Mobility and survival of Salmonella Typhimurium and human adenovirus from spiked sewage sludge applied to soil columns

Aims: This study investigated the survival and transport of sewage sludge-borne pathogenic organisms in soils. Methods and Results: Undisturbed soil cores were treated with Salmonella enterica ssp. enterica serovar Typhimurium-lux (STM-lux) and human adenovirus (HAdV)-spiked sewage sludge. Following an artificial rainfall event, these pathogens were analysed in the leachate and soil sampled from different depths (0-5 cm, 5-10 cm and 10-20 cm) after 24 h, 1 and 2 months. Significantly more STM-lux and HAdV leached through the soil cores when sewage sludge was present. Significantly more STM-lux were found at all soil depths, at all time periods in the sewage sludge treatments, compared to the controls. The rate of decline of STM-lux in the controls was more rapid than in the sewage sludge treatments. Survival and transport of HAdV were minimal. Conclusions: The presence of sewage sludge can significantly influence the transport and survival of bacterial pathogens in soils, probably because of the presence of organic matter. Environmental contamination by virus is unlikely because of strong soil adsorption. Significance and Impact of the Study: This study suggests that groundwater contamination from vertical movement of pathogens is a potential risk and that it highlights the importance of the treatment requirements for biosolids prior to their application to land

Fourier transform ion cyclotron resonance MS reveals the presence of a water molecule in an enzyme transition-state analogue complex

The structures of several powerful inhibitors of hydrolytic enzymes resemble that of the altered substrate in the transition state, except that a hydrogen atom replaces one substituent (typically the leaving group). To test the hypothesis that a water molecule might be present in the gap resulting from this replacement, we examined a transition-state analogue complex formed by Escherichia coli cytidine deaminase by Fourier transform ion cyclotron resonance MS in electrospray mode. Upon nebularization from aqueous solution under conditions (pH 5.6) where the enzyme is active, cytidine deaminase remains dimeric in the vapor phase. In the presence of inhibitor, the enzyme's exact mass can be used to infer the presence at each active site of zinc, 5-fluoro-3,4-dihydrouridine, and a single water molecule

Effect of Long-Term Zinc Pollution on Soil Microbial Community Resistance to Repeated Contamination

The aim of the study was to compare the effects of stress (contamination trials) on the microorganisms in zinc-polluted soil (5,018 mg Zn kg−1 soil dry weight) and unpolluted soil (141 mg Zn kg−1 soil dw), measured as soil respiration rate. In the laboratory, soils were subjected to copper contamination (0, 500, 1,500 and 4,500 mg kg−1 soil dw), and then a bactericide (oxytetracycline) combined with a fungicide (captan) along with glucose (10 mg g−1 soil dw each) were added. There was a highly significant effect of soil type, copper treatment and oxytetracycline/captan treatment. The initial respiration rate of chronically zinc-polluted soil was higher than that of unpolluted soil, but in the copper treatment it showed a greater decline. Microorganisms in copper-treated soil were more susceptible to oxytetracycline/captan contamination. After the successive soil contamination trials the decline of soil respiration was greater in zinc-polluted soil than in unpolluted soil

The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor NF-κB. We have identified a non-steroidal estrogen receptor ligand, WAY-169916, that selectively inhibits NF-κB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis, the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model, after daily oral administration. In both models, a near complete reversal in hindpaw scores was observed as well as marked improvements in the histological scores. In the Lewis rat adjuvant model, WAY-169916 markedly suppresses the adjuvant induction of three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), and C-reactive protein (CRP). Gene expression experiments also demonstrate a global suppression of adjuvant-induced gene expression in the spleen, liver, and popliteal lymph nodes. Finally, WAY-169916 was effective in suppressing tumor necrosis factor-α-mediated inflammatory gene expression in fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest the utility of WAY-169916, and other compounds in its class, in treating RA through global suppression of inflammation via selective blockade of NF-κB transcriptional activity

Архетип свобода у контексті французької політичної теорії та історії

Розглянуто сучасні підходи щодо аналізу політичної ментальності. У межах політологічного аналізу окреслено коло проблем, які потребують вирішення з використанням підходів психології. Зроблено висновок про те, що архетип “свобода” становить важливий елемент політичної ментальності французів.Modern approaches of analysis of political mentality are considered. Within the limits of political science analysis outlined circle of problems which need decision with the use of approaches of psychology. A conclusion is done that archetype freedom makes the important element of political mentality of French’s

MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors

T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1214–224 epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design

Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16

Multipotent progenitor cells confirm their T cell–lineage identity in the CD4^–CD8^– double-negative (DN) pro-T cell DN2 stages, when expression of the essential transcription factor Bcl11b begins. In vivo and in vitro stage-specific deletions globally identified Bcl11b-controlled target genes in pro-T cells. Proteomics analysis revealed that Bcl11b associated with multiple cofactors and that its direct action was needed to recruit those cofactors to selective target sites. Regions near functionally regulated target genes showed enrichment for those sites of Bcl11b-dependent recruitment of cofactors, and deletion of individual cofactors relieved the repression of many genes normally repressed by Bcl11b. Runx1 collaborated with Bcl11b most frequently for both activation and repression. In parallel, Bcl11b indirectly regulated a subset of target genes by a gene network circuit via the transcription inhibitor Id2 (encoded by Id2) and transcription factor PLZF (encoded by Zbtb16); Id2 and Zbtb16 were directly repressed by Bcl11b, and Id2 and PLZF controlled distinct alternative programs. Thus, our study defines the molecular basis of direct and indirect Bcl11b actions that promote T cell identity and block alternative potentials

Homology modeling and molecular dynamics simulations of MUC1-9/H-2Kb complex suggest novel binding interactions

International audienceHuman MUC1 is over-expressed in human adenocarcinomas and has been used as a target for immunotherapy studies. The 9-mer MUC1-9 peptide has been identified as one of the peptides which binds to murine MHC class I H-2K. The structure of MUC1-9 in complex with H-2K has been modeled and simulated with classical molecular dynamics, based on the x-ray structure of the SEV9 peptide/H-2K complex. Two independent trajectories with the solvated complex (10 ns in length) were produced. Approximately 12 hydrogen bonds were identified during both trajectories to contribute to peptide/MHC complex, as well as 1-2 water mediated hydrogen bonds. Stability of the complex was also confirmed by buried surface area analysis, although the corresponding values were about 20% lower than those of the original x-ray structure. Interestingly, a bulged conformation of the peptide's central region, partially characterized as a -turn, was found exposed form the binding groove. In addition, P1 and P9 residues remained bound in the A and F binding pockets, even though there was a suggestion that P9 was more flexible. The complex lacked numerous water mediated hydrogen bonds that were present in the reference peptide x-ray structure. Moreover, local displacements of residues Asp4, Thr5 and Pro9 resulted in loss of some key interactions with the MHC molecule. This might explain the reduced affinity of the MUC1-9 peptide, relatively to SEV9, for the MHC class I H-2K