TY - JOUR A1 - Zurell, Damaris A1 - König, Christian A1 - Malchow, Anne-Kathleen A1 - Kapitza, Simon A1 - Bocedi, Greta A1 - Travis, Justin M. J. A1 - Fandos, Guillermo T1 - Spatially explicit models for decision-making in animal conservation and restoration JF - Ecography : pattern and diversity in ecology / Nordic Ecologic Society Oikos N2 - Models are useful tools for understanding and predicting ecological patterns and processes. Under ongoing climate and biodiversity change, they can greatly facilitate decision-making in conservation and restoration and help designing adequate management strategies for an uncertain future. Here, we review the use of spatially explicit models for decision support and to identify key gaps in current modelling in conservation and restoration. Of 650 reviewed publications, 217 publications had a clear management application and were included in our quantitative analyses. Overall, modelling studies were biased towards static models (79%), towards the species and population level (80%) and towards conservation (rather than restoration) applications (71%). Correlative niche models were the most widely used model type. Dynamic models as well as the gene-to-individual level and the community-to-ecosystem level were underrepresented, and explicit cost optimisation approaches were only used in 10% of the studies. We present a new model typology for selecting models for animal conservation and restoration, characterising model types according to organisational levels, biological processes of interest and desired management applications. This typology will help to more closely link models to management goals. Additionally, future efforts need to overcome important challenges related to data integration, model integration and decision-making. We conclude with five key recommendations, suggesting that wider usage of spatially explicit models for decision support can be achieved by 1) developing a toolbox with multiple, easier-to-use methods, 2) improving calibration and validation of dynamic modelling approaches and 3) developing best-practise guidelines for applying these models. Further, more robust decision-making can be achieved by 4) combining multiple modelling approaches to assess uncertainty, and 5) placing models at the core of adaptive management. These efforts must be accompanied by long-term funding for modelling and monitoring, and improved communication between research and practise to ensure optimal conservation and restoration outcomes. KW - adaptive management KW - biodiversity conservation KW - cost optimisation KW - ecosystem restoration KW - global change KW - predictive models Y1 - 2021 U6 - https://doi.org/10.1111/ecog.05787 SN - 1600-0587 IS - 4 SP - 1 EP - 16 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - König, Christian A1 - Weigelt, Patrick A1 - Taylor, Amanda A1 - Stein, Anke A1 - Dawson, Wayne A1 - Essl, Franz A1 - Pergl, Jan A1 - Pyšek, Petr A1 - Kleunen, Mark van A1 - Winter, Marten A1 - Chatelain, Cyrille A1 - Wieringa, Jan J. A1 - Krestov, Pavel A1 - Kreft, Holger T1 - Source pools and disharmony of the world’s island floras JF - Ecography N2 - Island disharmony refers to the biased representation of higher taxa on islands compared to their mainland source regions and represents a central concept in island biology. Here, we develop a generalizable framework for approximating these source regions and conduct the first global assessment of island disharmony and its underlying drivers. We compiled vascular plant species lists for 178 oceanic islands and 735 mainland regions. Using mainland data only, we modelled species turnover as a function of environmental and geographic distance and predicted the proportion of shared species between each island and mainland region. We then quantified the over- or under-representation of families on individual islands (representational disharmony) by contrasting the observed number of species against a null model of random colonization from the mainland source pool, and analysed the effects of six family-level functional traits on the resulting measure. Furthermore, we aggregated the values of representational disharmony per island to characterize overall taxonomic bias of a given flora (compositional disharmony), and analysed this second measure as a function of four island biogeographical variables. Our results indicate considerable variation in representational disharmony both within and among plant families. Examples of generally over-represented families include Urticaceae, Convolvulaceae and almost all pteridophyte families. Other families such as Asteraceae and Orchidaceae were generally under-represented, with local peaks of over-representation in known radiation hotspots. Abiotic pollination and a lack of dispersal specialization were most strongly associated with an insular over-representation of families, whereas other family-level traits showed minor effects. With respect to compositional disharmony, large, high-elevation islands tended to have the most disharmonic floras. Our results provide important insights into the taxon- and island-specific drivers of disharmony. The proposed framework allows overcoming the limitations of previous approaches and provides a quantitative basis for incorporating functional and phylogenetic approaches into future studies of island disharmony. KW - assembly processes KW - biotic filtering KW - dispersal filtering KW - environmental filtering KW - generalized dissimilarity modelling KW - island disharmony KW - island syndromes KW - source regions KW - vascular plants Y1 - 2020 VL - 44 IS - 1 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Müller, Marik A1 - Nedielkov, Ruslan A1 - Arndt, Katja M. T1 - Strategies for Enzymatic Inactivation of the Veterinary Antibiotic Florfenicol JF - Antibiotics N2 - Large quantities of the antibiotic florfenicol are used in animal farming and aquaculture, contaminating the ecosystem with antibiotic residues and promoting antimicrobial resistance, ultimately leading to untreatable multidrug-resistant pathogens. Florfenicol-resistant bacteria often activate export mechanisms that result in resistance to various structurally unrelated antibiotics. We devised novel strategies for the enzymatic inactivation of florfenicol in different media, such as saltwater or milk. Using a combinatorial approach and selection, we optimized a hydrolase (EstDL136) for florfenicol cleavage. Reaction kinetics were followed by time-resolved NMR spectroscopy. Importantly, the hydrolase remained active in different media, such as saltwater or cow milk. Various environmentally-friendly application strategies for florfenicol inactivation were developed using the optimized hydrolase. As a potential filter device for cost-effective treatment of waste milk or aquacultural wastewater, the hydrolase was immobilized on Ni-NTA agarose or silica as carrier materials. In two further application examples, the hydrolase was used as cell extract or encapsulated with a semi-permeable membrane. This facilitated, for example, florfenicol inactivation in whole milk, which can help to treat waste milk from medicated cows, to be fed to calves without the risk of inducing antibiotic resistance. Enzymatic inactivation of antibiotics, in general, enables therapeutic intervention without promoting antibiotic resistance. KW - aquaculture KW - antibiotic inactivation KW - enzyme optimization KW - enzymatic inactivation KW - florfenicol KW - immobilization KW - industrial farming Y1 - 2022 U6 - https://doi.org/10.3390/antibiotics11040443 SN - 2079-6382 VL - 11 IS - 4 SP - 1 EP - 18 PB - MDPI CY - Basel, Schweiz ER - TY - JOUR A1 - Taleb, Aiham A1 - Rohrer, Csaba A1 - Bergner, Benjamin A1 - De Leon, Guilherme A1 - Rodrigues, Jonas Almeida A1 - Schwendicke, Falk A1 - Lippert, Christoph A1 - Krois, Joachim T1 - Self-supervised learning methods for label-efficient dental caries classification JF - Diagnostics : open access journal N2 - High annotation costs are a substantial bottleneck in applying deep learning architectures to clinically relevant use cases, substantiating the need for algorithms to learn from unlabeled data. In this work, we propose employing self-supervised methods. To that end, we trained with three self-supervised algorithms on a large corpus of unlabeled dental images, which contained 38K bitewing radiographs (BWRs). We then applied the learned neural network representations on tooth-level dental caries classification, for which we utilized labels extracted from electronic health records (EHRs). Finally, a holdout test-set was established, which consisted of 343 BWRs and was annotated by three dental professionals and approved by a senior dentist. This test-set was used to evaluate the fine-tuned caries classification models. Our experimental results demonstrate the obtained gains by pretraining models using self-supervised algorithms. These include improved caries classification performance (6 p.p. increase in sensitivity) and, most importantly, improved label-efficiency. In other words, the resulting models can be fine-tuned using few labels (annotations). Our results show that using as few as 18 annotations can produce >= 45% sensitivity, which is comparable to human-level diagnostic performance. This study shows that self-supervision can provide gains in medical image analysis, particularly when obtaining labels is costly and expensive. KW - unsupervised methods KW - self-supervised learning KW - representation learning KW - dental caries classification KW - data driven approaches KW - annotation KW - efficient deep learning Y1 - 2022 U6 - https://doi.org/10.3390/diagnostics12051237 SN - 2075-4418 VL - 12 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Kindermann, Liana A1 - Dobler, Magnus A1 - Niedeggen, Daniela A1 - Chimbioputo Fabiano, Ezequiel A1 - Linstädter, Anja T1 - Dataset on woody aboveground biomass, disturbance losses, and wood density from an African savanna ecosystem JF - Data in Brief N2 - This dataset comprises tree inventories and damage assessments performed in Namibia's semi-arid Zambezi Region. Data were sampled in savannas and savanna woodlands along steep gradients of elephant population densities to capture the effects of those (and other) disturbances on individual-level and stand-level aboveground woody biomass (AGB). The dataset contains raw data on dendrometric measures and processed data on specific wood density (SWD), woody aboveground biomass, and biomass losses through disturbance impacts. Allometric proxies (height, canopy diameters, and in adult trees also stem circumferences) were recorded for n = 6,179 tree and shrub individuals. Wood samples were taken for each encountered species to measure specific wood density. These measurements have been used to estimate woody aboveground biomass via established allometric models, advanced through our improved methodologies and workflows that accounted for tree and shrub architecture shaped by disturbance impacts. To this end, we performed a detailed damage assessment on each woody individual in the field. In addition to estimations of standing biomass, our new method also delivered data on biomass losses to different disturbance agents (elephants, fire, and others) on the level of plant individuals and stands. The data presented here have been used within a study published with Ecological Indicators (Kindermann et al., 2022) to evaluate the benefits of our improved methodology in comparison to a standard reference method of aboveground biomass estimations. Additionally, it has been employed in a study on carbon storage and sequestration in vegetation and soils (Sandhage-Hofmann et al., 2021). The raw data of dendrometric measurements can be subjected to other available allometric models for biomass estimation. The processed data can be used to analyze disturbance impacts on woody aboveground biomass, or for regional carbon storage estimates. The data on species-specific wood density can be used for application to other dendrometric datasets to (re-) estimate biomass through allometric models requiring wood density. It can further be used for plant functional trait analyses. KW - Damage assessment KW - Disturbance impacts KW - Disturbance indicator KW - Elephant disturbance KW - Tree allometry KW - Specific wood density KW - Woody aboveground biomass KW - Wood specific gravity Y1 - 2022 U6 - https://doi.org/10.1016/j.dib.2022.108155 SN - 2352-3409 VL - 42 SP - 1 EP - 16 PB - Elsevier CY - Amsterdam, Niederlande ER - TY - JOUR A1 - Ruszkiewicz, Joanna A1 - Endig, Lisa A1 - Güver, Ebru A1 - Bürkle, Alexander A1 - Mangerich, Aswin T1 - Life-cycle-dependent toxicities of mono- and bifunctional alkylating agents in the 3R-compliant model organism C. elegans JF - Cells : open access journal N2 - Caenorhabditis elegans (C. elegans) is gaining recognition and importance as an organismic model for toxicity testing in line with the 3Rs principle (replace, reduce, refine). In this study, we explored the use of C. elegans to examine the toxicities of alkylating sulphur mustard analogues, specifically the monofunctional agent 2-chloroethyl-ethyl sulphide (CEES) and the bifunctional, crosslinking agent mechlorethamine (HN2). We exposed wild-type worms at different life cycle stages (from larvae L1 to adulthood day 10) to CEES or HN2 and scored their viability 24 h later. The susceptibility of C. elegans to CEES and HN2 paralleled that of human cells, with HN2 exhibiting higher toxicity than CEES, reflected in LC50 values in the high µM to low mM range. Importantly, the effects were dependent on the worms’ developmental stage as well as organismic age: the highest susceptibility was observed in L1, whereas the lowest was observed in L4 worms. In adult worms, susceptibility to alkylating agents increased with advanced age, especially to HN2. To examine reproductive effects, L4 worms were exposed to CEES and HN2, and both the offspring and the percentage of unhatched eggs were assessed. Moreover, germline apoptosis was assessed by using ced-1p::GFP (MD701) worms. In contrast to concentrations that elicited low toxicities to L4 worms, CEES and HN2 were highly toxic to germline cells, manifesting as increased germline apoptosis as well as reduced offspring number and percentage of eggs hatched. Again, HN2 exhibited stronger effects than CEES. Compound specificity was also evident in toxicities to dopaminergic neurons–HN2 exposure affected expression of dopamine transporter DAT-1 (strain BY200) at lower concentrations than CEES, suggesting a higher neurotoxic effect. Mechanistically, nicotinamide adenine dinucleotide (NAD+) has been linked to mustard agent toxicities. Therefore, the NAD+-dependent system was investigated in the response to CEES and HN2 treatment. Overall NAD+ levels in worm extracts were revealed to be largely resistant to mustard exposure except for high concentrations, which lowered the NAD+ levels in L4 worms 24 h post-treatment. Interestingly, however, mutant worms lacking components of NAD+-dependent pathways involved in genome maintenance, namely pme-2, parg-2, and sirt-2.1 showed a higher and compound-specific susceptibility, indicating an active role of NAD+ in genotoxic stress response. In conclusion, the present results demonstrate that C. elegans represents an attractive model to study the toxicology of alkylating agents, which supports its use in mechanistic as well as intervention studies with major strength in the possibility to analyze toxicities at different life cycle stages. KW - C. elegans KW - alkylating agents KW - mustards KW - life cycle toxicities KW - neurotoxicity KW - NAD+ Y1 - 2023 U6 - https://doi.org/10.3390/cells12232728 SN - 2073-4409 VL - 12 IS - 23 PB - MDPI CY - Basel ER - TY - JOUR A1 - Quarmby, Andrew A1 - Zhang, Martin A1 - Geisler, Moritz A1 - Javorsky, Tomas A1 - Mugele, Hendrik A1 - Cassel, Michael A1 - Lawley, Justin T1 - Risk factors and injury prevention strategies for overuse injuries in adult climbers BT - a systematic review JF - Frontiers in sports and active living N2 - Introduction Climbing is an increasingly popular activity and imposes specific physiological demands on the human body, which results in unique injury presentations. Of particular concern are overuse injuries (non-traumatic injuries). These injuries tend to present in the upper body and might be preventable with adequate knowledge of risk factors which could inform about injury prevention strategies. Research in this area has recently emerged but has yet to be synthesized comprehensively. Therefore, the aim of this study was to conduct a systematic review of the potential risk factors and injury prevention strategies for overuse injuries in adult climbers. Methods This systematic review was conducted in accordance with the PRISMA guidelines. Databases were searched systematically, and articles were deemed eligible based upon specific criteria. Research included was original and peer-reviewed, involving climbers, and published in English, German or Czech. Outcomes included overuse injury, and at least one or more variable indicating potential risk factors or injury prevention strategies. The methodological quality of the included studies was assessed with the Downs and Black Quality Index. Data were extracted from included studies and reported descriptively for population, climbing sport type, study design, injury definition and incidence/prevalence, risk factors, and injury prevention strategies. Results Out of 1,183 records, a total of 34 studies were included in the final analysis. Higher climbing intensity, bouldering, reduced grip/finger strength, use of a “crimp” grip, and previous injury were associated with an increased risk of overuse injury. Additionally, a strength training intervention prevented shoulder and elbow injuries. BMI/body weight, warm up/cool downs, stretching, taping and hydration were not associated with risk of overuse injury. The evidence for the risk factors of training volume, age/years of climbing experience, and sex was conflicting. Discussion This review presents several risk factors which appear to increase the risk of overuse injury in climbers. Strength and conditioning, load management, and climbing technique could be targeted in injury prevention programs, to enhance the health and wellbeing of climbing athletes. Further research is required to investigate the conflicting findings reported across included studies, and to investigate the effectiveness of injury prevention programs. Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023404031). KW - climbing KW - bouldering KW - overuse injuries KW - risk factors KW - injury prevention KW - systematic reveiw KW - climbing injuries Y1 - 2023 U6 - https://doi.org/10.3389/fspor.2023.1269870 SN - 2624-9367 VL - 5 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Puchkov, Dmytro A1 - Müller, Paul Markus A1 - Lehmann, Martin A1 - Matthäus, Claudia T1 - Analyzing the cellular plasma membrane by fast and efficient correlative STED and platinum replica EM JF - Frontiers in cell and developmental biology N2 - The plasma membrane of mammalian cells links transmembrane receptors, various structural components, and membrane-binding proteins to subcellular processes, allowing inter- and intracellular communication. Therefore, membrane-binding proteins, together with structural components such as actin filaments, modulate the cell membrane in their flexibility, stiffness, and curvature. Investigating membrane components and curvature in cells remains challenging due to the diffraction limit in light microscopy. Preparation of 5–15-nm-thin plasma membrane sheets and subsequent inspection by metal replica transmission electron microscopy (TEM) reveal detailed information about the cellular membrane topology, including the structure and curvature. However, electron microscopy cannot identify proteins associated with specific plasma membrane domains. Here, we describe a novel adaptation of correlative super-resolution light microscopy and platinum replica TEM (CLEM-PREM), allowing the analysis of plasma membrane sheets with respect to their structural details, curvature, and associated protein composition. We suggest a number of shortcuts and troubleshooting solutions to contemporary PREM protocols. Thus, implementation of super-resolution stimulated emission depletion (STED) microscopy offers significant reduction in sample preparation time and reduced technical challenges for imaging and analysis. Additionally, highly technical challenges associated with replica preparation and transfer on a TEM grid can be overcome by scanning electron microscopy (SEM) imaging. The combination of STED microscopy and platinum replica SEM or TEM provides the highest spatial resolution of plasma membrane proteins and their underlying membrane and is, therefore, a suitable method to study cellular events like endocytosis, membrane trafficking, or membrane tension adaptations. KW - plasma membrane KW - endocytosis KW - CLEM KW - STED KW - TEM KW - SEM KW - electron microscopy Y1 - 2023 U6 - https://doi.org/10.3389/fcell.2023.1305680 SN - 2296-634X VL - 11 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Küken, Anika A1 - Treves, Haim A1 - Nikoloski, Zoran T1 - A simulation-free constrained regression approach for flux estimation in isotopically nonstationary metabolic flux analysis with applications in microalgae JF - Frontiers in plant science : FPLS N2 - Introduction Flux phenotypes from different organisms and growth conditions allow better understanding of differential metabolic networks functions. Fluxes of metabolic reactions represent the integrated outcome of transcription, translation, and post-translational modifications, and directly affect growth and fitness. However, fluxes of intracellular metabolic reactions cannot be directly measured, but are estimated via metabolic flux analysis (MFA) that integrates data on isotope labeling patterns of metabolites with metabolic models. While the application of metabolomics technologies in photosynthetic organisms have resulted in unprecedented data from 13CO2-labeling experiments, the bottleneck in flux estimation remains the application of isotopically nonstationary MFA (INST-MFA). INST-MFA entails fitting a (large) system of coupled ordinary differential equations, with metabolite pools and reaction fluxes as parameters. Here, we focus on the Calvin-Benson cycle (CBC) as a key pathway for carbon fixation in photosynthesizing organisms and ask if approaches other than classical INST-MFA can provide reliable estimation of fluxes for reactions comprising this pathway. Methods First, we show that flux estimation with the labeling patterns of all CBC intermediates can be formulated as a single constrained regression problem, avoiding the need for repeated simulation of time-resolved labeling patterns. Results We then compare the flux estimates of the simulation-free constrained regression approach with those obtained from the classical INST-MFA based on labeling patterns of metabolites from the microalgae Chlamydomonas reinhardtii, Chlorella sorokiniana and Chlorella ohadii under different growth conditions. Discussion Our findings indicate that, in data-rich scenarios, simulation-free regression-based approaches provide a suitable alternative for flux estimation from classical INST-MFA since we observe a high qualitative agreement (rs=0.89) to predictions obtained from INCA, a state-of-the-art tool for INST-MFA. KW - metabolic flux analysis KW - INST-MFA KW - regression KW - 13C labeling KW - algae Y1 - 2023 U6 - https://doi.org/10.3389/fpls.2023.1140829 SN - 1664-462X VL - 14 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Langary, Damoun A1 - Küken, Anika A1 - Nikoloski, Zoran T1 - The effective deficiency of biochemical networks JF - Scientific reports N2 - The deficiency of a (bio)chemical reaction network can be conceptually interpreted as a measure of its ability to support exotic dynamical behavior and/or multistationarity. The classical definition of deficiency relates to the capacity of a network to permit variations of the complex formation rate vector at steady state, irrespective of the network kinetics. However, the deficiency is by definition completely insensitive to the fine details of the directionality of reactions as well as bounds on reaction fluxes. While the classical definition of deficiency can be readily applied in the analysis of unconstrained, weakly reversible networks, it only provides an upper bound in the cases where relevant constraints on reaction fluxes are imposed. Here we propose the concept of effective deficiency, which provides a more accurate assessment of the network’s capacity to permit steady state variations at the complex level for constrained networks of any reversibility patterns. The effective deficiency relies on the concept of nonstoichiometric balanced complexes, which we have already shown to be present in real-world biochemical networks operating under flux constraints. Our results demonstrate that the effective deficiency of real-world biochemical networks is smaller than the classical deficiency, indicating the effects of reaction directionality and flux bounds on the variation of the complex formation rate vector at steady state. Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-41767-1 SN - 2045-2322 VL - 13 PB - Springer Nature CY - London ER -