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Surface ozone monitoring sites in the tropics are limited, despite the risk that surface ozone poses to human health, tropical forest and crop productivity. Atmospheric chemistry models allow us to assess ozone exposure in unmonitored locations and evaluate the potential influence of changing policies and climate on air quality, human health and ecosystem integrity. Here, we utilise in situ ozone measurements from ground-based stations in the pan-tropics to evaluate ozone from the UK Earth system model, UKESM1, with a focus on remote sites. The study includes ozone data from areas with limited previous data, notably tropical South America, central Africa and tropical northern Australia. Evaluating UKESM1 against observations beginning in 1987 onwards, we show that UKESM1 is able to capture changes in surface ozone concentration at different temporal resolutions, albeit with a systematic high bias of 18.1 nmol mol−1 on average. We use the diurnal ozone range (DOR) as a metric for evaluation and find that UKESM1 captures the observed DOR (mean bias of 2.7 nmol mol−1 and RMSE of 7.1 nmol mol−1) and the trend in DOR with location and season. Results from this study reveal that hourly ozone concentrations from UKESM1 require bias correction before use for impact assessments based on human and ecosystem health. Indeed, hourly surface ozone data have been crucial to this study, and we encourage other modelling groups to include hourly surface ozone output as a default.

In this paper, the new dynamic geophysical and geochemical MUltiparametric DAtabase (MUDA) is presented. MUDA is a new infrastructure of the National Institute of Geophysics and Volcanology (INGV), published online in December 2023, with the aim of archiving and disseminating multiparametric data collected by multidisciplinary monitoring networks. MUDA is a MySQL relational database with a web interface developed in PHP, aimed at investigating possible correlations between seismic phenomena and variations in endogenous and environmental parameters in quasi real time. At present, MUDA collects data from different types of sensors such as hydrogeochemical probes for physical–chemical parameters in waters, meteorological stations, detectors of air radon concentration, diffusive flux of carbon dioxide (CO2) and seismometers belonging both to the National Seismic Network of INGV and to temporary networks installed in the framework of multidisciplinary research projects. MUDA publishes data daily, updated to the previous day, and offers the chance to view and download multiparametric time series selected for different time periods. The resultant dataset provides broad perspectives in the framework of future high-frequency and continuous multiparametric monitoring as a starting point to identify possible seismic precursors for short-term earthquake forecasting. MUDA can be accessed at https://doi.org/10.13127/muda (Massa et al., 2023).

This study investigates the rain-initiated mixing and variability in the mixing ratio of selected trace gases in the atmosphere over the central Amazon rain forest. It builds on comprehensive data from the Amazon Tall Tower Observatory (ATTO), spanning from 2013 to 2020 and comprising the greenhouse gases (GHGs) carbon dioxide (CO2) and methane (CH4); the reactive trace gases carbon monoxide (CO), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2); and selected volatile organic compounds (VOCs). Based on more than 1000 analyzed rainfall events, the study resolves the trace gas mixing ratio patterns before, during, and after the rain events, along with vertical mixing ratio gradients across the forest canopy. The assessment of the rainfall events was conducted independently for daytime and nighttime periods, which allows us to elucidate the influence of solar radiation. The mixing ratios of CO2, CO, and CH4 clearly declined during rainfall, which can be attributed to the downdraft-related entrainment of pristine air from higher altitudes into the boundary layer, a reduction of the photosynthetic activity under increased cloud cover, and changes in the surface fluxes. Notably, CO showed a faster reduction than CO2, and the vertical gradient of CO2 and CO is steeper than for CH4. Conversely, the O3 mixing ratio increased across all measurement heights in the course of the rain-related downdrafts. Following the O3 enhancement by up to a factor of 2, NO, NO2, and isoprene mixing ratios decreased. The temporal and vertical variability of the trace gases is intricately linked to the diverse sink and source processes, surface fluxes, and free-troposphere transport. Within the canopy, several interactions unfold among soil, atmosphere, and plants, shaping the overall dynamics. Also, the mixing ratio of biogenic VOCs (BVOCs) clearly varied with rainfall, driven by factors such as light, temperature, physical transport, and soil processes. Our results disentangle the patterns in the trace gas mixing ratio in the course of sudden and vigorous atmospheric mixing during rainfall events. By selectively uncovering processes that are not clearly detectable under undisturbed conditions, our results contribute to a better understanding of the trace gas life cycle and its interplay with meteorology, cloud dynamics, and rainfall in the Amazon.

The 2021 Tajogaite eruption at La Palma has represented a unique opportunity to investigate the characteristics of the mantle source feeding modern volcanism in the Canary Islands. With the aim of track the fingerprint of carbon in the local oceanic lithosphere-asthenosphere system, we report the isotopic composition of CO2 (δ13C values versus Vienna Pee Dee Belemnite) in olivine- and clinopyroxene-hosted fluid inclusions (FI) from the 2021 Tajogaite lavas and from lavas/ultramafic xenoliths (olivine-clinopyroxenites, clinopyroxenites, dunites and harzburgites) from the nearby 1677 San Antonio eruption cone/lavas, in an attempt to characterize the origin and evolution of carbon within the local mantle source. Our results indicate that the 2021 and 1677 lavas exhibit δ13C values ranging from −4.94‰ to −2.71‰ and CO2/3He ratios from 3.37 to 6.14 × 109. Ultramafic xenoliths fall in a comparable range of values despite showing higher CO2 concentrations. Our δ13C values fall within the range of carbon isotope results previously reported for the Dos Aguas cold spring located in the Taburiente Caldera (northern La Palma), suggesting an apparent carbon isotope homogeneity at the scale of the entire island. The (relatively narrow) δ13C vs. CO2/3He ratio range of La Palma samples is interpreted to reflect either i) variable extents of open-system degassing of a common mantle endmember having δ13C of ∼1.7‰, or ii) mixing between depleted mantle-like carbon (−6‰ < δ13C < −4‰) and crustal carbon (δ13C = 0‰) endmembers. Both models testify a crustal carbon component recycled in the local mantle. This component, also detected in mantle xenoliths from the neighboring island of El Hierro and the easternmost Lanzarote, indicates a regional characteristic of the mantle beneath the Canary Islands, interpreted as a result of infiltration of carbon-rich melts during past metasomatic events in the local mantle.

Purpose In an era when trabeculectomy surgeries in the United States are on the decline, ophthalmology residents may have limited opportunities to practice surgical techniques critical to success. However, key steps of trabeculectomy surgery can be introduced in a wet laboratory using a simple surgical model based on food items. Methods A fresh lime and chicken parts with skin, purchased from a grocery store, were utilized to practice trabeculectomy surgery. The white rind of a lime was used as a surrogate for human sclera and was incised to create a trabeculectomy flap. The flap was then successfully sewn down with 10–0 nylon suture using an operating microscope. The skin of the chicken part was used to re-create a fornix-based and limbus-based conjunctival incision, which was then sutured closed using 6–0 Vicryl suture. A survey of wet laboratory participants was conducted to assess the feasibility and efficacy of this technique. Results Survey respondents were divided into two groups, those who had performed ≥40 incisional glaucoma surgeries and those who had performed

A major barrier to adeno-associated virus (AAV) gene therapy is the inability to re-dose patients due to formation of vector-induced neutralizing antibodies (Nabs). Tolerogenic nanoparticles encapsulating rapamycin (ImmTOR) provide long-term and specific suppression of adaptive immune responses, allowing for vector re-dosing. Moreover, co-administration of hepatotropic AAV vectors and ImmTOR leads to an increase of transgene expression even after the first dose. ImmTOR and AAV Anc80 encoding the methylmalonyl-coenzyme A (CoA) mutase (MMUT) combination was tested in a mouse model of methylmalonic acidemia, a disease caused by mutations in the MMUT gene. Repeated co-administration of Anc80 and ImmTOR was well tolerated and led to nearly complete inhibition of immunoglobulin (Ig)G antibodies to the Anc80 capsid. A more profound decrease of plasma levels of the key toxic metabolite, plasma methylmalonic acid (pMMA), and disease biomarker, fibroblast growth factor 21 (FGF21), was observed after treatment with the ImmTOR and Anc80-MMUT combination. In addition, there were higher numbers of viral genomes per cell (vg/cell) and increased transgene expression when ImmTOR was co-administered with Anc80-MMUT. These effects were dose-dependent, with the higher doses of ImmTOR providing higher vg/cell and mRNA levels, and an improved biomarker response. Combining of ImmTOR and AAV can not only block the IgG response against capsid, but it also appears to potentiate transduction and enhance therapeutic transgene expression in the mouse model.

Abstract Post‐orogenic back‐arc magmatism is accompanied by hydrothermal ore deposits and mineralizations derived from mantle and crustal sources. We investigate Zannone Island (ZI), back‐arc Tyrrhenian basin, Italy, to define the source(s) of mineralizing hydrothermal fluids and their relationships with the regional petrological‐tectonic setting. On ZI, early Miocene thrusting was overprinted by late Miocene post‐orogenic extension and related hydrothermal alteration. Since active submarine hydrothermal outflow is reported close to the island, Zannone provides an ideal site to determine the P‐T‐X evolution of the long‐lived hydrothermal system. We combined field work with microstructural analyses on syn‐tectonic quartz veins and carbonate mineralizations, X‐ray diffraction analysis, microthermometry and element mapping of fluid inclusions (FIs), C, O, and clumped isotopes, and analyses of noble gases (He‐Ne‐Ar) and CO2 content in FIs. Our results document the evolution of a fluid system of magmatic origin with increasing mixing of meteoric fluids. Magmatic fluids were responsible for quartz veins precipitation at ∼125 to 150 MPa and ∼300°C–350°C. With the onset of extensional faulting, magmatic fluids progressively interacted with carbonate rocks and mixed with meteoric fluids, leading to (a) host rock alteration with associated carbonate and minor ore mineral precipitation, (b) progressive fluid neutralization, (c) cooling of the hydrothermal system (from ∼320°C to ∼86°C), and (d) embrittlement and fracturing of the host rocks. Both quartz and carbonate mineralizations show noble gases values lower than those from the adjacent active volcanic areas and submarine hydrothermal systems, indicating that the fossil‐to‐active hydrothermal history is associated with the emplacement of multiple magmatic intrusions.

The Aleutian Arc is remote and highly active volcanically. Its 4,000 km extent from mainland Alaska to Russia’s Kamchatka peninsula hosts over 140 volcanic centers of which about 50 have erupted in historic times. We present data of volcanic gas samples and gas emission measurements obtained during an expedition to the western-most segment of the arc in September 2015 in order to extend the sparse knowledge on volatile emissions from this remote but volcanically active region. Some of the volcanoes investigated here have not been sampled for gases before this writing. Our data show that all volcanoes host high-temperature magmatic-hydrothermal systems and have gas discharges typical of volcanoes in oceanic arcs. Based on helium isotopes, the western Aleutian Arc segment has minimal volatile contributions from the overriding crust. Volcanic CO2 fluxes from this arc segment are small, compared to the emissions from volcanoes on the Alaska Peninsula and mainland Alaska. The comparatively low CO2 emissions may be related to the lower sediment flux delivered to the trench in this part of the arc.

ImmTOR biodegradable nanoparticles encapsulating rapamycin have been shown to induce a durable tolerogenic immune response to co-administered biologics and gene therapy vectors. Prior mechanism of action studies have demonstrated selective biodistribution of ImmTOR to the spleen and liver following intravenous (IV) administration. In the spleen, ImmTOR has been shown to induce tolerogenic dendritic cells and antigen-specific regulatory T cells and inhibit antigen-specific B cell activation. Splenectomy of mice resulted in partial but incomplete abrogation of the tolerogenic immune response induced by ImmTOR. Here we investigated the ability of ImmTOR to enhance the tolerogenic environment in the liver. All the major resident populations of liver cells, including liver sinusoidal endothelial cells (LSECs), Kupffer cells (KC), stellate cells (SC), and hepatocytes, actively took up fluorescent-labeled ImmTOR particles, which resulted in downregulation of MHC class II and co-stimulatory molecules and upregulation of the PD-L1 checkpoint molecule. The LSEC, known to play an important role in hepatic tolerance induction, emerged as a key target cell for ImmTOR. LSEC isolated from ImmTOR treated mice inhibited antigen-specific activation of ovalbumin-specific OT-II T cells. The tolerogenic environment led to a multi-pronged modulation of hepatic T cell populations, resulting in an increase in T cells with a regulatory phenotype, upregulation of PD-1 on CD4+ and CD8+ T cells, and the emergence of a large population of CD4–CD8– (double negative) T cells. ImmTOR treatment protected mice in a concanavalin A-induced model of acute hepatitis, as evidenced by reduced production of inflammatory cytokines, infiltrate of activated leukocytes, and tissue necrosis. Modulation of T cell phenotype was seen to a lesser extent after administration by empty nanoparticles, but not free rapamycin. The upregulation of PD-1, but not the appearance of double negative T cells, was inhibited by antibodies against PD-L1 or CTLA-4. These results suggest that the liver may contribute to the tolerogenic properties of ImmTOR treatment.

Constraining the magmatic 3He/4He signature of fluids degassed from a magmatic system is crucial for making inferences on its mantle source. This is especially important in arc volcanism, where variations in the composition of the wedge potentially induced by slab sediment fluids must be distinguished from the effects of magma differentiation, degassing, and crustal contamination. The study of fluid inclusions (FIs) trapped in minerals of volcanic rocks is becoming an increasingly used methodology in geochemical studies that integrates the classical study of volcanic and geothermal fluids. Here, we report on the first noble gas (He, Ne, Ar) concentrations and isotopic ratios of FI in olivine (Ol) and pyroxene (Px) crystals separated from eruptive products of the Telica and Baru volcanoes, belonging to the Nicaraguan and Panamanian arc-segments of Central America Volcanic arc (CAVA). FIs from Telica yield air corrected 3He/4He (Rc/Ra) of 7.2–7.4 Ra in Ol and 6.1–7.3 in Px, while those from Baru give 7.1–8.0 Ra in Ol and 4.2–5.8 Ra in Px. After a data quality check and a comparison with previous 3He/4He measurements carried out on the same volcanoes and along CAVA, we constrained a magmatic Rc/Ra signature of 7.5 Ra for Telica and of 8.0 Ra for Baru, both within the MORB range (8 ± 1 Ra). These 3He/4He differences also reflect variations in the respective arc-segments, which cannot be explained by radiogenic 4He addition due to variable crust thickness, as the mantle beneath Nicaragua and Panama is at about 35 and 30 km, respectively. We instead highlight that the lowest 3He/4He signature observed in the Nicaraguan arc segment reflects a contamination of the underlying wedge by slab sediment fluids. Rc/Ra values up to 9.0 Ra are found at Pacaya volcano in Guatemala, where the crust is 45 km thick, while a 3He/4He signature of about 8.0 Ra was measured at Turrialba volcano in Costa Rica, which is similar to that of Baru, and reflects possible influence of slab melting, triggered by a change in subduction conditions and the contemporary subduction of the Galapagos hot-spot track below southern Costa Rica and western Panama.