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A genome-wide association study identifies markers and candidate genes affecting tolerance to the wheat pathogen Zymoseptoria tritici
Get PDFPlants defend themselves against pathogens using either resistance, measured as the host’s ability to limit pathogen multiplication, or tolerance, measured as the host’s ability to reduce the negative effects of infection. Tolerance is a promising trait for crop breeding, but its genetic basis has rarely been studied and remains poorly understood. Here, we reveal the genetic basis of leaf tolerance to the fungal pathogen Zymoseptoria tritici that causes the globally important septoria tritici blotch disease on wheat. Leaf tolerance to Z. tritici is a quantitative trait that was recently discovered in wheat by using automated image analyses that quantified the symptomatic leaf area and counted the number of pycnidia found on the same leaf. A genome-wide association study identified four chromosome intervals associated with tolerance and a separate chromosome interval associated with resistance. Within these intervals, we identified candidate genes, including wall-associated kinases similar to Stb6, the first cloned STB resistance gene. Our analysis revealed a strong negative genetic correlation between tolerance and resistance to STB, indicative of a trade-off. A trade-off between tolerance and resistance would hinder breeding simultaneously for both traits, but our findings suggest a way forward using marker-assisted breeding. We expect that the methods described here can be used to characterize tolerance to other fungal diseases that produce visible fruiting bodies, such as speckled leaf blotch on barley, potentially unveiling conserved tolerance mechanisms shared among plant species
Understanding and predicting animal movements and distributions in the Anthropocene
Get PDFPredicting animal movements and spatial distributions is crucial for our comprehension of ecological processes and provides key evidence for conserving and managing populations, species and ecosystems. Notwithstanding considerable progress in movement ecology in recent decades, developing robust predictions for rapidly changing environments remains challenging. To accurately predict the effects of anthropogenic change, it is important to first identify the defining features of human‐modified environments and their consequences on the drivers of animal movement. We review and discuss these features within the movement ecology framework, describing relationships between external environment, internal state, navigation and motion capacity. Developing robust predictions under novel situations requires models moving beyond purely correlative approaches to a dynamical systems perspective. This requires increased mechanistic modelling, using functional parameters derived from first principles of animal movement and decision‐making. Theory and empirical observations should be better integrated by using experimental approaches. Models should be fitted to new and historic data gathered across a wide range of contrasting environmental conditions. We need therefore a targeted and supervised approach to data collection, increasing the range of studied taxa and carefully considering issues of scale and bias, and mechanistic modelling. Thus, we caution against the indiscriminate non‐supervised use of citizen science data, AI and machine learning models. We highlight the challenges and opportunities of incorporating movement predictions into management actions and policy. Rewilding and translocation schemes offer exciting opportunities to collect data from novel environments, enabling tests of model predictions across varied contexts and scales. Adaptive management frameworks in particular, based on a stepwise iterative process, including predictions and refinements, provide exciting opportunities of mutual benefit to movement ecology and conservation. In conclusion, movement ecology is on the verge of transforming from a descriptive to a predictive science. This is a timely progression, given that robust predictions under rapidly changing environmental conditions are now more urgently needed than ever for evidence‐based management and policy decisions. Our key aim now is not to describe the existing data as well as possible, but rather to understand the underlying mechanisms and develop models with reliable predictive ability in novel situations
Extended modelling of molecular calcium signalling in platelets by combined recurrent neural network and partial least squares analyses
Get PDFPlatelets play critical roles in haemostasis and thrombosis. The platelet activation process is driven by agonist-induced rises in cytosolic [Ca2+]i, where the patterns of Ca2+ responses are still incompletely understood. In this study, we developed a number of techniques to model the [Ca2+]i curves of platelets from a single blood donor. Fura-2-loaded platelets were quasi-simultaneously stimulated with various agonists, i.e., thrombin, collagen, or CRP, in the presence or absence of extracellular Ca2+ entry, secondary mediator effects, or Ca2+ reuptake into intracellular stores. To understand the calibrated time curves of [Ca2+]i rises, we developed two non-linear models, a multilayer perceptron (MLP) network and an autoregressive network with exogenous inputs (NARX). The trained networks accurately predicted the [Ca2+]i curves for combinations of agonists and inhibitors, with the NARX model achieving an R2 of 0.64 for the trend prediction of unforeseen data. In addition, we used the same dataset for the construction of a partial least square (PLS) linear regression model, which estimated the explained variance of each input. The NARX model demonstrated that good fits could be obtained for the nanomolar [Ca2+]i curves modelled, whereas the PLS model gave useful interpretable information on the importance of each variable. These modelling results can be used for the development of novel platelet [Ca2+]i-inhibiting drugs, such as the drug 2-aminomethyl diphenylborinate, blocking Ca2+ entry in platelets, or for the evaluation of general platelet signalling defects in patients with a bleeding disorder
Early screening for Alzheimer’s disease: a scientific, ethical, and value-based framework for targeted screening in at-risk individuals
No full textAlthough curative therapies for Alzheimer's disease (AD) remain elusive, recent approval of disease-modifying treatments and advances of less- or non-invasive biomarkers have shifted the paradigm toward earlier detection, including asymptomatic individuals. Here, we propose a multidisciplinary framework, integrating scientific evidence, ethical principles, and value-based health care, to guide the responsible development and deployment of early detection programs for AD
Relationships between eveningness, bedtime procrastination, morning functioning, and skipping breakfast
Get PDFInter-relationships among eveningness, bedtime procrastination (BP), morning affect (MA), and breakfast skipping were investigated in 219 adults (aged 18-89, mean age = 26.2 years). Consistent with previous research, greater eveningness preference was associated with more BP, more breakfast skipping, and lower MA (i.e., less alert at awakening/requiring longer to fully awake). Two mediation models were tested: BP as a mediator between eveningness and MA, and MA as a mediator between eveningness and breakfast skipping. Results supported the first model, as more eveningness had an indirect effect through more BP to lower MA. The reversed model (BP mediating between MA as the predictor for eveningness) was also significant, indicating a bidirectional relationship. In contrast, MA did not mediate the relationship between eveningness and breakfast skipping, suggesting a more direct influence of time of day preference on eating behaviour. The reversed model (MA mediating between breakfast skipping as the predictor for eveningness) showed significance, but not after including covariates. These findings underscore the role of bedtime procrastination in undermining morning functioning, highlight a direct link between time of day preference and breakfast consumption, and suggest a bidirectional relationship between eveningness and MA. Longitudinal research may clarify causality and explore additional mediators
'Poetic fragments from the irritating archive' exhibited as part of 'The Living Library' exhibition at Being Human Festival (UK).
No full textPlatelets and circulating (tumor) cells: partners in promoting metastatic cancer.
No full textDespite being discovered decades ago, metastasis remains a formidable challenge in cancer treatment. During the intermediate phase of metastasis, tumor cells detach from primary tumor or metastatic sites and travel through the bloodstream and lymphatic system to distant tissues. These tumor cells in the circulation are known as circulating tumor cells (CTCs), and a higher number of CTCs has been linked to poor prognoses in various cancers. The blood is an inhospitable environment for any foreign cells, including CTCs, as they face numerous challenges, such as the shear stress within blood vessels and their interactions with blood and immune cells. However, the exact mechanisms by which CTCs survive the hostile conditions of the bloodstream remain enigmatic. Platelets have been studied for their interactions with tumor cells, promoting their survival, growth, and metastasis. This review explores the latest clinical methods for enumerating CTCs, recent findings on platelet-CTC crosstalk, and current research on antiplatelet therapy as a potential strategy to inhibit metastasis, offering new therapeutic insights.
RECENT FINDINGS
Laboratory and clinical data have provided insights into the role of platelets in promoting CTC survival, while clinical advancements in CTC enumeration offer improved prognostic tools.
SUMMARY
CTCs play a critical role in metastasis, and their interactions with platelets aid their survival in the hostile environment of the bloodstream. Understanding this crosstalk offers insights into potential therapeutic strategies, including antiplatelet therapy, to inhibit metastasis and improve cancer treatment outcomes
Zwischen angemesseneer Würdigung und euphorischer Lobeshymne – Spracheinstellungen in der Verwendung von Textsortenbezeichnungen
No full textTriple gains: more production, less nitrogen and greater diversity from cropland reallocation in England and Wales
Get PDFAgricultural production is the main driver of nitrogen pollution and diversity loss. This study assesses the potential of cropland reallocation to simultaneously increase production and decrease nitrogen balances, and its impact on crop diversity. Our technological specification extends the by-production approach by dynamically modelling the impact of the N balance from the previous year on current year crop production. We use a robust order-m data envelopment analysis to estimate the production frontier, and the Hill-Shannon index to assess crop diversity before and after optimal cropland reallocation. The application uses Farm Business Survey data from farms in England and Wales between 2015 and 2019. The results show that efficiency gains would have increased crop production by GBP 10.31 per ha and decreased the nitrogen balance by 1.05 kg per ha, when compared with a business-as-usual scenario. Reallocation, only focusing on increasing production, would have increased crop production by GBP 83.74 per hectare and reduced the nitrogen balance by 2.01 kg per ha. Reallocation, focusing on increasing production and decreasing the nitrogen balance, would have increased the former by GBP 71.88 per hectare and reduced the latter by 4.99 kg per ha. The median cropland diversity increases by approximately 0.24 species per farm in both reallocation scenarios. Our results suggest that farmers can simultaneously improve economic and environmental performance, which would increase crop diversity. Effective policies should address barriers to diversification and foster management practices that both increase production and decrease nitrogen balances