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The degradation of natural forests to modified forests threatens subtropical and tropical biodiversity worldwide. Yet, species responses to forest modification vary considerably. Furthermore, effects of forest modification can differ, whether with respect to diversity components (taxonomic or phylogenetic) or to local (α-diversity) and regional (β-diversity) spatial scales. This real-world complexity has so far hampered our understanding of subtropical and tropical biodiversity patterns in human-modified forest landscapes. In a subtropical South African forest landscape, we studied the responses of three successive plant life stages (adult trees, saplings, seedlings) and of birds to five different types of forest modification distinguished by the degree of within-forest disturbance and forest loss. Responses of the two taxa differed markedly. Thus, the taxonomic α-diversity of birds was negatively correlated with the diversity of all plant life stages and, contrary to plant diversity, increased with forest disturbance. Conversely, forest disturbance reduced the phylogenetic α-diversity of all plant life stages but not that of birds. Forest loss neither affected taxonomic nor phylogenetic diversity of any taxon. On the regional scale, taxonomic but not phylogenetic β-diversity of both taxa was well predicted by variation in forest disturbance and forest loss. In contrast to adult trees, the phylogenetic diversity of saplings and seedlings showed signs of contemporary environmental filtering. In conclusion, forest modification in this subtropical landscape strongly shaped both local and regional biodiversity but with contrasting outcomes. Phylogenetic diversity of plants may be more threatened than that of mobile species such as birds. The reduced phylogenetic diversity of saplings and seedlings suggests losses in biodiversity that are not visible in adult trees, potentially indicating time-lags and contemporary shifts in forest regeneration. The different responses of taxonomic and phylogenetic diversity to forest modifications imply that biodiversity conservation in this subtropical landscape requires the preservation of natural and modified forests.
Simultaneous and dose dependent melanoma cytotoxic and immune stimulatory activity of betulin
(2015)
Conventional cytostatic cancer treatments rarely result in the complete eradication of tumor cells. Therefore, new therapeutic strategies focus on antagonizing the immunosuppressive activity of established tumors. In particular, recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific antitumor immune response has raised the hopes of achieving the complete elimination of tumor tissue. Genistein, fingolimod and betulin have already been described as active compounds in different types of cancer. Herein, we applied an integrated screening approach to characterize both their cytostatic and their immune-modulating properties side-by-side. As will be described in detail, our data confirmed that all three compounds exerted proapoptotic and antiproliferative activity in different B16 melanoma cell lines to a given extent, as revealed by an MTT assay, CFSE and DAPI staining. However, while genistein and fingolimod also affected the survival of primary bone marrow (BM) derived DCs of C57BL/6 mice, betulin exhibited a lower cytotoxicity for BMDCs in comparison to the melanoma cells. Moreover, we could show for the first time, that only betulin caused a simultaneous, highly specific immune-stimulating activity, as measured by the IL-12p70 release of Toll-like receptor 4-stimulated BMDCs by ELISA, which was due to increased IL-12p35 mRNA expression. Interestingly, the activation of DCs resulted in enhanced T lymphocyte stimulation, indicated by increased IL-2 and IFN-γ production of cytotoxic T cells in spleen cell co-culture assays which led to a decreased viability of B16 cells in an antigen specific model system. This may overcome the immunosuppressive environment of a tumor and destroy tumor cells more effectively in vivo if the immune response is specific targeted against the tumor tissue by antigen-loaded dendritic cells. In summary, cytostatic agents, such as betulin, that simultaneously exhibit immune stimulatory activity may serve as lead compounds and hold great promise as a novel approach for an integrated cancer therapy.
African trypanosomes cause a parasitic disease known as sleeping sickness. Mitochondrial transcript maturation in these organisms requires a RNA editing reaction that is characterized by the insertion and deletion of U-nucleotides into otherwise non-functional mRNAs. Editing represents an ideal target for a parasite-specific therapeutic intervention since the reaction cycle is absent in the infected host. In addition, editing relies on a macromolecular protein complex, the editosome, that only exists in the parasite. Therefore, all attempts to search for editing interfering compounds have been focused on molecules that bind to proteins of the editing machinery. However, in analogy to other RNA-driven biochemical pathways it should be possible to stall the reaction by targeting its substrate RNAs. Here we demonstrate inhibition of editing by specific aminoglycosides. The molecules bind into the major groove of the gRNA/pre-mRNA editing substrates thereby causing a stabilization of the RNA molecules through charge compensation and an increase in stacking. The data shed light on mechanistic details of the editing process and identify critical parameters for the development of new trypanocidal compounds.
The involvement of the ubiquitin-proteasome system (UPS) in the course of various age-associated neurodegenerative diseases is well established. The single RING finger type E3 ubiquitin-protein ligase PARK2 is mutated in a Parkinson’s disease (PD) variant and was found to interact with ATXN2, a protein where polyglutamine expansions cause Spinocerebellar ataxia type 2 (SCA2) or increase the risk for Levodopa-responsive PD and for the motor neuron disease Amyotrophic lateral sclerosis (ALS). We previously reported evidence for a transcriptional induction of the multi-subunit RING finger Skp1/Cul/F-box (SCF) type E3 ubiquitin-protein ligase complex component FBXW8 in global microarray profiling of ATXN2-expansion mouse cerebellum and demonstrated its role for ATXN2 degradation in vitro. Now, we documented co-localization in vitro and co-immunoprecipitations both in vitro and in vivo, which indicate associations of FBXW8 with ATXN2 and PARK2. Both FBXW8 and PARK2 proteins are driven into insolubility by expanded ATXN2. Whereas the FBXW8 transcript upregulation by ATXN2- expansion was confirmed also in qPCR of skin fibroblasts and blood samples of SCA2 patients, a FBXW8 expression dysregulation was not observed in ATXN2-deficient mice, nor was a PARK2 transcript dysregulation observed in any samples. Jointly, all available data suggest that the degradation of wildtype and mutant ATXN2 is dependent on FBXW8, and that ATXN2 accumulation selectively modulates FBXW8 levels, while PARK2 might act indirectly through FBXW8. The effects of ATXN2-expansions on FBXW8 expression in peripheral tissues like blood may become useful for clinical diagnostics
Intrinsic motivations drive the acquisition of knowledge and skills on the basis of novel or surprising stimuli or the pleasure to learn new skills. In so doing, they are different from extrinsic motivations that are mainly linked to drives that promote survival and reproduction. Intrinsic motivations have been implicitly exploited in several psychological experiments but, due to the lack of proper paradigms, they are rarely a direct subject of investigation. This article investigates how different intrinsic motivation mechanisms can support the learning of visual skills, such as "foveate a particular object in space", using a gaze contingency paradigm. In the experiment participants could freely foveate objects shown in a computer screen. Foveating each of two “button” pictures caused different effects: one caused the appearance of a simple image (blue rectangle) in unexpected positions, while the other evoked the appearance of an always-novel picture (objects or animals). The experiment studied how two possible intrinsic motivation mechanisms might guide learning to foveate one or the other button picture. One mechanism is based on the sudden, surprising appearance of a familiar image at unpredicted locations, and a second one is based on the content novelty of the images. The results show the comparative effectiveness of the mechanism based on image novelty, whereas they do not support the operation of the mechanism based on the surprising location of the image appearance. Interestingly, these results were also obtained with participants that, according to a post experiment questionnaire, had not understood the functions of the different buttons suggesting that novelty-based intrinsic motivation mechanisms might operate even at an unconscious level.
kurz und kn@pp news : Nr. 33
(2015)
In this paper, we examine how the institutional design affects the outcome of bank bailout decisions. In the German savings bank sector, distress events can be resolved by local politicians or a state-level association. We show that decisions by local politicians with close links to the bank are distorted by personal considerations: While distress events per se are not related to the electoral cycle, the probability of local politicians injecting taxpayers’ money into a bank in distress is 30 percent lower in the year directly preceding an election. Using the electoral cycle as an instrument, we show that banks that are bailed out by local politicians experience less restructuring and perform considerably worse than banks that are supported by the savings bank association. Our findings illustrate that larger distance between banks and decision makers reduces distortions in the decision making process, which has implications for the design of bank regulation and supervision.
Against the background of the European debt crisis, the Research Center SAFE, in the fall of 2013, had issued a call for papers on the topic “Austerity and Economic Growth: Concepts for Europe”, with the objective of soliciting research proposals focusing on the nature of the relationship between austerity, debt sustainability and growth. Each of the five funded projects brought forth an academic paper and a shortened, non-technical policy brief. These policy papers are presented in the present collection of policy letters, edited by Alfons Weichenrieder.
The first paper by Alberto Alesina, Carlo Favero and Francesco Giavazzi looks into the question of how fiscal consolidations influence the real economy. Harris Dellas and Dirk Niepelt emphasize that fiscal austerity is a signal that investors use to tell apart governments with high and low default costs that accordingly will have a high or low probability of repayment.The paper by Benjamin Born, Gernot Müller and Johannes Pfeiffer,looks at the impact of austerity measures on government bond spreads. Oscar Jorda and Alan M. Taylor, in the fourth contribution, put into question whether the narrative records of fiscal consolidation plans are really exogenous. The final study by Enrique Mendoza, Linda Tesar and Jing Zhang suggests that fiscal consolidation should largely depend on expenditure cuts, rather than tax increases that may fail, when fiscal space is exhausted.