Luther\u27s Doctrine of the Two Kingdoms in the Context of His Theology

In this essay, the distinguished church historian of Heidelberg University gives us a guided tour through one of the most complex and controversial problems in the interpretation of Christian ethics. Luther’s “two kingdoms” doctrine has been variously praised and damned in recent theology. Thinkers such as Nygren, Althaus, and Ebeling have defended the doctrine as the source of a salutary political realism (since it reminds us that no social order as such will ever be identical with the kingdom of Christ), combined with a definite sense of Christian social responsibility (since the “kingdom on the left” is also God’s kingdom, in which his will-to-justice is to be enacted). On the other hand, theologians such as Barth and Bonhoeffer have condemned the doctrine as the source of a hopeless dualism and defeatism.https://scholar.csl.edu/ebooks/1041/thumbnail.jp

Einige Überlegungen zur Einwanderung von Bromus erectus HUDS. in Süd-Niedersachsen

The study aims at contributing to the discussion in which way Bromus erectus invaded into southernmost Lower Saxony throughout the 20th century. Basing on the data of distribution, and on the evaluation of the ratio “cover of Bromus erectus/cover of Brachypodium pinnatum” in numerous phytosociological publications, it should be considered that the path of invasion did not lead straightly from S to N. The direction along the Eastern and Northern surrounding of the Harz mountains, and from here southwards through the Leine valley seems more likely. This invasion was mainly released by the strong reduction of grazing by sheep and goats. On the other hand this change in land use favours the growth of shrub vegetation and, thus, reduces the area accessible to Bromus erectus

Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins

Epstein-Barr virus (EBV) establishes lifelong persistent infections in humans by latently infecting B cells, with occasional cycles of reactivation, virus production, and reinfection. Protective immunity against EBV is mediated by T cells, but the role of EBV-specific T helper (Th) cells is still poorly defined. Here, we study the Th response to the EBV lytic cycle proteins BLLF1 (gp350/220), BALF4 (gp110), and BZLF1 and show that glycoprotein-specific Th cells recognize EBV-positive cells directly; surprisingly, a much higher percentage of target cells than those expressing lytic cycle proteins were recognized. Antigen is efficiently transferred to bystander B cells by receptor-mediated uptake of released virions, resulting in recognition of target cells incubated with <1 virion/cell. T cell recognition does not require productive infection and occurs early after virus entry before latency is established. Glycoprotein-specific Th cells are cytolytic and inhibit proliferation of lymphoblastoid cell lines (LCL) and the outgrowth of LCL after infection of primary B cells with EBV. These results establish a novel role for glycoprotein-specific Th cells in the control of EBV infection and identify virion proteins as important immune targets. These findings have implications for the treatment of diseases associated with EBV and potentially other coated viruses infecting MHC class II–positive cells

Specific metaphase and interphase detection of the breakpoint region in 8q24 of burkitt lymphoma cells by triple-color fluorescence in situ hybridization

Triple fluorescence in situ hybridization with a plasmid DNA library from sorted human chromosomes 8 in combination with bacteriophage clones flanking the breakpoint in 8q24 of the Burkitt lymphoma cell line Jl was used for the specific delineation of this breakpoint in individual tumor cells. With this approach, tumor-specific breakpoints in translocation chromosomes can be detected at all stages of the cell cycle with high specificity

Rapid conditional knock-down–knock-in system for mammalian cells

RNA interference (RNAi) is a powerful tool to analyze gene function in mammalian cells. However, the interpretation of RNAi knock-down phenotypes can be hampered by off-target effects or compound phenotypes, as many proteins combine multiple functions within one molecule and coordinate the assembly of multimolecular complexes. Replacing the endogenous protein with ectopic wild-type or mutant forms can exclude off-target effects, preserve complexes and unravel specific roles of domains or modifications. Therefore, we developed a rapid-knock-down–knock-in system for mammalian cells. Stable polyclonal cell lines were generated within 2 weeks by simultaneous selection of two episomal vectors. Together these vectors mediated reconstitution and knock-down in a doxycycline-dependent manner to allow the analysis of essential genes. Depletion was achieved by an artificial miRNA-embedded siRNA targeting the untranslated region of the endogenous, but not the ectopic mRNA. To prove effectiveness, we tested 17 mutants of WDR12, a factor essential for ribosome biogenesis and cell proliferation. Loss-off function phenotypes were rescued by the wild-type and six mutant forms, but not by the remaining mutants. Thus, our system is suitable to exclude off-target effects and to functionally analyze mutants in cells depleted for the endogenous protein

Mammalian WDR12 is a novel member of the Pes1–Bop1 complex and is required for ribosome biogenesis and cell proliferation

Target genes of the protooncogene c-myc are implicated in cell cycle and growth control, yet the linkage of both is still unexplored. Here, we show that the products of the nucleolar target genes Pes1 and Bop1 form a stable complex with a novel member, WDR12 (PeBoW complex). Endogenous WDR12, a WD40 repeat protein, is crucial for processing of the 32S precursor ribosomal RNA (rRNA) and cell proliferation. Further, a conditionally expressed dominant-negative mutant of WDR12 also blocks rRNA processing and induces a reversible cell cycle arrest. Mutant WDR12 triggers accumulation of p53 in a p19ARF-independent manner in proliferating cells but not in quiescent cells. Interestingly, a potential homologous complex of Pes1–Bop1–WDR12 in yeast (Nop7p–Erb1p–Ytm1p) is involved in the control of ribosome biogenesis and S phase entry. In conclusion, the integrity of the PeBoW complex is required for ribosome biogenesis and cell proliferation in mammalian cells

Stringent doxycycline-dependent control of gene activities using an episomal one-vector system

Conditional expression systems are of pivotal importance for the dissection of complex biological phenomena. Here, we describe a novel EBV-derived episomally replicating plasmid (pRTS-1) that carries all the elements for conditional expression of a gene of interest via Tet regulation. The vector is characterized by (i) low background activity, (ii) high inducibility in the presence of doxycycline (Dox) and (iii) graded response to increasing concentrations of the inducer. The chicken beta actin promoter and an element of the murine immunoglobin heavy chain intron enhancer drive constitutive expression of a bicistronic expression cassette that encodes the highly Dox-sensitive reverse tetracycline controlled transactivator rtTA2(S)-M2 and a Tet repressor-KRAB fusion protein (tTS(KRAB)) (silencer) placed downstream of an internal ribosomal entry site. The gene of interest is expressed from the bidirectional promoter P(tet)bi-1 that allows simultaneous expression of two genes, of which one may be used as surrogate marker for the expression of the gene of interest. Tight down regulation is achieved through binding of the silencer tTS(KRAB) to P(tet)bi-1 in the absence of Dox. Addition of Dox releases repression and via binding of rtTA2(S)-M2 activates P(tet)bi-1