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Using NASA's Global‐scale Observations of the Limb and Disk (GOLD) imager, we report nightside ionospheric changes during the G5 super geomagnetic storm of 10 and 11 May 2024. Specifically, the nightside southern crest of the Equatorial Ionization Anomaly (EIA) was observed to merge with the aurora near the southern tip of South America. During the storm, the EIA southern crest was seen moving poleward as fast as 450 m/s. Furthermore, the aurora extended to mid‐latitudes reaching the southern tips of Africa and South America. The poleward shift of the equatorial ionospheric structure and equatorward motion of the aurora means there was no mid‐latitude ionosphere in this region. These observations offer unique insights into the ionospheric response to extreme geomagnetic disturbances, highlighting the complex interplay between solar activity and Earth's upper atmosphere. Plain Language Summary On Earth's nightside during the super geomagnetic storm that occurred on 10 May 2024, NASA's GOLD imager saw something new: a part of Earth's ionosphere, the southern peak of what typically appears as a double‐peaked structure in the ionospheric density at equatorial and low latitudes, merged with the aurora near the southern tip of South America. This has never been reported before. Additionally, the boundary of the aurora expanded further equatorward than usual. These observations of what happened in the Earth's ionosphere during this super storm are reported for the first time in this study. Key Points EIA crests between ∼70° and 35°W moved poleward, with northern and southern crest reaching ∼38°N and ∼35°S Mlat in the American sector Southern EIA crest moved poleward with a speed of ∼450 m/s near ∼55°W Glon during strong IMF Bz and d(Dst)/dt First observation of the merging of an EIA crest with the aurora indicating no mid‐latitude ionosphere

This chapter reviews fundamental properties and recent advances of diffuse and pulsating aurora. Diffuse and pulsating aurora often occurs on closed field lines and involves energetic electron precipitation by wave-particle interaction. After summarizing the definition, large-scale morphology, types of pulsation, and driving processes, we review observation techniques, occurrence, duration, altitude, evolution, small-scale structures, fast modulation, relation to high-energy precipitation, the role of ECH waves, reflected and secondary electrons, ionosphere dynamics, and simulation of wave-particle interaction. Finally we discuss open questions of diffuse and pulsating aurora.

Wave-particle interaction processes in the equatorial magnetosphere initiate time-dependent electron precipitation in the pulsating aurora. These electrons enter loss-cone and bounce between the two magnetically conjugate hemispheres, collide with the atmospheric constituents, and introduce additional time scales in electron precipitation dynamics. In this letter we present preliminary results of pulsating aurora formation using the time-dependent SuperThermal Electron Transport code, which considers the magnetosphere-ionosphere-atmosphere energy coupling between the two magnetically conjugate regions and discuss their contribution to the peculiarities of electron distribution function formation within the pulsating aurora.

The aetiology and progression of hypertension involves various endogenous systems, such as the renin angiotensin system, the sympathetic nervous system, and endothelial dysfunction. Recent data suggest that vascular inflammation may also play a key role in the pathogenesis of hypertension. This study sought to determine whether high intraluminal pressure results in vascular inflammation. Leukocyte adhesion was assessed in rat carotid arteries exposed to 1 h of high intraluminal pressure. The effect of intraluminal pressure on signaling mechanisms including reactive oxygen species production (ROS), arginase expression, and NFĸB translocation was monitored. 1 h exposure to high intraluminal pressure (120 mmHg) resulted in increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries. High intraluminal pressure also resulted in a downstream signaling cascade of ROS production, arginase expression, and NFĸB translocation. This process was found to be angiotensin II-independent and mediated by the mechanosensor caveolae, as caveolin-1 ( Cav1 )-deficient endothelial cells and mice were protected from pressure-induced vascular inflammatory signaling and leukocyte adhesion. Cav1 deficiency also resulted in a reduction in pressure-induced glomerular macrophage infiltration in vivo. These findings demonstrate Cav1 is an important mechanosensor in pressure-induced vascular and renal inflammation.

Background Dysferlin plays a key role in cell membrane repair; its absence or malfunction in patients with dysferlin‐deficient limb girdle muscular dystrophy leads to muscle fibre death. Muscle magnetic resonance (MR) imaging allows non‐invasive and repeatable measurements that can report on pathological changes observed in dysferlinopathy patients (DP). We aimed to demonstrate the feasibility of utilising volume‐localised 23Na spectroscopy as a novel approach to characterise muscle Na+ content and biexponential T2* at rest, and dynamically post‐exercise, in patients with dysferlinopathy and in matched healthy controls. Methods Adult DP and age and sex matched healthy volunteers (HV) were recruited and scanned on a 3 T clinical MR scanner. Following baseline scans, participants performed physiotherapist‐guided isometric dorsiflexion contractions until tibialis anterior (TA) muscle exhaustion. Dynamic volume‐localised sodium‐23 (23Na)‐ and proton (1H)‐MR scans were acquired serially for 35 min post‐exercise. MR data were analysed to determine TA lipid content, change in TA sodium content, biexponential sodium T2* properties and TA water 1H T2. Results Ten DP (mean age ± standard deviation [SD]: 38.0 ± 10.8 years; 80% female) and 10 HV (mean age ± SD: 38.9 ± 11.5 years) were scanned. Baseline muscle water 1H T2 and sodium concentration were significantly higher in DP compared to matched controls (1H T2 DP [SD] = 33.8 [2.7] ms, 1H T2 HV = 29.3 [1.1] ms, p < 0.001; [23Na]DP = 36.2 [11.4] mM, [23Na]HV = 19.6 [3.1] mM, p < 0.001). 1H T2 and sodium content in healthy controls showed significant post‐exercise elevation with a slower time‐to‐peak for sodium content compared to 1H T2. 1H T2 and sodium content change post‐exercise was highly variable in the DP group. Notably, 23Na dynamics in one DP with normal muscle fat fraction were similar to HV. Biexponential 23Na T2* was measured at baseline in HV (T2*slow = 13.4 [2.3] ms, T2*fast = 2.2 [1.3] ms), and DP (T2*slow = 14.0 [1.5] ms and T2*fast = 1.0 [0.5] m). Equivalent measurements post‐exercise revealed an increase in the fraction of the slow‐relaxing component in HV (p < 0.05), consistent with oedematous changes. Conclusions Assessment of TA muscle fat fraction, 1H T2, sodium content and sodium T2* relaxation properties revealed differences at baseline and in post‐exercise dynamics between patients with dysferlinopathy and matched controls. Post‐exercise 23Na recovery dynamics followed a well‐defined time course in HV. Heterogeneous alterations in sodium content and MR relaxation properties in DP may reflect altered ion homeostasis associated with chronic muscle damage.

Cold plasma of ionospheric origin has recently been found to be a much larger contributor to the magnetosphere of Earth than expected 1 , 2 – 3 . Numerous competing mechanisms have been postulated to drive ion escape to space, including heating and acceleration by wave–particle interactions 4 and a global electrostatic field between the ionosphere and space (called the ambipolar or polarization field) 5 , 6 . Observations of heated O + ions in the magnetosphere are consistent with resonant wave–particle interactions 7 . By contrast, observations of cold supersonic H + flowing out of the polar ionosphere 8 , 9 (called the polar wind) suggest the presence of an electrostatic field. Here we report the existence of a +0.55 ± 0.09 V electric potential drop between 250 km and 768 km from a planetary electrostatic field ( E ∥ ⊕ = 1.09 ± 0.17 μV m −1 ) generated exclusively by the outward pressure of ionospheric electrons. We experimentally demonstrate that the ambipolar field of Earth controls the structure of the polar ionosphere, boosting the scale height by 271%. We infer that this increases the supply of cold O + ions to the magnetosphere by more than 3,800%, in which other mechanisms such as wave–particle interactions can heat and further accelerate them to escape velocity. The electrostatic field of Earth is strong enough by itself to drive the polar wind 9 , 10 and is probably the origin of the cold H + ion population 1 that dominates much of the magnetosphere 2 , 3 . The ambipolar field of Earth controls the structure of the polar ionosphere and boosts its scale height by 271%, physically driving  the polar wind and acting as the source of the magnetospheric cold H + ion population.

The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA) results from low levels of survival motor neuron (SMN) protein; however, it is unclear how reduced SMN promotes SMA development. Here, we determined that ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse models of SMA, we observed widespread perturbations in ubiquitin homeostasis, including reduced levels of ubiquitin-like modifier activating enzyme 1 (UBA1). SMN physically interacted with UBA1 in neurons, and disruption of Uba1 mRNA splicing was observed in the spinal cords of SMA mice exhibiting disease symptoms. Pharmacological or genetic suppression of UBA1 was sufficient to recapitulate an SMA-like neuromuscular pathology in zebrafish, suggesting that UBA1 directly contributes to disease pathogenesis. Dysregulation of UBA1 and subsequent ubiquitination pathways led to β-catenin accumulation, and pharmacological inhibition of β-catenin robustly ameliorated neuromuscular pathology in zebrafish, Drosophila, and mouse models of SMA. UBA1-associated disruption of β-catenin was restricted to the neuromuscular system in SMA mice; therefore, pharmacological inhibition of β-catenin in these animals failed to prevent systemic pathology in peripheral tissues and organs, indicating fundamental molecular differences between neuromuscular and systemic SMA pathology. Our data indicate that SMA-associated reduction of UBA1 contributes to neuromuscular pathogenesis through disruption of ubiquitin homeostasis and subsequent β-catenin signaling, highlighting ubiquitin homeostasis and β-catenin as potential therapeutic targets for SMA.

5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs. 5‐FU treatment blocks miRNA export in small extracellular vesicles. Uracil residues (red) in normal cellular and small extracellular vesicle (sEV) RNA are frequently modified to pseudouridine (Ψ; blue) across multiple RNA subtypes. Exposure to 5‐FU inhibits pseudouridine formation and blocks miRNA export.

Dysferlin plays a key role in cell membrane repair; its absence or malfunction in patients with dysferlin-deficient limb girdle muscular dystrophy leads to muscle fibre death. Muscle magnetic resonance (MR) imaging allows non-invasive and repeatable measurements that can report on pathological changes observed in dysferlinopathy patients (DP). We aimed to demonstrate the feasibility of utilising volume-localised Na spectroscopy as a novel approach to characterise muscle Na content and biexponential T * at rest, and dynamically post-exercise, in patients with dysferlinopathy and in matched healthy controls. Adult DP and age and sex matched healthy volunteers (HV) were recruited and scanned on a 3 T clinical MR scanner. Following baseline scans, participants performed physiotherapist-guided isometric dorsiflexion contractions until tibialis anterior (TA) muscle exhaustion. Dynamic volume-localised sodium-23 ( Na)- and proton ( H)-MR scans were acquired serially for 35 min post-exercise. MR data were analysed to determine TA lipid content, change in TA sodium content, biexponential sodium T * properties and TA water H T . Ten DP (mean age ± standard deviation [SD]: 38.0 ± 10.8 years; 80% female) and 10 HV (mean age ± SD: 38.9 ± 11.5 years) were scanned. Baseline muscle water H T and sodium concentration were significantly higher in DP compared to matched controls ( H T [SD] = 33.8 [2.7] ms, H T  = 29.3 [1.1] ms, p < 0.001; [ Na]  = 36.2 [11.4] mM, [ Na]  = 19.6 [3.1] mM, p < 0.001). H T and sodium content in healthy controls showed significant post-exercise elevation with a slower time-to-peak for sodium content compared to H T . H T and sodium content change post-exercise was highly variable in the DP group. Notably, Na dynamics in one DP with normal muscle fat fraction were similar to HV. Biexponential Na T * was measured at baseline in HV (T *  = 13.4 [2.3] ms, T *  = 2.2 [1.3] ms), and DP (T *  = 14.0 [1.5] ms and T *  = 1.0 [0.5] m). Equivalent measurements post-exercise revealed an increase in the fraction of the slow-relaxing component in HV (p < 0.05), consistent with oedematous changes. Assessment of TA muscle fat fraction, H T , sodium content and sodium T * relaxation properties revealed differences at baseline and in post-exercise dynamics between patients with dysferlinopathy and matched controls. Post-exercise Na recovery dynamics followed a well-defined time course in HV. Heterogeneous alterations in sodium content and MR relaxation properties in DP may reflect altered ion homeostasis associated with chronic muscle damage.