Recent Submissions

  • Journal Article

    EFForTS-LGraf: A landscape generator for creating smallholder-driven land-use mosaics 

    Salecker, Jan; Dislich, Claudia; Wiegand, Kerstin; Meyer, Katrin M.; Pe´er, Guy
    PLOS ONE 2019; 14(9): Art. e0222949
    Spatially-explicit simulation models are commonly used to study complex ecological and socio-economic research questions. Often these models depend on detailed input data, such as initial land-cover maps to set up model simulations. Here we present the landscape generator EFFortS-LGraf that provides artificially-generated land-use maps of agricultural landscapes shaped by small-scale farms. EFForTS-LGraf is a process-based landscape generator that explicitly incorporates the human dimension of land-use change. The model generates roads and villages that consist of smallholder farming households. These smallholders use different establishment strategies to create fields in their close vicinity. Crop types are distributed to these fields based on crop fractions and specialization levels. EFForTS-LGraf model parameters such as household area or field size frequency distributions can be derived from household surveys or geospatial data. This can be an advantage over the abstract parameters of neutral landscape generators. We tested the model using oil palm and rubber farming in Indonesia as a case study and validated the artificially-generated maps against classified satellite images. Our results show that EFForTS-LGraf is able to generate realistic land-cover maps with properties that lie within the boundaries of landscapes from classified satellite images. An applied simulation experiment on landscape-level effects of increasing household area and crop specialization revealed that larger households with higher specialization levels led to spatially more homogeneous and less scattered crop type distributions and reduced edge area proportion. Thus, EFForTS-LGraf can be applied both to generate maps as inputs for simulation modelling and as a stand-alone tool for specific landscape-scale analyses in the context of ecological-economic studies of smallholder farming systems.
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  • Journal Article

    Extending Hyperspectral Imaging for Plant Phenotyping to the UV-Range 

    Brugger, Anna; Behmann, Jan; Paulus, Stefan; Luigs, Hans-Georg; Kuska, Matheus Thomas; Schramowski, Patrick; Kersting, Kristian; Steiner, Ulrike; Mahlein, Anne-Katrin
    Remote Sensing 2019; 11(12): Art. 1401
    Previous plant phenotyping studies have focused on the visible (VIS, 400–700 nm), near-infrared (NIR, 700–1000 nm) and short-wave infrared (SWIR, 1000–2500 nm) range. The ultraviolet range (UV, 200–380 nm) has not yet been used in plant phenotyping even though a number of plant molecules like flavones and phenol feature absorption maxima in this range. In this study an imaging UV line scanner in the range of 250–430 nm is introduced to investigate crop plants for plant phenotyping. Observing plants in the UV-range can provide information about important changes of plant substances. To record reliable and reproducible time series results, measurement conditions were defined that exclude phototoxic effects of UV-illumination in the plant tissue. The measurement quality of the UV-camera has been assessed by comparing it to a non-imaging UV-spectrometer by measuring six different plant-based substances. Given the findings of these preliminary studies, an experiment has been defined and performed monitoring the stress response of barley leaves to salt stress. The aim was to visualize the effects of abiotic stress within the UV-range to provide new insights into the stress response of plants. Our study demonstrated the first use of a hyperspectral sensor in the UV-range for stress detection in plant phenotyping.
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  • Journal Article

    Evolution of intron splicing towards optimized gene expression is based on various Cis- and Trans-molecular mechanisms 

    Frumkin, Idan; Yofe, Ido; Bar-Ziv, Raz; Gurvich, Yonat; Lu, Yen-Yun; Voichek, Yoav; Towers, Ruth; Schirman, Dvir; Krebber, Heike; Pilpel, Yitzhak
    PLOS Biology 2019; 17(8): Art. e3000423
    Splicing expands, reshapes, and regulates the transcriptome of eukaryotic organisms. Despite its importance, key questions remain unanswered, including the following: Can splicing evolve when organisms adapt to new challenges? How does evolution optimize inefficiency of introns' splicing and of the splicing machinery? To explore these questions, we evolved yeast cells that were engineered to contain an inefficiently spliced intron inside a gene whose protein product was under selection for an increased expression level. We identified a combination of mutations in Cis (within the gene of interest) and in Trans (in mRNA-maturation machinery). Surprisingly, the mutations in Cis resided outside of known intronic functional sites and improved the intron's splicing efficiency potentially by easing tight mRNA structures. One of these mutations hampered a protein's domain that was not under selection, demonstrating the evolutionary flexibility of multi-domain proteins as one domain functionality was improved at the expense of the other domain. The Trans adaptations resided in two proteins, Npl3 and Gbp2, that bind pre-mRNAs and are central to their maturation. Interestingly, these mutations either increased or decreased the affinity of these proteins to mRNA, presumably allowing faster spliceosome recruitment or increased time before degradation of the pre-mRNAs, respectively. Altogether, our work reveals various mechanistic pathways toward optimizations of intron splicing to ultimately adapt gene expression patterns to novel demands.
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  • Journal Article

    Strategic deployment of feature-based attentional gain in primate visual cortex 

    Kozyrev, Vladislav; Daliri, Mohammad Reza; Schwedhelm, Philipp; Treue, Stefan
    PLOS Biology 2019; 17(8): Art. e3000387
    Attending to visual stimuli enhances the gain of those neurons in primate visual cortex that preferentially respond to the matching locations and features (on-target gain). Although this is well suited to enhance the neuronal representation of attended stimuli, it is nonoptimal under difficult discrimination conditions, as in the presence of similar distractors. In such cases, directing attention to neighboring neuronal populations (off-target gain) has been shown to be the most efficient strategy, but although such a strategic deployment of attention has been shown behaviorally, its underlying neural mechanisms are unknown. Here, we investigated how attention affects the population responses of neurons in the middle temporal (MT) visual area of rhesus monkeys to bidirectional movement inside the neurons' receptive field (RF). The monkeys were trained to focus their attention onto the fixation spot or to detect a direction or speed change in one of the motion directions (the "target"), ignoring the distractor motion. Population activity profiles were determined by systematically varying the patterns' directions while maintaining a constant angle between them. As expected, the response profiles show a peak for each of the 2 motion directions. Switching spatial attention from the fixation spot into the RF enhanced the peak representing the attended stimulus and suppressed the distractor representation. Importantly, the population data show a direction-dependent attentional modulation that does not peak at the target feature but rather along the slopes of the activity profile representing the target direction. Our results show that attentional gains are strategically deployed to optimize the discriminability of target stimuli, in line with an optimal gain mechanism proposed by Navalpakkam and Itti.
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  • Journal Article

    Measuring crops in 3D: using geometry for plant phenotyping 

    Paulus, Stefan
    Plant Methods 2019; 15(1): Art. 103
    Using 3D sensing for plant phenotyping has risen within the last years. This review provides an overview on 3D traits for the demands of plant phenotyping considering different measuring techniques, derived traits and use-cases of biological applications. A comparison between a high resolution 3D measuring device and an established measuring tool, the leaf meter, is shown to categorize the possible measurement accuracy. Furthermore, different measuring techniques such as laser triangulation, structure from motion, time-of-flight, terrestrial laser scanning or structured light approaches enable the assessment of plant traits such as leaf width and length, plant size, volume and development on plant and organ level. The introduced traits were shown with respect to the measured plant types, the used measuring technique and the link to their biological use case. These were trait and growth analysis for measurements over time as well as more complex investigation on water budget, drought responses and QTL (quantitative trait loci) analysis. The used processing pipelines were generalized in a 3D point cloud processing workflow showing the single processing steps to derive plant parameters on plant level, on organ level using machine learning or over time using time series measurements. Finally the next step in plant sensing, the fusion of different sensor types namely 3D and spectral measurements is introduced by an example on sugar beet. This multi-dimensional plant model is the key to model the influence of geometry on radiometric measurements and to correct it. This publication depicts the state of the art for 3D measuring of plant traits as they were used in plant phenotyping regarding how the data is acquired, how this data is processed and what kind of traits is measured at the single plant, the miniplot, the experimental field and the open field scale. Future research will focus on highly resolved point clouds on the experimental and field scale as well as on the automated trait extraction of organ traits to track organ development at these scales.
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  • Journal Article

    Topoisomerase IV can functionally replace all type 1A topoisomerases in Bacillus subtilis 

    Reuß, Daniel R.; Faßhauer, Patrick; Mroch, Philipp Joel; Ul-Haq, Inam; Koo, Byoung-Mo; Pöhlein, Anja; Gross, Carol A.; Daniel, Rolf; Brantl, Sabine; Stülke, Jörg
    Nucleic Acids Research 2019; 47(10) p.5231-5242
    DNA topoisomerases play essential roles in chromosome organization and replication. Most bacteria possess multiple topoisomerases which have specialized functions in the control of DNA supercoiling or in DNA catenation/decatenation during recombination and chromosome segregation. DNA topoisomerase I is required for the relaxation of negatively supercoiled DNA behind the transcribing RNA polymerase. Conflicting results have been reported on the essentiality of the topA gene encoding topoisomerase I in the model bacterium Bacillus subtilis. In this work, we have studied the requirement for topoisomerase I in B. subtilis. All stable topA mutants carried different chromosomal amplifications of the genomic region encompassing the parEC operon encoding topoisomerase IV. Using a fluorescent amplification reporter system we observed that each individual topA mutant had acquired such an amplification. Eventually, the amplifications were replaced by a point mutation in the parEC promoter region which resulted in a fivefold increase of parEC expression. In this strain both type I topoisomerases, encoded by topA and topB, were dispensable. Our results demonstrate that topoisomerase IV at increased expression is necessary and sufficient to take over the function of type 1A topoisomerases.
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  • Journal Article

    Structural basis for RNA translocation by DEAH-box ATPases 

    Hamann, Florian; Enders, Marieke; Ficner, Ralf
    Nucleic Acids Research 2019; 47(8) p.4349-4362
    DEAH-box adenosine triphosphatases (ATPases) play a crucial role in the spliceosome-mediated excision of pre-mRNA introns. Recent spliceosomal cryo-EM structures suggest that these proteins utilize translocation to apply forces on ssRNAs rather than direct RNA duplex unwinding to ensure global rearrangements. By solving the crystal structure of Prp22 in different adenosine nucleotide-free states, we identified two missing conformational snapshots of genuine DEAH-box ATPases that help to unravel the molecular mechanism of translocation for this protein family. The intrinsic mobility of the RecA2 domain in the absence of adenosine di- or triphosphate (ADP/ATP) and RNA enables DEAH-box ATPases to adopt different open conformations of the helicase core. The presence of RNA suppresses this mobility and stabilizes one defined open conformation when no adenosine nucleotide is bound. A comparison of this novel conformation with the ATP-bound state of Prp43 reveals that these ATPases cycle between closed and open conformations of the helicase core, which accommodate either a four- or five-nucleotide stack in the RNA-binding tunnel, respectively. The continuous repetition of these states enables these proteins to translocate in 3'-5' direction along an ssRNA with a step-size of one RNA nucleotide per hydrolyzed ATP. This ATP-driven motor function is maintained by a serine in the conserved motif V that senses the catalytic state and accordingly positions the RecA2 domain.
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  • Journal Article

    Membrane Lipids, Waxes and Oxylipins in the Moss Model Organism Physcomitrella patens 

    Resemann, Hanno C.; Lewandowska, Milena; Gömann, Jasmin; Feussner, Ivo
    Plant and Cell Physiology 2019; 60(6) p.1166-1175
    The moss Physcomitrella patens receives increased scientific interest since its genome was sequenced a decade ago. As a bryophyte, it represents the first group of plants that evolved in a terrestrial habitat still without a vascular system that developed later in tracheophytes. It is easily transformable via homologous recombination, which enables the formation of targeted loss-of-function mutants. Even though genetics, development and life cycle in Physcomitrella are well studied nowadays, research on lipids in Physcomitrella is still underdeveloped. This review aims on presenting an overview on the state of the art of lipid research with a focus on membrane lipids, surface lipids and oxylipins. We discuss in this review that Physcomitrella possesses very interesting features regarding its membrane lipids. Here, the presence of very-long-chain polyunsaturated fatty acids (VLC-PUFA) still shows a closer similarity to marine microalgae than to vascular plants. Unlike algae, Physcomitrella has a cuticle comparable to vascular plants composed of cutin and waxes. The presence of VLC-PUFA in Physcomitrella also leads to a greater variability of signaling lipids even though the phytohormone jasmonic acid is not present in this organism, which is different to vascular plants. In summary, the research on lipids in Physcomitrella is still in its infancy, especially considering membrane lipids. We hope that this review will help to promote the further advancement of lipid research in this important model organism in the future, so we can better understand how lipids are involved in the evolution of land plants.
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  • Journal Article

    Antibody-driven capture of synaptic vesicle proteins on the plasma membrane enables the analysis of their interactions with other synaptic proteins 

    Richter, Katharina N.; Patzelt, Christina; Phan, Nhu T. N.; Rizzoli, Silvio O.
    Scientific Reports 2019; 9(1): Art. 9231
    Many organelles from the secretory pathway fuse to the plasma membrane, to exocytose different cargoes. Their proteins are then retrieved from the plasma membrane by endocytosis, and the organelles are re-formed. It is generally unclear whether the organelle proteins colocalize when they are on the plasma membrane, or whether they disperse. To address this, we generated here a new approach, which we tested on synaptic vesicles, organelles that are known to exo- and endocytose frequently. We tagged the synaptotagmin molecules of newly exocytosed vesicles using clusters of primary and secondary antibodies targeted against the luminal domains of these molecules. The antibody clusters are too large for endocytosis, and thus sequestered the synaptotagmin molecules on the plasma membrane. Immunostainings for other synaptic molecules then revealed whether they colocalized with the sequestered synaptotagmin molecules. We suggest that such assays may be in the future extended to other cell types and other organelles.
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  • Special Issue

    **TEST** Interview: The process and difficulties to publish research output in context of migration 

    Tester, Mia
    CeMig publication series; 2019, 2
    2019
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  • Journal Article

    COP9 Signalosome Interaction with UspA/Usp15 Deubiquitinase Controls VeA-Mediated Fungal Multicellular Development 

    Meister, Cindy; Thieme; Karl G.; Thieme, Sabine; Köhler, Anna M.; Schmitt, Kerstin; Valerius, Oliver; Braus, Gerhard H.
    Biomolecules 2019; 9(6): Art. 238
    COP9 signalosome (CSN) and Den1/A deneddylases physically interact and promote multicellular development in fungi. CSN recognizes Skp1/cullin-1/Fbx E3 cullin-RING ligases (CRLs) without substrate and removes their posttranslational Nedd8 modification from the cullin scaffold. This results in CRL complex disassembly and allows Skp1 adaptor/Fbx receptor exchange for altered substrate specificity. We characterized the novel ubiquitin-specific protease UspA of the mold Aspergillus nidulans, which corresponds to CSN-associated human Usp15 and interacts with six CSN subunits. UspA reduces amounts of ubiquitinated proteins during fungal development, and the uspA gene expression is repressed by an intact CSN. UspA is localized in proximity to nuclei and recruits proteins related to nuclear transport and transcriptional processing, suggesting functions in nuclear entry control. UspA accelerates the formation of asexual conidiospores, sexual development, and supports the repression of secondary metabolite clusters as the derivative of benzaldehyde (dba) genes. UspA reduces protein levels of the fungal NF-kappa B-like velvet domain protein VeA, which coordinates differentiation and secondary metabolism. VeA stability depends on the Fbx23 receptor, which is required for light controlled development. Our data suggest that the interplay between CSN deneddylase, UspA deubiquitinase, and SCF-Fbx23 ensures accurate levels of VeA to support fungal development and an appropriate secondary metabolism.
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  • Working Paper

    - TEST-Daten - Aspects of new ideas in cultural heritage 

    Günther, Jelka
    CeMIG publication series; 2019, 1
    CeMig, 2019
    Zusammenfassung kommt noch
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  • Journal Article

    Ultrafast optogenetic stimulation of the auditory pathway by targeting‐optimized Chronos 

    Keppeler, Daniel; Merino, Ricardo Martins; Lopez de la Morena, David; Bali, Burak; Huet, Antoine Tarquin; Gehrt, Anna; Wrobel, Christian; Subramanian, Swati; Dombrowski, Tobias; Wolf, Fred; et al.
    Rankovic, VladanNeef, AndreasMoser, Tobias
    The EMBO Journal 2018; 37(24): Art. e99649
    Optogenetic tools, providing non‐invasive control over selected cells, have the potential to revolutionize sensory prostheses for humans. Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. However, most channelrhodopsins do not support the high temporal fidelity pertinent to auditory coding because they require milliseconds to close after light‐off. Here, we biophysically characterized the fast channelrhodopsin Chronos and revealed a deactivation time constant of less than a millisecond at body temperature. In order to enhance neural expression, we improved its trafficking to the plasma membrane (Chronos‐ES/TS). Following efficient transduction of SGNs using early postnatal injection of the adeno‐associated virus AAV‐PHP.B into the mouse cochlea, fiber‐based optical stimulation elicited optical auditory brainstem responses (oABR) with minimal latencies of 1 ms, thresholds of 5 μJ and 100 μs per pulse, and sizable amplitudes even at 1,000 Hz of stimulation. Recordings from single SGNs demonstrated good temporal precision of light‐evoked spiking. In conclusion, efficient virus‐mediated expression of targeting‐optimized Chronos‐ES/TS achieves ultrafast optogenetic control of neurons.
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  • Journal Article

    Public provision of emergency obstetric care: a case study in two districts of Pakistan 

    Brückmann, Peter; Hashmi, Ashfa; Kuch, Marina; Kuhnt, Jana; Monfared, Ida; Vollmer, Sebastian
    BMJ Open 2019; 9(5): Art. e027187
    Objectives Pakistan is one out of five countries where together half of the global neonatal deaths occur. As the provision of services and facilities is one of the key elements vital to reducing this rate as well as the maternal mortality rate, this study investigates the status of the delivery of essential obstetric care provided by the public health sector in two districts in Khyber Pakhtunkhwa in 2015 aiming to highlight areas where critical improvements are needed. Setting We analysed data from a survey of 22 primary and secondary healthcare facilities as well as 85 community midwives (CMWs) in Haripur and Nowshera districts. Participants Using a structured questionnaire we evaluated the performance of emergency obstetric care (EmOC) signal functions and patient statistics in public health facilities. Also, 102 CMWs were interviewed about working hours, basic and specialised delivery service provision, referral system and patient statistics. Primary outcome measures We investigate the public provision of emergency obstetric care using seven key medical services identified by the United Nations (UN). Results Deliveries by public health cadres account for about 30% of the total number of births in these districts. According to the UN benchmark, only a small fraction of basic EmOC (2/18) and half of the comprehensive EmOC (2/4) facilities of the recommended minimum number were available to the population in both districts. Only a minority of health facilities and CMWs carry out several signal functions. Only 8% of the total births in one of the study districts are performed in public EmOC health facilities. Conclusions Both districts show a significant shortage of available public EmOC service provisions. Development priorities need to be realigned to improve the availability, accessibility and quality of EmOC service provisions by the public health sector alongside with existing activities to increase institutional births.
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  • Journal Article

    Formation and development of the male copulatory organ in the spider Parasteatoda tepidariorum involves a metamorphosis-like process 

    Quade, Felix Simon Christian; Holtzheimer, Jana; Frohn, Jasper; Töpperwien, Mareike; Salditt, Tim; Prpic, Nikola-Michael
    Scientific Reports 2019; 9(1): Art. 6945
    Spiders have evolved a unique male copulatory organ, the pedipalp bulb. The morphology of the bulb is species specific and plays an important role in species recognition and prezygotic reproductive isolation. Despite its importance for spider biodiversity, the mechanisms that control bulb development are virtually unknown. We have used confocal laser scanning microscopy (CLSM) and diffusible iodine-based contrast-enhanced micro computed tomography (dice-µCT) to study bulb development in the spider Parasteatoda tepidariorum. These imaging technologies enabled us to study bulb development in situ, without the use of destructive procedures for the first time. We show here that the inflated pedipalp tip in the subadult stage is filled with haemolymph that rapidly coagulates. Coagulation indicates histolytic processes that disintegrate tibia and tarsus, similar to histolytic processes during metamorphosis in holometabolous insects. The coagulated material contains cell inclusions that likely represent the cell source for the re-establishment of tarsus and tibia after histolysis, comparable to the histoblasts in insect metamorphosis. The shape of the coagulated mass prefigures the shape of the adult tarsus (cymbium) like a blueprint for the histoblasts. This suggests a unique role for controlled coagulation after histolysis in the metamorphosis-like morphogenesis of the male pedipalp.
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  • Journal Article

    Mortality of Different Populus Genotypes in Recently Established Mixed Short Rotation Coppice with Robinia pseudoacacia L. 

    Rebola-Lichtenberg, Jessica; Schall, Peter; Annighöfer, Peter; Ammer, Christian; Leinemann, Ludger; Polle, Andrea; Euring, Dejuan
    Forests 2019; 10(5): Art. 410
    Short rotation coppices play an increasing role in providing wooden biomass for energy. Mixing fast-growing tree species in short rotation coppices may result in complementary e ects and increased yield. The aim of this study was to analyze the e ect on mortality of eight di erent poplar genotypes (Populus sp.) in mixed short rotation coppices with three di erent provenances of the N-fixing tree species black locust (Robinia pseudoacacia L.). Pure and mixed stands were established at two sites of contrasting fertility. Survival of poplar was assessed for each tree two times a year, for a period of three years. In the first two years, high variation in mortality was observed between the genotypes, but no significant di erences between pure and mixed stands were identified. However, three years after planting, higher mortality rates were observed in the mixtures across all poplar genotypes in comparison to pure stands. The expected advantage on growth of combining an N-fixing tree with an N-demanding tree species, such as poplar, was overshadowed by the Robinia’s dominance and competitiveness.
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  • Journal Article

    Biodiversity data integration—the significance of data resolution and domain 

    König, Christian; Weigelt, Patrick; Schrader, Julian; Taylor, Amanda; Kattge, Jens; Kreft, Holger
    PLOS Biology 2019; 17(3): Art. e3000183
    ecent years have seen an explosion in the availability of biodiversity data describing the distribution, function, and evolutionary history of life on earth. Integrating these heterogeneous data remains a challenge due to large variations in observational scales, collection purposes, and terminologies. Here, we conceptualize widely used biodiversity data types according to their domain (what aspect of biodiversity is described?) and informational resolution (how specific is the description?). Applying this framework to major data providers in biodiversity research reveals a strong focus on the disaggregated end of the data spectrum, whereas aggregated data types remain largely underutilized. We discuss the implications of this imbalance for the scope and representativeness of current macroecological research and highlight the synergies arising from a tighter integration of biodiversity data across domains and resolutions. We lay out effective strategies for data collection, mobilization, imputation, and sharing and summarize existing frameworks for scalable and integrative biodiversity research. Finally, we use two case studies to demonstrate how the explicit consideration of data domain and resolution helps to identify biases and gaps in global data sets and achieve unprecedented taxonomic and geographical data coverage in macroecological analyses.
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  • Journal Article

    A Theoretical Framework to Derive Simple, Firing-Rate-Dependent Mathematical Models of Synaptic Plasticity 

    Lappalainen, Janne; Herpich, Juliane; Tetzlaff, Christian
    Frontiers in Computational Neuroscience 2019; 13: Art. 26
    Synaptic plasticity serves as an essential mechanism underlying cognitive processes as learning and memory. For a better understanding detailed theoretical models combine experimental underpinnings of synaptic plasticity and match experimental results. However, these models are mathematically complex impeding the comprehensive investigation of their link to cognitive processes generally executed on the neuronal network level. Here, we derive a mathematical framework enabling the simplification of such detailed models of synaptic plasticity facilitating further mathematical analyses. By this framework we obtain a compact, firing-rate-dependent mathematical formulation, which includes the essential dynamics of the detailed model and, thus, of experimentally verified properties of synaptic plasticity. Amongst others, by testing our framework by abstracting the dynamics of two well-established calcium-dependent synaptic plasticity models, we derived that the synaptic changes depend on the square of the presynaptic firing rate, which is in contrast to previous assumptions. Thus, the here-presented framework enables the derivation of biologically plausible but simple mathematical models of synaptic plasticity allowing to analyze the underlying dependencies of synaptic dynamics from neuronal properties such as the firing rate and to investigate their implications in complex neuronal networks.
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  • Journal Article

    Signal peptide peptidase activity connects the unfolded protein response to plant defense suppression by Ustilago maydis 

    Pinter, Niko; Hach, Christina Andrea; Hampel, Martin; Rekhter, Dmitrij; Zienkiewicz, Krzysztof; Feussner, Ivo; Poehlein, Anja; Daniel, Rolf; Finkernagel, Florian; Heimel, Kai
    PLOS Pathogens 2019; 15(4): Art. e1007734
    The corn smut fungus Ustilago maydis requires the unfolded protein response (UPR) to maintain homeostasis of the endoplasmic reticulum (ER) during the biotrophic interaction with its host plant Zea mays (maize). Crosstalk between the UPR and pathways controlling pathogenic development is mediated by protein-protein interactions between the UPR regulator Cib1 and the developmental regulator Clp1. Cib1/Clp1 complex formation results in mutual modification of the connected regulatory networks thereby aligning fungal proliferation in planta, efficient effector secretion with increased ER stress tolerance and long-term UPR activation in planta. Here we address UPR-dependent gene expression and its modulation by Clp1 using combinatorial RNAseq/ChIPseq analyses. We show that increased ER stress resistance is connected to Clp1-dependent alterations of Cib1 phosphorylation, protein stability and UPR gene expression. Importantly, we identify by deletion screening of UPR core genes the signal peptide peptidase Spp1 as a novel key factor that is required for establishing a compatible biotrophic interaction between U. maydis and its host plant maize. Spp1 is dispensable for ER stress resistance and vegetative growth but requires catalytic activity to interfere with the plant defense, revealing a novel virulence specific function for signal peptide peptidases in a biotrophic fungal/plant interaction.
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  • Journal Article

    Hypertension screening, awareness, treatment, and control in India: A nationally representative cross-sectional study among individuals aged 15 to 49 years 

    Prenissl, Jonas; Manne-Goehler, Jennifer; Jaacks, Lindsay M.; Prabhakaran, Dorairaj; Awasthi, Ashish; Bischops, Anne Christine; Atun, Rifat; Bärnighausen, Till; Davies, Justine I.; Vollmer, Sebastian; et al.
    Geldsetzer, Pascal
    PLOS Medicine 2019; 16(5): Art. e1002801
    BACKGROUND: Evidence on where in the hypertension care process individuals are lost to care, and how this varies among states and population groups in a country as large as India, is essential for the design of targeted interventions and to monitor progress. Yet, to our knowledge, there has not yet been a nationally representative analysis of the proportion of adults who reach each step of the hypertension care process in India. This study aimed to determine (i) the proportion of adults with hypertension who have been screened, are aware of their diagnosis, take antihypertensive treatment, and have achieved control and (ii) the variation of these care indicators among states and sociodemographic groups. METHODS AND FINDINGS: We used data from a nationally representative household survey carried out from 20 January 2015 to 4 December 2016 among individuals aged 15-49 years in all states and union territories (hereafter "states") of the country. The stages of the care process-computed among those with hypertension at the time of the survey-were (i) having ever had one's blood pressure (BP) measured before the survey ("screened"), (ii) having been diagnosed ("aware"), (iii) currently taking BP-lowering medication ("treated"), and (iv) reporting being treated and not having a raised BP ("controlled"). We disaggregated these stages by state, rural-urban residence, sex, age group, body mass index, tobacco consumption, household wealth quintile, education, and marital status. In total, 731,864 participants were included in the analysis. Hypertension prevalence was 18.1% (95% CI 17.8%-18.4%). Among those with hypertension, 76.1% (95% CI 75.3%-76.8%) had ever received a BP measurement, 44.7% (95% CI 43.6%-45.8%) were aware of their diagnosis, 13.3% (95% CI 12.9%-13.8%) were treated, and 7.9% (95% CI 7.6%-8.3%) had achieved control. Male sex, rural location, lower household wealth, and not being married were associated with greater losses at each step of the care process. Between states, control among individuals with hypertension varied from 2.4% (95% CI 1.7%-3.3%) in Nagaland to 21.0% (95% CI 9.8%-39.6%) in Daman and Diu. At 38.0% (95% CI 36.3%-39.0%), 28.8% (95% CI 28.5%-29.2%), 28.4% (95% CI 27.7%-29.0%), and 28.4% (95% CI 27.8%-29.0%), respectively, Puducherry, Tamil Nadu, Sikkim, and Haryana had the highest proportion of all adults (irrespective of hypertension status) in the sampled age range who had hypertension but did not achieve control. The main limitation of this study is that its results cannot be generalized to adults aged 50 years and older-the population group in which hypertension is most common. CONCLUSIONS: Hypertension prevalence in India is high, but the proportion of adults with hypertension who are aware of their diagnosis, are treated, and achieve control is low. Even after adjusting for states' economic development, there is large variation among states in health system performance in the management of hypertension. Improvements in access to hypertension diagnosis and treatment are especially important among men, in rural areas, and in populations with lower household wealth.
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