New Sequencing Methods: New Data and New Challenges

Die Sequenzierung von DNA gehört heute zum Standardrepertoire der biologischen und medizinischen Forschung. Das um die Mitte der 2000er Jahre etablierte Next Generation Sequencing (NGS) war der wichtigste Auslöser für diese Entwicklung. NGS führte zu großen Erkenntnisgewinnen in den molekularen Biowissenschaften. Die neue Technologie liefert allerdings Daten, die Wissenschaft und Gesellschaft vor neue Herausforderungen stellen. Schon jetzt lässt sich in diesem Feld eine technikgetriebene Eigendynamik feststellen, die zu Transformationsprozessen in der Wissenschaft führt, wo sich neue Forschungsfelder herausbilden, aber auch in der Gesellschaft, in der Fragen von Identität zunehmend anhand von genetischen Analysen verhandelt werden. Today, DNA sequencing is part of the standard repertoire of biological and medical research. Next generation sequencing (NGS), established around the mid-2000s, was the main catalyst for this development. NGS has led to major knowledge gains in the molecular life sciences. However, the new technology provides data that pose new challenges that both science and society still must learn to deal with. A technology-driven dynamic can already be observed in this field, leading to transformation processes in science, where new fields of research are emerging, but also in society, where questions of identity are increasingly being negotiated based on genetic analyses

Technikgeschichte im Geschichtsunterricht?

Unsere Welt ist durchgehend technisch durchsetzt. Die wissenschaftliche Technikhistoriografie untersucht diese technische Durchsetztheit in ihrer historischen Entwicklung unter Einsatz der historisch-kritischen Methode. Wie aber können die Zugänge und Erkenntnisse dieser geschichtswissenschaftlichen Teildisziplin in den aktuellen Geschichtsunterricht integriert werden? Der Beitrag nennt Beispiele für die Praxis und liefert Literaturhinweise sowie Links zu digitalen Ressourcen.Technology is both fundamental and pervasive in the world we live in. The modern historiography of technology examines this history using the arsenal of methods of historical science. But how can we integrate its approaches and findings into history teaching? The paper suggests topics and provides references as well as links to digital resources

Olig2 regulates Sox10 expression in oligodendrocyte precursors through an evolutionary conserved distal enhancer

The HMG-domain transcription factor Sox10 is expressed throughout oligodendrocyte development and is an important component of the transcriptional regulatory network in these myelin-forming CNS glia. Of the known Sox10 regulatory regions, only the evolutionary conserved U2 enhancer in the distal 5′-flank of the Sox10 gene exhibits oligodendroglial activity. We found that U2 was active in oligodendrocyte precursors, but not in mature oligodendrocytes. U2 activity also did not mediate the initial Sox10 induction after specification arguing that Sox10 expression during oligodendroglial development depends on the activity of multiple regulatory regions. The oligodendroglial bHLH transcription factor Olig2, but not the closely related Olig1 efficiently activated the U2 enhancer. Olig2 bound U2 directly at several sites including a highly conserved one in the U2 core. Inactivation of this site abolished the oligodendroglial activity of U2 in vivo. In contrast to Olig2, the homeodomain transcription factor Nkx6.2 repressed U2 activity. Repression may involve recruitment of Nkx6.2 to U2 and inactivation of Olig2 and other activators by protein–protein interactions. Considering the selective expression of Nkx6.2 at the time of specification and in differentiated oligodendrocytes, Nkx6.2 may be involved in limiting U2 activity to the precursor stage during oligodendrocyte development

Disability History - Behinderung sichtbar machen: Emanzipationsbewegung und Forschungsfeld

Was verrät der Umgang mit Behinderung über moderne Gesellschaften? Während in Arbeiten von Disability Historians zu lesen ist, dass die Linse "Behinderung" einen ganz neuen, kritischen Blick auf Kultur und Gesellschaft und ihren Umgang mit Diversität ermögliche, erweckt die Durchsicht der großen Synthesen etwa zur bundesrepublikanischen Zeitgeschichte den Eindruck, dass es offenbar auch ohne diese Kategorie geht. Weder kommen Menschen mit Behinderung dort vor, noch wird "Behinderung" als Strukturkategorie verstanden. Dies erstaunt umso mehr, als die Relevanz des Phänomens nicht bestritten werden kann: Etwa ein Siebtel der Weltbevölkerung lebt mit einer körperlichen, seelischen oder kognitiven Behinderung. In der Bundesrepublik ist dieser Wert kaum niedriger. Der Anteil derjenigen, die wir heute als Menschen mit Behinderungen bezeichnen würden, dürfte in früheren Gesellschaften - legt man zum Beispiel die an Teilhabechancen orientierte Definition des deutschen Sozialgesetzbuches (SGB) IX zugrunde - mitunter noch größer gewesen sein. Die Geschichte dieser Menschen und des gesellschaftlichen Umgangs mit ihnen wurde von der historischen Forschung lange Zeit vernachlässigt. Die seit den 1980er-Jahren im Kontext der angelsächsischen Emanzipationsbewegung entstandene Disability History rückt beides ins Zentrum

Kindlin-2 controls bidirectional signaling of integrins.

Control of integrin activation is required for cell adhesion and ligand-induced signaling. Here we report that loss of the focal adhesion protein Kindlin-2 in mice results in peri-implantation lethality caused by severe detachment of the endoderm and epiblast from the basement membrane. We found that Kindlin-2-deficient cells were unable to activate their integrins and that Kindlin-2 is required for talin-induced integrin activation. Furthermore, we demonstrate that Kindlin-2 is required for integrin outside-in signaling to enable firm adhesion and spreading. Our findings provide evidence that Kindlin-2 is a novel and essential element of bidirectional integrin signaling

Replacement of mouse Sox10 by the Drosophila ortholog Sox100B provides evidence for co-option of SoxE proteins into vertebrate-specific gene-regulatory networks through altered expression

AbstractNeural crest cells and oligodendrocytes as the myelinating glia of the central nervous system exist only in vertebrates. Their development is regulated by complex regulatory networks, of which the SoxE-type high-mobility-group domain transcription factors Sox8, Sox9 and Sox10 are essential components. Here we analyzed by in ovo electroporation in chicken and by gene replacement in the mouse whether the Drosophila ortholog Sox100B can functionally substitute for vertebrate SoxE proteins. Sox100B overexpression in the chicken neural tube led to the induction of neural crest cells as previously observed for vertebrate SoxE proteins. Furthermore, many aspects of neural crest and oligodendrocyte development were surprisingly normal in mice in which the Sox10 coding information was replaced by Sox100B arguing that Sox100B integrates well into the gene-regulatory networks that drive these processes. Our results therefore provide strong evidence for a model in which SoxE proteins were co-opted to these gene-regulatory networks mainly through the acquisition of novel expression patterns. However, later developmental defects in several neural crest derived lineages in mice homozygous for the Sox100B replacement allele indicate that some degree of functional specialization and adaptation of SoxE protein properties have taken place in addition to the co-option event

Comparative Proteomic Analysis Reveals Varying Impact on Immune Responses in Phorbol 12-Myristate-13-Acetate-Mediated THP-1 Monocyte-to-Macrophage Differentiation

Macrophages are sentinels of the innate immune system, and the human monocytic cell line THP-1 is one of the widely used in vitro models to study inflammatory processes and immune responses. Several monocyte-to-macrophage differentiation protocols exist, with phorbol 12-myristate-13-acetate (PMA) being the most commonly used and accepted method. However, the concentrations and duration of PMA treatment vary widely in the published literature and could affect the probed phenotype, however their effect on protein expression is not fully deciphered. In this study, we employed a dimethyl labeling-based quantitative proteomics approach to determine the changes in the protein repertoire of macrophage-like cells differentiated from THP-1 monocytes by three commonly used PMA-based differentiation protocols. Employing an integrated network analysis, we show that variations in PMA concentration and duration of rest post-stimulation result in downstream differences in the protein expression and cellular signaling processes. We demonstrate that these differences result in altered inflammatory responses, including variation in the expression of cytokines upon stimulation with various Toll-like receptor (TLR) agonists. Together, these findings provide a valuable resource that significantly expands the knowledge of protein expression dynamics with one of the most common in vitro models for macrophages, which in turn has a profound impact on the immune as well as inflammatory responses being studied