Centre Marc Bloch

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    31325 research outputs found

    Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii

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    Ribose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis; however, the importance and homeostasis of R5P in the intracellular parasite Toxoplasma gondii remain enigmatic. Here, we show that the cytoplasmic sedoheptulose-1,7-bisphosphatase (SBPase) is dispensable. Still, its co-deletion with transaldolase (TAL) impairs the double mutant’s growth and increases 13 C-glucose-derived flux into pentose sugars via the transketolase (TKT) enzyme. Deletion of the latter protein affects the parasite’s fitness but is not lethal and is correlated with an increased carbon flux via the oxidative pentose phosphate pathway. Further, loss of TKT leads to a decline in 13 C incorporation into glycolysis and the TCA cycle, resulting in a decrease in ATP levels and the inability of phosphoribosyl-pyrophosphate synthetase (PRPS) to convert R5P into 5′-phosphoribosyl-pyrophosphate and thereby contribute to the production of AMP and IMP. Likewise, PRPS is essential for the lytic cycle. Not least, we show that RuPE-mediated metabolic compensation is imperative for the survival of the ΔsbpaseΔtal strain. In conclusion, we demonstrate that multiple routes can flexibly supply R5P to enable parasite growth and identify catalysis by TKT and PRPS as critical enzymatic steps. Our work provides novel biological and therapeutic insights into the network design principles of intracellular parasitism in a clinically-relevant pathogen.This research was supported by the Guangdong Major Project of Basic and Applied Basic Research (2020B0301030007 to LHX); National Natural Science Foundation of China (32002305 to NBX); Laboratory for Lingnan Modern Agriculture Project (NT2021007 to YYF); Natural Science Foundation of Guangdong Province (2022A1515011104 to NBX); 111 Project (D20008 to LHX); and Innovation Team Project of Guangdong University (2019KCXTD001 to YYF). Supplementary funding was provided via a Core Research Grant to NG (CRG/2021/000919) by the Department of Science and Technology – Science and Engineering Research Board (DST-SERB), India. NG also acknowledges the extended support of the Senior fellowship by the DBT–Wellcome Trust (India Alliance, IA/S/19/1/504263). The funders had no role in the design, data collection, analysis, preparation or decision to publish this work.Peer Reviewe

    Farm adaptation to stricter nutrient management legislation and the implications for future livestock production: a review

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    Stricter nutrient surplus and lower emission targets are placing adaptation pressure on livestock farms in European countries, while the public debate on how farms should react upon this pressure is controversial. In this paper, we performed an integrative literature review on different farm adaptation options, including (i) structural adaptation, (ii) technological adaptation, (iii) manure redistribution, and (iv) farm system conversion. Our analysis showed that stricter environmental legislation, together with complementary supply- and demand-related drivers, induced various farm responses. These ranged from easy to implement solutions (e.g. moderate livestock destocking to the legal levels combined with the adoption of emission abatement technologies) to novel niche concepts (e.g. animal husbandry without slaughtering). Possible reactions of farmers differed in their complexity and feasibility across different farm types and involved different trade-offs between environmental and socioeconomic interests. Future livestock production is expected to be diverse with different coexisting models that combine features of different adaptation options. The private and public sustainability of these models depends on their ability to simultaneously address multiple emerging challenges (e.g. emission reduction, animal welfare, biosecurity, and circularity). Current technological solutions often focus on a single objective (e.g. emission reduction). Integrated and multifunctional solutions (e.g. low-emission animal welfare barns compatible with biosecurity measures) are not yet sufficiently adopted, which calls for a rethinking and shifting in priorities in legislation and funding schemes.Open Access funding enabled and organized by Projekt DEAL.Bundesministerium für Bildung und Forschunghttp://dx.doi.org/10.13039/501100002347Leibniz-Zentrum für Agrarlandschaftsforschung (ZALF) e.V. (3493)Peer Reviewe

    Variable habitat use supports fine-scale population differentiation of a freshwater piscivore (northern pike, Esox lucius) along salinity gradients in brackish lagoons

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    In mobile animals, selection pressures resulting from spatio-temporally varying ecological factors often drive adaptations in migration behavior and associated physiological phenotypes. These adaptations may manifest in ecologically and genetically distinct ecotypes within populations. We studied a meta-population of northern pike ( Esox lucius ) in brackish environments and examined intrapopulation divergence along environmental gradients. Behavioral phenotypes in habitat use were characterized via otolith microchemistry in 120 individuals sampled from brackish lagoons and adjacent freshwater tributaries. We genotyped 1514 individual pike at 33 highly informative genetic markers. The relationship between behavioral phenotype and genotype was examined in a subset of 101 pikes for which both phenotypic and genomic data were available. Thermosaline differences between juvenile and adult life stages indicated ontogenetic shifts from warm, low-saline early habitats towards colder, higher-saline adult habitats. Four behavioral phenotypes were found: Freshwater residents, anadromous, brackish residents, and cross-habitat individuals, the latter showing intermediary habitat use between brackish and freshwater areas. Underlying the behavioral phenotypes were four genotypes, putative freshwater, putative anadromous, and two putatively brackish genotypes. Through phenotype-genotype matching, three ecotypes were identified: (i) a brackish resident ecotype, (ii) a freshwater ecotype expressing freshwater residency or anadromy, and (iii) a previously undescribed intermediary cross-habitat ecotype adapted to intermediate salinities, showing limited reliance on freshwater. Life-time growth of all ecotypes was similar, suggesting comparable fitness. By combining genetic data with lifelong habitat use and growth as a fitness surrogate, our study revealed strong differentiation in response to abiotic environmental gradients, primarily salinity, indicating ecotype diversity in coastal northern pike is higher than previously believed.Peer Reviewe

    Tailored to Women, Provided to Men? Gendered Occupational Inequality in Access to Flexible Working-Time Arrangements

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    Numerous policy-makers and social scientists promote flexible working as a means to reconcile work and family life, often explicitly targeting women. Accordingly, one might expect that flexible working-time arrangements are more prevalent in occupations with a high share of female employees. Yet, previous evidence indicates the opposite. To address this puzzle, we investigate the occupational opportunity structures for flexible working. A devaluation argument proposes that employers perceive female-typed work as being of lower value, thus inhibiting the provision of flexible working-time arrangements in tfemale-dominated occupations. We evaluate this argument against alternative explanations, namely differences in the ability to bargain for flexible working and in structural or practical barriers to flexible working. Descriptive results based on German panel data (GSOEP, 2003–2017) enriched with occupational-level information confirm that female-dominated occupations provide the least access to flexible work. Linear probability models with yearly fixed-effects indicate that power resources and structural barriers account for differences in flexible working between male-dominated and integrated occupations; yet an unexplained disadvantage for female-dominated occupations remains. Moreover, this disadvantage has grown between 2003 and 2017. We interpret this result as support of a cultural devaluation of female-dominated occupations in access to flexible working-time arrangements. Our findings highlight that the empirical reality of gendered occupational opportunity structures contradicts the gendered policy discourse on flexible work.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Humboldt-Universität zu Berlin (1034)Peer Reviewe

    Cloud-to-Ground Lightning in Cities: Seasonal Variability and Influential Factors

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    Urban-induced land use changes have a significant impact on local weather patterns, leading to increased hydro-meteorological hazards in cities. Despite substantial threats posed to humans, understanding atmospheric hazards related to urbanisation, such as thunderstorms, lightning, and convective precipitation, remains unclear. This study aims to analyse seasonal variability of cloud-to-ground (CG) lightning in the five large metropolitans in Bangladesh utilising six years (2015–2020) of Global Lightning Detection Network (popularly known as GLD360) data. It also investigates factors influencing CG strokes. The analysis revealed substantial seasonal fluctuations in CG strokes, with a noticeable increase in lightning activity during the pre-monsoon months from upwind to metropolitan areas across the five cities. Both season and location appear to impact the diurnal variability of CG strokes in these urban centres. Bivariate regression analysis indicated that precipitation and particulate matter (PM) significantly influence lightning generation, whilst population density, urban size, and mean surface temperature have negligible effects. A sensitivity test employing a random forest (RF) model underscored the pivotal role of PM in CG strokes in four of the five cities assessed, highlighting the enduring impact of extreme pollution on lightning activity. Despite low causalities from CG lightning, the risk of property damage remains high in urban environments. This study provides valuable insights for shaping public policies in Bangladesh, a globally recognised climate hotspot.Open Access funding enabled and organized by CAUL and its Member InstitutionsCurtin UniversityPeer Reviewe

    Educational science since 1990: Reduction, segmentation, identity problems—The loss of significance of a discipline

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    Der Beitrag untersucht die Sozialgestalt der Erziehungswissenschaft seit der Vereinigung 1990, die als historische Zäsur auch deshalb gilt, weil sie eine lange Phase distanzierter Selbstbeobachtung der Disziplin markiert. Gestützt auf Indikatoren zur Infrastruktur der Disziplin im Hochschulsystem, auf ihre Stellung in der außeruniversitären Forschung sowie in der evaluativen Beobachtung und angesichts der Nachfrage nach erziehungswissenschaftlicher Expertise wird insgesamt ein Bedeutungsverlust der Disziplin konstatiert, weil die Erziehungswissenschaft sich weder akademisch mit Professoren noch im Wissenschaftssystem insgesamt als eigenständige Forschungskraft behaupten kann.The article examines the social form of educational science since its unification in 1990, which is also considered a historical turning point because it marks a long phase of distanced self-observation of the discipline. Based on indicators on the infrastructure of the discipline in the higher education system, on its position in non-university research as well as in evaluative observation, and in view of the demand for educational expertise, an overall loss of importance of the discipline is noted overall, because educational science cannot assert itself as an independent research force either academically with professors or in the science system as a whole.Open Access funding enabled and organized by Projekt DEAL.Humboldt-Universität zu Berlin (1034)Peer Reviewe

    Association between resting-state connectivity patterns in the defensive system network and treatment response in spider phobia—a replication approach

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    Although highly effective on average, exposure-based treatments do not work equally well for all patients with anxiety disorders. The identification of pre-treatment response-predicting patient characteristics may enable patient stratification. Preliminary research highlights the relevance of inhibitory fronto-limbic networks as such. We aimed to identify pre-treatment neural signatures differing between exposure treatment responders and non-responders in spider phobia and to validate results through rigorous replication. Data of a bi-centric intervention study comprised clinical phenotyping and pre-treatment resting-state functional connectivity (rsFC) data of n  = 79 patients with spider phobia (discovery sample) and n  = 69 patients (replication sample). RsFC data analyses were accomplished using the Matlab-based CONN-toolbox with harmonized analyses protocols at both sites. Treatment response was defined by a reduction of >30% symptom severity from pre- to post-treatment (Spider Phobia Questionnaire Score, primary outcome). Secondary outcome was defined by a reduction of >50% in a Behavioral Avoidance Test (BAT). Mean within-session fear reduction functioned as a process measure for exposure. Compared to non-responders and pre-treatment, results in the discovery sample seemed to indicate that responders exhibited stronger negative connectivity between frontal and limbic structures and were characterized by heightened connectivity between the amygdala and ventral visual pathway regions. Patients exhibiting high within-session fear reduction showed stronger excitatory connectivity within the prefrontal cortex than patients with low within-session fear reduction. Whereas these results could be replicated by another team using the same data (cross-team replication), cross-site replication of the discovery sample findings in the independent replication sample was unsuccessful. Results seem to support negative fronto-limbic connectivity as promising ingredient to enhance response rates in specific phobia but lack sufficient replication. Further research is needed to obtain a valid basis for clinical decision-making and the development of individually tailored treatment options. Notably, future studies should regularly include replication approaches in their protocols.Peer Reviewe

    Achieving net zero greenhouse gas emissions critical to limit climate tipping risks

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    Under current emission trajectories, temporarily overshooting the Paris global warming limit of 1.5 °C is a distinct possibility. Permanently exceeding this limit would substantially increase the probability of triggering climate tipping elements. Here, we investigate the tipping risks associated with several policy-relevant future emission scenarios, using a stylised Earth system model of four interconnected climate tipping elements. We show that following current policies this century would commit to a 45% tipping risk by 2300 (median, 10–90% range: 23–71%), even if temperatures are brought back to below 1.5 °C. We find that tipping risk by 2300 increases with every additional 0.1 °C of overshoot above 1.5 °C and strongly accelerates for peak warming above 2.0 °C. Achieving and maintaining at least net zero greenhouse gas emissions by 2100 is paramount to minimise tipping risk in the long term. Our results underscore that stringent emission reductions in the current decade are critical for planetary stability.EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)https://doi.org/10.13039/100010661Peer Reviewe

    Integrated monitoring and modeling to disentangle the complex spatio-temporal dynamics of urbanized streams under drought stress

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    We have a poor understanding of how urban drainage and other engineered components interact with more natural hydrological processes in green and blue spaces to generate stream flow. This limits the scientific evidence base for predicting and mitigating the effects of future development of the built environment and climate change on urban water resources and their ecosystem services. Here, we synthesize > 20 years of environmental monitoring data to better understand the hydrological function of the 109-km 2 Wuhle catchment, an important tributary of the river Spree in Berlin, Germany. More than half (56%) of the catchment is urbanized, leading to substantial flow path alterations. Young water from storm runoff and rapid subsurface flow provided around 20% of stream flow. However, most of it was generated by older groundwater (several years old), mainly recharged through the rural headwaters and non-urban green spaces. Recent drought years since 2018 showed that this base flow component has reduced in response to decreased recharge, causing deterioration in water quality and sections of the stream network to dry out. Attempts to integrate the understanding of engineered and natural processes in a traditional rainfall-runoff model were only partly successful due to uncertainties over the catchment area, effects of sustainable urban drainage, adjacent groundwater pumping, and limited conceptualization of groundwater storage dynamics. The study highlights the need for more extensive and coordinated monitoring and data collection in complex urban catchments and the use of these data in more advanced models of urban hydrology to enhance management.Open Access funding enabled and organized by Projekt DEAL.Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB) im Forschungsverbund Berlin e.V. (3473)Peer Reviewe

    Optimal Boundary Control of the Isothermal Semilinear Euler Equation for Gas Dynamics on a Network

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    The analysis and boundary optimal control of the nonlinear transport of gas on a network of pipelines is considered. The evolution of the gas distribution on a given pipe is modeled by an isothermal semilinear compressible Euler system in one space dimension. On the network, solutions satisfying (at nodes) the Kirchhoff flux continuity conditions are shown to exist in a neighborhood of an equilibrium state. The associated nonlinear optimization problem then aims at steering such dynamics to a given target distribution by means of suitable (network) boundary controls while keeping the distribution within given (state) constraints. The existence of local optimal controls is established and a corresponding Karush–Kuhn–Tucker (KKT) stationarity system with an almost surely non-singular Lagrange multiplier is derived.Open Access funding enabled and organized by Projekt DEAL.Weierstraß-Institut für Angewandte Analysis und Stochastik, Leibniz-Institut im Forschungsverbund Berlin e.V. (3510)Peer Reviewe

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