Foucault and the Madness of Classifying Our Madness

This paper notes the re-ignited controversy surrounding the publication of a new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), suggesting that the early work of Michel Foucault can explain why the mere diagnosis of or criteria for mental illness remains a heated flashpoint. In particular, it argues that Foucault articulates a common issue within the philosophical foundations of psychiatry and psychology that the paper terms the ‘subjectivity problem.’ It observes, using Foucault’s work, that these disciplines treat not just simple objects but complex subjects that are capable of interacting with that labelling and who are shaped by it. Drawing on the related work of Ian Hacking on kind-making as world-making, the article fleshes out why the subjectivity problem remains persistent within psychiatry and psychology as forms of knowledge, preventing them from operating as many commentators might desire them to – as pure and objective sciences. Finally, the paper reflects on the relationship of psychiatry and psychology as forms of knowledge, the manner in which they constitute their objects, and how this might shape the biopolitical episteme in which we find ourselves today

Material Loops - Wege in eine kreislauffähige Zukunft

Material Loops – Wege in eine kreislauffähige Zukunft — Bei der not-wendigen Transformation in eine zukunftsfähige Wirtschaftsform wie eine Circular Society spielt die gesamte Bandbreite der Designdisziplin eine entscheidende Rolle. Während das klassische Produktdesign an Relevanz verliert, beginnen Perspektiven eines nachhaltigen Designs eine führende Rolle auf individueller, kollektiver, urbaner und globaler Ebene zu übernehmen. Wie können Objekte so gestaltet werden, dass sie am Ende ihres Lebens einen positiven Effekt auf die Umwelt haben? Wie können endliche Ressourcen in einen Materialkreislauf zurückgeführt werden? Wie sehen die Materialkreisläufe und -verwertungssysteme der Zukunft aus

Bid chimeras indicate that most BH3-only proteins can directly activate Bak and Bax, and show no preference for Bak versus Bax

The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members of the Bcl-2 protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak and Bax to induce conformation change, oligomerization and pore formation in mitochondria. BH3-only proteins, with the exception of Bid, are intrinsically disordered and therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess the hydrophobic membrane targeting domains found on the native BH3-only molecule. To generate each BH3-only protein as a recombinant protein that could efficiently target mitochondria, we developed recombinant Bid chimeras in which the BH3 domain was replaced with that of other BH3-only proteins (Bim, Puma, Noxa, Bad, Bmf, Bik and Hrk). The chimeras were stable following purification, and each immunoprecipitated with full-length Bcl-xL according to the specificity reported for the related BH3 peptide. When tested for activation of Bak and Bax in mitochondrial permeabilization assays, Bid chimeras were ~1000-fold more effective than the related BH3 peptides. BH3 sequences from Bid and Bim were the strongest activators, followed by Puma, Hrk, Bmf and Bik, while Bad and Noxa were not activators. Notably, chimeras and peptides showed no apparent preference for activating Bak or Bax. In addition, within the BH3 domain, the h0 position recently found to be important for Bax activation, was important also for Bak activation. Together, our data with full-length proteins indicate that most BH3-only proteins can directly activate both Bak and Bax

Identification of protein stability determinants in chloroplasts

Although chloroplast protein stability has long been recognised as a major level of post-translational regulation in photosynthesis and gene expression, the factors determining protein stability in plastids are largely unknown. Here, we have identified stability determinants in vivo by producing plants with transgenic chloroplasts that express a reporter protein whose N- and C-termini were systematically modified. We found that major stability determinants are located in the N-terminus. Moreover, testing of all 20 amino acids in the position after the initiator methionine revealed strong differences in protein stability and indicated an important role of the penultimate N-terminal amino acid residue in determining the protein half life. We propose that the stability of plastid proteins is largely determined by three factors: (i) the action of methionine aminopeptidase (the enzyme that removes the initiator methionine and exposes the penultimate N-terminal amino acid residue), (ii) an N-end rule-like protein degradation pathway, and (iii) additional sequence determinants in the N-terminal region

Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP

Over a decade ago Polymerase δ interacting protein of 38 kDa (PDIP38) was proposed to play a role in DNA repair. Since this time, both the physiological function and subcellular location of PDIP38 has remained ambiguous and our present understanding of PDIP38 function has been hampered by a lack of detailed biochemical and structural studies. Here we show, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX. Our structural analysis revealed that PDIP38 is composed of two conserved domains separated by an α/β linker region. The N-terminal (YccV-like) domain of PDIP38 forms an SH3-like β-barrel, which interacts specifically with CLPX, via the adaptor docking loop within the N-terminal Zinc binding domain of CLPX. In contrast, the C-terminal (DUF525) domain forms an immunoglobin-like β-sandwich fold, which contains a highly conserved putative substrate binding pocket. Importantly, PDIP38 modulates the substrate specificity of CLPX and protects CLPX from LONM-mediated degradation, which stabilises the cellular levels of CLPX. Collectively, our findings shed new light on the mechanism and function of mitochondrial PDIP38, demonstrating that PDIP38 is a bona fide adaptor protein for the mitochondrial protease, CLPXP

First Community-Wide, Comparative Cross-Linking Mass Spectrometry Study

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats. Such consensus formats should become accepted in the field and be shown to lead to reproducible results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. Our study therefore builds the framework for establishing best practice guidelines to conduct cross-linking experiments, perform data analysis, and define reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results

Effects of glucagon-like peptide 1 (7-36 amide) on glucose kinetics during somatostatin-induced suppression of insulin secretion in healthy men

Glucagon-like peptide 1 (GLP-1) is known to stimulate insulin secretion and biosynthesis, but has also been shown to decrease insulin requirements in type 1 diabetic subjects suggesting insulin-independent effects. To assess whether GLP-1 exerts also direct effects on whole-body glucose metabolism, 6,6-D2-glucose kinetics were measured in 8 healthy volunteers receiving once GLP-1, once saline during hyperglycemic glucose clamping, while somatostatin with replacement amounts of insulin, glucagon and growth hormone was infused. Even though endogenous insulin secretion could not be blocked completely (increased plasma concentrations of C-peptide and proinsulin), somatostatin infusion resulted in stable insulin and glucagon plasma levels in both protocols (GLP-1 vs. placebo: NS). After 3 h of GLP-1 infusion, peripheral glucose disappearance significantly increased compared to placebo (p textless 0.03) despite of somatostatin-induced suppression of insulin and glucagon secretion. Thus, GLP-1 infusion seems to have direct stimulatory effects on peripheral glucose metabolism in man

Lektionen der Vergangenheit - Das Arts and Crafts Movement x Nachhaltigkeit

Eine Rebellion gegen das ‚machine age‘ – als solche verstand sich das Arts and Crafts Movement, das sich in der zweiten Hälfte des 19. Jahrhunderts in England herausbildete. Was können wir heute, in Zeiten der Klimakrise, Ressourcenknappheit und einem ökologisch sowie sozial nicht-nachhaltigen Wirtschaftssystem vom Arts and Crafts Movement lernen? In diesem Vortrag werden die Transformationserfahrungen der viktorianischen Reformer:innen unter dem Aspekt ihrer Zukunftsfähigkeit betrachtet und versucht, die Ansätze des Arts and Crafts Movement mit dem gegenwärtigen Diskurs um nachhaltiges Design in Beziehung zu setzen

Michel Foucault and the critique of psychiatry

This thesis argues that a metaphysical unease pervades the project of psychiatry, and that a philosophically fruitful way of examining this unease is through the work of Michel Foucault. My claim is that in highlighting the critique of certain philosophies of the human sciences that Foucault maintains throughout his work, we can come to a comprehensive understanding of the open philosophical questions that rest at the heart of any contemporary psychiatric project. In the first part of this thesis, I argue that there are three essential epistemic problems, implicitly highlighted by Foucault, that form the grounds on which a psychiatric knowledge is built. These are the "subjectivity problem," the "separation problem," and the "conceptual problem." In the second part of this thesis, I argue that these epistemological problems have ontological, political, and ethical consequences. Ontological problems for psychiatry arise when I interrogate the techniques and technologies that give psychiatry an empirical foundation, as well as the manner in which they target life through creating bodies and modes of being. Political problems arise for psychiatry when individuals question the nature of their diagnosis, and the manner in which it identifies them. Ethical problems arise from the manner in which psychiatric diagnoses function within our political and juridical systems and is one of central concern to psychiatry and its patients, yet a dimension that is elided in many conceptualisations of the role and function of psychiatry. This thesis reaches three key conclusions. Firstly, that psychiatry is a discourse and discipline that is wider than the parts of it that function as a science, and that trying to conceptualise the nature of the whole through the scientific idealisation of its parts is unhelpful. Secondly, that psychiatric knowledge cannot be separated from its practice, or the other roles and functions that psychiatry performs within our society. Thirdly, that psychiatry can have no fixed nature or utopian state, and that there are essential compromises involved in the way in which we choose to conceptualise it as a form of knowledge and as a social practice. Fixing the nature of psychiatry as scientific or otherwise threatens to place the fundamental philosophical questions of epistemology, ontology, politics, or ethics beyond further argument or consideration and close off broader discussion. My contention is that the work of Foucault assists us in clearing a space for new images of psychiatry and, more importantly, its broader discussion within our communities