We present a new data set of annual historical (1750 -2014) anthropogenic chemically reactive gases (CO, CH 4 , NH 3 , NO X , SO 2 , NMVOC), carbonaceous aerosols (BC and OC), and CO 2 developed with the 25Community Emissions Database System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emissions species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emissions species are consistently estimated using the same activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with 30 monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low-and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions uncertainty, and publication of the system as open source software. 35Geosci. Model Dev. Discuss.,

Interleukin-3 (IL-3) is a cytokine which stimulates the proliferation and differentiation of hematopoietic progenitors into multiple cell lineages. The 1H, 15N, and 13C NMR resonances of a recombinant human IL-3 variant (SC-65369) have been assigned using two- and three-dimensional NMR techniques on uniformly 13C/15N-enriched protein. Five helical segments (residues 16-26, 42-50, 55-65, 73-82, and 104-120) and three reverse turns (residues 51-54, 68-71, and 87-90) were identified from the pattern of sequential NOE connectivities, NH(i)-C alpha H(i) scalar coupling constants (3JNH alpha), amide hydrogen exchange data, and the deviation of 13C alpha, 13C beta, 13CO, and C alpha H chemical shifts from random-coil values. Long-range NOEs indicate that the global folding pattern of human IL-3 is a four-helical bundle with an up-up-down-down arrangement of helices that is similar to that of other members of the cytokine family, such as granulocyte-macrophage colony stimulating factor (GM-CSF). A fifth short helix (helix A', residues 42-50) is located in the loop connecting the first and second helices. The absence of helix A' in the corresponding structures of GM-CSF and interleukin-5 suggests that it may be important for recognition of IL-3 by its receptor. The existence of at least two forms of the protein that differ in local conformation was implied from the observation of a limited set of doubled resonances in which each doublet partner had a similar pattern of short-, medium-, and long-range NOEs. The majority of the doubled resonances were close in sequence or space to a proline-rich sequence, which suggested that the different conformational forms of SC-65369 may be caused by slow cis-trans isomerization of proline peptide bonds.

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Serum Response Factor (SRF) is a ubiquitously expressed transcription factor and master regulator of the actin cytoskeleton. We have previously shown, that SRF is essential for megakaryocyte maturation and platelet formation and function. Here we elucidate the role of SRF in neutrophils, the primary defense against infections. To study the effect of loss of SRF in neutrophils, we crossed Srffl/fl mice with select Cre-expressing mice and studied neutrophil function in vitro and in vivo. Despite normal neutrophil numbers, neutrophil function is severely impaired in mice in whom Srf is selectively deleted in the hematopoietic system (Srf KO). Srf KO neutrophils fail to migrate to sites of inflammation in vivo. In a model mimicking lung infection by nebulization of lipopolysaccharide (LPS), significantly fewer neutrophils are recruited to the inflamed lungs 4 and 24 hours after LPS administration as evident by cell numbers retrieved in the bronchoalveolar lavage fluid (BAL, total cells: WT 0.568 ± 0.093x106 vs. KO 0.128 ± 0.024x106 at 4 hours and WT 1.337 ± 0.369x106 vs. KO 0.347 ± 0.045x106 at 24 hours; p <0.005 at 4 hours, p < 0.05 at 24 hours). Similarly, in an in vivo peritonitis model, where all other immune cells normally express Srf, significantly fewer Srf KO than WT neutrophils are recruited to the inflamed peritoneal space resulting in significantly reduced Srf KO neutrophil numbers in the peritoneal lavage fluid. To directly assess neutrophil migration and chemotaxis we performed in vitro transwell assays and assessed neutrophil migration in the Dunn chamber assay. Srf KO neutrophils show a significant migration defect in response to fMLP and KC. We next assessed actin polymerization in Srf WT and KO neutrophils. Srf KO neutrophils fail to polymerize globular actin to filamentous actin in response to fMLP. Neutrophil polarization in response to cytokine stimuli is markedly decreased. In addition, Srf KO neutrophils show markedly reduced adhesion. Integrins play an essential role in neutrophil adhesion and migration. Srf KO neutrophils show normal expression of the integrin LFA1 (CD11a/CD18), however, Mac1 (CD11b/CD18) expression is markedly increased on the cell surface as assessed by flow cytometry and Immunofluorescent staining, despite reduced mRNA expression. We find that trafficking of Mac1, essential for directed cell migration, is disrupted in Srf KO neutrophils, likely contributing to the migratory defect. Migration and cellular adhesion are essential for normal cell function, but also for malignant processes such as metastasis, thus underscoring an essential function for SRF and its pathway in health and disease. Disclosures: No relevant conflicts of interest to declare.