Georg Herwegh und die literarische Zeitung

Edgar Bauer

Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.

OBJECTIVE Short-chain enoyl-CoA hydratase (ECHS1) is a multifunctional mitochondrial matrix enzyme that is involved in the oxidation of fatty acids and essential amino acids such as valine. Here, we describe the broad phenotypic spectrum and pathobiochemistry of individuals with autosomal-recessive ECHS1 deficiency. METHODS Using exome sequencing, we identified ten unrelated individuals carrying compound heterozygous or homozygous mutations in ECHS1. Functional investigations in patient-derived fibroblast cell lines included immunoblotting, enzyme activity measurement, and a palmitate loading assay. RESULTS Patients showed a heterogeneous phenotype with disease onset in the first year of life and course ranging from neonatal death to survival into adulthood. The most prominent clinical features were encephalopathy (10/10), deafness (9/9), epilepsy (6/9), optic atrophy (6/10), and cardiomyopathy (4/10). Serum lactate was elevated and brain magnetic resonance imaging showed white matter changes or a Leigh-like pattern resembling disorders of mitochondrial energy metabolism. Analysis of patients' fibroblast cell lines (6/10) provided further evidence for the pathogenicity of the respective mutations by showing reduced ECHS1 protein levels and reduced 2-enoyl-CoA hydratase activity. While serum acylcarnitine profiles were largely normal, in vitro palmitate loading of patient fibroblasts revealed increased butyrylcarnitine, unmasking the functional defect in mitochondrial β-oxidation of short-chain fatty acids. Urinary excretion of 2-methyl-2,3-dihydroxybutyrate - a potential derivative of acryloyl-CoA in the valine catabolic pathway - was significantly increased, indicating impaired valine oxidation. INTERPRETATION In conclusion, we define the phenotypic spectrum of a new syndrome caused by ECHS1 deficiency. We speculate that both the β-oxidation defect and the block in l-valine metabolism, with accumulation of toxic methacrylyl-CoA and acryloyl-CoA, contribute to the disorder that may be amenable to metabolic treatment approaches.

Johann Georg Albrechtsberger, Brustbild

Signatur des Originals: S 36/G04626

Infrared regime of SU(2) with one adjoint Dirac flavor

SU(2) gauge theory with one Dirac flavor in the adjoint representation is investigated on a lattice. Initial results for the gluonic and mesonic spectrum, static potential from Wilson and Polyakov loops, and the anomalous dimension of the fermionic condensate from the Dirac mode number are presented. The results found are not consistent with conventional confining behavior, pointing instead tentatively towards a theory lying within or very near the onset of the conformal window, with the anomalous dimension of the fermionic condensate in the range 0.9≲γ∗≲0.95. The implications of our work for building a viable theory of strongly interacting dynamics beyond the standard model are discussed.

Georg Büchner und das Lustspiel der Romantik : eine Studie über Leonce und Lena

von Armin Renker

From The Hague to Geneva: The protection of civilians and refugees in the perspective of legal history, 1899-1951

The presentation proposed here shall focus on international (and as far as possible some cases of national) legal protection of civilians and refugees between the first Hague Convention of 1899 and the Geneva Convention for the Protection of Refugees in 1951. An analysis of international legal texts as well as, if possible, some exemplary national constitutions will form the core of the presentation, which will try to find out, to what extent not only the civilian population remaining close to front-line fighting, but also under occupation was supposed to be protected by legal norms, but also to what extent the issue of forcing civilian to leave their homes became part of the international legal discourse as well as of international legal norms.