104 research outputs found

    Genome-wide analysis of intracellular pH reveals quantitative control of cell division rate by pHc in Saccharomyces cerevisiae.

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    BACKGROUND: Because protonation affects the properties of almost all molecules in cells, cytosolic pH (pH(c)) is usually assumed to be constant. In the model organism yeast, however, pH(c )changes in response to the presence of nutrients and varies during growth. Since small changes in pH(c )can lead to major changes in metabolism, signal transduction, and phenotype, we decided to analyze pH(c )control. RESULTS: Introducing a pH-sensitive reporter protein into the yeast deletion collection allowed quantitative genome-wide analysis of pH(c )in live, growing yeast cultures. pH(c )is robust towards gene deletion; no single gene mutation led to a pH(c )of more than 0.3 units lower than that of wild type. Correct pH(c )control required not only vacuolar proton pumps, but also strongly relied on mitochondrial function. Additionally, we identified a striking relationship between pH(c )and growth rate. Careful dissection of cause and consequence revealed that pH(c )quantitatively controls growth rate. Detailed analysis of the genetic basis of this control revealed that the adequate signaling of pH(c )depended on inositol polyphosphates, a set of relatively unknown signaling molecules with exquisitely pH sensitive properties. CONCLUSIONS: While pH(c )is a very dynamic parameter in the normal life of yeast, genetically it is a tightly controlled cellular parameter. The coupling of pH(c )to growth rate is even more robust to genetic alteration. Changes in pH(c )control cell division rate in yeast, possibly as a signal. Such a signaling role of pH(c )is probable, and may be central in development and tumorigenesis

    Trauma and Outcomes of Mentalization-Based Therapy for Individuals With Borderline Personality Disorder

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    Objective:Recent meta-analyses suggest that many patients with borderline personality disorder have a history of complex trauma. Although trauma is central in mentalization-based approaches to the understanding of borderline personality disorder, surprisingly little is known about the effects of trauma on outcomes of mentalization-based treatment (MBT). This article investigates the prevalence and impact of childhood trauma among patients with borderline personality disorder participating in a randomized controlled trial (RCT) comparing day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP).Methods:All 114 patients from the original multicenter RCT in the Netherlands were included in this study. Childhood trauma was assessed at baseline (with the Childhood Trauma Questionnaire), and its impact on symptom severity, interpersonal functioning, and borderline pathology was investigated through multilevel modeling for 36 months after the start of treatment.Results:Childhood trauma was common among patients with borderline personality disorder referred to MBT, with more than 85% meeting cutoff criteria for substantial childhood trauma. Childhood trauma had little impact on outcomes of either MBT-DH or MBT-IOP in terms of improved borderline personality disorder features or interpersonal functioning. However, patients with substantial childhood trauma seemed to improve more rapidly with MBT-DH, as compared with MBT-IOP, in terms of symptom severity. In addition, patients with a history of emotional neglect showed more rapid changes in symptoms of borderline personality disorder with MBT-DH compared with MBT-IOP.Conclusions:Findings are discussed in the context of a social communicative approach to borderline personality disorder, with a focus on the need to address trauma in MBT

    Etherscapes: Massless, Elastic, Technology and Control

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    This thesis is an exploration into the ether of the digital aesthetic. It attempts to capture a segment of the continually morphing space then deconstruct and analyse it through electronic and new media art. Herein you will find a questioning of technology and control within electronic and new media art as an investigation into better understanding the current media image and visual culture that so powerfully influences the modern social construct. By nature this argument has existed for some years but only now with advancements in technology and more affordable realisation of ideas by media artists, the topic of the digital aesethetic, technology and control has become relevant for popular debate. As war lingers in our minds, terrorism hits headlines, and experiements in cloning human DNA take place, the technology that society demands can only necessarily be seen as a major contributing factor to today's strange times. However, strange or not, the questions I wish to discuss; Does technology determine contemporary society or do we determine technology? Where does the control exist

    Day hospital versus intensive outpatient mentalization-based treatment: 3-year follow-up of patients treated for borderline personality disorder in a multicentre randomized clinical trial

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    BackgroundTwo types of mentalization-based treatment (MBT), day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP), have been shown to be effective in treating patients with borderline personality disorder (BPD). This study evaluated trajectories of change in a multi-site trial of MBT-DH and MBT-IOP at 36 months after the start of treatment.MethodsAll 114 patients (MBT-DH n = 70, MBT-IOP n = 44) from the original multicentre trial were assessed at 24, 30 and 36 months after the start of treatment. The primary outcome was symptom severity measured with the Brief Symptom Inventory. Secondary outcome measures included borderline symptomatology, personality and interpersonal functioning, quality of life and self-harm. Data were analysed using multilevel modelling and the intention-to-treat principle.ResultsPatients in both MBT-DH and MBT-IOP maintained the substantial improvements made during the intensive treatment phase and showed further gains during follow-up. Across both conditions, 83% of patients improved in terms of symptom severity, and 97% improved on borderline symptomatology. No significant differences were found between MBT-DH and MBT-IOP at 36 months after the start of treatment. However, trajectories of change were different. Whereas patients in MBT-DH showed greater improvement during the intensive treatment phase, patients in MBT-IOP showed greater continuing improvement during follow-up.ConclusionsPatients in both conditions showed sim

    The Self Model and the Conception of Biological Identity in Immunology

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    The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity
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