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Effects of tree fall on soil Collembola: Disentangling the role of gap formation and deadwood addition
http://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100004543 China Scholarship CouncilOpen-Access-Publikationsfonds 202
Tree species richness affects the trophic structure of soil oribatid mites via litter functional diversity and canopy cover: Evidence from stable isotope analysis (15N, 13C)
http://dx.doi.org/10.13039/501100004543 China Scholarship Councilhttp://dx.doi.org/10.13039/501100011506 Key Laboratory of Zoological Systematics and Evolution, Chinese Academy of Scienceshttp://dx.doi.org/10.13039/501100002367 Chinese Academy of Scienceshttp://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of Chin
Update on preclinical models of cancer therapy‐related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association ( HFA ) of the ESC , the ESC Council of Cardio‐Oncology, and the ESC Working Group on Cellular Biology of the Heart
New anticancer therapies with potential cardiovascular side effects are continuously being introduced into clinical practice, with new and often unexpected toxicities becoming apparent only after clinical introduction. These unknown toxicities should be identified and understood beforehand to better prepare patients and physicians, enabling the implementation of effective treatments. Therefore, there is a crucial need for appropriate preclinical models to understand the biological basis of their cardiotoxicity. This scientific statement summarizes the preclinical models hitherto used, from in vitro two‐ and three‐dimensional human systems to small and large animals, to pinpoint the molecular mechanisms behind the cardiotoxicity of new‐generation anticancer therapies, particularly immunotherapies, and to develop potential cardioprotective strategies. Furthermore, it discusses how preclinical models have contributed to the provocative concept of heart failure being potentially tumorigenic and how the discovery of drugs with both anticancer and cardioprotective actions has revealed a common mechanistic basis for heart failure and cancer. Finally, it discusses the existing gaps between preclinical models and clinical observations in patients, how these discrepancies affect regulatory pathways and the drug development process in cardio‐oncology and provides recommendations for closing these gaps
From fields to factories: Special economic zones, foreign direct investment, and labour markets in Vietnam
http://dx.doi.org/10.13039/501100006456 Federal Ministry of Economic Co-operation and Developmen
Expansion of the Stereochemical Space of Triterpenes by Mining Noncanonical Oxidosqualene Cyclases Across the Diversity of Green Plants
Soil organic carbon thresholds control fertilizer effects on carbon accrual in croplands worldwide
Abstract Initiatives to restore soil fertility and mitigate global warming rely on rebuilding soil organic carbon (SOC). Nitrogen (N) fertilization is crucial for crop yields but affects SOC unpredictably due to varying responses of particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) pools to initial SOC levels. To clarify these effects, here, by combining a global meta-analysis with continental-scale field experiments, we determine that an initial SOC threshold of 15 g C kg −1 controls the effect of N fertilization on POC and MAOC. In SOC-poor soils (< 15 g C kg −1 ), N fertilizer increases plant-derived C inputs and promotes soil aggregation, favouring POC accumulation. Conversely, in SOC-rich soils, N fertilizer stimulates microbial metabolic efficiency, leading to larger necromass production and stabilization by mineral protection, observed as more pronounced MAOC accrual. Our findings reveal how SOC thresholds shape the response of active and stable carbon pools to N fertilization, with consequences for SOC accrual in cropland soils globally
Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency
Uncertainty remains about the effect of intravenous (i.v.) iron on outcomes for heart failure (HF) with iron deficiency. In the present study, we summarize the efficacy and safety of i.v. iron from six trials (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID and FAIR-HF2), including 7,175 patients. In comparison to prior analyses, this meta-analysis added new data from FAIR-HF2, used a harmonized and robust Bayesian approach and included individual participant data from five trials. Patients assigned to i.v. iron, compared with those assigned to placebo, had lower rates for the composite endpoint of recurrent HF hospitalizations and cardiovascular mortality at 12 months (risk ratio (RR) = 0.72 (95% confidence interval (CI) = 0.55-0.89)) and for the complete length of follow-up (RR = 0.81 (95% CI = 0.63-0.97)). Each component of the primary endpoint contributed to the beneficial effect of i.v. iron at both 12 months and the complete length of follow-up: recurrent HF hospitalizations (RR = 0.69 (95% CI = 0.48-0.88) and RR = 0.78 (95% CI = 0.55-0.98), respectively) and cardiovascular mortality (hazard ratio (HR) = 0.80 (95% CI = 0.61-1.03) and HR = 0.87 (95% CI = 0.73-1.04), respectively). All-cause mortality at 12 months and for the complete length of follow-up (HR = 0.82 (95% CI = 0.65-1.03)) and HR = 0.92 (95% CI = 0.80-1.07), respectively, indicated the overall safety of i.v. iron treatment. Treatment effects were greatest in the first year after randomization when the doses of i.v. iron provided are highest. These findings suggest that treating iron deficiency in patients with HF significantly reduces cardiovascular events and also suggests further investigation of optimal dosing of i.v. iron
PHluorin-conjugated secondary nanobodies as a tool for measuring synaptic vesicle exocytosis and endocytosis
Abstract Neuronal communication relies on synaptic vesicle recycling, which has long been investigated by live imaging approaches. Synapto-pHluorins, genetically encoded reporters that incorporate a pH-sensitive variant of GFP within the lumen of the synaptic vesicle, have been especially popular. However, they require genetic manipulation, implying that a tool combining their excellent reporter properties with the ease of use of classical immunolabeling would be desirable. We introduce this tool here, relying on primary antibodies against the luminal domain of synaptotagmin 1, decorated with secondary single-domain antibodies (nanobodies) carrying a pHluorin moiety. The application of the antibodies and nanobodies to cultured neurons results in labeling their recycling vesicles, without the need for any additional manipulations. The labeled vesicles respond to stimulation, in the expected fashion, and the pHluorin signals enable the quantification of both exo- and endocytosis. We conclude that pHluorin-conjugated secondary nanobodies are a convenient tool for the analysis of vesicle recycling.Open-Access-Publikationsfonds 202
Three-dimensional structure of entire hydrated murine hearts at histological resolution
Imaging the entire cardiomyocyte network in entire small animal hearts at single cell resolution is a formidable challenge. Optical microscopy provides sufficient contrast and resolution in 2d, however fails to deliver non-destructive 3d reconstructions with isotropic resolution. It requires several invasive preparation steps, which introduce structural artefacts, namely dehydration, physical slicing and staining, or for the case of light sheet microscopy also clearing of the tissue. Our goal is to provide 3d reconstructions of the cardiomyocyte network in entire hydrated murine hearts, and to develop a methodology for quantitative analysis of heart pathologies based on X-ray phase contrast computed tomography (XPCT). We have used XPCT at two beamlines of the extremely brilliant source (EBS) at the European Synchrotron Radiation Facility (ESRF) to scan wild-type murine hearts at high resolution, as well as a series of murine hearts of different pathological models, at reduced resolution and higher throughput. All hearts were obtained from the small animal facility of the university medical center in Göttingen. The hearts were fixed in formalin, stored and measured non-destructively in phosphate buffer solution. The high resolution dataset allows to discern individual cardiomyocytes in the tissue. All datasets have been analyzed using semi-automated image segmentation of the ventricles, rotation into a common coordinate system, classification into different anatomical compartments, and finally the structure tensor approach. A 3d streamline representation of the cardiomyocyte orientation vector field is provided. The different cardiovascular disease models are analysed based on metrics derived from the 3d structure tensor. An entire hydrated murine heart has been covered at an isotropic voxel size of 1.6 μ m (distributed over several volumes). A binned and fused dataset of this heart is available at 3.2 μ m, and has been analyzed by the structure tensor approach to yield the ventricular cardiomyocyte network or mesh, i.e. the aggregation of the cardiomyocyte chains in particular in the ventricular wall. Semi-automatic determination of structural metrics is already achieved and the corresponding tools and resulting data are made publically available. XPCT using extremely brilliant undulator radiation is close to achieve single cell reconstruction in an entire small animal organ.Open-Access-Publikationsfonds 202