Kapitel 24. Theorien des Wandels und der Gestaltung von Strukturen

Abschnitt 5 nimmt eine Bestandsaufnahme von Theorien vor, die in einem weiten Sinne Wandel untersuchen. „Theorien des Wandels“ ist ein Überbegriff für all diejenigen Theorien, die helfen, aktuelle Dynamiken der Klimakrise zu verstehen und sowohl die stattfindenden als auch die notwendigen Transformationen zu fassen

Kapitel 2: Perspektiven zur Analyse und Gestaltung von Strukturen für ein klimafreundliches Leben

Kapitel 2 systematisiert entlang von vier Perspektiven in den Sozialwissenschaften weit verbreitete Theorien zur Analyse und Gestaltung von Strukturen klimafreundlichen Lebens. Das Kapitel möchte Leser_innen des Berichts bewusst machen, mit wie grundlegend unterschiedlichen Zugängen Forscher_innen Strukturen klimafreundlichen Lebens analysieren. Dies ist wichtig, um zu verstehen, dass es nie nur eine, sondern immer mehrere Perspektiven auf Strukturen klimafreundlichen Lebens gibt. Dieses Bewusstsein hilft, die Komplexität der Sozialwissenschaften und damit die Komplexität der Aufgabe – Strukturen für ein klimafreundliches Leben zu gestalten – zu erfassen. Unterschiedliche Zugänge zu sehen, bedeutet auch, ein besseres Verständnis von konfligierenden Problemdiagnosen, Zielhorizonten und Gestaltungsoptionen zu entwickeln und – idealerweise – damit umgehen zu können

Artificial Modulation of the Gating Behavior of a K+ Channel in a KvAP-DNA Chimera

We present experiments where the gating behavior of a voltage-gated ion channel is modulated by artificial ligand binding. We construct a channel-DNA chimera with the KvAP potassium channel reconstituted in an artificial membrane. The channel is functional and the single channel ion conductivity unperturbed by the presence of the DNA. However, the channel opening probability vs. bias voltage, i.e., the gating, can be shifted considerably by the electrostatic force between the charges on the DNA and the voltage sensing domain of the protein. Different hybridization states of the chimera DNA thus lead to different response curves of the channel

Hum. Mol. Genet.

Spinal muscular atrophy (SMA), the most common hereditary motor neuron disease in children and young adults is caused by mutations in the telomeric survival motor neuron (SMN1) gene. The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels of full-length SMN protein. The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood. Using yeast two-hybrid techniques, we identified hnRNP-R and the highly related gry- rbp/hnRNP-Q as novel SMN interaction partners. These proteins have previously been identified in the context of RNA processing, in particular mRNA editing, transport and splicing. hnRNP-R and gry-rbp/hnRNP-Q interact with wild-type Smn but not with truncated or mutant Smn forms identified in SMA. Both proteins are widely expressed and developmentally regulated with expression peaking at E19 in mouse spinal cord. hnRNP-R binds RNA through its RNA recognition motif domains. Interestingly, hnRNP-R is predominantly located in axons of motor neurons and co-localizes with Smn in this cellular compartment. Thus, this finding could provide a key to understand a motor neuron-specific Smn function in SMA

Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?

Spinal muscular atrophy (SMA), the most common hereditary motor neuron disease in children and young adults is caused by mutations in the telomeric survival motor neuron (SMN1) gene. The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels of full-length SMN protein. The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood. Using yeast two-hybrid techniques, we identified hnRNP-R and the highly related gry- rbp/hnRNP-Q as novel SMN interaction partners. These proteins have previously been identified in the context of RNA processing, in particular mRNA editing, transport and splicing. hnRNP-R and gry-rbp/hnRNP-Q interact with wild-type Smn but not with truncated or mutant Smn forms identified in SMA. Both proteins are widely expressed and developmentally regulated with expression peaking at E19 in mouse spinal cord. hnRNP-R binds RNA through its RNA recognition motif domains. Interestingly, hnRNP-R is predominantly located in axons of motor neurons and co-localizes with Smn in this cellular compartment. Thus, this finding could provide a key to understand a motor neuron-specific Smn function in SMA

Binding Interaction of HMGB4 with Cisplatin-Modified DNA

Proteins in the HMG family are important transcription factors. They recognize cisplatin-damaged DNA lesions with a structure-specific preference and account for more than 70% of all proteins that interact with the cisplatin 1,2-intrastrand d(GpG) cross-link. HMGB4, a new member of the mammalian HMGB protein family expressed preferentially in the testis, was generated recombinantly, and its interactions with cisplatin-modified DNA were investigated in vitro. The binding affinities of the two individual DNA-binding domains of HMGB4 to DNA carrying a cisplatin 1,2-intrastrand d(GpG) cross-link are weaker than those of the DNA-binding domains of HMGB1. Full-length HMGB4, however, has a 28-fold stronger binding affinity (K[subscript d] = 4.35 nM) for the platinated adduct compared to that of HMGB1 (K[subscript d] = 120 nM), presumably because the former lacks a C-terminal acidic tail. The residue Phe37 plays a critical role in stabilizing the binding complex of HMGB4 with the cisplatin-modified DNA, as it does for HMGB1. Hydroxyl radical footprinting analysis of the HMGB4/platinated DNA complex reveals a footprinting pattern very different from that of HMGB1, however, revealing very little binding asymmetry with respect to the platinated lesion. An in vitro repair assay revealed that HMGB4, at 1 μM, interferes with repair of cisplatin 1,2-intrastrand cross-link damage by >90% compared to control, whereas HMGB1 at the same concentration inhibits repair by 45%. This repair inhibition capability is highly dependent on both the binding affinity and the size of the proteins. The putative role of HMGB4 in the mechanism of action of cisplatin, and especially its potential relevance to the hypersensitivity of testicular germ cell tumors to cisplatin, are discussed.National Cancer Institute (U.S.) (Grant CA034992