Kognitiver Kapitalismus : Wider eine fragwuerdige Diagnose

Sociologists of work necessarily recognise the intimate connections between transformations of capitalism and trends in the labour process and employment relations. Such connections are a central inheritance from the classical sociology of Durkheim, Marx and Weber. Though the rise of postmodernism, with its emphasis on culture, language and identity has loosened such ties, the inter-relations remain in contemporary social theory from Castells to Beck and back. In this short article the theme is capitalism at work. The argument is that contemporary social theory has generally put forward deeply flawed conceptions of the pathways between capitalist political economy and work/employment relations. The article begins with a brief commentary on some of Ithe general characteristics of social theory concerning the workings of capitalism, before a more detailed exposition and critique of an increasingly influential variant – cognitive capitalism. Drawing on our own and other labour process research, within that critique, we offer some observations towards a more realistic picture of capitalism at work, including the importance of financialization of the economy

Europa en la cartografía medieval

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Serum brain-derived neurotrophic factor (BDNF) is not regulated by testosterone in transmen

Brain morphology significantly differs between the sexes. It has been shown before that some of these differences are attributable to the sex-specific hormonal milieu. Brain-derived neurotrophic factor (BDNF) is involved in myriads of neuroplastic processes and shows a sexual dimorphism. Transsexual persons may serve as a model to study sex steroid-mediated effects on brain plasticity. We have recently demonstrated that serum levels of BDNF are reduced in transwomen following 12 months of cross-sex hormone treatment. We now wanted to look at the effects of testosterone treatment on BDNF in transmen. In contrast to our initial hypothesis, BDNF levels did not significantly change, despite dramatic changes in the sex-hormonal milieu. Our data indicate that testosterone does not seem to play a major role in the regulation of BDNF in females

Mental, behavioral and neurodevelopmental disorders in the ICD-11 : An international perspective on key changes and controversies

The Author(s). 2020Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO's focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.Peer reviewedFinal Published versio

Actually existing capitalism : some digital delusions

Contemporary labour process analysis (LPA) emphasises the intimate connections between transformations of capitalism and trends in work and employment. Within social theory influential images of labour such as Reich’s (1993) symbolic analysts or Castell’s (1996) self-programmable workers, ultimately derive from conception of the broader economy, in this case informational capitalism or the knowledge economy. Their diagnosis is based on the following assumptions. First, the sources of profit, productivity and power in the new economy are said to be (variously) intangible, immaterial or weightless (knowledge, creativity, information, intellectual assets). Digital products are reproducible at low cost for high returns, enabling capitalism to overcome scarcity and ‘the limits of time and space’ (Castells 2001, p. 5). Second, that knowledge-intensive, intellectual or professional work is either in the majority or becoming the majority in advanced post-industrial societies. Third, there has been a decisive shift of power from capital to labour given that ‘(knowledge) ‘remains with the employee and in no real sense is it ever of the firm. It is impossible to separate knowledge from the knower’ (Despres and Hiltrop, 1995, p. 11). Fourth, that traditional, hierarchical structures and practices of management are no longer appropriate, with the best practice being to hire talented people, then leave them alone (Florida 2002, p. 132). Fifth, corporate forms have mutated into decentralised, flat, networked organisations. Extensive critique of these claims have been made elsewhere and we will not repeat them here (Thompson et al 2001; Thompson and Harley 2012). What we do want to do is look in more detail at a related, but newer version that comes under the heading of cognitive capitalism, in part because it will facilitate a more extended engagement with issues of digital industries and labour

Mycobacterium tuberculosis Infection and Innate Responses in a New Model of Lung Alveolar Macrophages.

Lung alveolar macrophages (AMs) are in the first line of immune defense against respiratory pathogens and play key roles in the pathogenesis of Mycobacterium tuberculosis (Mtb) in humans. Nevertheless, AMs are available only in limited amounts for in vitro studies, which hamper the detailed molecular understanding of host-Mtb interactions in these macrophages. The recent establishment of the self-renewing and primary Max Planck Institute (MPI) cells, functionally very close to lung AMs, opens unique opportunities for in vitro studies of host-pathogen interactions in respiratory diseases. Here, we investigated the suitability of MPI cells as a host cell system for Mtb infection. Bacterial, cellular, and innate immune features of MPI cells infected with Mtb were characterized. Live bacteria were readily internalized and efficiently replicated in MPI cells, similarly to primary murine macrophages and other cell lines. MPI cells were also suitable for the determination of anti-tuberculosis (TB) drug activity. The primary innate immune response of MPI cells to live Mtb showed significantly higher and earlier induction of the pro-inflammatory cytokines TNFα, interleukin 6 (IL-6), IL-1α, and IL-1β, as compared to stimulation with heat-killed (HK) bacteria. MPI cells previously showed a lack of induction of the anti-inflammatory cytokine IL-10 to a wide range of stimuli, including HK Mtb. By contrast, we show here that live Mtb is able to induce significant amounts of IL-10 in MPI cells. Autophagy experiments using light chain 3B immunostaining, as well as LysoTracker labeling of acidic vacuoles, demonstrated that MPI cells efficiently control killed Mtb by elimination through phagolysosomes. MPI cells were also able to accumulate lipid droplets in their cytoplasm following exposure to lipoproteins. Collectively, this study establishes the MPI cells as a relevant, versatile host cell model for TB research, allowing a deeper understanding of AMs functions in this pathology

Lipoarabinomannan mannose caps do not affect mycobacterial virulence or the induction of protective immunity in experimental animal models of infection and have minimal impact on in vitro inflammatory responses

Mannose-capped lipoarabinomannan (ManLAM) is considered an important virulence factor of Mycobacterium tuberculosis. However, while mannose caps have been reported to be responsible for various immunosuppressive activities of ManLAMobserved in vitro, there is conflicting evidence about their contribution to mycobacterial virulence in vivo. Therefore, we used Mycobacterium bovis BCG and M.?tuberculosis mutants that lack the mannose cap of LAM to assess the role of ManLAM in the interaction of mycobacteria with the host cells, to evaluate vaccine-induced protection and to determine its importance in M.?tuberculosis virulence. Deletion of the mannose cap did not affect BCG survival and replication in macrophages, although the capless mutant induced a somewhat higher production of TNF. In dendritic cells, the capless mutant was able to induce the upregulation of co-stimulatory molecules and the only difference we detected was the secretion of slightly higher amounts of IL-10 as compared to the wild type strain. In mice, capless BCG survived equally well and induced an immune response similar to the parental strain. Furthermore, the efficacy of vaccination against a M. tuberculosis challenge in low-dose aerosol infection models in mice and guinea pigs was not affected by the absence of the mannose caps in the BCG. Finally, the lack of the mannose cap in M. tuberculosis did not affect its virulence in mice nor its interaction with macrophages in vitro. Thus, these results do not support a major role for the mannose caps of LAM in determining mycobacterial virulence and immunogenicity in vivo in experimental animal models of infection, possibly because of redundancy of function.This work was supported by grant ImmunovacTB, ref. 37388 of the FP6 from the European Union, the NEWTBVAC project, ref. 241745 of the FP7 from the EU and by a grant from the Gulbenkian Foundation and TBVI. AAB, GTR, SSG, CN and SVC were supported by fellowships from Fundacao para a Ciencia e a Tecnologia (FCT) from the Portuguese Government. FM was supported by Wellcome Trust grant 073237. JG is financially supported by the Netherlands Organization for Scientific Research (NWO) through a VENI research grant (016.101.001). AAB is enrolled in the PhD Program in Experimental Biology and Biomedicine (PDBEB), Center for Neuroscience and Cell Biology, University of Coimbra, Portugal. We thank Marion Sparrius, Amsterdam, for technical assistance

Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation

We acknowledge scientific discussions with Drs. Anne O'Garra, Luke Alderwick, and Apoorva Bhatt.Background: Lipoglycans modulate the initiation of immune responses by interacting with TLR2. Results: A hypermannosylated lipomannan variant, once recognized by the immune system, enhance both innate responses and Th17 differentiation. Conclusion: Altered lipoglycan structures are differently recognised by innate immune cells with an impact on the adaptive immune response. Significance: Specific lipoglycan structures may be useful to modulate immune responses. Resume: Toll-like receptors (TLRs) recognize pathogens by interacting with pathogen-associated molecular patterns, such as the phosphatidylinositol-based lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM). Such structures are present in several pathogens, including Mycobacterium tuberculosis, being important for the initiation of immune responses. It is well established that the interaction of LM and LAM with TLR2 is a process dependent on the structure of the ligands. However, the implications of structural variations on TLR2 ligands for the development of T helper (Th) cell responses or in the context of in vivo responses are less studied. Herein, we used Corynebacterium glutamicum as a source of lipoglycan intermediates for host interaction studies. In this study, we have deleted a putative glycosyltransferase, NCgl2096, from C. glutamicum and found that it encodes for a novel α(1→2)arabinofuranosyltransferase, AftE. Biochemical analysis of the lipoglycans obtained in the presence (wild type) or absence of NCgl2096 showed that AftE is involved in the biosynthesis of singular arabinans of LAM. In its absence, the resulting molecule is a hypermannosylated (hLM) form of LAM. Both LAM and hLM were recognized by dendritic cells, mainly via TLR2, and triggered the production of several cytokines. hLM was a stronger stimulus for in vitro cytokine production and, as a result, a more potent inducer of Th17 responses. In vivo data confirmed hLM as a stronger inducer of cytokine responses and suggested the involvement of pattern recognition receptors other than TLR2 as sensors for lipoglycans.Margarida Saraiva Supported by Fundação para a Ciência e Tecnologia (FCT), Portugal, Personal Grant PTDC/SAU-MII/101977/2008; Gurdyal S. Besra Supported by a Personal Research Chair from James Bardrick, a Royal Society Wolfson Research Merit Award, a Lister Institute-Jenner research fellowship, the Medical Research Council, and Wellcome Trust Grant 081569/Z/06/Z. António G. Castro Supported by FCT, Portugal, Project Grant PTDC/SAU-MII/101977/2008. Jeroen Geurtsen Supported by the Netherlands Organization for Scientific Research (NWO) through a VENI research grant (016.101.001)

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy