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Este estudo foi desenvolvido para testar a viabilidade do bioensaio aborto polínico (AP) em botões florais de Tradescantia pallida var. purpurea na avaliação de genotoxicidade da água superficial. Uma nova metodologia foi desenvolvida visando o objetivo de avaliar e comparar diferentes períodos de recuperação para o bioensaio de exposição aguda a água, e encontrar o tempo necessário para que a célula em estádio de tétrade se desenvolva e atinja o estádio de grão de pólen. Diferentes períodos de recuperação foram testados e o tempo de 28h foi suficiente para que as células passassem do estádio de tétrades para grão de pólen. As frequências médias de aborto polínico encontradas neste período foram de 5,07 para a água poluída e de 11,0 e 2,90 para os controles positivo e negativo, respectivamente. Houve relação positiva entre as respostas dos biomarcadores frente à água poluída (r = 0,480; p = 0,028). Os achados deste estudo mostram que o bioensaio de aborto polínico em Tradescantia pallida var. purpurea (Trad-AP) é sensível e eficiente quando comparado ao bioensaio tradicional de micronúcleos (Trad-MCN), podendo ser empregado com êxito no biomonitoramento da água superficial.

Monitoring, reporting, and verification frameworks for greenhouse gas emissions are being developed by countries across the world to keep track of progress towards national emission reduction targets. Data assimilation plays an important role in monitoring frameworks, combining different sources of information to achieve the best possible estimate of fossil fuel emissions and, as a consequence, better estimates for fluxes from the natural biosphere. Robust estimates for fossil fuel emissions rely on accurate estimates of uncertainties corresponding to different pieces of information. We describe prior uncertainties in CO2 and CO fossil fuel fluxes, paying special attention to spatial error correlations and the covariance structure between CO2 and CO. This represents the first time that prior uncertainties in CO2 and the important co-emitted trace gas CO are defined consistently, with error correlations included, which allows us to make use of the synergy between the two trace gases to better constrain CO2 fossil fuel fluxes. CO:CO2 error correlations differ by sector, depending on the diversity of sub-processes occurring within a sector, and also show a large range of values between pixels within the same sector. For example, for other stationary combustion, pixel correlation values range from 0.1 to 1.0, whereas for road transport, the correlation is mostly larger than 0.6. We illustrate the added value of our definition of prior uncertainties using closed-loop numerical experiments over mainland Europe and the UK, which isolate the influence of using error correlations between CO2 and CO and the influence of prescribing more detailed information about prior emission uncertainties. For the experiments, synthetic in situ observations are used, allowing us to validate the results against a “truth”. The “true” emissions are made by perturbing the prior emissions (from an emission inventory) according to the prescribed prior uncertainties. We find that using our realistic definition of prior uncertainties helps our data assimilation system to differentiate more easily between CO2 fluxes from biogenic and fossil fuel sources. Using improved prior emission uncertainties, we find fewer geographic regions with significant deviations from the prior compared to when using default prior uncertainties (32 vs. 80 grid cells of 0.25°×0.3125°, with an absolute difference of more than 1 kg s−1 between the prior and posterior), but these deviations from the prior almost consistently move closer to the prescribed true values, with 92 % showing an improvement, in contrast to the default prior uncertainties, where 61 % show an improvement. We also find that using CO provides additional information on CO2 fossil fuel fluxes, but this is only the case if the CO:CO2 error covariance structure is defined realistically. Using the default prior uncertainties, the CO2 fossil fuel fluxes move farther away from the truth in many geographical regions (with 50 % showing an improvement compared to 94 % when advanced prior uncertainties are used). With the default uncertainties, the maximum deviation of fossil fuel CO2 from the prescribed truth is about 7 % in both the prior and posterior results. With the advanced uncertainties, this is reduced to 3 % in the posterior results.

Under the Paris Agreement, countries report their anthropogenic greenhouse gas emissions in national inventories, which are used to track progress towards mitigation goals, but they must be independently verified. Atmospheric observations of CO2, interpreted using inverse methods, can potentially provide that verification. Conventional CO2 inverse methods infer natural CO2 fluxes by subtracting a priori estimates of fuel combustion from the a posteriori net CO2 fluxes, assuming that a priori knowledge for combustion emissions is better than for natural fluxes. We describe an inverse method that uses measurements of CO2 and carbon monoxide (CO), a trace gas that is co-emitted with CO2 during combustion, to report self-consistent combustion emissions and natural fluxes of CO2. We use an ensemble Kalman filter and the GEOS-Chem atmospheric transport model to explore how satellite observations of CO and CO2 collected by the TROPOspheric Monitoring Instrument (TROPOMI) and Orbiting Carbon Observatory-2 (OCO-2), respectively, can improve understanding of combustion emissions and natural CO2 fluxes across the UK and mainland Europe in 2018–2021. We assess the value of using satellite observations of CO2, with and without CO, above what is already available from the in situ network. Using CO2 satellite observations leads to small corrections to a priori emissions that are inconsistent with in situ observations, due partly to the insensitivity of the atmospheric CO2 column to CO2 emission changes. When we introduce satellite CO observations, we find better agreement with our in situ inversion and a better model fit to atmospheric CO2 observations. Our regional mean a posteriori combustion CO2 emission ranges from 4.6–5.0 Gt a−1 (1.5 %–2.4 % relative standard deviation), with all inversions reporting an overestimate for Germany's wintertime emissions. Our national a posteriori CO2 combustion emissions are highly dependent on the assumed relationship between CO2 and CO uncertainties, as expected. Generally, we find better results when we use grid-scale-based a priori CO2:CO uncertainty estimates rather than a fixed relationship between the two species.

Abstract Fossil fuel subsidies continue to be a considerable barrier to meeting the targets of the Paris Agreement. It is thus crucial to understand the political economy of fossil fuel subsidies and their reform. To understand these mechanisms in the developed world, we use a database of different types of fossil fuel subsidy reforms among Organisation for Economic Co-operation and Development (OECD) countries. We find evidence for four intertwined processes i) a market-power mechanism: higher market shares for renewables ease fossil fuel subsidy reforms, and ii) a policy mechanism: reforms reduce the levels of fossil fuel subsidies. Importantly, both effects are contingent on iii) a polity mechanism where institutional quality influences the feasibility and effectiveness of political reforms, and iv) a feedback mechanism where systemic lock-ins determine the effectiveness of market competition. Our results even suggest that reforms carried out by effective governments with low corruption control are associated with increasing subsidies per capita. Renewable energy support can however provide a leverage point to break path-dependencies in fossil fuel-based economies. This turns out to be more effective when coupled with improvements to institutional quality and the insulation of political processes from pro-subsidy interests.

Abstract Background The VPS50 protein functions in synaptic and dense core vesicle acidification, and perturbations of VPS50 function produce behavioral changes in Caenorhabditis elegans. Patients with mutations in VPS50 show severe developmental delay and intellectual disability, characteristics that have been associated with autism spectrum disorders (ASDs). The mechanisms that link VPS50 mutations to ASD are unknown. Results To examine the role of VPS50 in mammalian brain function and behavior, we used the CRISPR/Cas9 system to generate knockouts of VPS50 in both cultured murine cortical neurons and living mice. In cultured neurons, KO of VPS50 did not affect the number of synaptic vesicles but did cause mislocalization of the V-ATPase V1 domain pump and impaired synaptic activity, likely as a consequence of defects in vesicle acidification and vesicle content. In mice, mosaic KO of VPS50 in the hippocampus altered synaptic transmission and plasticity and generated robust cognitive impairments. Conclusions We propose that VPS50 functions as an accessory protein to aid the recruitment of the V-ATPase V1 domain to synaptic vesicles and in that way plays a crucial role in controlling synaptic vesicle acidification. Understanding the mechanisms controlling behaviors and synaptic function in ASD-associated mutations is pivotal for the development of targeted interventions, which may open new avenues for therapeutic strategies aimed at ASD and related conditions.

Abstract Background Pathomics facilitates automated, reproducible and precise histopathology analysis and morphological phenotyping. Similar to molecular omics, pathomics datasets are high-dimensional, but also face large outlier variability and inherent data missingness, making quick and comprehensible data analysis challenging. To facilitate pathomics data analysis and interpretation as well as support a broad implementation we developed tRigon (Toolbox foR InteGrative (path-)Omics data aNalysis), a Shiny application for fast, comprehensive and reproducible pathomics analysis. Results tRigon is available via the CRAN repository ( https://cran.r-project.org/web/packages/tRigon ) with its source code available on GitLab ( https://git-ce.rwth-aachen.de/labooratory-ai/trigon ). The tRigon package can be installed locally and its application can be executed from the R console via the command ‘tRigon::run_tRigon()’. Alternatively, the application is hosted online and can be accessed at https://labooratory.shinyapps.io/tRigon . We show fast computation of small, medium and large datasets in a low- and high-performance hardware setting, indicating broad applicability of tRigon. Conclusions tRigon allows researchers without coding abilities to perform exploratory feature analyses of pathomics and non-pathomics datasets on their own using a variety of hardware.

Background: Modifiable lifestyle factors exert a substantial influence on the development of various diseases. The COVID-19 pandemic necessitated the implementation of containment measures to mitigate the viral spread, which affected the maintenance of healthy habits. Methods: Changes in lifestyle factors (e.g. physical activity, nutrition, smoking, drinking alcohol) within a cohort of German women at increased risk of breast cancer (BC) or ovarian cancer (OC) were evaluated through an anonymous web-based survey. The self-reported assessment of mental health was conducted using the PHQ-4 questionnaire. This tool combines two items from the Patient Health Questionnaire for Depression (PHQ-2) and two queries from the Generalized Anxiety Disorder Scale (GAD-2). Potential predictors of lifestyle changes were determined via multiple logistic regression analysis. A heuristic model was employed to project potential long-term consequences on BC incidence. Results: During the pandemic, 41.6 % of respondents reported reduced engagement in physical activity (PA), whereas 14.3 % reported increased engagement in PA. A score ≥5 on the PHQ-2 scale emerged as an independent risk factor for reduced PA (OR 12.719; 95 % CI 1.089–148.549; p = 0.043). By the heuristic approach, we projected an increase of BC by 3384 cases in Germany by 2030, which is attributable to the alterations in PA patterns during the pandemic. Discussion: Impaired mental health during the pandemic constituted a risk factor for unfavorable changes in PA. Consequently, a surge in BC may arise due to decreased engagement in PA. Healthcare professionals must remain aware of the potential risk factors that facilitate adverse alterations in modifiable risk factors caused by pandemic-related contingency measures or similar future events.

There are broad calls in national and international forest policy processes for basing decision-making on the best obtainable scientific knowledge. Simultaneously, there is also a need to accommodate plural values and objectives people and society in general have associated with forests. An essential step for building an evidence base that accommodates pluralistic understandings is to capture informant views on forest policies and the alternatives they offer to better prepare for future scenarios. This article draws on research experts’ views in Finland, Sweden, Norway, and Denmark, gathered from interviews between February and May 2023. An existing gap to bridge is understanding to what extent such views differ or correlate across the study countries. By systematizing on the similarities and differences in opinions, we develop a synopsis of future needs and uncertainties in policies across the studied countries, concluding with recommendations for determining the use of Nordic forests. Despite divergence in personal views and uncertainties about the future, most respondents saw a need for inclusive policymaking, policy coherence and integration, and changes in forest management. We find that strengthening evidence-basis, stakeholder participation, adaptive governance, and integrative forest management are challenges for future policy making.

Acute (AW) and chronic (CW) workload imbalances, including their ratio (ACWR), are largely associated with increased injury risk. However, the inclusion of personal endurance performance (EP) in this calculation as a means of improving accuracy has been neglected in previous studies. The aim of this longitudinal observational study was to evaluate the relevance of the high metabolic load distance (ACWRHMLD) to EP in relation to non-contact injuries. Twenty-three German male first division soccer players (age: 24.5 ± 3.5 years; VO2max: 53.7 ± 4.9 mL/min/kg; v4: 15.2 ± 0.9 km/h) were analyzed. Eleven players with non-contact injuries were identified and matched with players without any injuries within the same time interval. Players were monitored using GPS and LPS tracking to calculate ACWRHMLD on a daily basis over the course of one competitive season. Relationships between different endurance performance parameters (v2, v4, vLT, VO2max) and the ACWRHMLD, AW, CW were established for statistical analysis. An area under the curve analysis (AUC) was performed. Based on the four weeks preceding the non-contact injuries, the CW, especially for the last two weeks before the injury, proved to be the most suitable parameter to estimate the risk of injury. The highest significant AUC value (0.81, 95% CI: 0.59–1.00) was calculated for the CW (last week before injury) in relation to the vLT (suitable cut-off: 0.04 km; sensitivity: 78%, specificity: 80%). With regard to the injury rate, the ACWRHMLD seems to be the most appropriate method of calculation, especially for CW related to EP (vLT). The sole use of ACWR, AW, and CW is not recommended.

Background: Spinometry is a radiation-free method to three-dimensional spine imaging that provides additional information about the functional gait patterns related to the pelvis and lower extremities. This radiation-free technology uses the surface topography of the trunk to analyze surface asymmetry and identify bony landmarks, thereby aiding the assessment of spinal deformity and supporting long-term treatment regimes. Especially reliable dynamic spinometric data for spine and pelvis are necessary to evaluate the management of non-specific back pain. Research aim: This study aims to generate reliable dynamic spinometric data for spine and pelvis parameters that can serve as reference data for future studies and clinical practice. Methods: This study assessed 366 subjects (185 females) under static and 360 subjects (181 females) under dynamic (walking on a treadmill at 3 km/h and 5 km/h) conditions. The DIERS Formetric 4Dmotion® system uses stripes of light to detect the surface topography of the spine and pelvis and identifies specific landmarks to analyze the spine during standing and walking. Results: Relevant gender effects were calculated for lordotic angle (ηp2 = 0.22) and pelvic inclination (ηp2 = 0.26). Under static conditions, female subjects showed larger values for both parameters (lordotic angle: 41.6 ± 8.60°; pelvic inclination: 25.5 ± 7.49°). Regarding speed effects, three relevant changes were observed (sagittal imbalance: ηp2 = 0.74, kyphotic angle: ηp2 = 0.13, apical deviation: ηp2 = 0.11). The most considerable changes were observed between static condition and 3 km/h, especially for sagittal imbalance and lordotic angle. For these parameters, relevant effect sizes (d > 0.8) were calculated between static and 3 km/h for males and females. Concerning clinical vertebral parameters, only lordotic angle and pelvic inclination were correlated with each other (r = 0.722). Conclusion: This study generated a gender-specific reference database of asymptomatic individuals for static and dynamic spinometry. It demonstrated that the DIERS Formetric 4Dmotion® system could capture natural changes in static and dynamic situations and catalogue functional adaptations of spino-pelvic statics at different speeds. The lordotic angle is an indirect marker of pelvic inclination, allowing spinometry to identify individuals at risk even under dynamic conditions.

Trypanosomatid parasites are kinetoplastid protists that compartmentalize glycolytic enzymes in unique peroxisome-related organelles called glycosomes. The heterohexameric AAA-ATPase complex of PEX1-PEX6 is anchored to the peroxisomal membrane and functions in the export of matrix protein import receptor PEX5 from the peroxisomal membrane. Defects in PEX1, PEX6 or their membrane anchor causes dysfunction of peroxisomal matrix protein import cycle. In this study, we functionally characterized a putative Trypanosoma PEX1 orthologue by bioinformatic and experimental approaches and show that it is a true PEX1 orthologue. Using yeast two-hybrid analysis, we demonstrate that TbPEX1 can bind to TbPEX6. Endogenously tagged TbPEX1 localizes to glycosomes in the T. brucei parasites. Depletion of PEX1 gene expression by RNA interference causes lethality to the bloodstream form trypanosomes, due to a partial mislocalization of glycosomal enzymes to the cytosol and ATP depletion. TbPEX1 RNAi leads to a selective proteasomal degradation of both matrix protein import receptors TbPEX5 and TbPEX7. Unlike in yeast, PEX1 depletion did not result in an accumulation of ubiquitinated TbPEX5 in trypanosomes. As PEX1 turned out to be essential for trypanosomatid parasites, it could provide a suitable drug target for parasitic diseases. The results also suggest that these parasites possess a highly efficient quality control mechanism that exports the import receptors from glycosomes to the cytosol in the absence of a functional TbPEX1-TbPEX6 complex.

Abstract How cells regulate gene expression in a precise spatiotemporal manner during organismal development is a fundamental question in biology. Although the role of transcriptional condensates in gene regulation has been established, little is known about the function and regulation of these molecular assemblies in the context of animal development and physiology. Here we show that the evolutionarily conserved DEAD-box helicase DDX-23 controls cell fate in Caenorhabditis elegans by binding to and facilitating the condensation of MAB-10, the C. elegans homolog of mammalian NGFI-A-binding (NAB) protein. MAB-10 is a transcriptional cofactor that functions with the early growth response (EGR) protein LIN-29 to regulate the transcription of genes required for exiting the cell cycle, terminal differentiation, and the larval-to-adult transition. We suggest that DEAD-box helicase proteins function more generally during animal development to control the condensation of NAB proteins important in cell identity and that this mechanism is evolutionarily conserved. In mammals, such a mechanism might underlie terminal cell differentiation and when dysregulated might promote cancerous growth.

Abstract Background Global longitudinal strain (GLS) and global myocardial work index (GWI) allow early detection of subclinical changes in left ventricular (LV) systolic function. The aim of the study was to investigate the immediate effects of maximum physical exercise by different exercise testing methods on early post exercise LV deformation parameters in competitive athletes and to analyze their correlation with cardiopulmonary exercise capacity. Methods To reach maximum physical exercise, cardiopulmonary exercise testing (CPET) was performed by semi-recumbent ergometer in competitive handball players (n = 13) and by treadmill testing in competitive football players (n = 19). Maximum oxygen uptake (VO2max) indexed to body weight (relative VO2max) was measured in all athletes. Transthoracic echocardiography and blood pressure measurements were performed at rest and 5 min after CPET in all athletes. GLS, GWI and their changes before and after CPET (ΔGLS, ΔGWI) were correlated with (relative) VO2max. Results In handball and football players, GLS and GWI did not differ significantly before and after CPET. There were no significant correlations between GLS and relative VO2max, but moderate correlations were found between ΔGWI and relative VO2max in handball (r = 0.631; P = 0.021) and football players (r = 0.592; P = 0.008). Furthermore, handball (46.7 ml/min*kg ± 4.7 ml/min*kg vs. 37.4 ml/min*kg ± 4.2; P = 0.004) and football players (58.3 ml/min*kg ± 3.7 ml/min*kg vs. 49.7 ml/min*kg ± 6.8; P = 0.002) with an increased ΔGWI after CPET showed a significant higher relative VO2max. Conclusion Maximum physical exercise has an immediate effect on LV deformation, irrespective of the used testing method. The correlation of relative VO2max with ΔGWI in the early post exercise period, identifies ΔGWI as an echocardiographic parameter for characterizing the current individual training status of athletes.

Abstract Background Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software. Methods We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis on the same section, e.g., the size of cardiomyocyte nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis. Results In both animals and humans, HeartJ-based histology quantification revealed significant hypertrophy of cardiomyocytes reflecting other parameters of hypertrophy and rarefaction of microvasculature and enabling the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease confirming the translatability of our murine cardiac hypertrophy model. HeartJ enables a rapid analysis that would not be feasible by manual methods. The pipeline has little hardware requirements and is freely available. Conclusions In summary, our analysis pipeline can facilitate effective and objective quantitative histological analyses in preclinical and clinical heart samples.

Plasma-activated water (PAW) generated from tap water has gained attention as a disinfectant when used directly in its pure form. Little is known about the application of PAW for bacterial inactivation in aqueous environments because its use in fluids results in dilutions. We investigated the effect of PAW in aqueous suspensions simulating such dilutions, and we focused on the minimal addition of PAW volumes to bacterial aqueous suspensions still resulting in high inactivation rates. The antimicrobial effect was highly dependent on the activation of PAW. An increase in activation power from 90 to 100 W resulted in a greater microbial reduction with an identical 10 min activation time. The susceptibility to PAW dilutions was analyzed in detail regarding nine Gram-negative species out of Enterobacterales and other waterborne microorganisms as well as four Gram-positive species present in two different matrices, in saline and in tap water, at high concentrations simulating massive contamination situations. For this purpose, the PAW activation setting of 90 W and 30 min was defined in order to be able to differentiate the limitations of inactivation in individual bacterial species. The Gram-negatives in saline demonstrated susceptibility when one volume unit of PAW was added. However, twice the PAW volume was necessary for inactivation when bacteria were present in tap water. Gram-positive microorganisms were more robust, indicated by prolonged contact times before inactivation. Our results indicate that PAW can be used for bacterial decontamination processes in aqueous environments when added in surplus. Optimized activation settings such as electric power to generate PAW and the contact times to the samples increase the effect of the inactivation a wide range of bacteria, regardless of their resistance profiles.

Abstract Background The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. Methods In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR’s technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. Discussion CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. Trial registration CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).