Brentano und Kleist vor Friedrichs "Mönch am Meer" : Aspekte eines Umbruchs in der Geschichte der Wahrnehmung

In den "Empfindungen vor Friedrichs Seelandschaft" von Brentano und Kleist läßt sich ein wahrnehmungsgeschichtlich signifikanter Bruch nachweisen. Geht Brentano von der romantischen Konzeption der Sehnsucht aus, so stehen hinter dem Text Kleists die Theorie des Erhabenen und die Assoziation des Panoramas. Diese konkurrierenden Positionen gründen in unterschiedlichen Begriffen vom Subjekt.In the "Empfindungen vor Friedrichs Seelandschaft" by Brentano and Kleist we can trace a break which is relevant in terms of the history of perception. While Brentano bases his argument on the Romantic concept of longing ("Sehnsucht"), Kleist´s text is influenced by the theory of the sublime and the association of the panorama. These competing positions arise from different concepts of the subject

Poiesis des Körpers : Künstlerische Produktivität und Konstruktion des Leibes in der erotischen Dichtung des klassischen Goethe

Goethes Römische Elegien und Venezianische Epigramme entfalten eine "Poiesis des Körpers" in einem doppelten Sinn. In ihren selbstreflexiven poetologischen Passagen zeigen sie Liebe und Sexualität als die Affektbasis der Hervorbringung von Kunst, die sich selbst erotisch auflädt. Sie entwerfen damit eine Anthropologie des künstlerischen Prozesses in nuce. Damit verzahnt ist die Arbeit an einem neuen Blick auf den weiblichen Körper und an der Konstitution eines spezifischen Geschlechtskörpers des Künstlers selbst. Dieser Vorgang beinhaltet zugleich eine Verschiebung und Umformierung der Sexualität. Diese Aspekte werden in Zusammenhang gebracht 1. mit epochenspezifischen kulturhistorischen Phänomenen (Attitude und Tableau vivant; Blick auf die antiken Statuen; Konjunktur des Pygmalionmythos) 2. mit Goethes ästhetischen Reflexionen. Im Zusammenhang mit der Bestimmung des ambivalenten Verhältnisses von Kunst und Natur entwerfen diese eine Ästhetik des lebendigen Kunstwerks: Kunst wird in Natur verankert und in Analogie zum natürlichen Leben - so die Leitmetaphorik - "gezeugt" und "geboren". Diese Gesichtspunkte umreißen eine Art Biologie der Kunst, in die sich die erotische Dichtung nahtlos einfügt, indem sie Kunstschöpfung auf Sexualität bezieht

Eros und Gewissen : Literarische Psychologie in Ludwig Tiecks Erzählung "Der getreue Eckart und der Tannenhäuser"

Es gehört wohl zu den wichtigsten Leistungen der jüngeren Romantikforschung, die starre Grenze zwischen Aufklärung und Romantik geschleift zu haben. Wo sich früher zwei monolithische Einheiten gegenüberstanden, zeigen sich inzwischen, ohne daß dadurch der Epochencharakter beider prinzipiell verabschiedet würde, gemeinsame Problemlagen, Kontinuitäten, Übergänge und Transformationen. Dieser Befund bewahrheitet sich, wenn man den herkömmlichen Fragenkreis der Literaturwissenschaft in Richtung einer sozialhistorisch fundierten Geschichte des Subjekts, des Ichs, der Seele erweitert. Die Romantik, hat Hartmut Böhme geschrieben, formuliere "das Unbewußte der Aufklärung. Sie ist nicht deren Opposition, sondern die Komplettierung der bürgerlichen Subjektproduktion [...]". Tatsächlich spielt die Literatur seit der Frühromantik eine durchaus avantgardistische Rolle bei der "Entdeckung des Unbewußten", die in den letzten Jahren anhand vorwiegend theoretischer Texte rekonstruiert worden ist. [...] Ludwig Tiecks Märchenerzählung "Der getreue Eckart und der Tannenhäuser" von 1799 [...], die die Germanistik zumeist in einer Mischung aus Hilflosigkeit und Geringschätzung links liegen gelassen hat, schreitet in einem mythisierenden Szenarium von hoher Raffinesse die Sehnsüchte und inneren Zwänge aus, die sich am Ende der bürgerlichen Aufklärung ausgebildet haben. Er macht auf diese Weise nicht weniger als eine neue psychische Struktur, das Resultat lang- wie kurzfristiger sozialer Prozesse, sichtbar, und zwar in einem doppelten Sinn: Denn diese ist nicht nur auf Inhaltsebene Gegenstand der Erzählung, sondern schreibt sich strukturbildend dem Text selbst ein. In psychogenetischer Perspektive wird erkennbar, daß sich die Romantik, selbst wo sie es will, nicht von dem befreien kann, was ihr die Aufklärung hinterlassen hat

Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia

We report on a serum autoantibody associated with cerebellar ataxia. Immunohistochemical studies of sera from four patients referred for autoantibody testing revealed binding of high-titer (up to 1:5,000) IgG antibodies, mainly IgG1, to the molecular layer, Purkinje cell layer, and white matter on mouse, rat, porcine, and monkey cerebellum sections. The antibody bound to PC somata, dendrites, and axons, resulting in a binding pattern similar to that reported for anti-Ca/anti-ARHGAP26, but did not react with recombinant ARHGAP26. Extensive control studies were performed to rule out a broad panel of previously described paraneoplastic and non-paraneoplastic anti-neural autoantibodies. The characteristic binding pattern as well as double staining experiments suggested inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) as the target antigen. Verification of the antigen included specific neutralization of the tissue reaction following preadsorption with ITPR1 (but not ARHGAP26) and a dot-blot assay with purified ITPR1 protein. By contrast, anti-ARHGAP26-positive sera did not bind to ITPR1. In a parallel approach, a combination of histoimmunoprecipitation and mass spectrometry also identified ITPR1 as the target antigen. Finally, a recombinant cell-based immunofluorescence assay using HEK293 cells expressing ITPR1 and ARHGAP26, respectively, confirmed the identification of ITPR1. Mutations of ITPR1 have previously been implicated in spinocerebellar ataxia with and without cognitive decline. Our findings suggest a role of autoimmunity against ITPR1 in the pathogenesis of autoimmune cerebellitis and extend the panel of diagnostic markers for this disease

Исследование гидродинамики и теплообмена при неизотермическом течении углеводородной вязкой среды в трубопроводе, проложенном в районе многолетнемерзлых грунтов

В процессе исследования проводились расчеты изменений полей скорости, распределений температуры по длине трубопровода; зависимости теплового пограничного слоя от длины трубопровода. Анализировались процессы конвективного теплообмена в условиях развивающегося потока и формирования теплового и динамического пограничных слоев по длине. В результате исследования был произведен сравнительный анализ интегро-дифференциальных и точных методов моделирования динамики и теплообмена при течении углеводородных сред в трубопроводах на начальных участках в режимах вязкостно-инерционного ламинарного и турбулентного течения и теплообмена.In the course of the study, calculations were made of changes in the velocity fields and temperature distributions along the pipeline; the dependence of the thermal boundary layer on the length of the pipeline. The processes of convective heat transfer under the conditions of the developing flow and the formation of thermal and dynamic boundary layers along the length were analyzed. The study resulted in a comparative analysis of integro-differential and accurate methods for modelling the dynamics and heat transfer during the flow of hydrocarbon media in pipelines in the initial sections in the modes of viscous-inertial laminar and turbulent flow and heat transfer

A Spectrum of Neural Autoantigens, Newly Identified by Histo-Immunoprecipitation, Mass Spectrometry, and Recombinant Cell-Based Indirect Immunofluorescence

BackgroundA plurality of neurological syndromes is associated with autoantibodies against neural antigens relevant for diagnosis and therapy. Identification of these antigens is crucial to understand the pathogenesis and to develop specific immunoassays. Using an indirect immunofluorescence assay (IFA)-based approach and applying different immunoprecipitation (IP), chromatographic and mass spectrometric protocols was possible to isolate and identify a spectrum of autoantigens from brain tissue.MethodsSera and CSF of 320 patients suspected of suffering from an autoimmune neurological syndrome were comprehensively investigated for the presence of anti-neural IgG autoantibodies by IFA using mosaics of biochips with brain tissue cryosections and established cell-based recombinant antigen substrates as well as immunoblots. Samples containing unknown brain tissue-specific autoantibodies were subjected to IP with cryosections of cerebellum and hippocampus (rat, pig, and monkey) immobilized to glass slides or with lysates produced from homogenized tissue, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, tryptic digestion, and matrix-assisted laser desorption/ionization–time of flight mass spectrometry analysis. Identifications were confirmed by IFA with recombinant HEK293 cells and by neutralizing the patients’ autoantibodies with the respective recombinantly expressed antigens in the tissue-based immunofluorescence test.ResultsMost samples used in this study produced speckled, granular, or homogenous stainings of the hippocampal and cerebellar molecular and/or granular layers. Others exclusively stained the Purkinje cells. Up to now, more than 20 different autoantigens could be identified by this approach, among them ATP1A3, CPT1C, Flotillin1/2, ITPR1, NBCe1, NCDN, RGS8, ROCK2, and Syntaxin-1B as novel autoantigens.DiscussionThe presented antigen identification strategy offers an opportunity for identifying up to now unknown neural autoantigens. Recombinant cell substrates containing the newly identified antigens can be used in serology and the clinical relevance of the autoantibodies can be rapidly evaluated in cohort studies

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling

Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants. Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19. Results: We observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions. Discussion: We propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8+ T cells in COVID-19 severity.</p

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest