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Observations of planet Earth from space are a critical resource for science and society. Satellite measurements represent very large investments and United States (US) agencies organize their effort to maximize the return on that investment. The US National Research Council conducts a survey of Earth science and applications to prioritize observations for the coming decade. The most recent survey prioritized a visible to shortwave infrared imaging spectrometer and a multispectral thermal infrared imager to meet a range of needs for studying Surface Biology and Geology (SBG). SBG will be the premier integrated observatory for observing the emerging impacts of climate change by characterizing the diversity of plant life and resolving chemical and physiological signatures. It will address wildfire risk, behavior, and recovery as well as responses to hazards such as oil spills, toxic minerals in minelands, harmful algal blooms, landslides, and other geological hazards. The SBG team analyzed needed instrument characteristics (spatial, temporal, and spectral resolutions, measurement uncertainty) and assessed the cost, mass, power, volume, and risk of different architectures. We present an overview of the Research and Applications trade-study analysis of algorithms, calibration and validation needs, and societal applications with specifics of substudies detailed in other articles in this special collection. We provide a value framework to converge from hundreds down to three candidate architectures recommended for development. The analysis identified valuable opportunities for international collaboration to increase the revisit frequency, adding value for all partners, leading to a clear measurement strategy for an observing system architecture., (© 2022 Jet Propulsion Laboratory. California Institute of Technology. Government sponsorship acknowledged. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The enhanced seasonal amplitude of atmospheric CO 2 has been viewed so far primarily as a Northern Hemisphere phenomenon. Yet, analyses of atmospheric CO 2 records from 49 stations between 1980 and 2018 reveal substantial trends and variations in this amplitude globally. While no significant trends can be discerned before 2000 in most places, strong positive trends emerge after 2000 in the southern high latitudes. Using factorial simulations with an atmospheric transport model and analyses of surface ocean P co 2 observations, we show that the increase is best explained by the onset of increasing seasonality of air-sea CO 2 exchange over the Southern Ocean around 2000. Underlying these changes is the long-term ocean acidification trend that tends to enhance the seasonality of the air-sea fluxes, but this trend is modified by the decadal variability of the Southern Ocean carbon sink. The seasonal variations of atmospheric CO 2 thus emerge as a sensitive recorder of the variations of the Southern Ocean carbon sink.

High-resolution space-based spectral imaging of the Earth's surface delivers critical information for monitoring changes in the Earth system as well as resource management and utilization. Orbiting spectrometers are built according to multiple design parameters, including ground sampling distance (GSD), spectral resolution, temporal resolution, and signal-to-noise ratio. Different applications drive divergent instrument designs, so optimization for wide-reaching missions is complex. The Surface Biology and Geology component of NASA's Earth System Observatory addresses science questions and meets applications needs across diverse fields, including terrestrial and aquatic ecosystems, natural disasters, and the cryosphere. The algorithms required to generate the geophysical variables from the observed spectral imagery each have their own inherent dependencies and sensitivities, and weighting these objectively is challenging. Here, we introduce intrinsic dimensionality (ID), a measure of information content, as an applications-agnostic, data-driven metric to quantify performance sensitivity to various design parameters. ID is computed through the analysis of the eigenvalues of the image covariance matrix, and can be thought of as the number of significant principal components. This metric is extremely powerful for quantifying the information content in high-dimensional data, such as spectrally resolved radiances and their changes over space and time. We find that the ID decreases for coarser GSD, decreased spectral resolution and range, less frequent acquisitions, and lower signal-to-noise levels. This decrease in information content has implications for all derived products. ID is simple to compute, providing a single quantitative standard to evaluate combinations of design parameters, irrespective of higher-level algorithms, products, applications, or disciplines., (© 2022 Jet Propulsion Laboratory and The Authors, California Institute of Technology. Government sponsorship acknowledged. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The atmospheric concentration of methane has more than doubled since the start of the Industrial Revolution. Methane is the second-most-abundant greenhouse gas created by human activities and a major driver of climate change. This APS-Optica report provides a technical assessment of the current state of monitoring U.S. methane emissions from oil and gas operations, which accounts for roughly 30% of U.S. anthropogenic methane emissions. The report identifies current technological and policy gaps and makes recommendations for the federal government in three key areas: methane emissions detection, reliable and systematized data and models to support mitigation measures, and effective regulation.

Remote sensing has transformed the monitoring of life on Earth by revealing spatial and temporal dimensions of biological diversity through structural, compositional and functional measurements of ecosystems. Yet, many aspects of Earth's biodiversity are not directly quantified by reflected or emitted photons. Inclusive integration of remote sensing with field-based ecology and evolution is needed to fully understand and preserve Earth's biodiversity. In this Perspective, we argue that multiple data types are necessary for almost all draft targets set by the Convention on Biological Diversity. We examine five key topics in biodiversity science that can be advanced by integrating remote sensing with in situ data collection from field sampling, experiments and laboratory studies to benefit conservation. Lowering the barriers for bringing these approaches together will require global-scale collaboration., (© 2022. Springer Nature Limited.)

We assess the detectability of COVID-like emissions reductions in global atmospheric CO 2 concentrations using a suite of large ensembles conducted with an Earth system model. We find a unique fingerprint of COVID in the simulated growth rate of CO 2 sampled at the locations of surface measurement sites. Negative anomalies in growth rates persist from January 2020 through December 2021, reaching a maximum in February 2021. However, this fingerprint is not formally detectable unless we force the model with unrealistically large emissions reductions (2 or 4 times the observed reductions). Internal variability and carbon-concentration feedbacks obscure the detectability of short-term emission reductions in atmospheric CO 2 . COVID-driven changes in the simulated, column-averaged dry air mole fractions of CO 2 are eclipsed by large internal variability. Carbon-concentration feedbacks begin to operate almost immediately after the emissions reduction; these feedbacks reduce the emissions-driven signal in the atmosphere carbon reservoir and further confound signal detection., (© 2021. American Geophysical Union. All Rights Reserved.)

The COVID-19 global pandemic and associated government lockdowns dramatically altered human activity, providing a window into how changes in individual behavior, enacted en masse, impact atmospheric composition. The resulting reductions in anthropogenic activity represent an unprecedented event that yields a glimpse into a future where emissions to the atmosphere are reduced. Furthermore, the abrupt reduction in emissions during the lockdown periods led to clearly observable changes in atmospheric composition, which provide direct insight into feedbacks between the Earth system and human activity. While air pollutants and greenhouse gases share many common anthropogenic sources, there is a sharp difference in the response of their atmospheric concentrations to COVID-19 emissions changes, due in large part to their different lifetimes. Here, we discuss several key takeaways from modeling and observational studies. First, despite dramatic declines in mobility and associated vehicular emissions, the atmospheric growth rates of greenhouse gases were not slowed, in part due to decreased ocean uptake of CO 2 and a likely increase in CH 4 lifetime from reduced NO x emissions. Second, the response of O 3 to decreased NO x emissions showed significant spatial and temporal variability, due to differing chemical regimes around the world. Finally, the overall response of atmospheric composition to emissions changes is heavily modulated by factors including carbon-cycle feedbacks to CH 4 and CO 2 , background pollutant levels, the timing and location of emissions changes, and climate feedbacks on air quality, such as wildfires and the ozone climate penalty., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Live woody vegetation is the largest reservoir of biomass carbon, with its restoration considered one of the most effective natural climate solutions. However, terrestrial carbon fluxes remain the largest uncertainty in the global carbon cycle. Here, we develop spatially explicit estimates of carbon stock changes of live woody biomass from 2000 to 2019 using measurements from ground, air, and space. We show that live biomass has removed 4.9 to 5.5 PgC year -1 from the atmosphere, offsetting 4.6 ± 0.1 PgC year -1 of gross emissions from disturbances and adding substantially (0.23 to 0.88 PgC year -1 ) to the global carbon stocks. Gross emissions and removals in the tropics were four times larger than temperate and boreal ecosystems combined. Although live biomass is responsible for more than 80% of gross terrestrial fluxes, soil, dead organic matter, and lateral transport may play important roles in terrestrial carbon sink., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The terrestrial carbon sink has significantly increased in the past decades, but the underlying mechanisms are still unclear. The current synthesis of process-based estimates of land and ocean sinks requires an additional sink of 0.6 PgC yr -1 in the last decade to explain the observed airborne fraction. A concurrent global fire decline was observed in association with tropical agriculture expansion and landscape fragmentation. Here we show that a decline of 0.2 ± 0.1 PgC yr -1 in fire emissions during 2008-2014 relative to 2001-2007 also induced an additional carbon sink enhancement of 0.4 ± 0.2 PgC yr -1 attributable to carbon cycle feedbacks, amounting to a combined sink increase comparable to the 0.6 PgC yr -1 budget imbalance. Our results suggest that the indirect effects of fire, in addition to the direct emissions, is an overlooked mechanism for explaining decadal-scale changes in the land carbon sink and highlight the importance of fire management in climate mitigation.

Global ecology - the study of the interactions among the Earth's ecosystems, land, atmosphere and oceans - depends crucially on global observations: this paper focuses on space-based observations of global terrestrial ecosystems. Early global ecology relied on an extrapolation of detailed site-level observations, using models of increasing complexity. Modern global ecology has been enabled largely by vegetation indices (greenness) from operational space-based imagery but current capabilities greatly expand scientific possibilities. New observations from spacecraft in orbit allowed an estimation of gross carbon fluxes, photosynthesis, biomass burning, evapotranspiration and biomass, to create virtual eddy covariance sites in the sky. Planned missions will reveal the dimensions of the diversity of life itself. These observations will improve our understanding of the global productivity and carbon storage, land use, carbon cycle-climate feedback, diversity-productivity relationships and enable improved climate forecasts. Advances in remote sensing challenge ecologists to relate information organised by biome and species to new data arrayed by pixels and develop theory to address previously unobserved scales., (© 2019 Jet Propulsion Lab, California Institute of Technology New Phytologist © 2019 New Phytologist Trust.)

Northern hemisphere evergreen forests assimilate a significant fraction of global atmospheric CO 2 but monitoring large-scale changes in gross primary production (GPP) in these systems is challenging. Recent advances in remote sensing allow the detection of solar-induced chlorophyll fluorescence (SIF) emission from vegetation, which has been empirically linked to GPP at large spatial scales. This is particularly important in evergreen forests, where traditional remote-sensing techniques and terrestrial biosphere models fail to reproduce the seasonality of GPP. Here, we examined the mechanistic relationship between SIF retrieved from a canopy spectrometer system and GPP at a winter-dormant conifer forest, which has little seasonal variation in canopy structure, needle chlorophyll content, and absorbed light. Both SIF and GPP track each other in a consistent, dynamic fashion in response to environmental conditions. SIF and GPP are well correlated ( R 2 = 0.62-0.92) with an invariant slope over hourly to weekly timescales. Large seasonal variations in SIF yield capture changes in photoprotective pigments and photosystem II operating efficiency associated with winter acclimation, highlighting its unique ability to precisely track the seasonality of photosynthesis. Our results underscore the potential of new satellite-based SIF products (TROPOMI, OCO-2) as proxies for the timing and magnitude of GPP in evergreen forests at an unprecedented spatiotemporal resolution., Competing Interests: The authors declare no conflict of interest.

We have compared a suite of recent global CO 2 atmospheric inversion results to independent airborne observations and to each other, to assess their dependence on differences in northern extratropical (NET) vertical transport and to identify some of the drivers of model spread. We evaluate posterior CO 2 concentration profiles against observations from the High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Pole-to-Pole Observations (HIPPO) aircraft campaigns over the mid-Pacific in 2009-2011. Although the models differ in inverse approaches, assimilated observations, prior fluxes, and transport models, their broad latitudinal separation of land fluxes has converged significantly since the Atmospheric Carbon Cycle Inversion Intercomparison (TransCom 3) and the REgional Carbon Cycle Assessment and Processes (RECCAP) projects, with model spread reduced by 80% since TransCom 3 and 70% since RECCAP. Most modeled CO 2 fields agree reasonably well with the HIPPO observations, specifically for the annual mean vertical gradients in the Northern Hemisphere. Northern Hemisphere vertical mixing no longer appears to be a dominant driver of northern versus tropical (T) annual flux differences. Our newer suite of models still gives northern extratropical land uptake that is modest relative to previous estimates (Gurney et al., 2002; Peylin et al., 2013) and near-neutral tropical land uptake for 2009-2011. Given estimates of emissions from deforestation, this implies a continued uptake in intact tropical forests that is strong relative to historical estimates (Gurney et al., 2002; Peylin et al., 2013). The results from these models for other time periods (2004-2014, 2001-2004, 1992-1996) and reevaluation of the TransCom 3 Level 2 and RECCAP results confirm that tropical land carbon fluxes including deforestation have been near neutral for several decades. However, models still have large disagreements on ocean-land partitioning. The fossil fuel (FF) and the atmospheric growth rate terms have been thought to be the best-known terms in the global carbon budget, but we show that they currently limit our ability to assess regional-scale terrestrial fluxes and ocean-land partitioning from the model ensemble., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Chevallier showed a column CO 2 ([Formula: see text]) anomaly of ±0.5 parts per million forced by a uniform net biosphere exchange (NBE) anomaly of 2.5 gigatonnes of carbon over the tropical continents within a year, so he claimed that the inferred NBE uncertainties should be larger than presented in Liu et al We show that a much concentrated NBE anomaly led to much larger [Formula: see text] perturbations., (Copyright © 2018, American Association for the Advancement of Science.)

The contemporary Arctic carbon balance is uncertain, and the potential for a permafrost carbon feedback of anywhere from 50 to 200 petagrams of carbon (Schuur et al ., 2015) compromises accurate 21st-century global climate system projections. The 42-year record of atmospheric CO 2 measurements at Barrow, Alaska (71.29 N, 156.79 W), reveals significant trends in regional land-surface CO 2 anomalies (ΔCO 2 ), indicating long-term changes in seasonal carbon uptake and respiration. Using a carbon balance model constrained by ΔCO 2 , we find a 13.4% decrease in mean carbon residence time (50% confidence range = 9.2 to 17.6%) in North Slope tundra ecosystems during the past four decades, suggesting a transition toward a boreal carbon cycling regime. Temperature dependencies of respiration and carbon uptake suggest that increases in cold season Arctic labile carbon release will likely continue to exceed increases in net growing season carbon uptake under continued warming trends.

Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3 + CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1 + terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation. Mtb-specific CD4 T cells in granulomas display a tissue-parenchymal CXCR3 + CX3CR1 - PD-1 hi CTLA-4 + phenotype. However, most granuloma CD4 T cells are found within the outer lymphocyte cuff and few localize to the myeloid cell core containing the bacilli. Using the intravascular stain approach, we find essentially all Mtb-specific CD4 T cells in granulomas have extravasated across the vascular endothelium into the parenchyma. Therefore, it is unlikely to be that lung-homing defects introduced by terminal differentiation limit the migration of CD4 T cells into granulomas following primary Mtb infection of macaques. However, intralesional positioning defects within the granuloma may pose a major barrier to T-cell-mediated immunity during tuberculosis.

NASA's Orbiting Carbon Observatory-2 (OCO-2) mission was motivated by the need to diagnose how the increasing concentration of atmospheric carbon dioxide (CO 2 ) is altering the productivity of the biosphere and the uptake of CO 2 by the oceans. Launched on 2 July 2014, OCO-2 provides retrievals of the column-averaged CO 2 dry-air mole fraction ([Formula: see text]) as well as the fluorescence from chlorophyll in terrestrial plants. The seasonal pattern of uptake by the terrestrial biosphere is recorded in fluorescence and the drawdown of [Formula: see text] during summer. Launched just before one of the most intense El Niños of the past century, OCO-2 measurements of [Formula: see text] and fluorescence record the impact of the large change in ocean temperature and rainfall on uptake and release of CO 2 by the oceans and biosphere., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Quantifying gross primary production (GPP) remains a major challenge in global carbon cycle research. Spaceborne monitoring of solar-induced chlorophyll fluorescence (SIF), an integrative photosynthetic signal of molecular origin, can assist in terrestrial GPP monitoring. However, the extent to which SIF tracks spatiotemporal variations in GPP remains unresolved. Orbiting Carbon Observatory-2 (OCO-2)'s SIF data acquisition and fine spatial resolution permit direct validation against ground and airborne observations. Empirical orthogonal function analysis shows consistent spatiotemporal correspondence between OCO-2 SIF and GPP globally. A linear SIF-GPP relationship is also obtained at eddy-flux sites covering diverse biomes, setting the stage for future investigations of the robustness of such a relationship across more biomes. Our findings support the central importance of high-quality satellite SIF for studying terrestrial carbon cycle dynamics., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Spaceborne observations of carbon dioxide (CO 2 ) from the Orbiting Carbon Observatory-2 are used to characterize the response of tropical atmospheric CO 2 concentrations to the strong El Niño event of 2015-2016. Although correlations between the growth rate of atmospheric CO 2 concentrations and the El Niño-Southern Oscillation are well known, the magnitude of the correlation and the timing of the responses of oceanic and terrestrial carbon cycle remain poorly constrained in space and time. We used space-based CO 2 observations to confirm that the tropical Pacific Ocean does play an early and important role in modulating the changes in atmospheric CO 2 concentrations during El Niño events-a phenomenon inferred but not previously observed because of insufficient high-density, broad-scale CO 2 observations over the tropics., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In the version of this Comment previously published, in Box 1, the spacing of the GEDI footprints should have read 60 m along the track, not 25 m. Also the second affiliation for Susan Ustin was incorrect, she is only associated with the University of California, Davis. These errors have now been corrected.

Megafires have lasting social, ecological, and economic impacts and are increasing in the western contiguous United States. Because of their infrequent nature, there is a limited sample of megafires to investigate their unique behavior, drivers, and relationship to forest management practices. One approach is to characterize critical information pre-, during, and post-fire using remote sensing. In August 2013, the Rim Fire burned 104,131 ha and in September 2014, the King Fire burned 39,545 ha. Both fires occurred in California's Sierra Nevada. The areas burned by these fires were fortuitously surveyed by airborne campaigns, which provided the most recent remote sensing technologies not currently available from satellite. Technologies include an imaging spectrometer spanning the visible to shortwave infrared (0.38-2.5 μm), a multispectral, high-spatial resolution thermal infrared (3.5-13 μm) spectroradiometer, and Light Detection and Ranging that provide spatial resolutions of pixels from 1 × 1 m to 35 × 35 m. Because of the unique information inherently derived from these technologies before the fires, the areas were subsequently surveyed after the fires. We processed and provide free dissemination of these airborne datasets as products of surface reflectance, spectral metrics and forest structural metrics ( http://dx.doi.org/10.3334/ORNLDAAC/1288). These data products provide a unique opportunity to study relationships among and between remote sensing observations and fuel and fire characteristics (e.g., fuel type, condition, structure, and fire severity). The novelty of these data is not only in the unprecedented types of information available from them before, during, and after two megafires, but also in the synergistic use of multiple state of the art technologies for characterizing the environment. The synergy of these data can provide novel information that can improve maps of fuel type, structure, abundance, and condition that may improve predictions of megafire behavior and effects, thus aiding management before, during, and after such events. Key questions that these data could address include: What drives, extinguishes, and results from megafires? How does megafire behavior relate to fire and fuel management? How does the size and severity of a megafire affect the ecological recovery of the system?, (© 2016 by the Ecological Society of America.)

Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P = 0.035) and also significantly reduced uptake of [(18)F]-2-fluoro-2-deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P = 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Terrestrial ecosystem and carbon cycle feedbacks will significantly impact future climate, but their responses are highly uncertain. Models and tipping point analyses suggest the tropics and arctic/boreal zone carbon-climate feedbacks could be disproportionately large. In situ observations in those regions are sparse, resulting in high uncertainties in carbon fluxes and fluxes. Key parameters controlling ecosystem carbon responses, such as plant traits, are also sparsely observed in the tropics, with the most diverse biome on the planet treated as a single type in models. We analyzed the spatial distribution of in situ data for carbon fluxes, stocks and plant traits globally and also evaluated the potential of remote sensing to observe these quantities. New satellite data products go beyond indices of greenness and can address spatial sampling gaps for specific ecosystem properties and parameters. Because environmental conditions and access limit in situ observations in tropical and arctic/boreal environments, use of space-based techniques can reduce sampling bias and uncertainty about tipping point feedbacks to climate. To reliably detect change and develop the understanding of ecosystems needed for prediction, significantly, more data are required in critical regions. This need can best be met with a strategic combination of remote and in situ data, with satellite observations providing the dense sampling in space and time required to characterize the heterogeneity of ecosystem structure and function., (© 2014 John Wiley & Sons Ltd.)

Ecologists are increasingly tackling questions that require significant infrastucture, large experiments, networks of observations, and complex data and computation. Key hypotheses in ecology increasingly require more investment, and larger data sets to be tested than can be collected by a single investigator's or s group of investigator's labs, sustained for longer than a typical grant. Large-scale projects are expensive, so their scientific return on the investment has to justify the opportunity cost-the science foregone because resources were expended on a large project rather than supporting a number of individual projects. In addition, their management must be accountable and efficient in the use of significant resources, requiring the use of formal systems engineering and project management to mitigate risk of failure. Mapping the scientific method into formal project management requires both scientists able to work in the context, and a project implementation team sensitive to the unique requirements of ecology. Sponsoring agencies, under pressure from external and internal forces, experience many pressures that push them towards counterproductive project management but a scientific community aware and experienced in large project science can mitigate these tendencies. For big ecology to result in great science, ecologists must become informed, aware and engaged in the advocacy and governance of large ecological projects.

Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. Patients who have TB require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here, we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low-molecular-weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced VEGF expression in both species. In tumors, antiangiogenic, specifically anti-VEGF, treatments can "normalize" their vasculature, reducing hypoxia and creating a window of opportunity for concurrent chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those vessels that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery was increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential avenue to improve delivery and efficacy of current treatment regimens.

Feedbacks from the terrestrial carbon cycle significantly affect future climate change. The CO2 concentration dependence of global terrestrial carbon storage is one of the largest and most uncertain feedbacks. Theory predicts the CO2 effect should have a tropical maximum, but a large terrestrial sink has been contradicted by analyses of atmospheric CO2 that do not show large tropical uptake. Our results, however, show significant tropical uptake and, combining tropical and extratropical fluxes, suggest that up to 60% of the present-day terrestrial sink is caused by increasing atmospheric CO2. This conclusion is consistent with a validated subset of atmospheric analyses, but uncertainty remains. Improved model diagnostics and new space-based observations can reduce the uncertainty of tropical and temperate zone carbon flux estimates. This analysis supports a significant feedback to future atmospheric CO2 concentrations from carbon uptake in terrestrial ecosystems caused by rising atmospheric CO2 concentrations. This feedback will have substantial tropical contributions, but the magnitude of future carbon uptake by tropical forests also depends on how they respond to climate change and requires their protection from deforestation.

Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.

With a host of new antitubercular chemotherapeutics in development, methods to assess the activity of these agents beyond mouse efficacy are needed to prioritize combinations for clinical trials. Lesions in Mycobacterium tuberculosis-infected rabbits are hypoxic, with histopathologic features that closely resemble those of human tuberculous lesions. Using [(18)F]2-fluoro-deoxy-d-glucose ([(18)F]FDG) positron emission tomography-computed tomography (PET-CT) imaging, we studied the dynamics of tuberculosis infection in rabbits, revealing an initial inflammatory response followed by a consolidative chronic disease. Five weeks after infection, as much as 23% of total lung volume was abnormal, but this was contained and to some extent reversed naturally by 9 weeks. During development of this chronic state, individual lesions in the same animal had very different fates, ranging from complete resolution to significant progression. Lesions that remained through the initial stage showed an increase in volume and tissue density over time by CT. Initiation of chemotherapy using either isoniazid (INH) or rifampin (RIF) during chronic infection reduced bacterial load with quantitative changes in [(18)F]FDG uptake, lesion density and total lesion volume measured by CT. The [(18)F]FDG PET uptake in lesions was significantly reduced with as little as 1 week of treatment, while the volume and density of lesions changed more slowly. The results from this study suggest that rabbits may be a useful surrogate species for evaluating novel chemotherapies and understanding changes in both PET and CT scans in human clinical trials.

The carbapenems imipenem and meropenem in combination with clavulanic acid reduced the bacterial burden in Mycobacterium tuberculosis-infected macrophages by 2 logs over 6 days. Despite poor stability in solution and a short half-life in rodents, treatment of chronically infected mice revealed significant reductions of bacterial burden in the lungs and spleens. Our results show that meropenem has activity in two in vivo systems, but stability and pharmacokinetics of long-term administration will offer significant challenges to clinical evaluation.

Geoengineering methods are intended to reduce climate change, which is already having demonstrable effects on ecosystem structure and functioning in some regions. Two types of geoengineering activities that have been proposed are: carbon dioxide (CO(2)) removal (CDR), which removes CO(2) from the atmosphere, and solar radiation management (SRM, or sunlight reflection methods), which reflects a small percentage of sunlight back into space to offset warming from greenhouse gases (GHGs). Current research suggests that SRM or CDR might diminish the impacts of climate change on ecosystems by reducing changes in temperature and precipitation. However, sudden cessation of SRM would exacerbate the climate effects on ecosystems, and some CDR might interfere with oceanic and terrestrial ecosystem processes. The many risks and uncertainties associated with these new kinds of purposeful perturbations to the Earth system are not well understood and require cautious and comprehensive research.

• It is well established that individual organisms can acclimate and adapt to temperature to optimize their functioning. However, thermal optimization of ecosystems, as an assemblage of organisms, has not been examined at broad spatial and temporal scales. • Here, we compiled data from 169 globally distributed sites of eddy covariance and quantified the temperature response functions of net ecosystem exchange (NEE), an ecosystem-level property, to determine whether NEE shows thermal optimality and to explore the underlying mechanisms. • We found that the temperature response of NEE followed a peak curve, with the optimum temperature (corresponding to the maximum magnitude of NEE) being positively correlated with annual mean temperature over years and across sites. Shifts of the optimum temperature of NEE were mostly a result of temperature acclimation of gross primary productivity (upward shift of optimum temperature) rather than changes in the temperature sensitivity of ecosystem respiration. • Ecosystem-level thermal optimality is a newly revealed ecosystem property, presumably reflecting associated evolutionary adaptation of organisms within ecosystems, and has the potential to significantly regulate ecosystem-climate change feedbacks. The thermal optimality of NEE has implications for understanding fundamental properties of ecosystems in changing environments and benchmarking global models., (© 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.)

Although erythropoietin (Epo) is the cytokine known to regulate erythropoiesis, erythropoietin receptor (EpoR) expression and associated activity beyond haematopoietic tissue remain uncertain. Here we show that mice with EpoR expression restricted to haematopoietic tissues (Tg) develop obesity and insulin resistance. Tg-mice exhibit a decrease in energy expenditure and an increase in white fat mass and adipocyte number. Conversely, Epo treatment of wild-type (WT)-mice increases energy expenditure and reduces food intake and fat mass accumulation but shows no effect in body weight of Tg-mice. EpoR is expressed at a high level in white adipose tissue and in the proopiomelanocortin (POMC) neurons of the hypothalamus. Although Epo treatment in WT-mice induces the expression of the polypeptide hormone precursor, POMC, mice lacking EpoR show reduced levels of POMC in the hypothalamus. This study provides the first evidence that mice lacking EpoR in non-haematopoietic tissue become obese and insulin resistant with loss of Epo regulation of energy homeostasis.

Three-dimensional micro computed tomography (microCT) offers the opportunity to capture images liver structures and lesions in mice with a high spatial resolution. Non-invasive microCT allows for accurate calculation of vessel tortuosity and density, as well as liver lesion volume and distribution. Longitudinal monitoring of liver lesions is also possible. However, distinguishing liver lesions from variations within a normal liver is impossible by microCT without the use of liver- or tumor-specific contrast-enhancing agents. The combination of microCT for morphologic imaging with functional imaging, such as positron emission tomography (PET) or single photon emission tomography (SPECT), offers the opportunity for better abdominal imaging and assessment of structure discrepancies visible by functional imaging. This paper describes methods of current microCT imaging options for imaging of liver lesions compared to other imaging techniques in small animals., (Published by Elsevier Inc.)

Purpose: To compare contrast-enhanced micro-computed tomography (microCT) and nonenhanced respiratory-triggered magnetic resonance imaging (MRI) in an animal model of metastatic pheochromocytoma. Animal models are becoming important in the study of cancer treatment and imaging is useful in minimizing the number of animals needed and reducing costs associated with autopsies. However, the choice of imaging modality is still evolving., Materials and Methods: Adult female nude mice were injected by tail vein with a mouse pheochromocytoma (MPC) cell line (MPC 4/30PRR) to create a metastatic model. After optimizing imaging techniques, eight mice were imaged with both respiratory triggered MRI and microCT and the findings were verified histologically., Results: MicroCT and MRI were approximately equal in their ability to detect hepatic metastases at a size threshold of 350 microm. In the lungs, MRI was more sensitive than microCT, detecting lesions 0.6 mm in diameter versus 1 mm for microCT. Additionally, MRI was more sensitive for lesions in the kidneys, bone, ovaries, and adrenal glands. MRI demonstrated a higher contrast-to-noise ratio (CNR) than microCT., Conclusion: In addition to the advantage of not exposing the animal to ionizing radiation, MRI provided a more complete assessment of the extent of metastases in this model compared to microCT., (Copyright (c) 2009 Wiley-Liss, Inc.)

RGS5 is a potent GTPase-activating protein for G(ialpha) and G(qalpha) that is expressed strongly in pericytes and is present in vascular smooth muscle cells. To study the role of RGS5 in blood vessel physiology, we generated Rgs5-deficient mice. The Rgs5(-/-) mice developed normally, without obvious defects in cardiovascular development or function. Surprisingly, Rgs5(-/-) mice had persistently low blood pressure, lower in female mice than in male mice, without concomitant cardiac dysfunction, and a lean body habitus. The examination of the major blood vessels revealed that the aortas of Rgs5(-/-) mice were dilated compared to those of control mice, without altered wall thickness. Isolated aortic smooth muscle cells from the Rgs5(-/-) mice exhibited exaggerated levels of phosphorylation of vasodilator-stimulated phosphoprotein and extracellular signal-regulated kinase in response to stimulation with either sodium nitroprusside or sphingosine 1-phosphate. The results of this study, along with those of previous studies demonstrating that RGS5 stability is under the control of nitric oxide via the N-end rule pathway, suggest that RGS5 may balance vascular tone by attenuating vasodilatory signaling in vivo in opposition to RGS2, another RGS (regulator of G protein signaling) family member known to inhibit G protein-coupled receptor-mediated vasoconstrictor signaling. Blocking the function or the expression of RGS5 may provide an alternative approach to treat hypertension.

Objectives: Comparison of intravenous Fenestra VC-enhanced computed tomography (CT) with gadopentetate dimeglumine and Ferucarbotran contrast-enhanced magnetic resonance imaging (MRI) for the in vivo imaging of hepatic ischemia/reperfusion injury (IRI) in a murine model., Material and Methods: After induction of hepatic IRI by left liver lobe (LLL) ischemia (30, 45, and 75 minutes) and reperfusion (4 hours and 24 hours), a total of 130 mice were imaged either by Fenestra VC-enhanced 3-D CT or by dynamic, T1-weighed gadopentetate dimeglumine or static, T2*-weighed Ferucarbotran 2-D MRI (4.7 T)., Results: Detection of liver tissue damage as a consequence of IRI was not possible by CT or MRI without the use of contrast media. (1) Mice subjected to liver IRI (45 minutes of ischemia) and injected with Fenestra VC showed a distinct liver enhancement of the viable liver tissue or a nonenhancement of the necrotic tissue. The Fenestra VC CT-unenhanced liver volume increased as a function of time of ischemia and reperfusion. The unenhanced liver volume also correlated positively with serum liver enzyme activities and damage scores from liver histology. (2) The signal intensities (SI) between normal liver tissue and livers subjected to 30 minutes of ischemia were not different on dynamic gadopentetate dimeglumine-enhanced magnetic resonance images. More severe IRI as induced by 45 or 75 minutes of ischemia was characterized by (a) early hyperenhancement of regions in the LLL with rapid increase of SI higher than that observed in the undamaged liver within the first few minutes and (b) delayed hyperenhancement in the later course after gadopentetate dimeglumine injection, respectively. (3) Ferucarbotran MRI detected signs of IRI after only 30 minutes of liver ischemia and hence detected IRI earlier than Fenestra VC or gadopentetate dimeglumine. With longer duration of ischemia, Ferucarbotran SI increased in the LLL, but viable and necrotic tissues were not clearly distinguishable., Conclusions: MicroCT with Fenestra VC enhancement and MRI using either gadopentetate dimeglumine or Ferucarbotran enhancement of the liver revealed that all techniques allow in vivo determination of hepatic IRI as a function of the duration of ischemia and reperfusion of the liver. However, Fenestra VC-enhanced CT of the murine liver is superior to gadopentetate dimeglumine and Ferucarbotran for localization, quantification, and differentiation of viable from metabolically inactive/damaged liver tissue after hepatic ischemia/reperfusion but Fenestra VC is less sensitive than Ferucarbotran to detect the early onset of subtle consequences of hepatic IRI.

Understanding the history of how humans have interacted with the rest of nature can help clarify the options for managing our increasingly interconnected global system. Simple, deterministic relationships between environmental stress and social change are inadequate. Extreme drought, for instance, triggered both social collapse and ingenious management of water through irrigation. Human responses to change, in turn, feed into climate and ecological systems, producing a complex web of multidirectional connections in time and space. Integrated records of the co-evolving human-environment system over millennia are needed to provide a basis for a deeper understanding of the present and for forecasting the future. This requires the major task of assembling and integrating regional and global historical, archaeological, and paleoenvironmental records. Humans cannot predict the future. But, if we can adequately understand the past, we can use that understanding to influence our decisions and to create a better, more sustainable and desirable future.

The contribution of stem and progenitor cell dysfunction and depletion in normal aging remains incompletely understood. We explored this concept in the Klotho mouse model of accelerated aging. Analysis of various tissues and organs from young Klotho mice revealed a decrease in stem cell number and an increase in progenitor cell senescence. Because klotho is a secreted protein, we postulated that klotho might interact with other soluble mediators of stem cells. We found that klotho bound to various Wnt family members. In a cell culture model, the Wnt-klotho interaction resulted in the suppression of Wnt biological activity. Tissues and organs from klotho-deficient animals showed evidence of increased Wnt signaling, and ectopic expression of klotho antagonized the activity of endogenous and exogenous Wnt. Both in vitro and in vivo, continuous Wnt exposure triggered accelerated cellular senescence. Thus, klotho appears to be a secreted Wnt antagonist and Wnt proteins have an unexpected role in mammalian aging.