Between “Local Knowledge” and “Global Reach”:: Diarrhoeal Diseases Control and the International Health Agenda

Der Aufsatz geht der Produktion medizinischen Wissens im Kontext globaler Programme zur Krankheitsbekämpfung zwischen den 1960er und 1990er Jahren nach. Am Beispiel der Eindämmung von Durchfallerkrankungen, eine der Hauptursachen für Kindersterblichkeit in ärmeren Ländern, wird der enge Zusammenhang von institutionellen, ideologischen und technologischen Faktoren behandelt. Die detaillierte Rekonstruktion der Schaffung von Wissen und politischen Direktiven im Umfeld der zentralen Initiativen der weltweiten Diarrhoeal Diseases Control-Programme hilft die divergierenden Positionen zu Gesundheit, wissenschaftlichen Agenden und Politik in der Weltgesundheitsorganisation, aber auch von Forschungsinstituten in Südasien sowie US-amerikanischen Entwicklungsagenturen zu erkennen. Das zentrale Argument des Nahblicks auf diese Konstellation lautet, dass biomedizinischer ‚Fortschritt’ zwar von entscheidender Bedeutung für den Beginn weltweiter Gesundheitsprogramme war, jedoch eine äußerst geringe Rolle in der konkreten Zielsetzung und Entfaltung spielte. Verfolgt man gleichermaßen die Forschungspraxis wie die ideologische Rahmung der Gesundheitspolitik, entsteht ein komplexes Bild des Agenda-Setting und der Ergebnisse von Weltgesundheitsprogrammen

The Aesthetic Self. The Importance of Aesthetic Taste in Music and Art for Our Perceived Identity

To what extent do aesthetic taste and our interest in the arts constitute who we are? In this paper, we present a series of empirical findings that suggest an Aesthetic Self Effect supporting the claim that our aesthetic engagements are a central component of our identity. Counterfactual changes in aesthetic preferences, for example, moving from liking classical music to liking pop, are perceived as altering us as a person. The Aesthetic Self Effect is as strong as the impact of moral changes, such as altering political partisanship or religious orientation, and significantly stronger than for other categories of taste, such as food preferences (Study 1). Using a multidimensional scaling technique to map perceived aesthetic similarities among musical genres, we determined that aesthetic distances between genres correlate highly with the perceived difference in identity (Study 2). Further studies generalize the Aesthetic Self Effect beyond the musical domain: general changes in visual art preferences, for example from more traditional to abstract art, also elicited a strong Self Effect (Study 3). Exploring the breadth of this effect we also found an Anaesthetic Self Effect. That is, hypothetical changes from aesthetic indifference to caring about music, art, or beauty are judged to have a significant impact on identity. This effect on identity is stronger for aesthetic fields compared to leisure activities, such as hiking or playing video games (Study 4). Across our studies, the Anaesthetic Self Effect turns out to be stronger than the Aesthetic Self Effect. Taken together, we found evidence for a link between aesthetics and identity: we are aesthetic selves. When our tastes in music and the arts or our aesthetic interests change we take these to be transformative changes.Peer Reviewe

Predicting neuronal activity with simple models of the threshold type: Adaptive Exponential Integrate-and-Fire model with two compartments

An adaptive Exponential Integrate-and-Fire (aEIF) model was used to predict the activity of layer-V-pyramidal neurons of rat neocortex under random current injection. A new protocol has been developed to extract the parameters of the aEIF model using an optimal filtering technique combined with a black-box numerical optimization. We found that the aEIF model is able to accurately predict both subthreshold fluctuations and the exact timing of spikes, reasonably close to the limits imposed by the intrinsic reliability of pyramidal neurons

Fabry-Perot interference and spin filtering in carbon nanotubes

We study the two-terminal transport properties of a metallic single-walled carbon nanotube with good contacts to electrodes, which have recently been shown [W. Liang et al, Nature 441, 665-669 (2001)] to conduct ballistically with weak backscattering occurring mainly at the two contacts. The measured conductance, as a function of bias and gate voltages, shows an oscillating pattern of quantum interference. We show how such patterns can be understood and calculated, taking into account Luttinger liquid effects resulting from strong Coulomb interactions in the nanotube. We treat back-scattering in the contacts perturbatively and use the Keldysh formalism to treat non-equilibrium effects due to the non-zero bias voltage. Going beyond current experiments, we include the effects of possible ferromagnetic polarization of the leads to describe spin transport in carbon nanotubes. We thereby describe both incoherent spin injection and coherent resonant spin transport between the two leads. Spin currents can be produced in both ways, but only the latter allow this spin current to be controlled using an external gate. In all cases, the spin currents, charge currents, and magnetization of the nanotube exhibit components varying quasiperiodically with bias voltage, approximately as a superposition of periodic interference oscillations of spin- and charge-carrying ``quasiparticles'' in the nanotube, each with its own period. The amplitude of the higher-period signal is largest in single-mode quantum wires, and is somewhat suppressed in metallic nanotubes due to their sub-band degeneracy.Comment: 12 pages, 6 figure

Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and I healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+)T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation

Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity

Defects of the intracellular enzyme 3' repair exonuclease 1 (Trex1) cause the rare autoimmune condition Aicardi-Goutières syndrome and are associated with systemic lupus erythematosus. Trex1(-/-) mice develop type I IFN-driven autoimmunity, resulting from activation of the cytoplasmic DNA sensor cyclic GMP-AMP synthase by a nucleic acid substrate of Trex1 that remains unknown. To identify cell types responsible for initiation of autoimmunity, we generated conditional Trex1 knockout mice. Loss of Trex1 in dendritic cells was sufficient to cause IFN release and autoimmunity, whereas Trex1-deficient keratinocytes and microglia produced IFN but did not induce inflammation. In contrast, B cells, cardiomyocytes, neurons, and astrocytes did not show any detectable response to the inactivation of Trex1. Thus, individual cell types differentially respond to the loss of Trex1, and Trex1 expression in dendritic cells is essential to prevent breakdown of self-tolerance ensuing from aberrant detection of endogenous DNA

Homeostatic adaptation to endoplasmic reticulum stress depends on Ire1 kinase activity

Uncoupling of Ire1’s RNAse and kinase activities reveals that its auto-phosphorylation is important for resolution of the unfolded protein response. (See also a related paper by Chawla et al. in this issue)

The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology

Central nervous system (CNS)-resident cells such as microglia, oligodendrocytes and astrocytes are gaining increasing attention in respect to their contribution to CNS pathologies including multiple sclerosis (MS). Several studies have demonstrated the involvement of pro-inflammatory glial subsets in the pathogenesis and propagation of inflammatory events in MS and its animal models. However, it has only recently become clear that the underlying heterogeneity of astrocytes and microglia can not only drive inflammation, but also lead to its resolution through direct and indirect mechanisms. Failure of these tissue-protective mechanisms may potentiate disease and increase the risk of conversion to progressive stages of MS, for which currently available therapies are limited. Using proteomic analyses of cerebrospinal fluid specimens from patients with MS in combination with experimental studies, we here identify Heparin-binding EGF-like growth factor (HB-EGF) as a central mediator of tissue-protective and anti-inflammatory effects important for the recovery from acute inflammatory lesions in CNS autoimmunity. Hypoxic conditions drive the rapid upregulation of HB-EGF by astrocytes during early CNS inflammation, while pro-inflammatory conditions suppress trophic HB-EGF signaling through epigenetic modifications. Finally, we demonstrate both anti-inflammatory and tissue-protective effects of HB-EGF in a broad variety of cell types in vitro and use intranasal administration of HB-EGF in acute and post-acute stages of autoimmune neuroinflammation to attenuate disease in a preclinical mouse model of MS. Altogether, we identify astrocyte-derived HB-EGF and its epigenetic regulation as a modulator of autoimmune CNS inflammation and potential therapeutic target in MS. Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages