Projections indicate an elevation of the atmospheric CO 2 concentration ([CO 2 ]) concomitant with an intensification of drought for this century, increasing the challenges to food security. On the one hand, drought is a main environmental factor responsible for decreasing crop productivity and grain quality, especially when occurring during the grain-filling stage. On the other hand, elevated [CO 2 ] is predicted to mitigate some of the negative effects of drought. Sorghum (Sorghum bicolor) is a C 4 grass that has important economical and nutritional values in many parts of the world. Although the impact of elevated [CO 2 ] and drought in photosynthesis and growth has been well documented for sorghum, the effects of the combination of these two environmental factors on plant metabolism have yet to be determined. To address this question, sorghum plants (cv BRS 330) were grown and monitored at ambient (400 mmol mol 21 ) or elevated (800 mmol mol 21 ) [CO 2 ] for 120 d and subjected to drought during the grainfilling stage. Leaf photosynthesis, respiration, and stomatal conductance were measured at 90 and 120 d after planting, and plant organs (leaves, culm, roots, prop roots, and grains) were harvested. Finally, biochemical composition and intracellular metabolites were assessed for each organ. As expected, elevated [CO 2 ] reduced the stomatal conductance, which preserved soil moisture and plant fitness under drought. Interestingly, the whole-plant metabolism was adjusted and protein content in grains was improved by 60% in sorghum grown under elevated [CO 2 ].Global food demand is projected to increase up to 110% by the middle of this century (Tilman et al., 2011; Alexandratos and Bruinsma, 2012), particularly due to a rise in world population that is likely to plateau at about 9 billion people (Godfray et al., 2010 (NOAA, 2015). According to the A2 emission scenario from the U.S. Environmental Protection Agency, in the absence of explicit climate change policy, atmospheric CO 2 concentrations will reach 800 mmol mol 21 by the end of this century. The increasing atmospheric [CO 2 ] is resulting in global climate changes, such as reduction in water availability and elevation in temperature. These factors are expected to heavily influence food production in the next years (Godfray and Garnett, 2014;Magrin et al., 2014). Sorghum (Sorghum bicolor) is a C 4 grass, considered a staple food grain for millions of the poorest and most food-insecure people in the semiarid tropics of Africa, Asia, and Central America, serving as an important source of energy, proteins, vitamins, and minerals (Taylor et al., 2006). Moreover, this crop is used for animal feed and as industrial raw material in developed countries such as the United States, which is the main world producer (FAO, 2015). With a fully sequenced genome (Paterson et al., 2009) and over 45,000 accessions representing a large geographic and genetic diversity, sorghum is a good model system in which to study the impact of global climate changes in C 4 grasses. ...

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Key Points• Low free protein S and low total protein S levels could not identify subjects at risk for venous thrombosis in a population-based study.• Protein S testing and subsequent testing on PROS1 mutations should not be considered in unselected patients with venous thrombosis.In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based casecontrol study (n 5 5317). Subjects were regarded protein S deficient when protein S levels were <2.5th percentile of the controls. Free and total protein S deficiency was not associated with venous thrombosis: free protein S < 53 U/dL, odds ratio [OR] 0.82 (95% confidence interval [CI], 0.56-1.21) and total protein S < 68 U/dL, OR 0.90 (95% CI, 0.62-1.31). When lower cutoff values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels <0.10th percentile of free protein S (<33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level <1st percentile (<46 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) <2.5th percentile. Mutations in PROS1 were detected in 5 patients and 5 controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis. (Blood. 2013;122(18):3210-3219)

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