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Nitric oxide (NO) is an intermediate of various microbial nitrogen cycle processes, and the open-ocean and coastal areas are generally a source of NO to the atmosphere. However, our knowledge about its distribution and the main production processes in coastal areas and estuaries is rudimentary at best. To this end, dissolved NO concentrations were measured for the first time in surface waters along the lower Elbe Estuary and Port of Hamburg area in July 2021. The discrete surface water samples were analyzed using a chemiluminescence NO analyzer connected to a stripping unit. The NO concentrations ranged from below the limit of detection (9.1 pM) to 17.7 pM, averaging 12.5 pM, and were supersaturated in the surface layer of both the lower Elbe Estuary and the Port of Hamburg area, indicating that the study site was a source of NO to the atmosphere during the study period. On the basis of a comprehensive comparison of NO concentrations with parallel nutrient, oxygen, and nitrous oxide concentration measurements, we conclude that the observed distribution of dissolved NO most likely resulted from nitrification. In the Port of Hamburg, however, nitrifier denitrification and/or denitrification might also affect the NO distribution.

Spatial soil databases can help model complex phenomena in which soils are a decisive factor – for example, evaluating agricultural potential or estimating carbon storage capacity. The Latin America and Caribbean Soil Information System, SISLAC, is a regional initiative promoted by the Food and Agriculture Organization's (FAO) Latin America and the Caribbean Soil Partnership to contribute to sustainable management of soil. SISLAC includes data from 49 084 soil profiles distributed unevenly across the continent, making it the region's largest soil database. In addition, there are other soil databases in the region with about 40 000 soil profiles that can be integrated into SISLAC and improve it. However, some problems hinder its usages, such as the quality of the data and their high dimensionality. The objective of this research is evaluate the quality of the SISLAC data and the other available soil databases to generate a new improved version that meets the minimum quality requirements to be used for different purposes or practical applications. The results show that 15 % of the existing soil profiles had an inaccurate description of the diagnostic horizons and 17 % of the additional profiles already existed in SISLAC; therefore, a total of 32 % of profiles were excluded for these two reasons. Further correction of an additional 4.5 % of existing inconsistencies improved overall data quality. The improved database consists of 66 746 profiles and is available for public use at https://doi.org/10.5281/zenodo.7876731 (Díaz-Guadarrama and Guevara, 2023). This revised version of SISLAC data offers the opportunity to generate information that helps decision-making on issues in which soils are a decisive factor. It can also be used to plan future soil surveys in areas with low density or where updated information is required.

Nitrous oxide (N2O) is a greenhouse gas, with a global warming potential 298 times that of carbon dioxide. Estuaries can be sources of N2O, but their emission estimates have significant uncertainties due to limited data availability and high spatiotemporal variability. We investigated the spatial and seasonal variability of dissolved N2O and its emissions along the Elbe Estuary (Germany), a well-mixed temperate estuary with high nutrient loading from agriculture. During nine research cruises performed between 2017 and 2022, we measured dissolved N2O concentrations, as well as dissolved nutrient and oxygen concentrations along the estuary, and calculated N2O saturations, flux densities, and emissions. We found that the estuary was a year-round source of N2O, with the highest emissions in winter when dissolved inorganic nitrogen (DIN) loads and wind speeds are high. However, in spring and summer, N2O saturations and emissions did not decrease alongside lower riverine nitrogen loads, suggesting that estuarine in situ N2O production is an important source of N2O. We identified two hotspot areas of N2O production: the Port of Hamburg, a major port region, and the mesohaline estuary near the maximum turbidity zone (MTZ). N2O production was fueled by the decomposition of riverine organic matter in the Hamburg Port and by marine organic matter in the MTZ. A comparison with previous measurements in the Elbe Estuary revealed that N2O saturation did not decrease alongside the decrease in DIN concentrations after a significant improvement of water quality in the 1990s that allowed for phytoplankton growth to re-establish in the river and estuary. The overarching control of phytoplankton growth on organic matter and, subsequently, on N2O production highlights the fact that eutrophication and elevated agricultural nutrient input can increase N2O emissions in estuaries.

Metabolic activities in estuaries, especially these of large rivers, profoundly affect the downstream coastal biogeochemistry. Here, we unravel the impacts of large industrial port facilities, showing that elevated metabolic activity in the Hamburg port (Germany) increases total alkalinity (TA) and dissolved inorganic carbon (DIC) runoff to the North Sea. The imports of particulate inorganic carbon, particulate organic carbon, and particulate organic nitrogen (PIC, POC, and PON) from the upstream Elbe River can fuel up to 90 % of the TA generated in the entire estuary via calcium carbonate (CaCO3) dissolution. The remaining at least 10 % of TA generation can be attributed to anaerobic metabolic processes such as denitrification of remineralized PON or other pathways. The Elbe Estuary as a whole adds approximately 15 % to the overall DIC and TA runoff. Both the magnitude and partitioning among these processes appear to be sensitive to climatic and anthropogenic changes. Thus, with increased TA loads, the coastal ocean (in particular) would act as a stronger CO2 sink, resulting in changes to the overall coastal system's capacity to store CO2.

Estuaries are nutrient filters and change riverine nutrient loads before they reach coastal oceans. Their morphology have been extensively changed by anthropogenic activities like draining, deepening and dredging to meet economic and social demand, causing significant regime changes like tidal amplifications and in some cases to hyper-turbid conditions. Furthermore, increased nutrient loads, especially nitrogen, mainly by agriculture cause coastal eutrophication. Estuaries can either act as a sink or as a source of nitrate, depending on environmental and geomorphological conditions. These factors vary along an estuary, and change nitrogen turnover in the system. Here, we investigate the factors controlling nitrogen turnover in the hyper-turbid Ems estuary (Northern Germany), which has been strongly impacted by human activities. During two research cruises in August 2014 and June 2020, we measured water column properties, dissolved inorganic nitrogen, dual stable isotopes of nitrate and dissolved nitrous oxide concentration along the estuary. We found that three distinct biogeochemical zones exist along the estuary. A strong fractionation (∼26 ‰) of nitrate stable isotopes points towards nitrate removal via water column denitrification in the hyper-turbid tidal river, driven by anoxic conditions in deeper water layers. In the middle reaches of the estuary nitrification gains importance, turning this section into a net nitrate source. The outer reaches are dominated by mixing, with nitrate uptake in 2020. We find that the overarching control on biogeochemical nitrogen cycling, zonation and nitrous oxide production in the Ems estuary is exerted by suspended particulate matter concentrations and the linked oxygen deficits.

Ocean alkalinity enhancement (OAE) aims to transfer carbon dioxide (CO2) from the atmosphere to the ocean by increasing the capacity of seawater to store CO2. The potential effects of OAE-induced changes in seawater chemistry on marine biology must be assessed to understand if OAE, operated at a climate-relevant scale, would be environmentally sustainable. Here, we describe the design of the Ocean Alkalinity Enhancement Pelagic Impact Intercomparison Project (OAEPIIP) – a standardised OAE microcosm experiment with plankton communities to be conducted worldwide. OAEPIIP provides funding for participating laboratories to conduct OAE experiments in their local environments. This paper constitutes a detailed manual on the standardised methodology that shall be adopted by all OAEPIIP participants. The individual studies will provide new insights into how plankton communities respond to OAE. The synthesis of these standardised studies, without publication bias, will reveal common OAE-responses that occur across geographic and environmental gradients and are therefore particularly important to determine. The funding available to OAEPIIP and the resulting data will be shared to maximise their value and accessibility. The globally coordinated effort has potential to promote scientific consensus about the potential effects of OAE on diverse plankton communities. Such consensus, through inclusion of the global community, will provide a sounder base to facilitate political decision making as to whether OAE should be scaled up or not.

Understanding the impacts that mineral grain size and seawater salinity have on magnesium hydroxide (Mg(OH)2) dissolution and secondary calcium carbonate (CaCO3) precipitation is critical for the success of ocean alkalinity enhancement. We tested Mg(OH)2 dissolution kinetics in seawater using three Mg(OH)2 grain sizes (, 63–180 and >180 µm) at three salinities (∼36, ∼28 and ∼20). While Mg(OH)2 dissolution occurred more quickly the smaller the grain size, salinity did not significantly impact measured rates. Our results also demonstrate that grain size can impact secondary CaCO3 precipitation, suggesting that an optimum grain size exists for ocean alkalinity enhancement (OAE) using solid Mg(OH)2. Of the three grain sizes tested, the medium grain size (63–180 µm) was optimal in terms of delaying secondary CaCO3 precipitation. We hypothesise that in the lowest-grain-size experiments, the higher surface area provided numerous CaCO3 precipitation nuclei, while the slower dissolution of bigger grain sizes maintained a higher alkalinity and pH at the surface of particles, increasing CaCO3 precipitation rates and making them observable much more quickly than for the intermediate grain size. Salinity also played a role in CaCO3 precipitation, where the decrease in magnesium (Mg) allowed secondary precipitation to occur more quickly, similar in effect size to another known inhibitor, i.e. dissolved organic carbon (DOC). In summary, our results suggest that OAE efficiency as influenced by CaCO3 precipitation depends not only on seawater composition but also on the physical properties of the alkaline feedstock used.

Gigatonne-scale atmospheric carbon dioxide removal (CDR) will almost certainly be needed to supplement the emission reductions required to keep global warming between 1.5–2 °C. Ocean alkalinity enhancement (OAE) is an emerging marine CDR method with the addition of pulverised minerals to the surface ocean being one widely considered approach. A concern of this approach is the potential for dissolution products released from minerals to impact phytoplankton communities. We conducted an experiment with 10 pelagic mesocosms (M1–M10) in Raunefjorden, Bergen, Norway, to assess the implications of simulated silicate- and calcium-based mineral OAE on a coastal plankton community. Five mesocosms (M1, M3, M5, M7, and M9) were enriched with silicate (∼ 75 µmol L−1 Na2SiO3), alkalinity along a gradient from 0 to ∼ 600 µmol kg−1, and magnesium in proportion to alkalinity additions. The other five mesocosms (M2, M4, M6, M8, M10) were enriched with alkalinity along the same gradient and calcium in proportion to alkalinity additions. The experiment explored many components of the plankton community, from microbes to fish larvae, and here we report on the influence of simulated mineral based OAE on diatom silicification. Macronutrients (nitrate and phosphate) limited silicification at the onset of the experiment until nutrient additions on day 26. Silicification was significantly greater in the silicate-based mineral treatment, with all genera except Cylindrotheca displaying an increase in silicification as a result of the increased concentration of dissolved silicate. In contrast to the effect of differences in dissolved silicate concentrations between the two mineral treatments, increases in alkalinity only influenced the silicification of two genera, Pseudo-nitzschia and Nitzschia. The four other genera (Arcocellulus, Cylindrotheca, Skeletonema, and Thalassiosira) investigated here displayed no significant changes in silicification as a result of alkalinity increases between 0 and 600 µmol kg−1 above natural levels. In summary, our findings illustrate that the enhancement of alkalinity via simulated silicate- and calcium-based methods has limited genus-specific impacts on the silicification of diatoms. This research underscores the importance of understanding the full breadth of different OAE approaches, their risks, co-benefits, and potential for interactive effects.

Abstract Estuaries play an important role in connecting the global carbon cycle across the land-to-ocean continuum, but little is known about Australia’s contribution to global CO2 emissions. Here we present an Australia-wide assessment, based on CO2 concentrations for 47 estuaries upscaled to 971 assessed Australian estuaries. We estimate total mean (±SE) estuary CO2 emissions of 8.67 ± 0.54 Tg CO2-C yr−1, with tidal systems, lagoons, and small deltas contributing 94.4%, 3.1%, and 2.5%, respectively. Although higher disturbance increased water-air CO2 fluxes, its effect on total Australian estuarine CO2 emissions was small due to the large surface areas of low and moderately disturbed tidal systems. Mean water-air CO2 fluxes from Australian small deltas and tidal systems were higher than from global estuaries because of the dominance of macrotidal subtropical and tropical systems in Australia, which have higher emissions due to lateral inputs. We suggest that global estuarine CO2 emissions should be upscaled based on geomorphology, but should also consider land-use disturbance, and climate.

Light is critical to coral growth through endosymbiont photosynthesis but can also act with elevated temperatures to cause coral bleaching. When more light is absorbed than can be used for photosynthesis, elevated irradiance can damage symbiont photosynthetic machinery. Hence, solar-radiation management through shading has been suggested to alleviate coral bleaching during marine heatwaves. Acropora divaricata and Acropora kenti were tested at two temperatures with 30% shading and an unshaded control to determine the relative impacts of light and temperature on coral bleaching severity. The coral bleaching response was assessed by photochemical (pulse amplitude modulated fluorometry), physiological (symbiont density, chlorophyll a concentration, catalase activity, and lipid peroxidation), and physical (mean intensity of grey or ‘percentage whiteness’) markers. Shading significantly reduced the bleaching response in A. divaricata, whilst for some parameters A. kenti responded negatively to shade. In A. divaricata, shading prevented photochemical collapse up to the experiment’s maximum 4.4 degree-heating weeks (DHW). Biomarkers of coral bleaching stress responded to shade and water temperature at 4.4 DHW; catalase activity was greatest in the shaded and ambient temperature treatment. Shading did not reduce the effects of bleaching in A. kenti; the mean intensity of grey and light saturation coefficient was greatest in the shaded treatment. Shading did, however, reduce lipid peroxidation at 3 DHW. Our results suggest shading during thermal stress may only protect some coral species, highlighting the need to consider species-specific responses when evaluating the potential efficacy of coral bleaching interventions.

Ocean alkalinity enhancement (OAE) via the enhanced weathering of alkaline minerals is a promising carbon dioxide removal (CDR) technology. Theoretically, these includes iron and steel slags, although their dissolution kinetics in seawater are unknown. Here, we conducted lab-scale experiments to assess the alkalinity generation potential and dissolution kinetics of various slags in seawater. We show that the alkalinity generated per mass of iron slag was logarithmic, i.e., higher amounts of iron slag added had diminishing alkalinity returns. In contrast, the relatively quick dissolution of steel slags and their linear generation of alkalinity per mass of feedstock dissolved in seawater makes them better OAE candidates. Furthermore, despite the presence of potentially toxic metals in these feedstocks, their low to non-existent presence as dissolution products suggests that harmful concentrations should not be reached, at least for the slag tested here. Finally, if all steel slag produced annually was used for OAE, between 10 and 22 gigatonnes of CO2 could be captured cumulatively by 2,100, highlighting significant CDR potential by slags.

Abstract Certain cellular processes are dose-dependent, requiring specific quantities or stoichiometries of gene products, as exemplified by haploinsufficiency and sex-chromosome dosage compensation. Understanding dosage-sensitive processes requires tools to quantitatively modulate protein abundance. Here we present CasTuner, a CRISPR-based toolkit for analog tuning of endogenous gene expression. The system exploits Cas-derived repressors that are quantitatively tuned by ligand titration through a FKBP12F36V degron domain. CasTuner can be applied at the transcriptional or post-transcriptional level using a histone deacetylase (hHDAC4) fused to dCas9, or the RNA-targeting CasRx, respectively. We demonstrate analog tuning of gene expression homogeneously across cells in mouse and human cells, as opposed to KRAB-dependent CRISPR-interference systems, which exhibit digital repression. Finally, we quantify the system’s dynamics and use it to measure dose-response relationships of NANOG and OCT4 with their target genes and with the cellular phenotype. CasTuner thus provides an easy-to-implement tool to study dose-responsive processes in their physiological context.

Ocean artificial upwelling has been suggested to boost primary production and increase harvestable resources such as fish. Yet, for this ecosystem-based approach to work, an effective energy transfer up the food web is required. Here, we studied the trophic role of microzooplankton under artificial upwelling via biomass and community composition as well as grazing rates on phytoplankton. Using mesocosms in the oligotrophic ocean, we supplied nutrient-rich deep water at varying intensities (low to high) and addition modes (a Singular large pulse or smaller Recurring pulses). Deep-water fertilization created a diatom-dominated bloom that scaled with the amount of inorganic nutrients added, but also Synechococcus-like cells, picoeukaryotes and nanophytoplankton increased in abundance with added nutrients. After 30 days, towards the end of the experiment, coccolithophores bloomed under recurring upwelling of high intensity. Across all upwelling scenarios, the microzooplankton community was dominated by ciliates, dinoflagellates (mixo- and heterotrophic) and radiolarians. Under the highest upwelling intensity, the average grazing rates of Synechococcus-like cells, picoeukaryotes and nanophytoplankton by microzooplankton were 0.35 d-1 ± 0.18 (SD), 0.09 d-1 ± 0.12 (SD), and 0.11 d-1 ± 0.13 (SD), respectively. There was little temporal variation in grazing of nanophytoplankton but grazing of Synechococcus-like cells and picoeukaryotes were more variable. There were positive correlations between abundance of these groups and grazing rates, suggesting a response in the microzooplankton community to prey availability. The average phytoplankton to microzooplankton ratio (biovolume) increased with added deep water, and this increase was highest in the Singular treatment, reaching ~30 (m3 m-3), whereas the phytoplankton to total zooplankton biomass ratio (weight) increased from ~1 under low upwelling to ~6 (g g-1) in the highest upwelling but without a difference between the Singular and the Recurring mode. Several smaller, recurring upwelling events increased the importance of microzooplankton compared with one large pulse of deep water. Our results demonstrate that microzooplankton would be an important component for trophic transfer if artificial upwelling would be carried out at scale in the oligotrophic ocean.

Abstract For a short period during early development of mammalian embryos, both X chromosomes in females are active, before dosage compensation is ensured through X‐chromosome inactivation. In female mouse embryonic stem cells (mESCs), which carry two active X chromosomes, increased X‐dosage affects cell signaling and impairs differentiation. The underlying mechanisms, however, remain poorly understood. To dissect X‐dosage effects on the signaling network in mESCs, we combine systematic perturbation experiments with mathematical modeling. We quantify the response to a variety of inhibitors and growth factors for cells with one (XO) or two X chromosomes (XX). We then build models of the signaling networks in XX and XO cells through a semi‐quantitative modeling approach based on modular response analysis. We identify a novel negative feedback in the PI3K/AKT pathway through GSK3. Moreover, the presence of a single active X makes mESCs more sensitive to the differentiation‐promoting Activin A signal and leads to a stronger RAF1‐mediated negative feedback in the FGF‐triggered MAPK pathway. The differential response to these differentiation‐promoting pathways can explain the impaired differentiation propensity of female mESCs.

Ocean alkalinity enhancement (OAE) is a proposed method to counteract climate change by increasing the alkalinity of the surface ocean and thus the chemical storage capacity of seawater for atmospheric CO2. The impact of OAE on marine ecosystems, including phytoplankton communities which make up the base of the marine food web, is largely unknown. To investigate the influence of OAE on phytoplankton communities, we enclosed a natural plankton community from coastal Tasmania for 22 d in nine microcosms during a spring bloom. Microcosms were split into three groups, (1) the unperturbed control, (2) the unequilibrated treatment where alkalinity was increased (+495 ± 5.2 µmol kg−1) but seawater CO2 was not in equilibrium with atmospheric CO2, and (3) the equilibrated treatment where alkalinity was increased (+500 ± 3.2 µmol kg−1) and seawater CO2 was in equilibrium with atmospheric CO2. Both treatments have the capacity to increase the inorganic carbon sink of seawater by 21 %. We found that simulated OAE had significant but generally moderate effects on various groups in the phytoplankton community and on heterotrophic bacteria. More pronounced effects were observed for the diatom community where silicic acid drawdown and biogenic silica build-up were reduced at increased alkalinity. Observed changes in phytoplankton communities affected the temporal trends of key biogeochemical parameters such as the organic matter carbon-to-nitrogen ratio. Interestingly, the unequilibrated treatment did not have a noticeably larger impact on the phytoplankton (and heterotrophic bacteria) community than the equilibrated treatment, even though the changes in carbonate chemistry conditions were much more severe. This was particularly evident from the occurrence and peak of the phytoplankton spring bloom during the experiment, which was not noticeably different from the control. Altogether, the inadvertent effects of increased alkalinity on the coastal phytoplankton communities appear to be rather limited relative to the enormous climatic benefit of increasing the inorganic carbon sink of seawater by 21 %. We note, however, that more detailed and widespread investigations of plankton community responses to OAE are required to confirm or dismiss this first impression.

Ocean alkalinity enhancement (OAE) is a method that can remove carbon dioxide (CO2) from the atmosphere and counteract ocean acidification through the dissolution of alkaline minerals. Currently, critical knowledge gaps exist regarding the dissolution of different minerals suitable for OAE in natural seawater. Of particular importance is to understand how much alkaline mineral can be dissolved before secondary precipitation of calcium carbonate (CaCO3) occurs, since secondary CaCO3 precipitation reduces the atmospheric CO2 uptake potential of OAE. Using two types of mineral proposed for OAE, quick lime (CaO) and hydrated lime (Ca(OH)2), we show that both (<63 µm of diameter) dissolved in seawater within a few hours. No CaCO3 precipitation occurred at a saturation state (ΩA) of ∼5, but CaCO3 precipitation in the form of aragonite occurred above an ΩA value of 7. This limit is lower than expected for typical pseudo-homogeneous precipitation, i.e. in the presence of colloids and organic matter. Secondary precipitation at low ΩA (∼ 7) was the result of heterogeneous precipitation onto mineral surfaces, most likely onto the added CaO and Ca(OH)2 particles. Most importantly, runaway CaCO3 precipitation was observed, a condition where significantly more total alkalinity (TA) was removed than initially added. Such runaway precipitation could reduce the OAE CO2 uptake efficiency from ∼ 0.8 mol of CO2 per mole of added TA down to 0.1 mol of CO2 per mole of TA. Runaway precipitation appears to be avoidable by dilution below the critical ΩA threshold of 5, ideally within hours of the mineral additions to minimise initial CaCO3 precipitation. Finally, OAE simulations suggest that for the same ΩA threshold, the amount of TA that can be added to seawater would be more than 3 times higher at 5 ∘C than at 30 ∘C. The maximum TA addition could also be increased by equilibrating the seawater to atmospheric CO2 levels (i.e. to a pCO2 of ∼ 416 µatm) during addition. This would allow for more TA to be added in seawater without inducing CaCO3 precipitation, using OAE at its CO2 removal potential.

A scalable and diastereoselective synthesis of four icafolin-methyl plant metabolites bearing a 4-hydroxy-2-isoxazoline scaffold is described. The key to success was a practical cyclocondensation of 3,5-difluoronitromethane with α-formylbutyrolactone and a multigram-scale Grieco dehydration protocol, performed in continuous flow.

Objectives: To evaluate health-related quality of life (HRQOL) six years post-radical cystectomy in patients with muscle-invasive bladder cancer, comparing orthotopic ileal neobladder (ONB) and ileal conduit (IC). Therefore, the study aims to analyze the under-investigated long-term impact of standard bladder cancer treatments on HRQOL and provide insights into the HRQOL differences associated with these two common urinary diversion methods., Patients and Methods: This prospective study included 39 patients with urothelial carcinoma treated with ONB or IC at our center between 03/2013 and 01/2023. Patients with variant histology, metastasis, neoadjuvant chemotherapy, or benign indications for cystectomy were excluded. HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire preoperatively, at four and six years postoperatively. Statistical analyses included Chi-square tests, T-tests, and logistic regression models., Results: Of the patients, 64% (25/39) underwent ONB, and 76.9% (30/39) were male, with an average age of 69 years. No significant differences in overall good HRQOL (GHS > 70) were observed between ONB and IC at six years (IC: 60 ± 22; ONB: 69 ± 23, p = 0.2). Patients with IC reported higher insomnia at both follow-ups (4 years: p = 0.01; 6 years: p = 0.03). Emotional function remained stable in ONB patients but declined in IC patients from the fourth to sixth years (p = 0.04)., Conclusion: Long-term HRQOL did not significantly differ between ONB and IC up to six years post-radical cystectomy. Both urinary diversion methods can be offered to patients, with tailored discussions in terms of HRQOL., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Inflammation-induced oligodendrocyte death and CNS demyelination are key features of multiple sclerosis (MS). Inflammation-triggered endoplasmic reticulum (ER) stress and oxidative stress promote tissue damage in MS and in its preclinical animal model, experimental autoimmune encephalitis (EAE). Compound AA147 is a potent activator of the ATF6 signaling arm of the unfolded protein response (UPR) that can also induce antioxidant signaling through activation of the NRF2 pathway in neuronal cells. Previous work showed that AA147 protects multiple tissues against ischemia/reperfusion damage through ATF6 and/or NRF2 activation; however, its therapeutic potential in neuroinflammatory disorders remains unexplored. Here, we demonstrate that AA147 ameliorated the clinical symptoms of EAE and reduced ER stress, oligodendrocyte loss, and demyelination. Additionally, AA147 suppressed T cells in the CNS without altering the peripheral immune response. Importantly, AA147 significantly increased the expressions of Grp78, an ATF6 target gene, in oligodendrocytes, while enhancing levels of Grp78 as well as Ho-1, an NRF2 target gene, in microglia. In cultured oligodendrocytes, AA147 promoted nuclear translocation of ATF6, but not NRF2. Intriguingly, AA147 altered the microglia activation profile, possibly by triggering the NRF2 pathway. AA147 was not therapeutically beneficial during the acute EAE stage in mice lacking ATF6 in oligodendrocytes, indicating that protection primarily involves ATF6 activation in these cells. Overall, our results suggest AA147 as a potential therapeutic opportunity for MS by promoting oligodendrocyte survival and regulating microglia status through distinct mechanisms., (© 2025 Wiley Periodicals LLC.)

After nearly a decade of HIV pre-exposure prophylaxis (PrEP) rollout in sub-Saharan Africa, there has been limited study of PrEP messaging in news media. We selected twenty South African newspapers with the highest circulation volumes to retrieve articles published in 2012-2021 mentioning PrEP ( N  = 249). Using inductive content analysis, we developed a structured codebook to characterise PrEP-related content and sentiments, as well as their evolution over time, in the South African press. Many articles espoused favourable attitudes towards PrEP (52%), but a sizeable fraction espoused unfavourable attitudes (11%). Relative to PrEP-favourable articles, PrEP-unfavourable articles were significantly more likely to emphasise the drawbacks/consequences of PrEP use, including adherence/persistence requirements (52% vs. 24%, p  = .007), cost (48% vs. 11%, p  < .001), and risk compensation (52% vs. 5%, p  < .001). Nevertheless, the presence of these drawbacks/consequences in print media largely declined over time. Key populations (e.g. adolescents, female sex workers) were frequently mentioned potential PrEP candidates. Despite message variations over time, prevention effectiveness and adherence/persistence requirements were the most widely cited PrEP benefits and drawbacks, respectively. Study findings demonstrate the dynamic nature of PrEP coverage in the South African press, likely in response to PrEP scale-up and real-world PrEP implementation during the study period.

Background and Objectives: Cesarean section (c-section) rates among nulliparous, term, singleton, and vertex (NTSV) pregnancies are increasing, posing risk to the infant and birthing parent. To reach the Healthy People 2030 goal of an NTSV c-section rate below 23.6%, teams must remain aware of their NTSV c-section rate and implement mechanisms to reduce it. This project was conducted to assess the impact of quality improvement interventions implemented by family medicine residents to reduce a hospital's NTSV rate., Methods: From 2021 to 2023, family medicine residents were educated on evidenced-based diagnosis of labor dystocia, failed induction of labor, arrest of dilation, and arrest of descent in first-time birthing parents. Learning was reinforced by implementing the Colorado Perinatal Care Quality Collaborative's labor dystocia checklist. Quarterly assessment of the hospital's NTSV rate and checklist utilization were monitored and widely reported., Results: After the implementation of a standard checklist, the NTSV c-section rate at the tertiary care center declined from 35.6% in 2020 to a sustained rate below the 2030 Healthy People goal of 23.6%. Notably, patients with public insurance saw the greatest reduction in NTSV c-section rates. Hospital staff highlighted the benefits of using the checklist, including more effective electronic documentation of labor progression, improvement in team dynamics, and increased team communication., Conclusions: Using a labor dystocia checklist is a successful method for teams to reduce NTSV c-section rates and can be used as a training tool for family medicine and obstetrics and gynecology residency programs that care for laboring persons.

Amber captures a snapshot of life and death from millions of years in the past. Here, the fate of three fossil Darwin wasps in Baltic amber is virtually dissected with the help of micro-CT scanning, to better understand the taphonomic processes that affected their preservation. The states of the fossils range from nearly perfect preservation, including remains of internal organs, to empty casts that were strongly affected by decomposition. We describe the three specimens as new taxa, Osparvis aurorae gen. et sp. nov., Grana harveydenti gen. et sp. nov. and Xorides? romeo sp. nov. Based on the taphonomic and morphological interpretations, we conclude that two specimens were trapped alive, and the third ended up in resin post-mortem. The morphology and classification of the specimens provide clues regarding their ecology, and we discuss their likely hosts and parasitation modes. Taken together, our three wasp fossils showcase how an integrative analysis of amber taphonomy, taxonomic association and morphology can shed light onto past biodiversity and offer valuable insights for interpreting their evolutionary history., (© 2024. The Author(s).)

Social media content creators or "influencers" are an increasingly influential voice in the public discourse generally, including global perceptions and practices related to health. In response, public health entities are increasingly embracing social media influencers (SMIs) as potential health promotion collaborators. Despite burgeoning interest in the potential of these partnerships, research evaluating this strategy remains limited. To address this gap, we conducted a scoping review to characterize and describe the current landscape of health promotion collaborations with SMIs with a focus on current practices. A search of six electronic databases (PubMed, SCOPUS, Communication & Mass Media Complete, CINAHL Plus, Web of Science, and APA PsycINFO) revealed wide-ranging and inconsistent approaches to these partnerships, including their optimal practices, data reported, and their evaluation criteria. Among the 658 articles initially identified, 15 publications met our inclusion criteria, spanning 7 countries, 8 social media platforms, 11 distinct health topics, and 21 different outcome measures. Basic information necessary for comparing across interventions was often lacking. We noted a lack of consensus on what constitutes an SMI with 53% of included studies lacking any definition or criteria. Although SMIs offer substantial promise as an emerging opportunity for health promotion, particularly for populations that may be otherwise difficult to identify or reach, this review highlights how the current lack of standardized methodologies and metrics prevents meaningful comparisons between collaborations and evaluations of their effectiveness. Based on these findings, we propose four key criteria to aid practitioners in the implementation and evaluation of SMI collaborations.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The synthesis of a library of halogenated rocaglate derivatives belonging to the flavagline class of natural products, of which silvestrol is the most prominent example, is reported. Their antiviral activity and cytotoxicity profile against a wide range of pathogenic viruses, including hepatitis E, Chikungunya, Rift Valley Fever virus and SARS-CoV-2, were determined. The incorporation of halogen substituents at positions 4', 6 and 8 was shown to have a significant effect on the antiviral activity of rocaglates, some of which even showed enhanced activity compared to CR-31-B and silvestrol.

Few animal groups can claim the level of wonder that cephalopods instill in the minds of researchers and the general public. Much of cephalopod biology, however, remains unexplored: the largest invertebrate brain, difficult husbandry conditions, and complex (meta-)genomes, among many other things, have hindered progress in addressing key questions. However, recent technological advancements in sequencing, imaging, and genetic manipulation have opened new avenues for exploring the biology of these extraordinary animals. The cephalopod molecular biology community is thus experiencing a large influx of researchers, emerging from different fields, accelerating the pace of research in this clade. In the first post-pandemic event at the Cephalopod International Advisory Council (CIAC) conference in April 2022, over 40 participants from all over the world met and discussed key challenges and perspectives for current cephalopod molecular biology and evolution. Our particular focus was on the fields of comparative and regulatory genomics, gene manipulation, single-cell transcriptomics, metagenomics, and microbial interactions. This article is a result of this joint effort, summarizing the latest insights from these emerging fields, their bottlenecks, and potential solutions. The article highlights the interdisciplinary nature of the cephalopod-omics community and provides an emphasis on continuous consolidation of efforts and collaboration in this rapidly evolving field., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Eutrophication due to excessive nutrient inputs is a major threat to coastal ecosystems worldwide, causing harmful algae blooms, seagrass loss and hypoxia. Decisions to combat eutrophication in the North Sea were made in the 1980s. Despite significant improvements during recent decades, high nitrogen loads and resulting eutrophication problems remain. In this study, long-term changes in nitrogen inputs to the Elbe Estuary (Germany) were characterized based on nitrogen data provided by the Elbe River Basin Community from 1985 to 2019. Additionally, surface water samples were taken at the weir separating the river from the estuary from 2011 to 2021 to characterize dissolved inorganic nitrogen concentrations and nitrate stable isotope composition. The findings suggest a close coupling of river discharge with the riverine nitrogen cycle. Nitrogen loads decreased disproportionately with decreasing discharge. This decrease is due to intensified nitrogen retention in the Elbe catchment, which can double nitrogen retention compared to average discharge conditions. Phytoplankton growth was enhanced by long residence times and high light availability at low water levels. This suggests that the recent decreases in nitrogen loads in the Elbe River were not only a result of management measures in the catchment but were also amplified by a recent long-lasting drought in the catchment. Based on projections from the Intergovernmental Panel on Climate Change, more frequent and extensive droughts are anticipated, which may lead to future seasonal shifts to nitrate limitation in the lower Elbe River., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The tropical Andes are a species-rich and nitrogen-limited system, susceptible to increased nitrogen (N) inputs from the atmosphere. However, our understanding of the impacts of increased N input on belowground systems, in particular on protists and their role in nutrient cycling, remains limited. We explored how increased N affects protists in tropical montane rainforests in Ecuador using high-throughput sequencing (HTS) of environmental DNA from two litter layers. In addition, we manipulated the amount of arbuscular mycorrhizal fungi (AMF) and mesofauna, both playing a significant role in N cycling and interacting in complex ways with protist communities. We found that N strongly affected protist community composition in both layers, while mesofauna reduction had a stronger effect on the lower layer. Changes in concentration of the AMF marker lipid had little effect on protists. In both layers, the addition of N increased phagotrophs and animal parasites and decreased plant parasites, while mixotrophs decreased in the upper layer but increased in the lower layer. In the upper layer with higher AMF concentration, mixotrophs decreased, while in the lower layer, photoautotrophs increased and plant parasites decreased. With reduced mesofauna, phagotrophs increased and animal parasites decreased in both layers, while plant parasites increased only in the upper layer. The findings indicate that to understand the intricate response of protist communities to environmental changes, it is critical to thoroughly analyze these communities across litter and soil layers, and to include HTS., (© 2023 The Authors. Journal of Eukaryotic Microbiology published by Wiley Periodicals LLC on behalf of International Society of Protistologists.)

The COVID-19 pandemic has not only led to massive global mortality and morbidity, but it has also fueled an infodemic of false and misleading information about COVID-19 and vaccines. The spread of misinformation and disinformation on vaccine safety and efficacy has contributed to vaccine hesitancy and distrust of public health institutions and has undermined the public health response to the COVID-19 pandemic. Because communication plays a monumental role in pandemic preparedness, a promising approach to countering the COVID-19 infodemic is empowering peers to serve as trusted messengers to provide accurate information using evidence-based communication approaches. With this in mind, we developed a massive open online course (MOOC) to provide the general public with the knowledge, skills, and resources to effectively navigate potentially contentious vaccine conversations with their peers, with a specific focus on parents. Within the first year of the course launch, 29,000 people had enrolled. Learners appreciated the information related to vaccine development, communication tips and techniques, and identifying and responding to vaccine misinformation. Over 1,000 learners who completed the course participated in an online evaluation survey. To address public distrust in healthcare providers, government, and science, our survey results indicate that peer-to-peer approaches to addressing vaccine hesitancy can empower community members to educate others and promote vaccine acceptance at scale.

The most common form of epilepsy among adults is mesial temporal lobe epilepsy (mTLE), with seizures often originating in the hippocampus due to abnormal electrical activity. The gold standard for the histopathological analysis of mTLE is histology, which is a two-dimensional technique. To fill this gap, we propose complementary three-dimensional (3D) X-ray histology. Herein, we used synchrotron radiation-based phase-contrast microtomography with 1.6 μm-wide voxels for the post mortem visualization of tissue microstructure in an intrahippocampal-kainate mouse model for mTLE. We demonstrated that the 3D X-ray histology of unstained, unsectioned, paraffin-embedded brain hemispheres can identify hippocampal sclerosis through the loss of pyramidal neurons in the first and third regions of the Cornu ammonis as well as granule cell dispersion within the dentate gyrus. Morphology and density changes during epileptogenesis were quantified by segmentations from a deep convolutional neural network. Compared to control mice, the total dentate gyrus volume doubled and the granular layer volume quadrupled 21 days after injecting kainate. Subsequent sectioning of the same mouse brains allowed for benchmarking 3D X-ray histology against well-established histochemical and immunofluorescence stainings. Thus, 3D X-ray histology is a complementary neuroimaging tool to unlock the third dimension for the cellular-resolution histopathological analysis of mTLE., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America.)

Purpose: Online patient portals represent widely available communication tools in pediatric oncology. Previous studies have not evaluated clinicians' perspectives on portal use, including issues related to access to adolescents' portals., Methods: We performed semistructured interviews with physicians and advanced practice providers (APPs) who care for children or adolescents with cancer. We performed thematic analysis of benefits, problems, and accommodations related to portal use in oncology., Results: We interviewed 29 physicians and 24 APPs representing 26 institutions. Participants described five themes of benefits provided by portals: (1) empowering adolescents, (2) improving efficiency and accuracy of communication, (3) promoting open and adaptive communication, (4) supporting parents in managing care, and (5) bolstering clinical relationships. Participants described eight themes of problems caused by portal access: (1) creating emotional distress and confusion, (2) increasing workload and changing workflows, (3) threatening adolescent confidentiality, (4) adolescents lacking interest to engage, (5) diminishing clinical relationship, (6) misusing portal messages, (7) diminishing quality of sensitive documentation, and (8) parents losing access to adolescents' records. Participants described three themes related to accommodations they made as a result of portal access: (1) modifying note writing, (2) providing anticipatory guidance about viewing results, and (3) adapting workflows. Some portal functions created either benefits or problems depending on the clinical context., Conclusion: Oncologists identified benefits and problems created by portal use, which were sometimes in tension, depending on the clinical context. To make portals useful, we must take steps to mitigate risks while preserving functionality for parents and adolescent patients.

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks., (© 2023. Springer Nature Limited.)

Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim to evaluate whether zebrafish larvae (ZFL) could serve as a vertebrate screening model to detect gentamicin-induced changes of kidney glomeruli and proximal tubules. To validate the model, we compared the results of ZFL with those obtained from kidney biopsies of gentamicin-treated mice. We used transgenic zebrafish lines expressing enhanced green fluorescent proteins in the glomerulus to visualize glomerular damage. Synchrotron radiation-based computed tomography (SRμCT) is a label-free approach providing three-dimensional representations of renal structures with micrometre resolution. Clinically used gentamicin concentrations induce nephrotoxicity and affect glomerular and proximal tubular morphology. Findings were confirmed in mice and ZFL. There was a strong correlation between fluorescent signals in ZFL, SRμCT- derived descriptors of glomerular and proximal tubular morphology and the histological analysis of mouse kidney biopsies. A combination of SRμCT and confocal microscopy provides unprecedented insights into anatomical structures of the zebrafish kidney. Based on our findings, we suggest to use ZFL as a predictive vertebrate screening model to study drug-induced nephrotoxicity and to bridge the gap between cell culture-based test systems and experiments in mammals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bolten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The formation of bromine azide from the bisazidobromate(I) anion or alternatively from Zhdankin's reagent, using a phosphonium bromide salt as a common starting point, is reported. After homolytic cleavage in the presence of alkenes or alcohols either 1,2-functionalization or alternatively the selective oxidation of secondary alcohols in the presence of primary alcohols occur. The scopes and limitations of the use of BrN 3 are covered.

Throughout the COVID-19 pandemic, vaccine communication has been a challenge, particularly as some populations may be highly distrustful of information from public health or government institutions. To better understand the different communication needs in Ukraine, an online survey panel of 168 Ukrainian participants viewed six COVID-19 vaccination ads with three variations on vaccine messaging appeals (potential economic impacts of COVID-19 infection COVID-19 disease outcomes, and social norms related to vaccination) and two different messengers (a peer or a health provider). The ad featuring a health outcome appeal delivered by a healthcare provider was most favored ( n = 53, 31.6%); however, across demographic categories, including vaccine hesitancy categories, participants expressed high levels of approval for all six variations of the COVID-19 vaccine ads. When participants ranked reasons why someone may not accept the COVID-19 vaccine, the most prevalent beliefs identified were that the vaccine was not safe, and that the vaccine was not effective. Findings from this study suggest that vaccine appeals focused on health outcomes delivered by healthcare providers are preferred by most individuals in Ukraine; however, individuals are motivated by a myriad of factors suggesting that for vaccine messaging to be most effective, communication should be varied in both appeal and messenger.

The correct interpretation of fossils and their reliable taxonomic placements are fundamental for understanding the evolutionary history of biodiversity. Amber inclusions often preserve more morphological information than compression fossils, but are often partially hidden or distorted, which can impede taxonomic identification. Here, we studied four new fossil species of Darwin wasps from Baltic and Dominican amber, using micro computed tomography (micro-CT) scans and 3D reconstructions to accurately interpret and increase the availability of morphological information. We then infer their taxonomic placement in a Bayesian phylogenetic analysis by combining morphological and molecular data of extant and fossil Darwin wasps and evaluate the impact and usefulness of the additional information from micro-CT scanning. The results show that although we gained significant morphological information from micro-CT scanning, especially concerning measurements and hidden dorsal and ventral structures, this did not impact subfamily-level placement for any of the four fossils. However, micro-CT scanning improved the precision of fossil placements at the genus level, which might be key in future dating and diversification analyses. Finally, we describe the four new fossil species as Rhyssa gulliveri sp. nov. in Rhyssinae , Triclistus levii sp. nov. in Metopiinae, Firkantus freddykruegeri gen. et. sp. nov. in Pimplinae and Magnocula sarcophaga gen. et sp. nov. in Phygadeuontinae. The first two species are the first known representatives of the subfamilies Rhyssinae and Metopiinae in amber., Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-023-00294-2., Competing Interests: Competing interestsThe authors have no conflicts of interest to disclose., (© The Author(s) 2023.)

Extrinsic and intrinsic factors impact diversity. On deep-time scales, the extrinsic impact of climate and geology are crucial, but poorly understood. Here, we use the inner ear morphology of ruminant artiodactyls to test for a deep-time correlation between a low adaptive anatomical structure and both extrinsic and intrinsic variables. We apply geometric morphometric analyses in a phylogenetic frame to X-ray computed tomographic data from 191 ruminant species. Contrasting results across ruminant clades show that neutral evolutionary processes over time may strongly influence the evolution of inner ear morphology. Extant, ecologically diversified clades increase their evolutionary rate with decreasing Cenozoic global temperatures. Evolutionary rate peaks with the colonization of new continents. Simultaneously, ecologically restricted clades show declining or unchanged rates. These results suggest that both climate and paleogeography produced heterogeneous environments, which likely facilitated Cervidae and Bovidae diversification and exemplifies the effect of extrinsic and intrinsic factors on evolution in ruminants., (© 2022. The Author(s).)

Few studies have examined the relationships between the different aspects of vaccination communication and vaccine attitudes. We aimed to evaluate the influence of three unique messaging appeal framings of vaccination from two types of messengers on COVID-19 vaccine acceptance in India. We surveyed 534 online participants in India using Amazon Mechanical Turk (MTurk) from December 2021 through January 2022. We assessed participants' perception of three messaging appeals of vaccination - COVID-19 disease health outcomes, social norms related to vaccination, and economic impact of COVID-19 - from two messengers, healthcare providers (HCP) and peers. Using a multivariable multinomial logistic regression, we examined participants' ad preference and vaccine hesitancy. Participants expressed a high level of approval for all of the ads, with >80% positive responses for all questions across ads. Overall ads delivered by health care workers were preferred by a majority of participants in our study (n = 381, 71.4%). Ad preference ranged from 3.6% (n = 19) social norm/peer ad to 32.4% (n = 173) health outcome/HCP ad and half of participants preferred the health outcome ad (n = 279, 52.3%). Additionally, vaccine hesitancy was not related to preference ( p  = .513): HCP vs. peer ads ( p  = .522); message type ( p  = .284). The results suggest that all three appeals tested were generally acceptable, as well as the two messenger types, although preference was for the health care provider messenger and health outcome appeal. Individuals are motivated and influenced by a multitude of factors, requiring vaccine messaging that is persuasive, salient, and induces contextually relevant action.

The Helmsdorf "princely" tomb, excavated at the beginning of the twentieth century, is one of the most important archaeological discoveries dating from the Early Bronze Age in central Germany. In addition to the burial inventory, which points to an elevated social position of the deceased, a number of highly fragmented skeletal remains were preserved. Forensic anthropological investigation identified three distinctive bone defects, the surfaces of which were macromorphologically and microscopically examined in greater detail. Micro-CT analyses were also carried out. The results of all examinations suggested that the defects represented three perimortem injuries. The wound morphology was indicative of the use of a bladed weapon. The combination of injuries and their locations supported the assumption of a targeted use of force to kill. A comparison of Early Bronze Age weapons and tools with the bone lesions led to the identification of a type of weapon possibly used in the attack., (© 2022. The Author(s).)