TY - JOUR A1 - Bolius, Sarah A1 - Wiedner, Claudia A1 - Weithoff, Guntram T1 - Low invasion success of an invasive cyanobacterium in a chlorophyte dominated lake JF - Scientific reports Y1 - 2019 SN - 2045-2322 VL - 9 PB - Macmillan Publishers Limited CY - London ER - TY - JOUR A1 - Feiner, Rebecca Christine A1 - Teschner, Julian A1 - Teschner, Kathrin E. A1 - Radukic, Marco T. A1 - Baumann, Tobias A1 - Hagen, Sven A1 - Hannappel, Yvonne A1 - Biere, Niklas A1 - Anselmetti, Dario A1 - Arndt, Katja Maren A1 - Müller, Kristian Mark T1 - rAAV Engineering for Capsid-Protein Enzyme Insertions and Mosaicism Reveals Resilience to Mutational, Structural and Thermal Perturbations JF - International journal of molecular sciences N2 - Recombinant adeno-associated viruses (rAAV) provide outstanding options for customization and superior capabilities for gene therapy. To access their full potential, facile genetic manipulation is pivotal, including capsid loop modifications. Therefore, we assessed capsid tolerance to modifications of the structural VP proteins in terms of stability and plasticity. Flexible glycine-serine linkers of increasing sizes were, at the genetic level, introduced into the 587 loop region of the VP proteins of serotype 2, the best studied AAV representative. Analyses of biological function and thermal stability with respect to genome release of viral particles revealed structural plasticity. In addition, insertion of the 29 kDa enzyme beta-lactamase into the loop region was tested with a complete or a mosaic modification setting. For the mosaic approach, investigation of VP2 trans expression revealed that a Kozak sequence was required to prevent leaky scanning. Surprisingly, even the full capsid modification with beta-lactamase allowed for the assembly of capsids with a concomitant increase in size. Enzyme activity assays revealed lactamase functionality for both rAAV variants, which demonstrates the structural robustness of this platform technology. KW - adeno-associated-virus KW - beta-lactamase KW - inverted terminal repeat (ITR) KW - loop modification KW - capsid stability Y1 - 2019 U6 - https://doi.org/10.3390/ijms20225702 SN - 1422-0067 VL - 20 IS - 22 PB - MDPI CY - Basel ER - TY - JOUR A1 - Ayzel, Georgy A1 - Izhitskiy, Alexander T1 - Climate Change Impact Assessment on Freshwater Inflow into the Small Aral Sea JF - Water N2 - During the last few decades, the rapid separation of the Small Aral Sea from the isolated basin has changed its hydrological and ecological conditions tremendously. In the present study, we developed and validated the hybrid model for the Syr Darya River basin based on a combination of state-of-the-art hydrological and machine learning models. Climate change impact on freshwater inflow into the Small Aral Sea for the projection period 2007-2099 has been quantified based on the developed hybrid model and bias corrected and downscaled meteorological projections simulated by four General Circulation Models (GCM) for each of three Representative Concentration Pathway scenarios (RCP). The developed hybrid model reliably simulates freshwater inflow for the historical period with a Nash-Sutcliffe efficiency of 0.72 and a Kling-Gupta efficiency of 0.77. Results of the climate change impact assessment showed that the freshwater inflow projections produced by different GCMs are misleading by providing contradictory results for the projection period. However, we identified that the relative runoff changes are expected to be more pronounced in the case of more aggressive RCP scenarios. The simulated projections of freshwater inflow provide a basis for further assessment of climate change impacts on hydrological and ecological conditions of the Small Aral Sea in the 21st Century. KW - Small Aral Sea KW - hydrology KW - climate change KW - modeling KW - machine learning Y1 - 2019 U6 - https://doi.org/10.3390/w11112377 SN - 2073-4441 VL - 11 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Wu, Hao A1 - Han, Yijie A1 - Rodriguez Sillke, Yasmina A1 - Deng, Hongzhang A1 - Siddiqui, Sophiya A1 - Treese, Christoph A1 - Schmidt, Franziska A1 - Friedrich, Marie A1 - Keye, Jacqueline A1 - Wan, Jiajia A1 - Qin, Yue A1 - Kühl, Anja A. A1 - Qin, Zhihai A1 - Siegmund, Britta A1 - Glauben, Rainer T1 - Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages JF - EMBO molecular medicine N2 - Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level. KW - cancer immunotherapy KW - lipid droplets KW - lipid metabolism KW - tumor microenvironment KW - tumor-associated macrophage Y1 - 2019 U6 - https://doi.org/10.15252/emmm.201910698 SN - 1757-4676 SN - 1757-4684 VL - 11 IS - 11 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Hsu, H. F. A1 - Krekhov, Andrey A1 - Tarantola, Marco A1 - Beta, Carsten A1 - Bodenschatz, Eberhardt T1 - Interplay between myosin II and actin dynamics in chemotactic amoeba JF - New journal of physics : the open-access journal for physics N2 - The actin cytoskeleton and its response to external chemical stimuli is fundamental to the mechano-biology of eukaryotic cells and their functions. One of the key players that governs the dynamics of the actin network is the motor protein myosin II. Based on a phase space embedding we have identified from experiments three phases in the cytoskeletal dynamics of starved Dictyostelium discoideum in response to a precisely controlled chemotactic stimulation. In the first two phases the dynamics of actin and myosin II in the cortex is uncoupled, while in the third phase the time scale for the recovery of cortical actin is determined by the myosin II dynamics. We report a theoretical model that captures the experimental observations quantitatively. The model predicts an increase in the optimal response time of actin with decreasing myosin II-actin coupling strength highlighting the role of myosin II in the robust control of cell contraction. KW - actin KW - myosin II KW - chemotaxis KW - oscillations KW - coupling KW - delay differential equation KW - contraction Y1 - 2019 U6 - https://doi.org/10.1088/1367-2630/ab5822 SN - 1367-2630 VL - 21 IS - 11 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Kielar, Charlotte A1 - Xin, Yang A1 - Xu, Xiaodan A1 - Zhu, Siqi A1 - Gorin, Nelli A1 - Grundmeier, Guido A1 - Möser, Christin A1 - Smith, David M. A1 - Keller, Adrian T1 - Effect of staple age on DNA origami nanostructure assembly and stability JF - Molecules N2 - DNA origami nanostructures are widely employed in various areas of fundamental and applied research. Due to the tremendous success of the DNA origami technique in the academic field, considerable efforts currently aim at the translation of this technology from a laboratory setting to real-world applications, such as nanoelectronics, drug delivery, and biosensing. While many of these real-world applications rely on an intact DNA origami shape, they often also subject the DNA origami nanostructures to rather harsh and potentially damaging environmental and processing conditions. Furthermore, in the context of DNA origami mass production, the long-term storage of DNA origami nanostructures or their pre-assembled components also becomes an issue of high relevance, especially regarding the possible negative effects on DNA origami structural integrity. Thus, we investigated the effect of staple age on the self-assembly and stability of DNA origami nanostructures using atomic force microscopy. Different harsh processing conditions were simulated by applying different sample preparation protocols. Our results show that staple solutions may be stored at -20 degrees C for several years without impeding DNA origami self-assembly. Depending on DNA origami shape and superstructure, however, staple age may have negative effects on DNA origami stability under harsh treatment conditions. Mass spectrometry analysis of the aged staple mixtures revealed no signs of staple fragmentation. We, therefore, attribute the increased DNA origami sensitivity toward environmental conditions to an accumulation of damaged nucleobases, which undergo weaker base-pairing interactions and thus lead to reduced duplex stability. KW - DNA origami KW - atomic force microscopy KW - stability KW - storage Y1 - 2019 U6 - https://doi.org/10.3390/molecules24142577 SN - 1420-3049 VL - 24 IS - 14 PB - MDPI CY - Basel ER - TY - JOUR A1 - Yan, Wenhao A1 - Chen, Dijun A1 - Schumacher, Julia A1 - Durantini, Diego A1 - Engelhorn, Julia A1 - Chen, Ming A1 - Carles, Cristel C. A1 - Kaufmann, Kerstin T1 - Dynamic control of enhancer activity drives stage-specific gene expression during flower morphogenesis JF - Nature Communications N2 - Enhancers are critical for developmental stage-specific gene expression, but their dynamic regulation in plants remains poorly understood. Here we compare genome-wide localization of H3K27ac, chromatin accessibility and transcriptomic changes during flower development in Arabidopsis. H3K27ac prevalently marks promoter-proximal regions, suggesting that H3K27ac is not a hallmark for enhancers in Arabidopsis. We provide computational and experimental evidence to confirm that distal DNase. hypersensitive sites are predictive of enhancers. The predicted enhancers are highly stage-specific across flower development, significantly associated with SNPs for flowering-related phenotypes, and conserved across crucifer species. Through the integration of genome-wide transcription factor (TF) binding datasets, we find that floral master regulators and stage-specific TFs are largely enriched at developmentally dynamic enhancers. Finally, we show that enhancer clusters and intronic enhancers significantly associate with stage-specific gene regulation by floral master TFs. Our study provides insights into the functional flexibility of enhancers during plant development, as well as hints to annotate plant enhancers. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-09513-2 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Schieferdecker, Anne A1 - Wendler, Petra T1 - Structural Mapping of Missense Mutations in the Pex1/Pex6 Complex JF - International journal of molecular sciences N2 - Peroxisome biogenesis disorders (PBDs) are nontreatable hereditary diseases with a broad range of severity. Approximately 65% of patients are affected by mutations in the peroxins Pex1 and Pex6. The proteins form the heteromeric Pex1/Pex6 complex, which is important for protein import into peroxisomes. To date, no structural data are available for this AAA+ ATPase complex. However, a wealth of information can be transferred from low-resolution structures of the yeast scPex1/scPex6 complex and homologous, well-characterized AAA+ ATPases. We review the abundant records of missense mutations described in PBD patients with the aim to classify and rationalize them by mapping them onto a homology model of the human Pex1/Pex6 complex. Several mutations concern functionally conserved residues that are implied in ATP hydrolysis and substrate processing. Contrary to fold destabilizing mutations, patients suffering from function-impairing mutations may not benefit from stabilizing agents, which have been reported as potential therapeutics for PBD patients. KW - Zellweger syndrome spectrum disorder (ZSSD) KW - Zellweger KW - structure KW - Pex1 KW - Pex6 KW - mutation Y1 - 2019 U6 - https://doi.org/10.3390/ijms20153756 SN - 1422-0067 VL - 20 IS - 15 PB - MDPI CY - Basel ER - TY - JOUR A1 - Hargis, Hailey A1 - Gotsch, Sybil G. A1 - Porada, Philipp A1 - Moore, Georgianne W. A1 - Ferguson, Briana A1 - Van Stan, John T. T1 - Arboreal epiphytes in the soil-atmosphere interface BT - how often are the biggest "buckets" in the canopy empty? JF - Geosciences N2 - Arboreal epiphytes (plants residing in forest canopies) are present across all major climate zones and play important roles in forest biogeochemistry. The substantial water storage capacity per unit area of the epiphyte "bucket" is a key attribute underlying their capability to influence forest hydrological processes and their related mass and energy flows. It is commonly assumed that the epiphyte bucket remains saturated, or near-saturated, most of the time; thus, epiphytes (particularly vascular epiphytes) can store little precipitation, limiting their impact on the forest canopy water budget. We present evidence that contradicts this common assumption from (i) an examination of past research; (ii) new datasets on vascular epiphyte and epi-soil water relations at a tropical montane cloud forest (Monteverde, Costa Rica); and (iii) a global evaluation of non-vascular epiphyte saturation state using a process-based vegetation model, LiBry. All analyses found that the external and internal water storage capacity of epiphyte communities is highly dynamic and frequently available to intercept precipitation. Globally, non-vascular epiphytes spend <20% of their time near saturation and regionally, including the humid tropics, model results found that non-vascular epiphytes spend similar to 1/3 of their time in the dry state (0-10% of water storage capacity). Even data from Costa Rican cloud forest sites found the epiphyte community was saturated only 1/3 of the time and that internal leaf water storage was temporally dynamic enough to aid in precipitation interception. Analysis of the epi-soils associated with epiphytes further revealed the extent to which the epiphyte bucket emptied-as even the canopy soils were often <50% saturated (29-53% of all days observed). Results clearly show that the epiphyte bucket is more dynamic than currently assumed, meriting further research on epiphyte roles in precipitation interception, redistribution to the surface and chemical composition of "net" precipitation waters reaching the surface. KW - precipitation KW - interception KW - bromeliad KW - vascular epiphyte KW - non-vascular epiphyte KW - lichens KW - bryophytes KW - water storage capacity Y1 - 2019 U6 - https://doi.org/10.3390/geosciences9080342 SN - 2076-3263 VL - 9 IS - 8 PB - MDPI CY - Basel ER - TY - JOUR A1 - Martin-Lopez, Berta A1 - Leister, Ines A1 - Cruz, Pedro Lorenzo A1 - Palomo, Ignacio A1 - Gret-Regamey, Adrienne A1 - Harrison, Paula A. A1 - Lavorel, Sandra A1 - Locatelli, Bruno A1 - Luque, Sandra A1 - Walz, Ariane T1 - Nature’s contributions to people in mountains BT - a review JF - PLoS one N2 - Mountains play a key role in the provision of nature’s contributions to people (NCP) worldwide that support societies’ quality of life. Simultaneously, mountains are threatened by multiple drivers of change. Due to the complex interlinkages between biodiversity, quality of life and drivers of change, research on NCP in mountains requires interdisciplinary approaches. In this study, we used the conceptual framework of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) and the notion of NCP to determine to what extent previous research on ecosystem services in mountains has explored the different components of the IPBES conceptual framework. We conducted a systematic review of articles on ecosystem services in mountains published up to 2016 using the Web of Science and Scopus databases. Descriptive statistical and network analyses were conducted to explore the level of research on the components of the IPBES framework and their interactions. Our results show that research has gradually become more interdisciplinary by studying higher number of NCP, dimensions of quality of life, and indirect drivers of change. Yet, research focusing on biodiversity, regulating NCP and direct drivers has decreased over time. Furthermore, despite the fact that research on NCP in mountains becoming more policy-oriented over time, mainly in relation to payments for ecosystem services, institutional responses remained underexplored in the reviewed studies. Finally, we discuss the relevant knowledge gaps that should be addressed in future research in order to contribute to IPBES. Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0217847 SN - 1932-6203 VL - 14 IS - 6 PB - PLoS CY - San Fransisco ER -