbens (NAc) similarly to drugs of abuse, we investigated changes in the morphology of neurons in this brain region following short- (4 weeks) and long-term (12 weeks) binge-like sucrose consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox staining to impregnate medium spiny neurons (MSNs) from the NAc core and shell of short- and long-term sucrose consuming rats and compared these to age-matched water controls. We show that prolonged binge-like sucrose consumption significantly decreased the total dendritic length of NAc shell MSNs compared to age-matched control rats. We also found that the restructuring of these neurons resulted primarily from reduced distal dendritic complexity. Conversely, we observed increased spine densities at the distal branch orders of NAc shell MSNs from long-term sucrose consuming rats. Combined, these results highlight the neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN morphology.

Like a burden

'Like A Burden' was an exhibition developed and presented for Metro Arts Galleries in 2015. It drew together several large scale fabric works 'Heavy Thinking'; 'Quick Draw II' and 'Well Hung' within the gallery space, along with a large series of ink and pencil drawings and a lecture performance recorded and projected as a digital video. This body of work foregrounds the activist feminist voice through quotation, citation and reiteration and is part of a broader practice strategy to re-perform a subjective feminist archive.

Promotion of a cancer-like phenotype, through chronic exposure to inflammatory cytokines and hypoxia in a bronchial epithelial cell line model

Globally, lung cancer accounts for approximately 20% of all cancer related deaths. Five-year survival is poor and rates have remained unchanged for the past four decades. There is an urgent need to identify markers of lung carcinogenesis and new targets for therapy. Given the recent successes of immune modulators in cancer therapy and the improved understanding of immune evasion by tumours, we sought to determine the carcinogenic impact of chronic TNF-α and IL-1β exposure in a normal bronchial epithelial cell line model. Following three months of culture in a chronic inflammatory environment under conditions of normoxia and hypoxia (0.5% oxygen), normal cells developed a number of key genotypic and phenotypic alterations. Important cellular features such as the proliferative, adhesive and invasive capacity of the normal cells were significantly amplified. In addition, gene expression profiles were altered in pathways associated with apoptosis, angiogenesis and invasion. The data generated in this study provides support that TNF-α, IL-1β and hypoxia promotes a neoplastic phenotype in normal bronchial epithelial cells. In turn these mediators may be of benefit for biomarker and/or immune-therapy target studies. This project provides an important inflammatory in vitro model for further immuno-oncology studies in the lung cancer setting.

Fighting like a girl … or a boy? An analysis of videos of violence between young girls posted on online fight websites

How young women engage in physical violence with other young women is an issue that raises specific concerns in both criminological literature and theories. Current theoretical explanations construct young women’s violence in one of two ways: young women are not physically violent at all, and adhere to an accepted performance of hegemonic femininity; or young women reject accepted performances of hegemonic femininity in favour of a masculine gendered performance to engage in violence successfully. This article draws on qualitative and quantitative data obtained from a structured observation and thematic analysis of 60 online videos featuring young women’s violent altercations. It argues that, contrary to this dichotomous construction, there appears to be a third way young women are performing violence, underpinned by masculine characteristics of aggression but upholding a hegemonic feminine gender performance. In making this argument, this article demonstrates that a more complex exploration and conceptualisation of young women’s violence, away from gendered constructs, is required for greater understanding of the issue.