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This study investigated two outbreaks of spontaneous poisoning by Baccharis coridifolia (Asteraceae) in early-weaned beef calves in Tacuarembó, Uruguay. A total of 34 affected calves showed signs of salivation, anorexia, apathy, marked dehydration, and diarrhea. Deaths occurred 36–72 h after consumption and mortality varied from 37.5% to 43.3% for outbreak 1 and outbreak 2, respectively. The main pathological findings include diffuse severe necrosis of the prestomachs and lymphoid tissues. Ultrastructurally, epithelial cells of the rumen showed swelling, lysis of the organelles, degradation of intercellular attachments, and degradation of the nuclear chromatin. Using LC-MS with diagnostic fragmentation filtering, 56 macrocyclic trichothecenes including glycosyl and malonyl conjugates were identified. The total concentration of macrocyclic trichothecenes, including conjugates, was estimated to be 1.2 ± 0.1 mg/g plant material. This is the first report of these malonyl–glucose conjugates from Baccharis coridifolia.

That fire facilitated the late Miocene C₄ grassland expansion is widely suspected but poorly documented. Fire potentially tied global climate to this profound biosphere transition by serving as a regional-to-local driver of vegetation change. In modern environments, seasonal extremes in moisture amplify the occurrence of fire, disturbing forest ecosystems to create niche space for flammable grasses, which in turn provide fuel for frequent fires. On the Indian subcontinent, C₄ expansion was accompanied by increased seasonal extremes in rainfall (evidenced by δ18Ocarbonate), which set the stage for fuel accumulation and fire-linked clearance during wet-to-dry seasonal transitions. Here, we test the role of fire directly by examining the abundance and distribution patterns of fire-derived polycyclic aromatic hydrocarbons (PAHs) and terrestrial vegetation signatures in n-alkane carbon isotopes from paleosol samples of the Siwalik Group (Pakistan). Two million years before the C₄ grassland transition, fire-derived PAH concentrations increased as conifer vegetation declined, as indicated by a decrease in retene. This early increase in molecular fire signatures suggests a transition to more fire-prone vegetation such as a C₃ grassland and/or dry deciduous woodland. Between 8.0 and 6.0 million years ago, fire, precipitation seasonality, and C₄-grass dominance increased simultaneously (within resolution) as marked by sharp increases in fire-derived PAHs, δ18Ocarbonate, and 13C enrichment in n-alkanes diagnostic of C₄ grasses. The strong association of evidence for fire occurrence, vegetation change, and landscape opening indicates that a dynamic fire–grassland feedback system was both a necessary precondition and a driver for grassland ecology during the first emergence of C₄ grasslands.

Purpose Ipsilateral combined fractures of the proximal femur, femoral shaft, and distal femur, though uncommon, present significant treatment challenges for orthopaedic surgeons. This retrospective study aims to investigate the intraoperative and long-term postoperative outcomes of this combination fracture when treated using a bridge–link type combined fixation system (BCFS). Patients and methods Four individuals received treatment at a level 1 trauma centre between January 2013 and December 2017 for combined fractures of the proximal femur, femoral shaft, and distal femur. The medical records of these patients were retrospectively examined. In addition to minimally invasive percutaneous plate osteosynthesis (MIO), all patients underwent BCFS. Results The median follow-up period for each patient was 28.5 months. The median duration of the surgical procedure was 176.0 min, with intraoperative haemorrhage measured at 470.0 ml. Among the cases, three patients showed firm union of the femoral shaft fractures. However, one patient experienced nonunion 12 months after the procedure, while another patient suffered from refracture of the femoral shaft and postoperative avascular necrosis of the femoral head. At the time of the last follow-up, the Friedman–Wyman functional scores were excellent in one case, good in two cases, and fair in one case. Conclusions Trifocal femoral fractures lack a widely approved therapeutic strategy. Nonetheless, BCFS may present itself as a viable alternative for treating this type of fracture, offering positive clinical outcomes.

Mercury has a unique and complex space environment with its weak global magnetic field, intense solar wind, tenuous exosphere, and magnetospheric plasma particles. This complex system makes Mercury an excellent science target to understand effects of the solar wind to planetary environments. In addition, investigating Mercury’s dynamic magnetosphere also plays a key role to understand extreme exoplanetary environment and its habitability conditions against strong stellar winds. BepiColombo, a joint mission to Mercury by the European Space Agency and Japan Aerospace Exploration Agency, will address remaining open questions using two spacecraft, Mio and the Mercury Planetary Orbiter. Mio is a spin-stabilized spacecraft designed to investigate Mercury’s space environment, with a powerful suite of plasma instruments, a spectral imager for the exosphere, and a dust monitor. Because of strong constraints on operations during its orbiting phase around Mercury, sophisticated observation and downlink plans are required in order to maximize science outputs. This paper gives an overview of the Mio spacecraft and its mission, operations plan, and data handling and archiving.

Diabetic retinopathy (DR), traditionally considered a microvascular complication, is now recognized as a neuroinflammatory disorder involving retinal glial cells. Aldose reductase (AKR1B1), a key enzyme in the polyol pathway, has been implicated in the hyperglycemia-induced inflammatory response in various cell types, although its role in retinal Müller glial cells under acute glucose stress remains unclear. This study investigates AKR1B1 activity and its contribution to inflammatory signaling in MIO-M1 human Müller cells exposed to acute hyperglycemia. AKR1B1 expression and activity, as well as NF-κB activation and COX-2 expression, were evaluated. Sorbinil, a specific AKR1B1 inhibitor, was used to determine the enzyme’s contribution to acute hyperglycemia-induced inflammation. Acute high-glucose treatment significantly increased AKR1B1 activity and sorbitol accumulation without affecting cell viability. In addition, activation of NF-κB and increased expression of cyclooxygenase-2 (COX-2) were observed, both of which were significantly reduced by Sorbinil. Our findings highlight the role of macroglia as active contributors to early inflammatory events in DR and suggest that transient hyperglycemic spikes are sufficient to trigger AKR1B1-dependent glial activation.

The study of 13 micromammal localities in the southern section of the Gormaget ravine (Alcoi Basin, SE Spain) and another 4 localities in the northern section has allowed us to define four local biozones in the dawn of the Pliocene, possibly recording the Mio-Pliocene boundary. The great density of localities close to the Mio-Pliocene boundary has enabled us to achieve a great resolution in the biozonation of the earliest Pliocene, only comparable in the Iberian Peninsula to the record of the Teruel Basin (NE Spain). We interpret these biozones in the light ofthe Neogene Mammal units and the European Land Mammal Ages, and correlate them with other local biozones defined for the same time span in the Iberian Peninsula.

β-adrenoceptors (BARs) are involved in vascular endothelial growth factor (VEGF) production during retinal neovascularization. Here, using human retinal endothelial and Müller cells (hRECs and MIO-M1, respectively), we evaluated the effects exerted by hypoxia on BARs, hypoxia-inducible factor-1α subunit (HIF-1α) and VEGF, as well as the involvement of BAR3 and nitric oxide synthase (NOS) enzymes in hypoxia-induced VEGF production. We altered oxygen availability through a hypoxic incubator. BARs, HIF-1 α and VEGF levels were evaluated. Cells were treated with the BAR3 antagonist SR59230A, different NOS inhibitors or the NO donor SNAP. The influence of the BAR3/NOS axis on hypoxic VEGF production was assessed. Hypoxia upregulated BAR3, HIF-1α and VEGF in hRECs and MIO-M1 cells. SR59230A counteracted hypoxia-dependent VEGF increase in both cell lines, exerting no effect on HIF-1α upregulation. Treatments with NOS inhibitors prevented the hypoxia-dependent VEGF increase, while SNAP abrogated the effect of SR59230A in reducing hypoxia-induced VEGF upregulation. The present results corroborate the hypothesis that in the hypoxic retina, BAR3 influence on VEGF production is mediated by NO and suggest that, at least in endothelial and Müller cells, BAR3 activity is necessary to allow the HIF-1-mediated VEGF upregulation.

An in-situ cosmic-dust instrument called the Mercury Dust Monitor (MDM) had been developed as a part of the science payload for the Mio (Mercury Magnetospheric Orbiter, MMO) stage of the joint European Space Agency (ESA)–JAXA Mercury-exploration mission. The BepiColombo spacecraft was successfully launched by an Ariane 5 rocket on October 20, 2018, and commissioning tests of the science payload were successfully completed in near-earth orbit before injection into a long journey to Mercury. MDM has a sensor consisting of four plates of piezoelectric lead zirconate titanate (PZT), which converts the mechanical stress (or strain) induced by dust-particle impacts into electrical signals. After the commencement of scientific operations, MDM will measure the impact momentum at which dust particles in orbit around the Sun collide with the sensor and record the arrival direction. This paper provides basic information concerning the MDM instrument and its predicted scientific operation as a future reference for scientific articles concerning the MDM’s observational data.

This paper describes the design and performance of the search coil magnetometers (SCM), which are part of the Plasma Wave Investigation (PWI) instrument onboard the BepiColombo/Mio spacecraft (Mercury Magnetospheric Orbiter), which will measure the electric field, plasma waves and radio waves for the first time in Mercury’s plasma environment. The SCM consists of two low-frequency orthogonal search coil sensors (LF-SC) measuring two components of the magnetic field (0.1 Hz – 20 kHz) in the spacecraft spin plane, and a dual-band search coil sensor (DB-SC) picking up the third component along the spin axis at both low-frequencies (LF: 0.1 Hz – 20 kHz) and high-frequencies (HF: 10 kHz – 640 kHz). The DB-SC and the two LF-SC sensors form a tri-axial configuration at the tip of a 4.6-m coilable mast (MAST-SC) extending from the spacecraft body, to minimize artificial magnetic field contamination emitted by the spacecraft electronics. After the successful launch of the spacecraft on 20 October 2018, an initial function check for the SCM was conducted. The nominal function and performance of the sensors and preamplifiers were confirmed, even with the MAST-SC being retracted and stowed in the spacecraft body, resulting in the detection of large interference signals likely from spacecraft electronics. The MAST-SC is scheduled for deployment after the Mercury orbit insertion of Mio in 2025, allowing the SCM to make the first higher frequency measurements of magnetic fluctuations in the Hermean magnetosphere and exosphere, and the local solar wind. These measurements will contribute to the investigation of fundamental problems in the Hermean plasma environment, including turbulence, magnetic reconnection, wave-particle interactions and particle acceleration.

Blood-based preparations are used in clinical practice for the treatment of several eye disorders. The aim of this study is to analyze the effect of freeze-drying blood-based preparations on the levels of growth factors and wound healing behaviors in an in vitro model. Platelet-rich plasma (PRP) and serum (S) preparations from the same Cord Blood (CB) sample, prepared in both fresh frozen (FF) and freeze-dried (FD) forms (and then reconstituted), were analyzed for EGF and BDNF content (ELISA Quantikine kit). The human MIO-M1 glial cell line (Moorfield/Institute of Ophthalmology, London, UK) was incubated with FF and FD products and evaluated for cell migration with scratch-induced wounding (IncuCyte S3 Essen BioScience), proliferation with cyclin A2 and D1 gene expression, and activation with vimentin and GFAP gene expression. The FF and FD forms showed similar concentrations of EGF and BDNF in both the S and PRP preparations. The wound healing assay showed no significant difference between the FF and FD forms for both S and PRP. Additionally, cell migration, proliferation, and activation did not appear to change in the FD forms compared to the FF ones. Our study showed that reconstituted FD products maintained the growth factor concentrations and biological properties of FF products and could be used as a functional treatment option.