Toward a Negative Anthropology

Can philosophy say what man is? What is gained or lost by making theoretical assumptions about the human being? This essay examines the “negative anthropology” of the early Frankfurt School by asking how Max Horkheimer, Theodor W. Adorno and Ulrich Sonnemann engage with the question “What is man?” Negative anthropology turns out to be more than the critique of philosophical anthropology: By understanding the human being as the ensemble of what it is not, negative anthropology avoids the predicament of spelling out what it could be, while holding on to the idea of man’s self-realization in history. What role does negative anthropology play as a component of critical social theory? To what extent can it count as a theoretical programme? Do certain historical situations demand anthropological assumptions more than others? To address these questions, this essay follows the early Frankfurt School’s altercations with anthropological philosophy.La philosophie peut-elle définir l’essence de l’homme ? Que gagne-t-on – ou perd-on – avec des déclarations métaphysiques sur l’être humain ? Cet essai explore l’ « anthropologie négative » de la première école de Francfort à travers les réponses de Walter Benjamin, Max Horkheimer, Theodor W. Adorno et Ulrich Sonnemann à la question : « qu’est-ce que l’homme » ? L’anthropologie négative apparaît alors comme plus qu’une critique de l’anthropologie philosophique. En appréhendant l’homme à travers tout ce qu’il n’est pas, elle évite la situation fâcheuse d’énoncer ce qu’il pourrait être, tout en préservant l’idée d’émancipation. Quel rôle l’anthropologie négative joue-t-elle en tant que composante d’une théorie sociale critique ? A quel point compte-t-elle dans son programme théorique ? Certaines situations historiques exigent-elles des énoncés anthropologiques plus que d’autres ? L’artice présent discute de ces questions en circonscrivant le conflit de la première Ecole de Francfort avec l’anthropologie philosophique.¿Puede acaso la filosofía determinar la esencia del hombre ? ¿Qué se gana o qué se pierde asumiendo determinaciones metafísicas sobre el ser humano ? Este ensayo examina la « antropología negativa » de la primera escuela de Frankfurt indagando el modo en que Walter Benjamin, Max Horkheimer, Theodor W. Adorno y Ulrich Sonnemann responden a la pregunta « ¿qué es el hombre? ». La antropología negativa aparece entonces como algo más que la crítica de la filosofía antropológica. Al comprender al hombre a partir de todo de lo que él no es, la antropología negativa evita la difícil situación de detallar lo que él podría ser, manteniendo al mismo tiempo la idea de emancipación. ¿Qué rol juega la antropología negativa en tanto componente de la teoría social crítica? ¿Hasta qué punto puede contar como programa teorético? ¿Acaso ciertas situaciones históricas exigen asumir supuestos antropológicos más que otras? Este ensayo discute tales interrogantes siguiendo el conflicto de la primera escuela de Frankfurt con la antropología filosófica

The C-type lectin receptor SIGNR3 binds to fungi present in commensal microbiota and influences immune regulation in experimental colitis

Inflammatory bowel disease is a condition of acute and chronic inflammation of the gut. An important factor contributing to pathogenesis is a dysregulated mucosal immunity against commensal bacteria and fungi. Host pattern- recognition receptors (PRRs) sense commensals in the gut and are involved in maintaining the balance between controlled responses to pathogens and overwhelming innate immune activation. C-type lectin receptors (CLRs) are PRRs recognizing glycan structures on pathogens and self-antigens. Here we examined the role of the murine CLR specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 (SIGNR3) in the recognition of commensals and its involvement in intestinal immunity. SIGNR3 is the closest murine homolog of the human dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) receptor recognizing similar carbohydrate ligands such as terminal fucose or high-mannose glycans. We discovered that SIGNR3 recognizes fungi present in the commensal microbiota. To analyze whether this interaction impacts the intestinal immunity against microbiota, the dextran sulfate sodium-induced colitis model was employed. SIGNR3(-/-) mice exhibited an increased weight loss associated with more severe colitis symptoms compared to wild-type control mice. The increased inflammation in SIGNR3(-/-) mice was accompanied by a higher level of TNF-α in colon. Our findings demonstrate for the first time that SIGNR3 recognizes intestinal fungi and has an immune regulatory role in colitis

Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS

Although the importance of reactive astrocytes during CNS pathology is well established, the function of astroglia in adult CNS homeostasis is less well understood. With the use of conditional, astrocyte-restricted protein synthesis termination, we found that selective paralysis of GFAP(+) astrocytes in vivo led to rapid neuronal cell loss and severe motor deficits. This occurred while structural astroglial support still persisted and in the absence of any major microvascular damage. Whereas loss of astrocyte function did lead to microglial activation, this had no impact on the neuronal loss and clinical decline. Neuronal injury was caused by oxidative stress resulting from the reduced redox scavenging capability of dysfunctional astrocytes and could be prevented by the in vivo treatment with scavengers of reactive oxygen and nitrogen species (ROS/RNS). Our results suggest that the subpopulation of GFAP(+) astrocytes maintain neuronal health by controlling redox homeostasis in the adult CNS

Adaptive Movement Compensation for In Vivo Imaging of Fast Cellular Dynamics within a Moving Tissue

In vivo non-linear optical microscopy has been essential to advance our knowledge of how intact biological systems work. It has been particularly enabling to decipher fast spatiotemporal cellular dynamics in neural networks. The power of the technique stems from its optical sectioning capability that in turn also limits its application to essentially immobile tissue. Only tissue not affected by movement or in which movement can be physically constrained can be imaged fast enough to conduct functional studies at high temporal resolution. Here, we show dynamic two-photon Ca2+ imaging in the spinal cord of a living rat at millisecond time scale, free of motion artifacts using an optical stabilization system. We describe a fast, non-contact adaptive movement compensation approach, applicable to rough and weakly reflective surfaces, allowing real-time functional imaging from intrinsically moving tissue in live animals. The strategy involves enslaving the position of the microscope objective to that of the tissue surface in real-time through optical monitoring and a closed feedback loop. The performance of the system allows for efficient image locking even in conditions of random or irregular movements

Two-photon imaging of neural activity and structural plasticity in the rodent spinal cord

In my PhD thesis, I used two‐photon imaging to investigate neuronal circuits and glia cells in the spinal cord of living mice. To achieve this, a major effort first was to establish a mouse spinal cord preparation suitable for stable and long‐lasting imaging experiments. Without adequate stabilisation, the spinal cord was prone to large‐scale movement artefacts clearly hampering high‐resolution imaging in vivo. To overcome these limitations, I employed strategies to optimise the animals posture, namely rigid clamping of the vertebral column to isolate the spinal cord from breathing‐related movements. In addition, I developed strategies to dampen tissue movements remaining after posture optimisation. These improvements made it possible to image the structural plasticity of genetically labelled microglia cells with subcellular resolution for many hours in anesthetized mice. In a paradigm of focal spinal cord injury, microglia became rapidly activated and displayed high levels of filopodial motility clearly directed towards the injury site. In addition, I adapted Ca2+ indicator loading techniques to stain neuronal networks in the mouse superficial dorsal horn to visualize activity patterns of painprocessing neurons. Despite the heavily myelinated surrounding tissue, neuronal populations within the first two laminae could be visualized after Ca2+ indicator loading. The preparation was sufficiently stable to for the first time resolve fast, individual Ca2+ transients in the spinal cord of living rodents. In agreement with the role of dorsal horn circuits in nociceptive processing I found low rates of spontaneous activity but could reliably evoke increased activity levels by electrical stimulation of primary afferent fibres in situ. Specifically, also natural sensory stimulation applied to the paw elicited Ca2+ transients in a subset of dorsal horn neurons. In a parallel project, I collaborated with Klas Kullander’s group to investigate activity patterns of identified Renshaw cells during an in vitro model of locomotion. Using two‐photon Ca2+ imaging in the isolated neonatal mouse SC, we found that several subclasses of Renshaw cells are differentially engaged in ongoing locomotion. In addition, the activities of the different Renshaw cell populations were correlated with subgroups of simultaneously recorded motoneurons. Afferent inputs delivered during ongoing locomotion perturbed the locomotor rhythm and the nature of perturbations depended on stimulus timing during either the flexor‐ or extensor‐related cycle phase. On the local circuit level, we observed that correlations between specific Renshaw cells and motoneuron subpopulations were boosted by sensory input and that this effect also depended on stimulus timing. In a broader context, these results can be interpreted as reflections of synaptic strengthening of developing locomotor modules by sensory inputs

Stochastic Claims Reserving Methods with State Space Representations: A Review

Often, the claims reserves exceed the available equity of non-life insurance companies and a change in the claims reserves by a small percentage has a large impact on the annual accounts. Therefore, it is of vital importance for any non-life insurer to handle claims reserving appropriately. Although claims data are time series data, the majority of the proposed (stochastic) claims reserving methods is not based on time series models. Among the time series models, state space models combined with Kalman filter learning algorithms have proven to be very advantageous as they provide high flexibility in modeling and an accurate detection of the temporal dynamics of a system. Against this backdrop, this paper aims to provide a comprehensive review of stochastic claims reserving methods that have been developed and analyzed in the context of state space representations. For this purpose, relevant articles are collected and categorized, and the contents are explained in detail and subjected to a conceptual comparison

Positional cloning of schizophrenia-related genes on chromosome 15q and association studies of rare variants of the gene encoding the potassium chloride co-transporter SLC12A6 with schizophrenia and bipolar disorder.

Sowohl die zu den Schizophrenien zählende periodische Katatonie als auch die bipolare Erkrankung werden gegenwärtig als multifaktoriell polygen bedingte Erkrankungen mit komplexem Vererbungsmodus verstanden. Für die periodische Katatonie wurden im Rahmen vorangegangener Kopplungsanalysen zwei chromosomale Loci auf Chromosom 15 und 22 bestätigt. Im ersten Teil dieser Arbeit wurde die Kandidatengenregion auf Chromosom 15q13 -15 mittels Feinkartierung einer Mehrgenerationsfamilie mit familiärer katatoner Schizophrenie (SCZD10, OMIM %605419) durch Genotypisierung zusätzlicher polymorpher Marker auf 7,7 cM zwischen den Markern D15S1042 und D15S182 verkleinert. Hierdurch konnten viele interessante Kandidatengene für die periodische Katatonie wie zum Beispiel RYR3, CX36 und auch SLC12A6 als krankheitsverursachend ausgeschlossen werden. Trotz Ausschluss in der untersuchten Familie stellt das für den Kalium-Chlorid-Kotransporter 3 codierende Gen SLC12A6 aufgrund seiner funktionellen Eigenschaften und vermuteten Bedeutung in der Pathogenese einiger neuro-psychiatrischer Erkrankungen wie zum Beispiel dem Andermann Syndrom (ACCPN, OMIM 218000) ein interessantes Kandidatengen für die periodische Katatonie und die bipolare Störung dar. Im zweiten Teil der vorliegenden Arbeit wurden zwei seltene SLC12A6-Varianten, die im Promotor bzw. der 5’-UTR-Region gelegenen SNPs 32418760 (G/A) und 32416574 (G/A), im Rahmen einer Fall-Kontroll-Studie auf Assoziation mit Erkrankungen des schizophrenen Formenkreises und der bipolaren Störung hin untersucht. Der Nachweis einer signifikanten Assoziation der G-Variante des proximal gelegenen SNP 32418760 mit der bipolaren Erkrankung und auch dem Gesamtkollektiv einerseits und einem Trend zur Assoziation für die G-Variante des zweiten SNP 32416574 andererseits, unterstützt die Hypothese, dass SLC12A6 eines von mehreren Risikogenen insbesondere für die bipolare Störung darstellt. In anschließenden funktionellen Untersuchungen als Teil einer naturwissenschaftlichen Doktorarbeit konnte eine mutmaßliche regulatorische Funktion der G-Variante des SNP 32418760 nachgewiesen werden. Zukünftig ist die weitere Untersuchung der verbleibenden Kandidatengene und deren funktioneller Bedeutung nötig, des weiteren unterstützen die hier erhobenen Ergebnisse die Forderung nach der Weiterentwicklung des gängigen pathophysiologischen Krankheitsverständnisses der endogenen Psychosen und deren aktuell verwendeter Klassifikation.Polygenic inheritance is assumed for both periodic catatonia, a clinical subtype of unsystematic schizophrenia, and bipolar disorder. Within a genomewide linkage study evidence for two major susceptibility loci on 15q15 and 22q13 was found. In the first part of this work members of a large family with periodic catatonia strongly supporting the chromosome 15q13–22 region were genotyped with additional polymorphic markers in order to narrow down the candidate region to 7.7 cM. Several candidate genes such as RYR3 and CX36 were excluded. SLC12A6, the gene encoding the potassium chloride co-transporter 3, is localized on chromosome 15q14, a region where linkage to schizophrenia and bipolar disorder has previously been shown. Recessive mutations of SLC12A6 cause severe peripheral neuropathy frequently associated with agenesis of the corpus callosum and psychoses (ACCPN). In the second part of this work a case-control study was performed to assess association of two rare SLC12A6 single nucleotide polymorphisms (G/A, G/A) in the promoter and 5'-UTR with bipolar disorder and schizophrenia in a large sample. The two G variants were found to be in linkage disequilibrium with each other, and significantly associated with bipolar disorder. Our data strongly suggest that rare variants of SLC12A6 may represent risk factors for bipolar disorder and schizophrenia with bipolar features. Further functional analysis support a putative regulatory function of the promoter variant