A splicing factor that is inactivated during in vivo heat shock is functionally equivalent to the [U4/U6.U5] triple snRNP-specific proteins.

One of the consequences of the heat shock response in a shutdown of pre-mRNA splicing, a phenomenon that can be reproduced in extracts prepared from heat-shocked cells. The block in splicing occurs before the covalent modifications that generate spliced mRNA at the level of spliceosome formation. We have used extracts prepared from heat-shocked cells as a complementation system to characterize and partially purify a protein factor that is inactivated during the in vivo heat shock. The activity functions in the formation of the active spliceosome by assembling U4/U6 and U5 snRNPs into a triple snRNP particle.One of the consequences of the heat shock response in a shutdown of pre-mRNA splicing, a phenomenon that can be reproduced in extracts prepared from heat-shocked cells. The block in splicing occurs before the covalent modifications that generate spliced mRNA at the level of spliceosome formation. We have used extracts prepared from heat-shocked cells as a complementation system to characterize and partially purify a protein factor that is inactivated during the in vivo heat shock. The activity functions in the formation of the active spliceosome by assembling U4/U6 and U5 snRNPs into a triple snRNP particle

Culture and Hallucinations: Overview and Future Directions

A number of studies have explored hallucinations as complex experiences involving interactions between psychological, biological, and environmental factors and mechanisms. Nevertheless, relatively little attention has focused on the role of culture in shaping hallucinations. This article reviews the published research, drawing on the expertise of both anthropologists and psychologists. We argue that the extant body of work suggests that culture does indeed have a significant impact on the experience, understanding, and labeling of hallucinations and that there may be important theoretical and clinical consequences of that observation. We find that culture can affect what is identified as a hallucination, that there are different patterns of hallucination among the clinical and nonclinical populations, that hallucinations are often culturally meaningful, that hallucinations occur at different rates in different settings; that culture affects the meaning and characteristics of hallucinations associated with psychosis, and that the cultural variations of psychotic hallucinations may have implications for the clinical outcome of those who struggle with psychosis. We conclude that a clinician should never assume that the mere report of what seems to be a hallucination is necessarily a symptom of pathology and that the patient’s cultural background needs to be taken into account when assessing and treating hallucinations

Expanding boundaries in psychiatry: uncertainty in the context of diagnosis-seeking and negotiation

Psychiatric diagnosis has become pervasive in modern culture, exerting an increasing influence on notions of personhood, identity practices and forms of self‐governing. The broadening of diagnostic categories and increasing awareness regarding popular diagnostic categories has led to an increased demand for formal diagnosis within clinical encounters. However, there is continuing ‘epistemological uncertainty’ (Fox 2000) surrounding these entities, in part due to their lack of associated clinical biomarkers and their ‘fuzzy boundaries’. Meanwhile, this diagnostic expansion has encountered resistance from those concerned with the alleged ‘over‐pathologisation’ of emotional distress. Drawing upon the concepts of ‘diagnostic cultures’ (Brinkmann 2016) and the ‘looping effects of human kinds’ (Hacking 1995), this article considers some of the competing forces acting upon the contested boundaries of diagnostic categories as they play out within diagnostic interactions. The study involved ethnographic observations of diagnostic encounters within several UK‐based mental health clinics. By focusing on interactions where diagnosis is negotiated, findings illustrate the role played by different kinds of diagnostic uncertainty in shaping these negotiations. It is argued that diagnostic reification plays a key role in the moral categorisation of patients, particularly where there is uncertainty regarding individual diagnostic status

Sensing the presence of gods and spirits across cultures and faiths.

Hearing the voice of God, feeling the presence of the dead, being possessed by a demonic spirit-such events are among the most remarkable human sensory experiences. They change lives and in turn shape history. Why do some people report experiencing such events while others do not? We argue that experiences of spiritual presence are facilitated by cultural models that represent the mind as "porous," or permeable to the world, and by an immersive orientation toward inner life that allows a person to become "absorbed" in experiences. In four studies with over 2,000 participants from many religious traditions in the United States, Ghana, Thailand, China, and Vanuatu, porosity and absorption played distinct roles in determining which people, in which cultural settings, were most likely to report vivid sensory experiences of what they took to be gods and spirits.Templeton Foundatio

Anthropology, Brokerage and Collaboration in the development of a Tongan Public Psychiatry: Local Lessons for Global Mental Health

The Global Mental Health (GMH) movement has revitalised questions of the translatability of psychiatric concepts and the challenges of community engagement in countries where knowledge of the biomedical basis for psychiatric diagnosis is limited or challenged by local cultural codes. In Tonga, the local psychiatrist Dr Puloka has successfully established a publicly accessible psychiatry that has raised admission rates for serious mental illness and addressed some of the stigma attached to diagnosis. On the basis of historical analysis and ethnographic fieldwork with healers, doctors and patients since 1998, this article offers an ethnographic contextualization of the development and reception of three key interventions during the 1990s inspired by traditional healing and reliant on the translation of psychiatric terms and diagnosis. Dr Puloka’s use of medical anthropological and transcultural psychiatry research informed a community engaged brokerage between the implications of psychiatric nosologies and local needs. As such it reveals deficiencies in current polarised positions on the GMH project and offers suggestions to address current challenges of the Global Mental Health movement

Access, accountability, and the proliferation of psychological therapy:On the introduction of the IAPT initiative and the transformation of mental healthcare

Psychological therapy today plays a key role in UK public mental health. In large part, this has been through the development of the (specifically English) Improving Access to Psychological Therapies (IAPT) programme. Through IAPT, millions of citizens have encountered interventions such as cognitive behaviour therapy, largely for the treatment of depression and anxiety. This article interrogates how this national response to problems of mental ill-health – and the problematization itself – was developed, accounted for, and sustained. By imbricating economic expertise with accounts of mental ill-health and mechanisms of treatment, IAPT has revivified psychological framings of pathology and therapy. However, it has done so in ways that are more familiar within biomedical contexts (e.g. through recourse to randomized controlled trial studies). Today, the initiative is a principal player in relation to which other services are increasingly developed. Indeed, in many respects IAPT has transformed from content to context within UK public mental health (in a process of what I term ‘contextification’). By documenting these developments, this paper contributes to re-centring questions about the place and role of psychology in contemporary healthcare. Doing so helps to complicate assumptions about the dominance of linear forms of (de)biomedicalization in health-systems

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Meaning in hoarding: perspectives of people who hoard on clutter, culture, and agency

Hoarding has become increasingly prominent in clinical practice and popular culture in recent years, giving rise to extensive research and commentary. Critical responses in the social sciences have criticised the cultural assumptions built in to the construct of ‘hoarding disorder’ and expressed fears that it may generate stigma outweighing its benefits; however, few of these studies have engaged directly with ‘hoarders’ themselves. This paper reports on in-depth, semi-structured interviews with ten individuals living in England, who received assessment and intervention for hoarding from Social Services. Their narratives drew on the cultural repertoire of values and discourses around waste and worth, the mediation of sociality and relationships through material objects, physical constraints on keeping order, and the role played by mental health. Analysing these perspectives anthropologically shows how dominant models of hoarding, such as the DSM-5 paradigm, potentially lend themselves to reductionist understandings that efface the meaning ‘hoarding’ may have and thereby deny agency to the person labelled as ‘hoarder’. More culturally informed analysis, by contrast, affords insights into the complex landscape of value, waste, social critique, emotion, interpersonal relationships and practical difficulties that may underlie hoarding cases, and points the way to more person-centred practice and analysis

Genetic identification of unique immunological responses in mice infected with virulent and attenuated Francisella tularensis

Francisella tularensis is a category A select agent based on its infectivity and virulence but disease mechanisms in infection remain poorly understood. Murine pulmonary models of infection were therefore employed to assess and compare dissemination and pathology and to elucidate the host immune response to infection with the highly virulent Type A F. tularensis strain Schu4 versus the less virulent Type B live vaccine strain (LVS). We found that dissemination and pathology in the spleen was significantly greater in mice infected with F. tularensis Schu4 compared to mice infected with F. tularensis LVS. Using gene expression rofiling to compare the response to infection with the two F. tularensis strains, we found that there were significant differences in the expression of genes involved in the apoptosis pathway, antigen processing and presentation pathways, and inflammatory response pathways in mice infected with Schu4 when compared to LVS. These transcriptional differences coincided with marked differences in dissemination and severity of organ lesions in mice infected with the Schu4 and LVS strains. Therefore, these findings indicate that altered apoptosis, antigen presentation and production of inflammatory mediators explain the differences in pathogenicity of F. tularensis Schu4 and LVS