Commentary: Nicotinic acetylcholine receptor α9 and α10 subunits are expressed in the brain of mice

Fil: Morley, Barbara J.. Boys Town National Research Hospita; Estados UnidosFil: Whiteaker, Paul. Barrow Neurological Institute; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Distinctive Roles For α7*- And α9*-Nicotinic Acetylcholine Receptors In Inflammatory And Autoimmune Responses In The Murine Experimental Autoimmune Encephalomyelitis Model Of Multiple Sclerosis

Previous studies have demonstrated immunosuppressive and anti-inflammatory effects of nicotine, including in the experimental autoimmune encephalomyelitis (EAE) model in mice of some forms of multiple sclerosis (MS). Other studies using knock-out (KO) mice have implicated nicotinic acetylcholine (ACh) receptors containing α7, α9, or β2 subunits (α7*-, α9*- or β2*-nAChR) in different, disease exacerbating or disease-ameliorating processes. These outcomes are in harmony with gene expression analyses showing nAChR subunit mRNA in many classes of immune system cell types. Consistent with influences on disease status, predictable effects of nAChR subunit (and subtype) KO, or of nicotine exposure, are seen on immune cell numbers and distribution and on cytokine levels or other markers of immunity, inflammation, demyelination, and axonal degradation. Providing support for our hypotheses about distinctive roles for nAChR subtypes in EAE, here we have used direct and adoptive EAE induction and a nAChR subunit gene double knock-out (DKO) strategy. Immune cell expression of nAChR α9 subunits as protein is demonstrated by immunostaining of isolated CD4+, CD8+, CD11b+ and CD11c+ cells from wild-type (WT) mice, but not in cells from nAChR α9 subunit KO animals. Nicotine exposure is protective against directly-induced EAE in WT or α7/α9 DKO animals relative to effects seen in WT/vehicle-treated mice, but, remarkably, EAE is exacerbated in vehicle-treated α7/α9 DKO mice. Brain lesion volume and intracranial inflammatory activity similarly are higher in DKO/vehicle than in WT/vehicletreated animals, although nicotine’s protective effects are seen in each instance. By contrast, in adoptive transfer studies, disease severity is attenuated and disease onset is delayed in recipients of splenocytes from WT animals treated with nicotine rather than with vehicle. Moreover, protection as seen in nicotine-treated WT animals is the same in recipients of splenocytes from nAChR α7/α9 DKO mice irrespective of their exposure to nicotine or vehicle. When combined with previous observations, these findings are consistent with disease exacerbation (or even induction) being mediated at least in part via α9*-nAChR in peripheral immune cells. They also suggest protective roles of central nervous system (CNS) α7*-nAChR. The results suggest that both α7*- and α9*-nAChR are potential targets of therapeutic ligands to modulate inflammation and autoimmunity

Dallas with balls: televized sport, soap opera and male and female pleasures

Two of the most popular of television genres, soap opera and sports coverage have been very much differentiated along gender lines in terms of their audiences. Soap opera has been regarded very much as a 'gynocentric' genre with a large female viewing audience while the audiences for television sport have been predominantly male. Gender differentiation between the genres has had implications for the popular image of each. Soap opera has been perceived as inferior; as mere fantasy and escapism for women while television sports has been perceived as a legitimate, even edifying experience for men. In this article the authors challenge the view that soap opera and television sport are radically different and argue that they are, in fact, very similar in a number of significant ways. They suggest that both genres invoke similar structures of feeling and sensibility in their respective audiences and that television sport is a 'male soap opera'. They consider the ways in which the viewing context of each genre is related to domestic life and leisure, the ways in which the textual structure and conventions of each genre invoke emotional identification, and finally, the ways in which both genres re-affirm gender identities

Gender in the neoliberalised global academy: the affective economy of women and leadership in South Asia

As higher education (HE) institutions globally become increasingly performative, competitive and corporatised in response to neoliberal rationalities, the exigencies of HE leadership are being realigned to accommodate its value system. This article draws on recent British Council-funded research, including 30 semi-structured interviews, to explore women’s engagement with leadership in HE in South Asia. A potent affective economy was discovered. Leadership was associated with affects such as competitiveness, aggression, impropriety, stress and anxiety, in ways that were intensified by highly patriarchal and corporatised HE cultures. Indeed, its difficulties and toxicities meant that leadership was rejected or resisted as an object of desire by many women. We illuminate how different forms of competition contribute to the affective economy of HE leadership. The research also raises wider questions about the possibilities of disrupting dominant neoliberal constructions of HE if those who question such values are excluded (or self-exclude) from leadership positions

Testing the credibility, feasibility and acceptability of an optimised behavioural intervention (OBI) for avoidant chronic low back pain patients: protocol for a randomised feasibility study

Background: Chronic back pain continues to be a costly and prevalent condition. The latest NICE guidelines issued in 2009 state that for patients with persistent back pain (of between six weeks and twelve months duration), who are highly distressed and/or disabled and for whom exercise, manual therapy and acupuncture has not been beneficial, the evidence supports a combination of around 100 hours of combined physical and psychological treatment. This is costly, and may prove unacceptable to many patients. A key recommendation of these guidelines was for further randomised controlled trials (RCTs) of psychological treatment and to target treatment to specific sub-groups of patients. Recent trials that have included psychological interventions have shown only moderate improvement at best, and results are not maintained long term. There is therefore a need to test theoretically driven interventions that focus on specific high-risk sub-groups, in which the intervention is delivered at full integrity against a credible control. Methods/design: A feasibility study of a pragmatic randomised controlled trial comparing psychologist-delivered Contextual Cognitive Behavioural Therapy (CCBT) against Treatment As Usual (TAU) physiotherapy delivered by physiotherapists for the treatment of chronic lower back pain in ‘avoidant’ patients. Ninety-two patients referred for physiotherapy will be recruited and randomised on a 1:1 basis to receive CCBT or TAU. Treatment groups will be balanced by centre and pain interference score. Primary outcomes include assessing the credibility and acceptability of the intervention, and to demonstrate proof of principle through a greater change in pain acceptance in the CCBT arm, measured by the Acceptance and Action –II and the Chronic Pain Acceptance questionnaires. In addition, the feasibility of carrying out a full trial will be explored with reference to recruitment and follow-up rates including the assessment of the burden of outcome measure completion. Secondary patient outcomes include disability, pain, fear of movement, mood, quality of life, and global recovery. Outcomes are measured at three and six months post-randomisation. Discussion: This paper details the rationale, design, therapist training system and recruitment methods to be used in a feasibility study which will inform the design and efficient implementation of a future definitive RCT

Genders at Work: Gender as a Geography of Power in the Academy

This chapter discusses contemporary research investigating how gender operates as a geography of power in the contemporary academy, particularly in relation to notions of ‘career’. Massey’s understanding of space as ‘a simultaneity of stories-so-far and places as collections of those stories’ (2005, p.11) shapes the research questions and a methodology of ‘spatial storytelling’ which foregrounds relationships between space and power in considering lived experiences of work and career. The chapter presents a selection of participants’ ‘stories-so-far’ which illustrate the complexity and dimensionality of lived, gendered experiences in the workplace and provide a basis for reflection on the opportunities these afford to resist sexism in the academy

Women's leadership in the Asian Century: does expansion mean inclusion?

This paper draws on British Council commissioned research in response to concerns about women's absence from senior leadership positions in higher education in South Asia. The study sought existing knowledge from literature, policies, and available statistics and collected original interview data from 30 academics in Afghanistan, Bangladesh, India, Nepal, Pakistan, and Sri Lanka. A central finding was that gender is not a category of analysis in higher education policy, research or statistical data in the region. Our interview data suggest that leadership was frequently not an object of desire for women. Being associated with particular types of masculinities, leadership often carried a heavy affective load for those women who transgressed patriarchal socio-cultural norms and disrupted the symbolic order of women being led by men. Leadership was frequently perceived and experienced by women in terms of navigating a range of ugly feelings and toxicities that depleted aspirations, well-being and opportunities

Ammonia-oxidizing archaea possess a wide range of cellular ammonia affinities

Nitrification, the oxidation of ammonia to nitrate, is an essential process in the biogeochemical nitrogen cycle. The first step of nitrification, ammonia oxidation, is performed by three, often co-occurring guilds of chemolithoautotrophs: ammonia-oxidizing bacteria (AOB), archaea (AOA), and complete ammonia oxidizers (comammox). Substrate kinetics are considered to be a major niche-differentiating factor between these guilds, but few AOA strains have been kinetically characterized. Here, the ammonia oxidation kinetic properties of 12 AOA representing all major cultivated phylogenetic lineages were determined using microrespirometry. Members of the genus Nitrosocosmicus have the lowest affinity for both ammonia and total ammonium of any characterized AOA, and these values are similar to previously determined ammonia and total ammonium affinities of AOB. This contrasts previous assumptions that all AOA possess much higher substrate affinities than their comammox or AOB counterparts. The substrate affinity of ammonia oxidizers correlated with their cell surface area to volume ratios. In addition, kinetic measurements across a range of pH values supports the hypothesis that—like for AOB—ammonia and not ammonium is the substrate for the ammonia monooxygenase enzyme of AOA and comammox. Together, these data will facilitate predictions and interpretation of ammonia oxidizer community structures and provide a robust basis for establishing testable hypotheses on competition between AOB, AOA, and comammox

Modifier Effects between Regulatory and Protein-Coding Variation

Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants