Unveiling mercury levels: Trophic habits influence on bioaccumulation in two Otariid species.

Mercury, a toxic metal released by various human activities, exerts environmental stress through its bioaccumulation and biomagnification, particularly in marine habitats. South American fur seals (Arctocephalus australis) and sea lions (Otaria flavescens) reproduce on the Atlantic coast of Uruguay. As top predators, they can accumulate toxic levels of mercury and are often used as sentinel species for monitoring ecosystem health. Fur seals prey on pelagic species, such as fish and squid, while sea lions consume coastal-benthic prey. We analyzed the total mercury concentration (THg) in hair and the trophic habits (δ13C and δ15N) of females from both species. The average THg concentration in adult female sea lions (30.5 ± 9.3 µg/g dry weight) was significantly higher than in fur seals (6.3 ± 2.5 µg/g dry weight). Additionally, the mean δ15N and δ13C values were significantly higher in sea lion (δ15N: 19.2 ± 0.6‰, δ13C: -13.8 ± 0.2‰) compared to fur seals (δ15N: 16.5 ± 0.5‰, δ13C: -15.5 ± 0.6‰). Our results suggest that different trophic levels and feedings areas affect the THg concentration in Uruguayan Otariids. Notably, at the intraspecific level, the THg concentration in sea lions increased with δ13C values, suggesting a link to coastal feeding habits. This indicates that coastal feeding behaviors, compared to feeding in pelagic environments, enhance mercury bioaccumulation in Otariids along the Uruguayan coast, with the discharge of freshwater from the Río de la Plata (one of the largest estuaries in South America) basin identified as a potential mercury source. THg concentrations found in female sea lion hair are the highest reported in Otariids globally. Mercury levels exceeded toxic thresholds observed in other mammals and could pose significant health risks. Our findings may explain why sea lions were particularly affected by the avian influenza outbreak in Uruguay compared to fur seals. Monitoring the declining sea lion population is crucial, making our results significant for integrated conservation and management strategies.

Assessing the Impact of (Poly)phenol-Rich Foods on Cardiometabolic Risk in Postmenopausal Women: A Dietary Trial.

Menopause is a critical stage in a woman's life in which cardiometabolic alterations appear, such as insulin resistance or a predisposition to visceral fat deposits, leading to an increased risk of cardiometabolic diseases (R-CMBs). New strategies to reduce the R-CMBs in postmenopausal women using natural compounds without adverse effects are desirable. In this sense, plant-based diets rich in fruits and vegetables could play a fundamental role due to the high content of bioactive compounds found in these diets, such as (poly)phenols, known for their antioxidant, anti-inflammatory and vasodilator properties. The aim of this research was to carry out a dietary trial to evaluate the effect of the daily intake of different (poly)phenol-rich foods (PP-rich foods) for 2 months on the modulation of the main cardiometabolic risk biomarkers of postmenopausal women. The results showed a slight improvement in blood pressure (BP), lipid profile and oxidative stress, endothelial function and inflammatory biomarkers. These findings suggest that daily consumption of PP-rich foods alleviated the R-CMBs of postmenopausal women by reducing the oxidative stress and, thus, the risk of cardiovascular events; however, the magnitude of the cardioprotective effect of (poly)phenols depends on inter-individual variability.

Synthesis and Characterisation of Core-Shell Microparticles Formed by Ni-Mn-Co Oxides.

In this work, core and core-shell microparticles formed by Ni-Mn-Co oxides with controlled composition were fabricated by an oxalate-assisted co-precipitation route, and their properties were analysed by diverse microscopy and spectroscopy techniques. The microparticles exhibit dimensions within the 2-6 µm range and mainly consist of NiO and NiMn2O4, the latter being promoted as the temperature of the treatment increases, especially in the shell region of the microparticles. Aspects such as the shell dimensions, the vibrational modes of the spinel compounds primarily observed in the shell region, the oxidation states of the cations at the surface of the microparticles, and the achievement of a Ni-rich 811 core and a Mn-rich 631 shell were thoroughly evaluated and discussed in this work.

Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study.

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4-4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12-40) cm. The median duration of teduglutide therapy was 19 (IQR 12-36) months, with 23 patients (74%) treated for > 1 year and 9 treated for > 3 years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5-22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028).   Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: •  Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. • Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate.

Barbed versus conventional suture in elective posterior spine surgery.

PURPOSE: Barbed sutures are tissue control devices that can reduce operating room time and costs. We analyzed the utility of barbed sutures in posterior spinal surgery in order to prove non-inferiority to conventional methods for wound closure. METHODS: A cohort of patients undergoing elective posterior spinal surgery in which barbed (prospective) versus conventional sutures (retrospective) were used was analyzed. The primary endpoint was the occurrence of wound healing complications or the need for surgical revision. Secondary endpoints included postoperative stay, readmission rate, and duration and cost of wound closure. RESULT: A total of 483 patients participated in the study, 183 in the Barbed group and 300 in the Conventional group. Wound dehiscence or seroma occurred in 3.8% and 2.7% of the Barbed and Conventional groups, respectively (p = 0.6588). Both superficial (1.6% versus 4.0%, P = 0.2378) and deep infections (2.7% versus 4.7%, p = 0.4124) occurred similarly in both groups. Overall, the rate of re-intervention due to wound healing problems was also similar (4.9% versus 5.3%, p = 0.9906), as well as, total median hospital stay, postoperative stay and 30-day re-admission rates. The average duration of wound closure (1.66 versus 4.16 min per level operated, p < 0.0001) strongly favored the Barbed group. The mean cost of wound closure per patient was higher in the Barbed group (43.23 € versus 22.67 €, p < 0.0001). CONCLUSIONS: In elective posterior spinal procedures, the use of barbed sutures significantly reduced the duration of wound closure. The wound healing process was not hindered and the added cost related to the suture material was small.

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma.

BACKGROUND: Sarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumours do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumour growth. METHODS: We developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n = 6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumour potential of IDH mutations found in two chondrosarcoma cases was analysed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses). FINDINGS: We treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumour growth. Enasidenib induced a profound remodelling of the transcriptomic landscape not associated to changes in the 5 mC methylation levels and its anti-tumour effects were associated with the repression of proliferative pathways such as those controlled by E2F factors. INTERPRETATION: Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas. FUNDING: Supported by the Spanish Research Agency/FEDER (grants PID2022-142020OB-I00; PID2019-106666RB-I00), the ISC III/FEDER (PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057); the GEIS group (GEIS-62); and the PCTI (Asturias)/FEDER (IDI/2021/000027).

Perioperative risk factors for major complications after bone replacement in decompressive craniectomy.

INTRODUCTION: Bone flap replacement after a decompressive craniectomy is a low complexity procedure, but with complications that can negatively impact the patient's outcome. A better knowledge of the risk factors for these complications could reduce their incidence. PATIENTS AND METHODS: A retrospective review of a series of 50 patients who underwent bone replacement after decompressive craniectomy at a tertiary center over a 10-year period was performed. Those clinical variables related to complications after replacement were recorded and their risk factors were analyzed. RESULTS: A total of 18 patients (36%) presented complications after bone flap replacement, of which 10 (55.5%) required a new surgery for their treatment. Most of the replacements (95%) were performed in the first 90 days after the craniectomy, with a tendency to present more complications compared to the subsequent period (37.8% vs 20%, p > 0.05). The most frequent complication was subdural hygroma, which appeared later than infection, the second most frequent complication. The need for ventricular drainage or tracheostomy and the mean time on mechanical ventilation, ICU admission, or waiting until bone replacement were greater in patients who presented post-replacement complications. Previous infections outside the nervous system or the surgical wound was the only risk factor for post-bone flap replacement complications (p = 0.031). CONCLUSIONS: Postoperative complications were recorded in more than a third of the patients who underwent cranial bone flap replacement, and at least half of them required a new surgery. A specific protocol aimed at controlling previous infections could reduce the risk of complications and help establish the optimal time for cranial bone flap replacement.

Exercise Intervention and Hospital-Associated Disability: A Nonrandomized Controlled Clinical Trial.

Importance: Inpatient exercise interventions may prevent, at least partly, hospital-associated disability (HAD) in older adults, but whether they also confer clinical benefits in the months following discharge is unclear. Objective: To examine the association of exercise and health education with HAD incidence in hospitalized older adults receiving acute hospital care at discharge and 3 months later. Design, Setting, and Participants: This single-center open-label, nonrandomized controlled clinical trial included patients aged 75 years or older seen at an acute care for elders unit at a tertiary public hospital in Madrid, Spain, from May 1, 2018, to June 30, 2022. Interventions: Patients were allocated to an intervention or control group. Both groups received usual care, but the intervention group also performed a supervised multicomponent exercise program (daily strength, balance, and walking exercises along with inspiratory muscle training) during hospitalization and received health education on how to exercise at home and telephone counseling during follow-up. Main Outcomes and Measures: The primary outcome was HAD incidence (determined by the Katz Index of Independence in Activities of Daily Living [hereafter, Katz Index]) at discharge and after 3 months compared with baseline (ie, 2 weeks before admission). Secondary outcomes included HAD incidence determined by the Barthel Index for Activities of Daily Living, ambulatory capacity decline at discharge and follow-up, changes in physical performance at discharge, and incidence of falls, readmissions, and mortality during the follow-up period. Results: The study included 260 patients (134 women [51.5%]; mean [SD] age, 87.4 [4.9] years [range, 75-105 years]; median hospital length of stay, 7 days [IQR, 5-10 days]), of whom 130 received the intervention and 130 were in the control group. Differences in HAD incidence did not reach statistical significance at discharge (odds ratio [OR], 0.62; 95% CI, 0.37-1.05; P = .08) or follow-up (OR, 0.65; 95% CI, 0.36-1.17; P = .15) when using the Katz Index. A lower HAD incidence was observed in the intervention group at discharge (OR, 0.47; 95% CI, 0.27-0.81; P = .01) and at follow-up (OR, 0.36; 95% CI, 0.20-0.66; P = .001) when using the Barthel Index for Activities of Daily Living. The intervention was also associated with a lesser decline in ambulatory capacity (OR, 0.55; 95% CI, 0.32-0.96; P = .03) and improved physical performance at discharge (Cohen d, 0.39; 95% CI, 0.12-0.65; P = .004). No significant associations were observed for readmissions, falls, or mortality. Conclusions and Relevance: In this nonrandomized controlled clinical trial, an exercise and health education intervention was not significantly associated with reduced HAD incidence when measured by the Katz Index. However, the benefits found for several secondary outcomes might support the implementation of in-hospital exercise programs for older patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03604640.

Management of heparin-induced thrombocytopenia during extracorporeal membrane oxygenation support: a case of neutropenia caused by argatroban anticoagulation.

We present the case of a man in his 70s admitted to the intensive care unit (ICU) after mitral valve replacement and coronary artery bypass graft surgery requiring extracorporeal membrane oxygenation support due to haemodynamic instability. He received anticoagulation therapy with heparin sodium and, after 5 days, the patient presented with thrombocytopenia and deep venous thrombosis. Heparin-induced thrombocytopenia was suspected based on a positive 4T score and confirmed by antiplatelet factor 4/heparin antibodies, so argatroban was initiated as an alternative anticoagulation therapy. In the following days the patient developed severe neutropenia requiring discontinuation of argatroban and the administration of granulocyte colony-stimulating factor. According to the Naranjo Adverse Drug Reaction Probability Scale, this event would be classified as a 'probable' argatroban-related adverse event. Argatroban should be conisdered as a possible cause of neutropenia and appropriate interventions need to be implemented due to the gravity of this adverse event in the ICU.

Hyperammonemic encephalopathy after tyrosine kinase inhibitors: A literature review and a case example.

OBJECTIVE: To review the evidence of uncommon but fatal adverse event of hyperammonemic encephalopathy by tyrosine kinase inhibitors (TKI) and the possible mechanisms underlying this condition and to describe the case of a patient that developed drug-induced hyperammonemic encephalopathy related to TKI. DATA SOURCES: Literature search of different databases was performed for studies published from 1 January 1992 to 7 May 2023. The search terms utilized were hyperammonemic encephalopathy, TKI, apatinib, pazopanib, sunitinib, imatinib, sorafenib, regorafenib, trametinib, urea cycle regulation, sorafenib, carbamoyl-phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase 1, Mitogen activated protein kinases (MAPK) pathway and mTOR pathway, were used individually search or combined. DATA SUMMARY: Thirty-seven articles were included. The articles primarily focused in hyperammonemic encephalopathy case reports, management of hyperammonemic encephalopathy, urea cycle regulation, autophagy, mTOR and MAPK pathways, and TKI. CONCLUSION: Eighteen cases of hyperammonemic encephalopathy were reported in the literature from various multitargeted TKI. The mechanism of this event is not well-understood but some authors have hypothesized vascular causes since some of TKI are antiangiogenic, however our literature review shows a possible relationship between the urea cycle and the molecular inhibition exerted by TKI. More preclinical evidence is required to unveil the biochemical mechanisms responsible involved in this process and clinical studies are necessary to shed light on the prevalence, risk factors, management and prevention of this adverse event. It is important to monitor neurological symptoms and to measure ammonia levels when manifestations are detected.

Predicting histological grade in symptomatic meningioma by an objective estimation of the tumoral surface irregularity.

INTRODUCTION: Predicting the histopathologic grade of meningioma is relevant because local recurrence is significantly greater in WHO grade II-III compared to WHO grade I tumours, which would ideally benefit from a more aggressive surgical strategy. It has been suggested that higher WHO grade tumours are more irregularly-shaped. However, irregularity is a subjective and observer-dependent feature. In this study, the tumour surface irregularity of a large series of meningiomas, measured upon preoperative MRI, is quantified and correlated with the WHO grade. METHODS: Unicentric retrospective observational study of a cohort of symptomatic meningiomas surgically removed in the time period between January 2015 and December 2022. Using specific segmentation software, the Surface Factor (SF) was calculated for each meningioma. SF is an objective parameter that compares the surface of a sphere (minimum surface area for a given volume) with the same volume of the tumour against the actual surface of the tumour. This ratio varies from 0 to 1, being 1 the maximum sphericity. Since irregularly-shaped meningiomas present proportionally greater surface area, the SF tends to decrease as irregularity increases. SF was correlated with WHO grade and its predictive power was estimated with ROC curve analysis. RESULTS: A total of 176 patients (64.7% females) were included in the study; 120 WHO grade I (71.9%), 43 WHO grade II (25.7%) and 4 WHO grade III (2.4%). A statistically significant difference was found between the mean SF of WHO grade I and WHO grade II-III tumours (0.8651 ±â€¯0.049 versus 0.7081 ±â€¯0.105, p < 0.0001). Globally, the SF correctly classified more than 90% of cases (area under ROC curve 0.940) with 93.3% sensibility and 80.9% specificity. A cutoff value of 0.79 yielded the maximum precision, with positive and negative predictive powers of 82.6% and 92.6%, respectively. Multivariate analysis yielded SF as an independent prognostic factor of WHO grade. CONCLUSION: The Surface Factor is an objective and quantitative parameter that helps to identify aggressive meningiomas preoperatively. A cutoff value of 0.79 allowed differentiation between WHO grade I and WHO grade II-III with high precision.

Fast Coevaporation of 1 µm Thick Perovskite Solar Cells.

Coevaporation of perovskite films allows for a fine control over the material stoichiometry and thickness but is typically slow, leading to several-hour processes to obtain thick films required for photovoltaic applications. In this work, we demonstrate the coevaporation of perovskite layers using faster deposition rates, obtaining 1 µm thick films in approximately 50 min. We observed distinct structural properties and obtained devices with efficiency exceeding 19%, demonstrating the relevance of this deposition process from a material perspective and also in view of potential industrialization.

Reliable, standardized measurements for cell mechanical properties.

Atomic force microscopy (AFM) has become indispensable for studying biological and medical samples. More than two decades of experiments have revealed that cancer cells are softer than healthy cells (for measured cells cultured on stiff substrates). The softness or, more precisely, the larger deformability of cancer cells, primarily independent of cancer types, could be used as a sensitive marker of pathological changes. The wide application of biomechanics in clinics would require designing instruments with specific calibration, data collection, and analysis procedures. For these reasons, such development is, at present, still very limited, hampering the clinical exploitation of mechanical measurements. Here, we propose a standardized operational protocol (SOP), developed within the EU ITN network Phys2BioMed, which allows the detection of the biomechanical properties of living cancer cells regardless of the nanoindentation instruments used (AFMs and other indenters) and the laboratory involved in the research. We standardized the cell cultures, AFM calibration, measurements, and data analysis. This effort resulted in a step-by-step SOP for cell cultures, instrument calibration, measurements, and data analysis, leading to the concordance of the results (Young's modulus) measured among the six EU laboratories involved. Our results highlight the importance of the SOP in obtaining a reproducible mechanical characterization of cancer cells and paving the way toward exploiting biomechanics for diagnostic purposes in clinics.

Spanish cardiac catheterization and coronary intervention registry. 32nd official report of the Interventional Cardiology Association of the Spanish Society of Cardiology (1990-2022).

INTRODUCTION AND OBJECTIVES: This article presents the annual activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC) for the year 2022. METHODS: All Spanish centers with catheterization laboratories were invited to participate. Data were collected online and were analyzed by an external company in collaboration with the members of the board of the ACI-SEC. RESULTS: A total of 111 centers participated. The number of diagnostic studies increased by 4.8% compared with 2021, while that of percutaneous coronary interventions (PCI) remained stable. PCIs on the left main coronary artery increased by 22%. The radial approach continued to be preferred for PCI (94.9%). There was an upsurge in the use of drug-eluting balloons, as well as in intracoronary imaging techniques, which were used in 14.7% of PCIs. The use of pressure wires also increased (6.3% vs 2021) as did plaque modification techniques. Primary PCI continued to grow and was the most frequent treatment (97%) in ST-segment elevation myocardial infarction. Most noncoronary procedures maintained their upward trend, particularly percutaneous aortic valve implantation, atrial appendage closure, mitral/tricuspid edge-to-edge therapy, renal denervation, and percutaneous treatment of pulmonary arterial disease. CONCLUSIONS: The Spanish cardiac catheterization and coronary intervention registry for 2022 reveals a rise in the complexity of coronary disease, along with a notable growth in procedures for valvular and nonvalvular structural heart disease.

Contrastsing synaptic roles of MDGA1 and MDGA2.

Neurodevelopmental disorders are frequently linked to mutations in synaptic organizing molecules. MAM domain containing glycosylphosphatidylinositol anchor 1 and 2 (MDGA1 and MDGA2) are a family of synaptic organizers suggested to play an unusual role as synaptic repressors, but studies offer conflicting evidence for their localization. Using epitope-tagged MDGA1 and MDGA2 knock-in mice, we found that native MDGAs are expressed throughout the brain, peaking early in postnatal development. Surprisingly, endogenous MDGA1 was enriched at excitatory, but not inhibitory, synapses. Both shRNA knockdown and CRISPR/Cas9 knockout of MDGA1 resulted in cell-autonomous, specific impairment of AMPA receptor-mediated synaptic transmission, without affecting GABAergic transmission. Conversely, MDGA2 knockdown/knockout selectively depressed NMDA receptor-mediated transmission but enhanced inhibitory transmission. Our results establish that MDGA2 acts as a synaptic repressor, but only at inhibitory synapses, whereas both MDGAs are required for excitatory transmission. This nonoverlapping division of labor between two highly conserved synaptic proteins is unprecedented.

Multimodal video and IMU kinematic dataset on daily life activities using affordable devices.

Human activity recognition and clinical biomechanics are challenging problems in physical telerehabilitation medicine. However, most publicly available datasets on human body movements cannot be used to study both problems in an out-of-the-lab movement acquisition setting. The objective of the VIDIMU dataset is to pave the way towards affordable patient gross motor tracking solutions for daily life activities recognition and kinematic analysis. The dataset includes 13 activities registered using a commodity camera and five inertial sensors. The video recordings were acquired in 54 subjects, of which 16 also had simultaneous recordings of inertial sensors. The novelty of dataset lies in: (i) the clinical relevance of the chosen movements, (ii) the combined utilization of affordable video and custom sensors, and (iii) the implementation of state-of-the-art tools for multimodal data processing of 3D body pose tracking and motion reconstruction in a musculoskeletal model from inertial data. The validation confirms that a minimally disturbing acquisition protocol, performed according to real-life conditions can provide a comprehensive picture of human joint angles during daily life activities.

Rhizobial nitrogen fixation efficiency shapes endosphere bacterial communities and Medicago truncatula host growth.

BACKGROUND: Despite the knowledge that the soil-plant-microbiome nexus is shaped by interactions amongst its members, very little is known about how individual symbioses regulate this shaping. Even less is known about how the agriculturally important symbiosis of nitrogen-fixing rhizobia with legumes is impacted according to soil type, yet this knowledge is crucial if we are to harness or improve it. We asked how the plant, soil and microbiome are modulated by symbiosis between the model legume Medicago truncatula and different strains of Sinorhizobium meliloti or Sinorhizobium medicae whose nitrogen-fixing efficiency varies, in three distinct soil types that differ in nutrient fertility, to examine the role of the soil environment upon the plant-microbe interaction during nodulation. RESULTS: The outcome of symbiosis results in installment of a potentially beneficial microbiome that leads to increased nutrient uptake that is not simply proportional to soil nutrient abundance. A number of soil edaphic factors including Zn and Mo, and not just the classical N/P/K nutrients, group with microbial community changes, and alterations in the microbiome can be seen across different soil fertility types. Root endosphere emerged as the plant microhabitat more affected by this rhizobial efficiency-driven community reshaping, manifested by the accumulation of members of the phylum Actinobacteria. The plant in turn plays an active role in regulating its root community, including sanctioning low nitrogen efficiency rhizobial strains, leading to nodule senescence in particular plant-soil-rhizobia strain combinations. CONCLUSIONS: The microbiome-soil-rhizobial dynamic strongly influences plant nutrient uptake and growth, with the endosphere and rhizosphere shaped differentially according to plant-rhizobial interactions with strains that vary in nitrogen-fixing efficiency levels. These results open up the possibility to select inoculation partners best suited for plant, soil type and microbial community. Video Abstract.

CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells.

The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1low cells present a migratory and invasive phenotype, while EWSR1::FLI1high cells are more proliferative. In this work, we described how the CD44 standard isoform (CD44s), a transmembrane protein involved in cell adhesion and migration, is overexpressed in the EWSR1::FLI1low phenotype. The functional characterization of CD44s (proliferation, clonogenicity, migration, and invasion ability) was performed in three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, and CADO-ES1). As a result, CD44s expression reduced cell proliferation in all the cell lines tested without affecting clonogenicity. Additionally, CD44s increased cell migration in A673 and MHH-ES1, without effects in CADO-ES1. As hyaluronan is the main ligand of CD44s, its effect on migration ability was also assessed, showing that high molecular weight hyaluronic acid (HMW-HA) blocked cell migration while low molecular weight hyaluronic acid (LMW-HA) increased it. Invasion ability was correlated with CD44 expression in A673 and MHH-ES1 cell lines. CD44s, upregulated upon EWSR1::FLI1 knockdown, regulates cell migration and invasion in Ewing sarcoma cells.