Legislation on biofuels production in the USA and Europe is directing food crops towards the production of grain-based ethanol, which can have detrimental consequences for soil carbon sequestration, nitrous oxide emissions, nitrate pollution, biodiversity and human health. An alternative is to grow lignocellulosic (cellulosic) crops on 'marginal' lands. Cellulosic feedstocks can have positive environmental outcomes and could make up a substantial proportion of future energy portfolios. However, the availability of marginal lands for cellulosic feedstock production, and the resulting greenhouse gas (GHG) emissions, remains uncertain. Here we evaluate the potential for marginal lands in ten Midwestern US states to produce sizeable amounts of biomass and concurrently mitigate GHG emissions. In a comparative assessment of six alternative cropping systems over 20 years, we found that successional herbaceous vegetation, once well established, has a direct GHG emissions mitigation capacity that rivals that of purpose-grown crops (-851 ± 46 grams of CO(2) equivalent emissions per square metre per year (gCO(2)e m(-2) yr(-1))). If fertilized, these communities have the capacity to produce about 63 ± 5 gigajoules of ethanol energy per hectare per year. By contrast, an adjacent, no-till corn-soybean-wheat rotation produces on average 41 ± 1 gigajoules of biofuel energy per hectare per year and has a net direct mitigation capacity of -397 ± 32 gCO(2)e m(-2) yr(-1); a continuous corn rotation would probably produce about 62 ± 7 gigajoules of biofuel energy per hectare per year, with 13% less mitigation. We also perform quantitative modelling of successional vegetation on marginal lands in the region at a resolution of 0.4 hectares, constrained by the requirement that each modelled location be within 80 kilometres of a potential biorefinery. Our results suggest that such vegetation could produce about 21 gigalitres of ethanol per year from around 11 million hectares, or approximately 25 per cent of the 2022 target for cellulosic biofuel mandated by the US Energy Independence and Security Act of 2007, with no initial carbon debt nor the indirect land-use costs associated with food-based biofuels. Other regional-scale aspects of biofuel sustainability, such as water quality and biodiversity, await future study.

The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.

Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line, 786-O, was chronically treated with sunitinib, and assayed for AXL, MET, epithelial mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by shRNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets VEGFR, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT associated gene expression changes including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/HUVEC co-culture models. The suppression of AXL or MET expression, and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture, and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes pro-metastatic behavior and angiogenesis. The inhibition of AXL and MET activity may overcome resistance induced by prolonged sunitinib therapy in metastatic RCC.

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Urbanization, a major driver of global change, profoundly impacts our physical and social world, for example, altering not just water and carbon cycling, biodiversity, and climate, but also demography, public health, and economy. Understanding these consequences for better scientific insights and effective decision-making unarguably requires accurate information on urban extent and its spatial distributions. We developed a method to map the urban extent from the defense meteorological satellite program/operational linescan system nighttime stable-light data at the global level and created a new global 1 km urban extent map for the year 2000. Our map shows that globally, urban is about 0.5% of total land area but ranges widely at the regional level, from 0.1% in Oceania to 2.3% in Europe. At the country level, urbanized land varies from about 0.01 to 10%, but is lower than 1% for most (70%) countries. Urbanization follows land mass distribution, as anticipated, with the highest concentration between 30°N and 45°N latitude and the largest longitudinal peak around 80°W. Based on a sensitivity analysis and comparison with other global urban area products, we found that our global product of urban areas provides a reliable estimate of global urban areas and offers the potential for producing a time-series of urban area maps for temporal dynamics analyses.

A perspective and review of recent progress in the catalytic co-pyrolysis of lignocellulosic biomass with polymers is presented.