Nutrient Cycling in Soils: Sulfur

Sulfur is an essential element required for normal plant growth, a fact that has been recognized since 1860 (Alway, 1940). It is considered a secondary macronutrient, following the primary macronutrients nitrogen, phosphorus, and potassium, but is needed by plants at levels comparable to P. Sulfur deficiency will impair basic plant metabolic functions, thus reducing both crop yield and quality. Deficiencies and responses to S amendments have been reported in crops worldwide (Tisdale et al., 1986; McGrath and Zhao, 1995; Scherer, 2001), and are becoming more common (Haneklaus et al., 2008). The likelihood of a response is determined by the balance between sulfur supply and crop demand. The main reasons for recent increases in documented S deficiencies include the reduction of SO2 emissions from various industrial sources, mainly coal-fired power plants, an increase in the use of high-analysis fertilizers with little S, decreased use of S-containing pesticides, greater S removals with ever-increasing crop yields, and continued losses through leaching and erosion of topsoil. As pointed out by Haneklaus et al. (2008), in only a few years, the reputation of S has changed from that of an undesirable pollutant to a limiting factor in crop production. In this chapter, we provide current information on the demand for S in various cropping systems, what we know about the soil supply of S, the best ways of assessing S status and managing S inputs, and how all of this information can be put together to optimize crop production. In each section, references will provide the reader with an opportunity to explore the topic in greater detail than can be given in these few pages

Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice

Prostate cancer is themost frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections

Assembly and Certification of ATLAS Muon Stations for the Middle and Outer Barrel at CERN

Roughly 400 of the approximately 700 muon stations of the ATLAS barrel belong to the middle and outer layer. Barrel Middle and Barrel Outer stations consist of both an MDT chamber and one or two RPC planes delivering the level-1 trigger information. While MDT chambers and individual RPC units are constructed at their home institutes, the assembly of the RPCs into planes, including the final cabling and the mounting of the trigger electronics, as well as the integration of MDTs and RPCs into muon stations takes place at CERN. MDT chambers, RPC planes and the completed stations have to pass a series of tests before being declared 'ready-for-installation'. Final certification criteria is the passing of a one-day cosmic ray test, for which a special setup has been built in building 899 (BB5). This note gives an overview over the work carried out in BB5, with emphasis on the cosmic ray test. Examples of abnormal chamber behavior will be discussed and a summary of common mistakes in station assembly or chamber cabling will be given. A second focus of the note is on the statistical analysis of the certification results

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium

Background<p></p> Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk.<p></p> Methods and Results<p></p> We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026).<p></p> Conclusion<p></p> Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings

Near-infrared molecular imaging of tumors via chemokine receptors CXCR4 and CXCR7

The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye®800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1–92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature