Since their discovery as pluripotent cytokines extractable from bone matrix, it has been speculated how bone morphogenetic proteins (BMPs) become released and activated from the extracellular matrix ...(ECM). In contrast to TGF‐βs, most investigated BMPs are secreted as bioactive prodomain (PD)–growth factor (GF) complexes (CPLXs). Recently, we demonstrated that PD‐dependent targeting of BMP‐7 CPLXs to the extracellular fibrillin microfibril (FMF) components fibrillin‐1 and ‐2 represents a BMP sequestration mechanism by rendering the GF latent. Understanding how BMPs become activated from ECM scaffolds such as FMF is crucial to elucidate pathomechanisms characterized by aberrant BMP activation and ECM destruction. Here, we describe a new MMP‐dependent BMP‐7 activation mechanism from ECM‐targeted pools via specific PD degradation. Using Edman sequencing and mutagenesis, we identified a new and conserved MMP‐13 cleavage site within the BMP‐7 PD. A degradation screen with different BMP family PDs and representative MMP family members suggested utilization of the identified site in a general MMP‐driven BMP activation mechanism. Furthermore, sandwich ELISA and solid phase cleavage studies in combination with bioactivity assays, single particle TEM, and in silico molecular docking experiments provided evidence that PD cleavage by MMP‐13 leads to BMP‐7 CPLX disintegration and bioactive GF release.
Bone morphogenic proteins (BMPs) are important growth regulators in embryogenesis and postnatal homeostasis. Their tight regulation is crucial for successful embryonic development as well as tissue ...homeostasis in the adult organism. BMP inhibition by natural extracellular biologic antagonists represents the most intensively studied mechanistic concept of BMP growth factor regulation. It was shown to be critical for numerous developmental programs, including germ layer specification and spatiotemporal gradients required for the establishment of the dorsal–ventral axis and organ formation. The importance of BMP antagonists for extracellular matrix homeostasis is illustrated by the numerous human connective tissue disorders caused by their mutational inactivation. Here, we will focus on the known functional interactions targeting BMP antagonists to the ECM and discuss how these interactions influence BMP antagonist activity. Moreover, we will provide an overview about the current concepts and investigated molecular mechanisms modulating BMP inhibitor function in the context of development and disease.
Studies on social cognition often use complex visual stimuli to asses neural processes attributed to abilities like “mentalizing” or “Theory of Mind” (ToM). During the processing of these stimuli, ...eye gaze, however, shapes neural signal patterns. Individual differences in neural operations on social cognition may therefore be obscured if individuals’ gaze behavior differs systematically. These obstacles can be overcome by the combined analysis of neural signal and natural viewing behavior. Here, we combined functional magnetic resonance imaging (fMRI) with eye-tracking to examine effects of unconstrained gaze on neural ToM processes in healthy individuals with differing levels of emotional awareness, i.e. alexithymia. First, as previously described for emotional tasks, people with higher alexithymia levels look less at eyes in both ToM and task-free viewing contexts. Further, we find that neural ToM processes are not affected by individual differences in alexithymia per se. Instead, depending on alexithymia levels, gaze on critical stimulus aspects reversely shapes the signal in medial prefrontal cortex (MPFC) and anterior temporoparietal junction (TPJ) as distinct nodes of the ToM system. These results emphasize that natural selective attention affects fMRI patterns well beyond the visual system. Our study implies that, whenever using a task with multiple degrees of freedom in scan paths, ignoring the latter might obscure important conclusions.
Catatonia is a neuropsychiatric syndrome with motor and behavioural symptoms. Though usually occurring in patients with schizophrenia and mood disorders, this syndrome may also be associated with ...neurological diseases or general medical conditions. Few cases of catatonia associated with autoimmune disorders have been described.
Here, we report the case of a 27-year-old woman diagnosed with Hashimoto's encephalitis (HE) who attempted suicide and infanticide by defenestration. As she presented risk factors for postpartum psychosis, she was treated principally with antipsychotics. Despite adequate treatment for psychosis, symptoms worsened and she developed catatonia. Complementary investigations showed elevated titres of anti-thyroglobulin and anti-thyroperoxidase antibodies (200 and 10 times, respectively, as compared to normal levels) and electroencephalography were suggestive of encephalopathy. In the presence of an otherwise unexplained neuropsychiatric condition, HE was suspected and oral prednisolone was introduced. Psychiatric symptoms improved dramatically within 72 h and the patient was still free of any symptom 3 years later.
Catatonia of organic aetiology should always be considered before a psychiatric aetiology especially in case of clinical worsening in spite of adequate psychotropic treatment. To our knowledge, this is the first description of catatonia associated with HE.
Ice ages within Europe forced many species to retreat to refugia, of which three major biogeographic basic types can be distinguished: "Mediterranean", "Continental" and "Alpine / Arctic" species. ...However, this classification often fails to explain the complex phylogeography of European species with a wide range of latitudinal and altitudinal distribution. Hence, we tested for the possibility that all three mentioned faunal elements are represented within one species. Our data was obtained by scoring 1,307 Euphydryas aurinia individuals (46 European locations) for 17 allozyme loci, and sequencing a subset of 492 individuals (21 sites) for a 626 base pairs COI fragment. Genetic diversity indices, F statistics, hierarchical analyses of molecular variance, individual-based clustering, and networks were used to explore the phylogeographic patterns. The COI fragment represented 18 haplotypes showing a strong geographic structure. All but one allozyme loci analysed were polymorphic with a mean FST of 0.20, supporting a pronounced among population structure. Interpretation of both genetic marker systems, using several analytical tools, calls for the recognition of twelve genetic groups. These analyses consistently distinguished different groups in Iberia (2), Italy, Provence, Alps (3), Slovenia, Carpathian Basin, the lowlands of West and Central Europe as well as Estonia, often with considerable additional substructures. The genetic data strongly support the hypothesis that E. aurinia survived the last glaciation in Mediterranean, extra-Mediterranean and perialpine refugia. It is thus a rare example of a model organism that combines attributes of faunal elements from all three of these sources. The observed differences between allozymes and mtDNA most likely result from recent introgression of mtDNA into nuclear allozyme groups. Our results indicate discrepancies with the morphologically-based subspecies models, underlining the need to revise the current taxonomy.
''Although practices of editing and mentoring are part of an author's daily activities, they have previously been largely neglected by the literary studies. The bilingual volume therefore assembles ...players from the fields of literary production and theories of authorship and the writing process, who discuss the development towards an opening up of the creative writing process. Their contributions encompass not only reports of experiences made by authors, editors, and mentors and insights into teaching methods applied in creative writing classes at higher education institutions in different European countries. They also explore theoretical approaches to an intersubjective literary practice as well as suggestions for the definition of a dialogic notion of literature in the age of online publishing.
Obwohl Praktiken des Lektorats und des Mentorats zum alltäglichen Bestandteil schriftstellerischer Tätigkeiten gehören, wurden sie von den Literaturwissenschaften bislang kaum untersucht. Der bilinguale Band versammelt Akteure aus dem literarischen Feld sowie der Autorschafts- und Schreibprozesstheorie, welche die Öffnung des Schreibprozesses grundlegend reflektieren. Ihre Beiträge umfassen nicht nur Erfahrungsberichte von Autor_innen, Lektor_innen und Mentor_innen sowie Einblicke in Lehrmethoden des literarischen Schreibens an Hochschulen in verschiedenen Ländern Europas, sondern auch theoretische Ansätze zu einer intersubjektiven literarischen Praxis sowie Entwürfe für dialogische Literaturbegriffe im Zeitalter des Publizierens im Internet.
Wen soll man wählen? Im Vorfeld der Bundestagswahl präsentieren die wichtigen Parteien in der MMW ihre gesundheitspolitischen Vorstellungen. In dieser Ausgabe: Die FDP.
Psychosis is more common in people with temporal lobe epilepsy than it is in the general population. Treatment can be difficult in these patients because of the complex interactions between ...antipsychotic and antiepileptic drugs. Some antipsychotic drugs also decrease the seizure threshold. We report the case of a 49-year-old man with a hypothalamic hamartoma, with a history of both gelastic and temporal lobe seizures. The patient was rendered seizure-free after three neurosurgical procedures but developed a drug-resistant paranoid psychosis. He was treated with electroconvulsive therapy (ECT). After two weeks with six stimulations that resulted in seizures, the psychiatric phenomena disappeared completely. There was no relapse of either the psychiatric symptoms or the seizures during the 42 months of follow-up. This case report suggests that ECT might be safe for psychosis in patients with a history of seizures that have previously been successfully treated with neurosurgery, although caution should be exercised in drawing general conclusions from a single case report.
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