The Pond 2 selenium volatilization study: A synthesis of five years of experimental results, 1990--1995

Microbial volatilization is a potential remedial measure to decrease the selenium inventory in Kesterson Reservoir soils. Past studies in both the field and the laboratory suggest that a significant percentage of the selenium inventory may be removed in this fashion. The objectives of this study include the quantification of selenium losses and a test of a pilot-scale design which in the future may be used in other parts of the Reservoir

Impact of improved maize varieties on food security in Eastern Zambia : A doubly robust analysis

This study investigates the impact of improved maize varieties on household food security in eastern Zambia using household survey data from a sample of over 800 rural households. Since treatment effect estimates are often prone to misspecification in either the treatment or outcome equation, we use the doubly robust inverse probability weighted regression adjustment method, complemented with propensity score matching on six different food security measures to obtain reliable impact estimates. Generally, we find a positive impact of improved maize adoption on food security across the two econometric approaches. Maize being the most important food staple in Zambia has a great bearing on the food security status of farm households. It is therefore imperative that a conducive environment is created that promotes the adoption of maize yield improving technologies.</p

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

DOK3 Negatively Regulates LPS Responses and Endotoxin Tolerance

Innate immune activation via Toll-like receptors (TLRs), although critical for host defense against infection, must be regulated to prevent sustained cell activation that can lead to cell death. Cells repeatedly stimulated with lipopolysaccharide (LPS) develop endotoxin tolerance making the cells hypo-responsive to additional TLR stimulation. We show here that DOK3 is a negative regulator of TLR signaling by limiting LPS-induced ERK activation and cytokine responses in macrophages. LPS induces ubiquitin-mediated degradation of DOK3 leading to SOS1 degradation and inhibition of ERK activation. DOK3 mice are hypersensitive to sublethal doses of LPS and have altered cytokine responses in vivo. During endotoxin tolerance, DOK3 expression remains stable, and it negatively regulates the expression of SHIP1, IRAK-M, SOCS1, and SOS1. As such, DOK3-deficient macrophages are more sensitive to LPS-induced tolerance becoming tolerant at lower levels of LPS than wild type cells. Taken together, the absence of DOK3 increases LPS signaling, contributing to LPS-induced tolerance. Thus, DOK3 plays a role in TLR signaling during both naïve and endotoxin-induced tolerant conditions

LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms

<p>Abstract</p> <p>Background</p> <p>IL-10 is a cytokine mainly produced by macrophages that plays key roles in tolerance to inhaled antigens and in lung homeostasis. Its regulation in alveolar macrophages (HAM), the resident lung phagocytes, remains however unknown.</p> <p>Methods</p> <p>The present study investigated the role of intracellular signalling and transcription factors controlling the production of IL-10 in LPS-activated HAM from normal nonsmoking volunteers.</p> <p>Results</p> <p>LPS (1–1000 pg/ml) induced <it>in vitro </it>IL-10 production by HAM, both at mRNA and protein levels. LPS also activated the phosphorylation of ERK, p38 and JNK MAPkinases (immunoblots) and Sp-1 nuclear activity (EMSA). Selective inhibitors of MAPKinases (respectively PD98059, SB203580 and SP600125) and of Sp-1 signaling (mithramycin) decreased IL-10 expression in HAM. In addition, whilst not affecting IL-10 mRNA degradation, the three MAPKinase inhibitors completely abolished Sp-1 activation by LPS in HAM.</p> <p>Conclusion</p> <p>These results demonstrate for the first time that expression of IL-10 in lung macrophages stimulated by LPS depends on the concomitant activation of ERK, p38 and JNK MAPKinases, which control downstream signalling to Sp-1 transcription factor. This study further points to Sp-1 as a key signalling pathway for IL-10 expression in the lung.</p

Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD

<p>Abstract</p> <p>Background</p> <p>Macrophages have been implicated in the pathogenesis of COPD. M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties. We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD. Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.</p> <p>Methods</p> <p>114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV₁63 ± 9% predicted, no steroids past 6 months). BAL was collected from 71 patients. CD163⁺macrophages were quantified in BAL and sputum cytospins. Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.</p> <p>Results</p> <p>Ex-smokers with COPD had a higher percentage, but lower number of CD163⁺macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×10⁴/ml, p = 0.001 respectively). The percentage CD163⁺M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001). BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163⁺BAL macrophages (Rs = 0.38, p = 0.003). No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.</p> <p>Conclusions</p> <p>Our data suggest that smoking cessation partially changes the macrophage polarization <it>in vivo </it>in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.</p

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis

The human CD14+ monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16+ monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by theCD16+CD163+MerTK+pSTAT3+ phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16+CD163+MerTK+pSTAT3+ cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16+CD163+MerTK+pSTAT3+ monocyte-to-macrophage differentiation program and its potential as a target for TB therapy,and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoringof treatment efficacy.Fil: Lastrucci, Claire. Centre National de la Recherche Scientifique; FranciaFil: Bénard, Alan. Centre National de la Recherche Scientifique; FranciaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pingris, Karine. Centre National de la Recherche Scientifique; FranciaFil: Souriant, Shanti. Centre National de la Recherche Scientifique; FranciaFil: Poincloux, Renaud. Centre National de la Recherche Scientifique; FranciaFil: Al Saati, Talal. Inserm; FranciaFil: Rasolofo, Voahangy. Pasteur Institute in Antananarivo; MadagascarFil: González Montaner, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Inwentarz, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Moraña, Eduardo José. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Kondova, Ivanela. Biomedical Primate Research Centre; Países BajosFil: Verreck, Franck A. W.. Biomedical Primate Research Centre; Países BajosFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Neyrolles, Olivier. Centre National de la Recherche Scientifique; FranciaFil: Maridonneau Parini, Isabel. Centre National de la Recherche Scientifique; FranciaFil: Lugo Villarino, Geanncarlo. Centre National de la Recherche Scientifique; FranciaFil: Cougoule, Celine. Centre National de la Recherche Scientifique; Franci