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Summary: Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis.

IntroductionIsolation and confinement are significant stressors during space travel that can impact crewmembers’ physical and mental health. Space travel has been shown to accelerate vascular aging and increase the risk of cardiovascular and cerebrovascular disorders. However, the effect of prolonged isolation and confinement on microvascular function has not yet been thoroughly investigated.MethodsRetinal vascular imaging was conducted on four crewmembers during- and post-8-month SIRIUS-21 space analog mission. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were measured. Pulse wave velocity (PWV), an indicator of arterial stiffness, was also measured.ResultsData from 4 participants was analyzed. These participants had a mean age of 34.75 ± 5.44 years, height of 170.00 ± 2.00 cm, weight of 74.50 ± 12.53 kg, and average BMI of 25.47 ± 3.94 kg/m2. During- and post-isolation, average CRVE showed an upward trend (Pearson’s r 0.784, R-square 0.62), suggesting a dilation of retinal venules, while AVR showed a downward trend (Pearson’s r −0.238, R-square 0.057), which is suggestive of a higher risk of cardiovascular and cerebrovascular dysfunctions. But neither of these trends were statistically significant. Additionally, the average PWV showed an upward trend during- and after-isolation across all crew members.ConclusionIsolation and confinement appear to contribute towards retinal vascular damage and arterial stiffness. This cautiously suggests an increased risk of cardiovascular and cerebrovascular disorders due to the contribution of the isolation in space flight. Further studies are needed to confirm and expand on these results as we prepare for future manned missions to the Moon and Mars.

Predicting range shifts of marine species under different CO2 emission scenarios is of paramount importance to understand spatial potential changes in a context of climate change and to ensure appropriate management, in particular in areas where resources are critical to fisheries. Important tools which use environmental variables to infer range limits and species habitat suitability are the species distribution models or SDMs. In this work, we develop an ensemble species distribution model (e-SDM) to assess past, present and future distributions under Representative Concentration Pathway (RCP) 8.5 of nine demersal species and hotspot areas for their two life stages (adult and juvenile) in the Adriatic and Western Ionian Seas in four time windows (1999-2003, 2014-2018, 2031-2035 and 2046-2050). The e-SDM has been developed using three different models (and sub-models), i.e. (i) generalized additive models (GAM), (ii) generalized linear mixed model (GLMM), (iii) gradient boosting machine (GBM), through the combination of density data in terms of numbers of individuals km2 and environmental variables. Then, we have determined the changes in the aggregation hotspots and distributions. Finally, we assess gains and losses areas (i.e. occupation area) in the future climate change scenario as new potential range shifts for the nine species and their life stages. The results show that densities of some key commercial species, such as Merluccius merluccius (European hake), Mullus barbatus (red mullet), and Lophius budegassa (anglerfish) will be shifting northwards.

The Mediterranean Forecasting System produces operational analyses and reanalyses and 10 d forecasts for many essential ocean variables (EOVs), from currents, temperature, salinity, and sea level to wind waves and pelagic biogeochemistry. The products are available at a horizontal resolution of 1/24∘ (approximately 4 km) and with 141 unevenly spaced vertical levels. The core of the Mediterranean Forecasting System is constituted by the physical (PHY), the biogeochemical (BIO), and the wave (WAV) components, consisting of both numerical models and data assimilation modules. The three components together constitute the so-called Mediterranean Monitoring and Forecasting Center (Med-MFC) of the Copernicus Marine Service. Daily 10 d forecasts and analyses are produced by the PHY, BIO, and WAV operational systems, while reanalyses are produced every ∼ 3 years for the past 30 years and are extended (yearly). The modelling systems, their coupling strategy, and their evolutions are illustrated in detail. For the first time, the quality of the products is documented in terms of skill metrics evaluated over a common 3-year period (2018–2020), giving the first complete assessment of uncertainties for all the Mediterranean environmental variable analyses.

Numerical models of ocean biogeochemistry are becoming the major tools used to detect and predict the impact of climate change on marine resources and to monitor ocean health. However, with the continuous improvement of model structure and spatial resolution, incorporation of these additional degrees of freedom into fidelity assessment has become increasingly challenging. Here, we propose a new method to provide information on the model predictive skill in a concise way. The method is based on the conjoint use of a k-means clustering technique, assessment metrics, and Biogeochemical-Argo (BGC-Argo) observations. The k-means algorithm and the assessment metrics reduce the number of model data points to be evaluated. The metrics evaluate either the model state accuracy or the skill of the model with respect to capturing emergent properties, such as the deep chlorophyll maximums and oxygen minimum zones. The use of BGC-Argo observations as the sole evaluation data set ensures the accuracy of the data, as it is a homogenous data set with strict sampling methodologies and data quality control procedures. The method is applied to the Global Ocean Biogeochemistry Analysis and Forecast system of the Copernicus Marine Service. The model performance is evaluated using the model efficiency statistical score, which compares the model–observation misfit with the variability in the observations and, thus, objectively quantifies whether the model outperforms the BGC-Argo climatology. We show that, overall, the model surpasses the BGC-Argo climatology in predicting pH, dissolved inorganic carbon, alkalinity, oxygen, nitrate, and phosphate in the mesopelagic and the mixed layers as well as silicate in the mesopelagic layer. However, there are still areas for improvement with respect to reducing the model–data misfit for certain variables such as silicate, pH, and the partial pressure of CO2 in the mixed layer as well as chlorophyll-a-related, oxygen-minimum-zone-related, and particulate-organic-carbon-related metrics. The method proposed here can also aid in refining the design of the BGC-Argo network, in particular regarding the regions in which BGC-Argo observations should be enhanced to improve the model accuracy via the assimilation of BGC-Argo data or process-oriented assessment studies. We strongly recommend increasing the number of observations in the Arctic region while maintaining the existing high-density of observations in the Southern Oceans. The model error in these regions is only slightly less than the variability observed in BGC-Argo measurements. Our study illustrates how the synergic use of modeling and BGC-Argo data can both provide information about the performance of models and improve the design of observing systems.

Abstract The attention of the scientific community, policymakers, and public opinion on the Medicanes has recently grown because of their increase in intensity and harmful potential. Although Medicanes may be influenced by pre-existing upper-ocean conditions, uncertainties remain about how such weather extremes influence ocean circulation. This work examines a condition that has been never described before in the Mediterranean, which involves the interplay between an atmospheric cyclone (Medicane Apollo—October 2021) and a cyclonic gyre located in the western Ionian Sea. During the event, the temperature in the core of the cold gyre dropped dramatically, due to a local maximum in the wind-stress curl, Ekman pumping, and relative vorticity. Cooling and vertical mixing of the surface layer combined with upwelling in the subsurface layer caused a shoaling of the Mixed Layer Depth, halocline, and nutricline. The resulting biogeochemical impacts included an increase in oxygen solubility, chlorophyll concentration, productivity at the surface, and decreases in the subsurface layer. The presence of a cold gyre along Apollo's trajectory leads to a different ocean response from that observed with previous Medicanes, endorsing the efficiency of a multi-platform observation system integrated into an operational model for future mitigation of weather-related damages.

The subsurface oxygen maximum (SOM) is observed in oligotrophic oceans and is associated with different physical and biological processes. This study characterizes the SOM in the Mediterranean Sea at the basin scale and investigates its driving mechanisms by analysing the output of the 1/24∘ resolution biogeochemical reanalysis provided by the Copernicus Marine Service for the 1999–2019 time period. We validated the model-derived oxygen concentration in the epipelagic layer at different spatial and temporal scales, including novel process comparisons with estimates from in situ observations. Moreover, using Biogeochemical Argo (BGC-Argo) float observations, we estimated the model uncertainty in reproducing the SOM concentration and depth in summer (13 mmol O2 m−3 and 13 m, respectively). The western and eastern Mediterranean Sea depicts different SOM signatures in summer, with higher oxygen values and shallower depths in the western Mediterranean. The concentrations and depths (in the ranges of 230–250 mmol O2 m−3 and 30–100 m, respectively) are in agreement with the estimations from the literature and show mesoscale variability patterns. The western Mediterranean also shows a stronger biological activity, specifically oxygen production and consumption, along the whole epipelagic layer and higher oxygen concentrations at the surface throughout the year, but heavy undersaturated waters are associated with winter deep convection in the northwestern Mediterranean Sea. A 1-year analysis conducted on selected areas that are representative of the heterogeneity of summer SOM highlighted that the SOM can actually be sustained by biological production (as in northwestern Mediterranean areas), or it can be a residual of the confinement of spring production (as in the central Ionian area) and vertical motions influence its depth (as in the Levantine subduction area).

The projected warming, nutrient decline, changes in net primary production, deoxygenation and acidification of the global ocean will affect marine ecosystems during the 21st century. Here, the climate change-related impacts on the marine ecosystems of the Mediterranean Sea in the middle and at the end of the 21st century are assessed using high-resolution projections of the physical and biogeochemical state of the basin under Representative Concentration Pathways (RCPs) 4.5 and 8.5. In both scenarios, the analysis shows changes in the dissolved nutrient contents of the euphotic and intermediate layers of the basin, net primary production, phytoplankton respiration and carbon stock (including phytoplankton, zooplankton, bacterial biomass and particulate organic matter). The projections also show uniform surface and subsurface reductions in the oxygen concentration driven by the warming of the water column and by the increase in ecosystem respiration as well as an acidification signal in the upper water column linked to the increase in the dissolved inorganic carbon content of the water column due to CO2 absorption from the atmosphere and the increase in respiration. The projected changes are stronger in the RCP8.5 (worst-case) scenario and, in particular, in the eastern Mediterranean due to the limited influence of the exchanges in the Strait of Gibraltar in that part of the basin. On the other hand, analysis of the projections under the RCP4.5 emission scenario shows a tendency to recover the values observed at the beginning of the 21st century for several biogeochemical variables in the second half of the period. This result supports the idea – possibly based on the existence in a system such as the Mediterranean Sea of a certain buffer capacity and renewal rate – that the implementation of policies for reducing CO2 emission could indeed be effective and could contribute to the foundation of ocean sustainability science and policies.

Background Ovarian adenocarcinoma (OVAD) frequently metastasizes to the peritoneal cavity and manifests by the formation of ascites, which constitutes a tumor-promoting microenvironment. In the peritoneal cavity, two developmentally, phenotypically and functionally distinct macrophage subsets, immunocompetent large peritoneal macrophages (LPM) and immunosuppressive small peritoneal macrophages (SPM), coexist. Because peroxisome proliferator-activated receptor γ (PPARγ) is a critical factor participating in macrophage differentiation and cooperates with CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor essential for SPM-to-LPM differentiation, PPARγ could be also involved in the regulation of SPM/LPM balance and could be a promising therapeutic target.Methods To evaluate the 15(S)-hydroxyeicosatetraenoic acid (HETE), a PPARγ endogenous ligand, impact on ovarian tumor growth, we intraperitoneally injected 15(S)-HETE into a murine ovarian cancer model. This experimental model consists in the intraperitoneally injection of ID8 cells expressing luciferase into syngeneic C57BL/6 female mice. This ID8 orthotopic mouse model is a well-established experimental model of end-stage epithelial OVAD. Tumor progression was monitored using an in vivo imaging system. Peritoneal immune cells in ascites were analyzed by flow cytometry and cell sorting. To determine whether the impact of 15(S)-HETE in tumor development is mediated through the macrophages, these cells were depleted by injection of liposomal clodronate. To further dissect how 15(S)-HETE mediated its antitumor effect, we assessed the tumor burden in tumor-bearing mice in which the PPARγ gene was selectively disrupted in myeloid-derived cells and in mice deficient of the recombination-activating gene Rag2. Finally, to validate our data in humans, we isolated and treated macrophages from ascites of individuals with OVAD.Results Here we show, in the murine experimental model of OVAD, that 15(S)-HETE treatment significantly suppresses the tumor growth, which is associated with the differentiation of SPM into LPM and the LPM residency in the peritoneal cavity. We demonstrate that C/EBPβ and GATA6 play a central role in SPM-to-LPM differentiation and in LPM peritoneal residence through PPARγ activation during OVAD. Moreover, this SPM-to-LPM switch is associated with the increase of the effector/regulatory T-cell ratio. Finally, we report that 15(S)-HETE attenuates immunosuppressive properties of human ovarian tumor-associated macrophages from ascites.Conclusion Altogether, these results promote PPARγ as a potential therapeutic target to restrain OVAD development and strengthen the use of PPARγ agonists in anticancer therapy.

The text is a written rendering (heavily edited transcription) of the Sensing Salon held in Stockholm, on February 3, 2023, for the question: How to engage citational practices that support collaboration/make space within the institutional context? This collective reading is divided into three parts: (I) a Tarot reading done by the two of us, which includes explanations for the meanings of the cards, the positions, etc.; (II) a collaborative reading, which took the form of a free-flowing conversation, involving many if not most of those present; and (III) we close this documentation of the session with a reading of a Celtic Cross for one of the cards in the first spread, using a preliminary version of a deck we are in the process of developing, the Echo Tarot Deck*. The layering of readings allows for the complexity and nuance the question for this reading demands. As we zoom in with this reading, a glimpse of another image of citational practices appears. *The Echo Deck was inspired by the poems of African American-Japanese American poet Ai Ogawa. A provisional version of deck, with all the cards still blank, was first used in readings during our residency at Amant in New York, in 2022.

Objectives: To determine the prevalence and factors associated with retinopathy in patients of the Comprehensive Diabetes Program of the San Genaro Health Center in Villa Chorrillos. Methods: Descriptive, observational, cross-sectional, prospective study; with a sample of 119 adults and older adults. Non-probabilistic convenience sampling was used. The variables studied were diabetic retinopathy, type of diabetic retinopathy, degree of diabetic retinopathy, age, sex, educational level, time of illness, time belonging to the program, type of treatment, personal history of arterial hypertension, personal history of dyslipidemia, mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), Body Mass Index (BMI), Glycosylated Hemoglobin (HbA1c), Total Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, creatinine clearance, microalbuminuria, visual efficiency of Snell-Sterling, associated ocular pathology and ocular pressure. Descriptive statistical methods were used. Results: The prevalence of diabetic retinopathy (DR) was 15.1%, of which 77.8% is nonproliferative RD and 22.2% proliferative RD. In relation to the degrees in Non-Proliferative DR, 64.3% is mild and 35.7% moderate; and in Proliferative DR, 25% is early, 25% high risk and 50% severe. The biochemical value that showed a considerable difference was microalbuminuria, reaching a value of 356.9 mg/dl/24hrs. Conclusions: The prevalence of retinopathy is 15.1%, of which 77.8% is non-proliferative retinopathy and 22.2% proliferative retinopathy and the associated factors were systolic blood pressure (p

IntroductionPeas, as legume crops, could play a major role in the future of food security in the context of worldwide human nutrient deficiencies coupled with the growing need to reduce consumption of animal products. However, pea yields, in terms of quantity and quality (i.e. grain content), are both susceptible to climate change, and more specifically to water deficits, which nowadays occur more frequently during crop growth cycles and tend to last longer. The impact of soil water stress on plant development and plant growth is complex, as its impact varies depending on soil water availability (through the modulation of elements available in the soil), and by the plant’s ability to acclimate to continuous stress or to memorize previous stress events.MethodTo identify the strategies underlying these plant responses to water stress events, pea plants were grown in controlled conditions under optimal water treatment and different types of water stress; transient (during vegetative or reproductive periods), recurrent, and continuous (throughout the plant growth cycle). Traits related to water, carbon, and ionome uptake and uses were measured and allowed the identification typical plant strategies to cope with water stress.ConclusionOur results highlighted (i) the common responses to the three types of water stress in shoots, involving manganese (Mn) in particular, (ii) the potential implications of boron (B) for root architecture modification under continuous stress, and (iii) the establishment of an “ecophysiological imprint” in the root system via an increase in nodule numbers during the recovery period.

Measurement(s) travel-related behavior • travel-related attitude Technology Type(s) Survey Factor Type(s) temporal interval Sample Characteristic - Organism Homo sapiens Sample Characteristic - Location United States of America Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.15141945

Abstract Tissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concerning challenge for regenerative medicine. We recently developed a model of induced tissue regeneration in adult mice allowing the comparison of the early steps of regenerative and scar healing processes. By using studies of gain and loss of function, specific cell depletion approaches, and hematopoietic chimeras we demonstrate here that tissue regeneration in adult mammals depends on an early and transient peak of granulocyte producing reactive oxygen species and an efficient efferocytosis specifically by tissue-resident macrophages. These findings highlight key and early cellular pathways able to drive tissue repair towards regeneration in adult mammals.