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Abstract Natural killer (NK) cells are an important first-line of defense against malignant cells. Because of the potential for increased cancer risk from astronaut exposure to space radiation, we determined whether microgravity present during spaceflight affects the body’s defenses against leukemogenesis. Human NK cells were cultured for 48 h under normal gravity and simulated microgravity (sμG), and cytotoxicity against K-562 (CML) and MOLT-4 (T-ALL) cells was measured using standard methodology or under continuous sμG. This brief exposure to sμG markedly reduced NK cytotoxicity against both leukemias, and these deleterious effects were more pronounced in continuous sμG. RNA-seq performed on NK cells from two additional healthy donors provided insight into the mechanism(s) by which sμG reduced cytotoxicity. Given our prior report of space radiation-induced human T-ALL in vivo, the reduced cytotoxicity against MOLT-4 is striking and raises the possibility that μG may increase astronaut risk of leukemogenesis during prolonged missions beyond LEO.

Introduction: Missions beyond low Earth orbit (LEO) will expose astronauts to ionizing radiation (IR) in the form of solar energetic particles (SEP) and galactic cosmic rays (GCR) including high atomic number and energy (HZE) nuclei. The gastrointestinal (GI) system is documented to be highly radiosensitive with even relatively low dose IR exposures capable of inducing mucosal lesions and disrupting epithelial barrier function. IR is also an established risk factor for colorectal cancer (CRC) with several studies examining long-term GI effects of SEP/GCR exposure using tumor-prone APC mouse models. Studies of acute short-term effects of modeled space radiation exposures in wildtype mouse models are more limited and necessary to better define charged particle- induced GI pathologies and test novel medical countermeasures (MCMs) to promote astronaut safety.Methods: In this study, we performed ground-based studies where male and female C57BL/6J mice were exposed to γ-rays, 50 MeV protons, or 1 GeV/n Fe-56 ions at the NASA Space Radiation Laboratory (NSRL) with histology and immunohistochemistry endpoints measured in the first 24 h post-irradiation to define immediate SEP/GCR-induced GI alterations.Results: Our data show that unlike matched γ-ray controls, acute exposures to protons and iron ions disrupts intestinal function and induces mucosal lesions, vascular congestion, epithelial barrier breakdown, and marked enlargement of mucosa-associated lymphoid tissue. We also measured kinetics of DNA double-strand break (DSB) repair using gamma-H2AX- specific antibodies and apoptosis via TUNEL labeling, noting the induction and disappearance of extranuclear cytoplasmic DNA marked by gamma-H2AX only in the charged particle-irradiated samples. We show that 18 h pre-treatment with curcumin-loaded nanolipoprotein particles (cNLPs) delivered via IV injection reduces DSB-associated foci levels and apoptosis and restore crypt villi lengths.Discussion: These data improve our understanding of physiological alterations in the GI tract immediately following exposures to modeled space radiations and demonstrates effectiveness of a promising space radiation MCM.

Antibody therapies for Alzheimer's Disease (AD) hold promise but have been limited by the inability of these proteins to migrate efficiently across the blood brain barrier (BBB). Central nervous system (CNS) gene transfer by vectors like adeno-associated virus (AAV) overcome this barrier by allowing the bodies' own cells to produce the therapeutic protein, but previous studies using this method to target amyloid-β have shown success only with truncated single chain antibodies (Abs) lacking an Fc domain. The Fc region mediates effector function and enhances antigen clearance from the brain by neonatal Fc receptor (FcRn)-mediated reverse transcytosis and is therefore desirable to include for such treatments. Here, we show that single chain Abs fused to an Fc domain retaining FcRn binding, but lacking Fc gamma receptor (FcγR) binding, termed a silent scFv-IgG, can be expressed and released into the CNS following gene transfer with AAV. While expression of canonical IgG in the brain led to signs of neurotoxicity, this modified Ab was efficiently secreted from neuronal cells and retained target specificity. Steady state levels in the brain exceeded peak levels obtained by intravenous injection of IgG. AAV-mediated expression of this scFv-IgG reduced cortical and hippocampal plaque load in a transgenic mouse model of progressive β-amyloid plaque accumulation. These findings suggest that CNS gene delivery of a silent anti-Aβ scFv-IgG was well-tolerated, durably expressed and functional in a relevant disease model, demonstrating the potential of this modality for the treatment of Alzheimer's disease.

Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias – decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis.

Un nuevo 1óbulo de lava fue extrusionado sobre el domo del Volcán de Colima a principia de marzo, 1991. En e1 primer día de actividad eruptiva, el nuevo 1óbulo del domo creció a un volumen aproximado de 2,200 m3 de forma circular con diametro de alrededor de 20m y altura de aproximadamente 6.5 m. Alrededor del lóbulo del domo se formó una depresión somera con intensa desgasificación. Se observaron fracturas radiales que se extendían a partir del lóbulo del domo indicando que el esfuerzo horizontal conpresivo principal estaba orientado radialmente al domo durante la extrusión. El fallamiento más prominente resultó en la formación de un pequeño graben, de aproximadamente 20m de ancho y bordeado por escarpes con 3 a 5 m de desplazamiento vertical extendiéndose hacia el NNW del nuevo lóbulo del domo. Observaciones geofísicas hechas sobre el domo en 1990 indican que la extrusión inicial del nuevo lóbulo estuvo controlada por una estructura preexistente. El lóbulo del domo se extrusión aproximadamente 30m al sur de la única fumarola de alta temperatura (350-375°) que se encontraba sobre el domo en 1990. Cuatro fumarolas monitoreadas durante marzo, mayo y diciembre 1990, se desgasificaron en estado constante en 1990 con flujos de masa bajos. Hubo poco cambio en la media de las temperaturas de las fumarolas. Las observaciones magnéticas terrestres obtenidas en diciembre de 1990 en un transecto sobre el campo de las fumarolas muestran una anomalía magnética de longitud de onda corta, 2000 nT, centrada en el campo de las fumarolas. Las rocas del domo muestran suceptibilidades magnéticas comparativamente bajas (8.42x 10·6-8 .06x 10·5 corregido por masa SI) y magnetizaciones remanentes altas (1.08-5.57 A/m). Nuestro modelo de los datos magnéticos, incorporando estas observaciones del magnetismo de las rocas, indica que la fuente de la anomalía magnética fue un cuerpo pequeño y somero de roca que fue calentada por los gases fumarólicos por encima de la temperatura de bloqueo NRM de las rocas del domo. Este cuerpo de roca caliente era alargado en dirección NNW y coincide exactamente con el escape oriental del graben formado durante la extrusión inicia1 del lóbulo de lava de marzo, 1991. La aplicación de un modelo númerico de transferencia de calor y de masa sugiere que las fumarolas que se desgasifiquen en un estado constante y con flujo de masa bajo en un magma somero empobrecido en volátiles crearán una anomalía térmica similar a la que se deduce en el módulo magnético. Los derrames de roca sobre las partes altas del Volcán son más intensos sobre las extensiones norte y sur del nuevo graben. La coincidencia de los rasgos estructurales y térmicos sugiere que el graben con orientación NNW que se formó durante la actividad de 1991 es una manifestaci6n superficial de una estructura mayor que corta la parte superior del Volcán y sobre la cual puede ocurrir deformación adicional en el futuro. doi: https://doi.org/10.22201/igeof.00167169p.1993.32.4.609

Aim: Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location: Tropical and subtropical moist forests. Time period: Current. Major taxa studied: Palms (Arecaceae). Methods: We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co-occurring non-palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results: On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long-term climate stability. Life-form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non-tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above-ground biomass, but the magnitude and direction of the effect require additional work. Conclusions: Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.

A growing body of evidence shows that aboveground and belowground communities and processes are intrinsically linked, and that feedbacks between these subsystems have important implications for community structure and ecosystem functioning. Almost all studies on this topic have been carried out from an empirical perspective and in specific ecological settings or contexts. Belowground interactions operate at different spatial and temporal scales. Due to the relatively low mobility and high survival of organisms in the soil, plants have longer lasting legacy effects belowground than aboveground. Our current challenge is to understand how aboveground–belowground biotic interactions operate across spatial and temporal scales, and how they depend on, as well as influence, the abiotic environment. Because empirical capacities are too limited to explore all possible combinations of interactions and environmental settings, we explore where and how they can be supported by theoretical approaches to develop testable predictions and to generalise empirical results. We review four key areas where a combined aboveground–belowground approach offers perspectives for enhancing ecological understanding, namely succession, agro-ecosystems, biological invasions and global change impacts on ecosystems. In plant succession, differences in scales between aboveground and belowground biota, as well as between species interactions and ecosystem processes, have important implications for the rate and direction of community change. Aboveground as well as belowground interactions either enhance or reduce rates of plant species replacement. Moreover, the outcomes of the interactions depend on abiotic conditions and plant life history characteristics, which may vary with successional position. We exemplify where translation of the current conceptual succession models into more predictive models can help targeting empirical studies and generalising their results. Then, we discuss how understanding succession may help to enhance managing arable crops, grasslands and invasive plants, as well as provide insights into the effects of global change on community re-organisation and ecosystem processes.

Author(s): T. W. Crowther (corresponding author) [1, 2]; K. E. O. Todd-Brown [3]; C. W. Rowe [2]; W. R. Wieder [4, 5]; J. C. Carey [6]; M. B. Machmuller [7]; [...]

Northern wetlands and bogs are a large source of biogenic methane (CH4) to the atmosphere and shape climate. There is then substantial interest in quantifying the effect sizes of controls on bog CH4 emissions. Yet quantification is complicated because wetland emissions are, like the controls that regulate them, spatially and temporarily heterogeneous within individual wetland systems. To account for this heterogeneity, we established 55 measurement plots in a sampling design that had extensive spatial, and repeated temporal, coverage over one ombrotrophic bog. This coverage allowed us to robustly estimate the effect sizes of known environmental controls on CH4 emissions such as temperature, water table depth (WTD), and plant functional composition. As expected, 89% of the cumulative measured flux came from 16% of the plots, with consistently high CH4 emissions over two consecutive growing seasons. Soil temperature exhibited the strongest control on emissions, while WTD and vegetation composition had much smaller relative effects compared to temperature. Interestingly, at high temperatures, WTD was a strong determinant of whether a plot had high versus lower emissions. Despite temperature's large effect size, the controls we measured only explained ∼29% of the variance in CH4 fluxes. Overall, our data confirm observations from other wetlands that CH4 emissions are highly variable at local scales, and yet our data also reveal that effect sizes can be quantified robustly within this heterogeneity. Highly‐replicated, local designs may therefore be useful for generating data that can serve to help refine wetland CH4 emissions uncertainties. Plain Language Summary: Wetlands are an important source of biogenic methane to the atmosphere. However methane emissions from wetland systems are very difficult to predict and model, and even harder to extrapolate given future climate warming. In this study, we measured methane emissions from many plots across an ombrotrophic bog to better constrain the size of the effects of commonly measured environmental controls on methane emissions. We found that soil temperature had a greater effect size than depth to water table and vegetation community on methane fluxes, although at high temperatures, shallow (wetter) water table depth (WTD) compounded high methane fluxes. Given the likelihood of future climate warming, methane emissions from wetlands are likely to increase further. Management of local factors like vegetation and WTD may help limit these methane emissions, but the strong temperature control suggests we should plan to aggressively reduce emissions from industrial sources to avert the wetland feedback to a warming climate. Key Points: Across 55 plots, during repeated measurements over 2 years a subset of 16% had consistently high CH4 emissionsSoil temperature had the largest effect size on CH4 fluxes, increasing fluxes ∼11 times with a temperature increase from 0°C to 19°CWater table depth had an additive effect on CH4 emissions as temperature increased, increasing fluxes from 0.04 to 0.42 g CH4 m−2 d−1 [ABSTRACT FROM AUTHOR]