Moreover, we were intrigued to find that BsaN suppresses a second PKS/NRPS cluster (BPSS0130, BPSS0303-BPSS0311, BPSS0328-BPSS0339) (Table 2), where almost identical homologs were identified in B. mallei and B. thailandensis by Biggins et al. and shown to produce an iron-chelating siderophore called Emricasan research buy malleilactone [45]. Disruption of the MAL

cluster in B. thailandensis reduced lethality following infection of C. elegans, and purified malleilactone was toxic to mammalian cells at micromolar concentrations. How the function of MAL fits within an overall regulatory framework that promotes virulence is not clear, although it is conceivable that BsaN-mediated suppression of MAL reduces the production of toxic products during infection, thereby promoting long term survival

within eukaryotic hosts. Alternatively, malleilactone itself may regulate virulence factor production similar to that reported for the P. aeruginosa siderophore pyoverdine [46]. Figure 7 Diagram of BsaN regulon. The BsaN LY2090314 datasheet regulon is shown Androgen Receptor signaling pathway Antagonists as part of a regulatory network, which is superseded by BprP activating transcriptions of T3SS3 apparatus genes (blue) including bsaN. The bicA gene is likely initially transcribed via read through of apparatus genes. BsaN-BicA function as a complex to activate T3SS3 translocon (purple), effector (yellow), accessory (grey) and regulatory (red) genes. Transcriptional activation is indicated by green arrows. BsaN-BicA also activate virAG, which in turn activates the bimA motility genes and the T6SS1 locus. BprC activates the T6SS1 tssAB apparatus genes. BsaN-BicA also activate a non-ribosomal polyketide synthesis locus and several metabolic genes. BsaN-repressed genes as indicated by red, blunted lines include T3SS3 apparatus genes and flagellar motility genes. Only genes which have been validated by qRT-PCR are shown. Until recently, BopA and BopE were the only two known T3SS

effector proteins in B. pseudomallei. The dearth of effectors is surprising when compared to other intracellular pathogens such as Shigella and Salmonella that are known to possess numerous effectors. We have independently identified BopC (BPSS1516) as a new T3SS3 effector based on its regulatory control by BsaN/BicA. bopC is transcribed in an operon encoding its chaperone (BPSS1517) and a transposase (BPSS1518) that are also activated by BsaN/BicA. Incidentally, Bupivacaine we had previously predicted by a genome-wide screen that BPSS1516 would encode a T3SS effector based on genomic colocalization with T3SS chaperones [47]. The BsaN regulatory motif we found in the promoters of the effectors was also recently reported to be associated with T3SS3 in a condition-dependent transcriptome study [48]. Of the T3SS3-linked effector proteins; BopA, BopC and BopE, our results suggest that BopA is the most critical for promoting cellular infection, consistent with prior studies linking BopA to intracellular survival of B.

Several lines of evidence further support the role of so2426 in the regulation of iron acquisition in S. oneidensis MR-1. A recent study applying gene network reconstruction to MR-1 indicated that SO2426 clusters with iron acquisition genes in a distinct iron-responsive network system [14]. Within this iron acquisition gene network were a number of members

of the SO2426 regulon proposed here, namely, so1188, so1190, so3025, so3030-3031-3032, so3063, and so4743 [14]. All of these genes, including so2426, were up-regulated under iron-depleted growth conditions compared to iron-replete conditions. Additionally, PD0332991 so3030 was up-regulated almost 14-fold in a fur mutant, while genes so3031-so3033 were up-regulated 4 to 11-fold [13]. A separate transcriptomic study with a fur deletion mutant revealed that the gene with the greatest expression change in the fur mutant LDN-193189 solubility dmso compared to the MR-1 wild-type strain was so2426, which showed a 30- and 26-fold increase in expression at the transcript level under aerobic and anaerobic growth conditions, respectively [12]. In addition to the enhanced expression

of so2426 in a fur mutant, this gene has been shown to be up-regulated under chromate [15, 41] and strontium [42] stress. The presence of a putative Fur-binding sequence in the promoter region of so2426 suggests that expression of this response regulator may be subject to multiple levels of regulatory control. Identification of a Fur box immediately 4��8C downstream of the -10 promoter element and up-regulation of so2426 expression in a fur deletion mutant are both consistent with repression of this gene by Fur under iron-sufficient conditions. Similarly, of those genes encoding transport and binding proteins, ftn, so1580, the so3030-3031-3032 operon, so4516, and so4743

are probable members of the Fur regulon based on their derepressed expression patterns in a S. oneidensis Δfur mutant and the presence of a putative Fur box in their respective upstream regions [12]. Collectively, these observations suggest cross-regulation of iron-responsive and other metal-responsive gene networks in S. oneidensis MR-1. SO2426 binds in region of PD173074 datasheet predicted recognition site upstream of alcA Given the potential overlap in the response of S. oneidensis to iron and other metals, we chose to focus on the S. oneidensis siderophore biosynthesis operon in testing the interaction of two recombinant versions of the SO2426 protein with its predicted binding motif. The direct involvement of so3030-3031-3032 in the production of hydroxamate-type siderophores was recently demonstrated with deletion mutants within this gene cluster [43].

As the normalized modal areas is ultrasmall for different H t values, we obtain the maximum propagation length of 2.49 × 103 μm for H t = 320 nm. The propagation length of the AHP waveguide increases 122% than that of the SHP waveguide on a substrate. Compared to the ideal condition of the SHP in air

cladding, the propagation length of the AHP waveguide is approximately equal to that of the SHP waveguide in air (2.38 × 103 μm) with a comparable normalized modal area. Thus, the introduced asymmetry to the structure of the SHP waveguide is vital to the extension of the propagation length while exerting little selleck chemical effect on the normalized modal area. The phenomenon in Figure 4b is similar to that in Figure 4a, but the performance of the silica-based AHP waveguide is better than that of the MgF2-based AHP waveguide. Figure 4 Propagation length and normalized modal area of silica- Selleckchem OICR-9429 and MgF 2 -based AHP waveguide versus height of mismatch. (a) Silica- and (b) MgF2-based AHP waveguide. The insets indicate electromagnetic energy density profiles of different

AZD2281 in vivo heights of mismatch. Conclusions In conclusion, we reveal that the AHP waveguide combining the advantages of symmetric (long-range) SP mode and hybrid plasmonic waveguides is capable of supporting long-range propagation of the guided waves with nanoscale mode confinement. The proposed structure is realized by introducing an asymmetry into the SHP waveguide. Theoretical calculations show that the AHP waveguide can eliminate the effect of a silica substrate on the guiding properties of the SHP waveguide and restores the symmetry of SP mode. Thus, the AHP waveguide on a substrate can perform the same as the SHP waveguide embedded in air cladding. Considering different materials of the low index gaps in the AHP waveguide, the performance of the silica-based AHP waveguide is better than the MgF2-based AHP waveguide. The proposed AHP waveguide can be conveniently fabricated by existing technologies like layered deposition or thermal oxidation. This may have practical applications

in highly integrated circuits as plasmonic interconnects. Acknowledgements This work was supported by the National Basic Research Program of China (2010CB327605), National Natural http://www.selleck.co.jp/products/MG132.html Science Foundation of China (61077049), Program for New Century Excellent Talents in University of China (NCET-08-0736), 111 Project of China and BUPT Excellent Ph. D. Students Foundation (CX201322). References 1. Polman A: Applied physics plasmonics applied. Science 2008, 322:868–869.CrossRef 2. Gramotnev DK, Bozhevlnyi SI: Plasmonic beyond the diffraction limit. Nature Photon 2010, 4:83–91.CrossRef 3. William LB, Alain D, Thomas WE: Surface plasmon subwavelength optics. Nature 2003, 424:824–830.CrossRef 4. Ozbay E: Plasmonics: merging photonics and electronics at nanoscale dimensions. Science 2006, 311:189–193.

Conclusion The present study provides insights into the use of dual therapy for effective decolonisation of MRSA in lesser period of time with reduced chances of relapse and emergence of resistant mutants. In the present study, use of single phage for nasal Caspase inhibitor decolonisation has been looked into, however, for this Luminespib research buy approach to be successful in clinical settings, need to study a cocktail of phages covering a larger spectrum of strains is required. Also, different delivery systems to achieve a sustained release of the phages may also be investigated. Additional file Additional file 1: Isolation of lytic bacteriophage specific for S. aureus ATCC strains as well as clinical isolates and host range determination. References

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Epidemiologic studies of an outbreak of nosocomial methicillin-resistant S. aureus infections. Infect Control 1981, 2:110–116. 2. Kluytmans J, Von Belkum A, Verburgh H: Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997, 10:505–520. 3. von Eiff C, Becker K, Machka K, Stammer H, Peters G: Hospital and community-acquired methicillin-resistant Staphylococcus aureus in Germany. Clin Microbiol Infect 2006, 12(Suppl 4):461. 4. Weems JJ, Beck LB: Nasal carriage of Staphylococcus aureus as a risk factor for skin and soft tissue 10058-F4 clinical trial infections. Current Infectious Disease Reports 2002, 4(5):420–425. 5. Ammerlaan HS, Kluytmans JA, Wertheim HF, Nouwen JL, Bonten MJ: Eradication of methicillin-resistant Staphylococcus aureus carriage: a systematic review. Clin Infect Dis 2009, 48:922–930. 6. Doebbeling BN, Reagan DR, Pfaller MA, Houston AK, Hollis RJ, Wenzel RP: Long-term efficacy of intranasal mupirocin ointment. A prospective cohort study of Staphylococcus aureus carriage. Arch Intern Med 1994, 54:1505–1508. 7. Fernandez C, Gaspar C, Torrellas A, Vindel A, Saez-Nieto JA, Cruzet F, Aguilar L: A double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of mupirocin calcium ointment for eliminating nasal carriage of Staphylococcus aureus among hospital Rucaparib personnel.

J Antimicrob Chemother 1995, 35:399–408. 8. Wills QF, Kerrigan C, Soothill JS: Experimental bacteriophage protection against Staphylococcus aureus abscesses in a rabbit model. Antimicrob Agents Chemother 2005, 49:1220–1221. 9. Capparelli R, Parlato M, Borriello G, Salvatore P, Iannelli D: Experimental phage therapy against Staphylococcus aureus in mice. Antimicrob Agents Chemother 2007, 51:2765–2773. 10. Sunagar R, Patil SA, Chandrakanth RK: Bacteriophage therapy for Staphylococcus aureus bacteremia in streptozotocin-induced diabetic mice. Research in Microbiol 2010, 161(10):854–860. 11. Hsieh SE, Lo HH, Chen ST, Lee MC, Tseng YH: Wide host range and strong lytic activity of Staphylococcus aureus lytic phage Stau2. Appl Environ Microbiol 2011, 77(3):756–761. 12.

Infection rates increased in all three groups at seven dpi, but the number of TE/3’2J/B2 virus-infected mosquitoes remained significantly higher than TE/3’2J (P = 0.0094) and TE/3’2J/GFP (P = 0.0020). TE/3’2J and TE/3’2J/GFP virus infection rates did not differ significantly at four or seven dpi. All mosquitoes exhibiting a Apoptosis inhibitor disseminated infection had detectable Cilengitide virus in the midgut. Five of 12 mosquitoes

(42%) with detectable TE/3’2J/B2 virus in the midgut exhibited disseminated infection at day four while no virus was detected in carcasses of mosquitoes infected with TE/3’2J or TE/3’2J/GFP virus. At seven dpi, 61% (14 of 23) of TE/3’2J/B2 virus-infected mosquitoes had disseminated infections, as compared to 40% (4 of 10) for TE/3’2J- and 38% (3 of 8) for TE/3’2J/GFP-infected mosquitoes. Significantly higher average TE/3’2J/B2 virus KPT-8602 price titers were found in the midgut at seven dpi (P = 0.0446 TE/3’2J:TE/3’2J/B2; P = 0.0439 TE/3’2J/GFP:TE/3’2J/B2; unpaired Student’s t test) and in mosquito carcasses at seven dpi (P = 0.0043 TE/3’2J:TE/3’2J/B2; P = 0.0038 TE/3’2J/GFP:TE/3’2J/B2).

Average TE/3’2J/B2 titers in the midgut at four dpi were not statistically higher (P = 0.1023 TE/3’2J:TE/3’2J/B2, P = 0.1115 TE/3’2J/GFP:TE/3’2J/B2). At four and seven dpi, infection and dissemination titers were not statistically different between TE/3’2J and TE/3’2J/GFP viruses. Figure 6 Infection and dissemination of TE/3’2J, TE/3’2J/GFP, and TE/3’2J/B2 viruses in Ae. aegypti mosquitoes following oral bloodmeal. At the indicated day post-bloodmeal, viral titers were determined for A) midguts and remaining B) mosquito carcass. n = 48 per group. “”TE/3″”‘ = TE/3’2J, “”GFP”" = TE/3’2J-GFP, “”B2″” = TE/3’2J/B2. Horizontal line represents the mean for each data set. (*) above data set indicates that the mean TE/3’2J/B2 titer is significantly higher than TE/3’2J and

TE/3’2J/GFP infections. (**) below the infection and dissemination rates indicates significantly higher infection and dissemination rates as compared to TE/3’2J virus infection. Due to the lack of dissemination positive mosquitoes in the Day 4 TE/3 and GFP samples (Figure B), statistical significance of the Day 4 B2 group Acetophenone as compared to the TE/3 and GFP groups could not be determined. Ae. aegypti mortality associated with TE/3’2J/B2 virus infection Mosquito mortality assays were performed to determine the effects of virus infection on mosquito survival. From observations made during determination of infectious virus titers in orally infected mosquitoes, we predicted that TE/3’2J/B2 virus was able to kill mosquitoes more effectively than TE/3’2J or TE/3’2J/GFP. Female mosquitoes were given a bloodmeal containing 1 × 107 PFU/ml of TE/3’2J, TE/3’2J/GFP, TE/3’2J/B2, or cell culture medium only.

The presence of several glycolytic enzymes in PCM and not in BCM supports the notion that central metabolic processes are in different states in find more planktonic and biofilm cultures and that those different metabolic states likely have a large impact on the observed pathogenic effects on HKs described here. Functional annotation clustering of upregulated transcripts revealed over-represented annotation

clusters associated with response to bacteria, regulation of transcription, inflammation, and signal transduction (Figure 2). The gene ontology term mTOR inhibitor review “”response to glucocorticoid stimulus”" was interesting as glucocorticoids are anti-inflammatory hormones. Genes involved in cyclic adenosine monophosphate (cAMP) signaling were also interesting since cAMP is involved in several fundamental cellular processes and may be partially responsible for the observed effects induced by BCM. Functional annotation clustering of downregulated

transcripts revealed over-represented annotation clusters associated with transcription and metabolism. The downregulation of genes associated with these processes may indicate a general cessation in BCM treated cells. Transcriptional responses of HKs to BCM revealed the upregulation of pro-inflammatory genes, including transcripts for pro-inflammatory transcription factors, cytokines, and apoptosis related genes. Among these were members of the AP-1 family of transcription factors and regulators of the NFkB pro-inflammatory transcription factor, TNFAIP3 (A20) and NFkBIA. Expression of these genes indicated active regulation of the NFkB pathway. NFkB regulates the expression this website of many

genes involved in immune and inflammatory responses (i.e. cytokine and chemokine genes) and often acts in synergy with AP-1 to mediate inflammatory responses [33, 34]. NFkB and AP-1 are activated by pro-inflammatory cytokines such as TNF-α and IL-1β which act through MAPK-dependent signal cascades resulting in the production of additional cytokines [35–38]. The transcription factor egr1, which was highly upregulated 3-mercaptopyruvate sulfurtransferase in BCM treated HKs, is also involved in the regulation of pathophysiologically important genes relating to inflammation, apoptosis, and differentiation [39–41]. The upregulation of these early response transcription factors indicates that four hours of treatment with BCM induces a swift inflammatory response in HKs relative to PCM. We previously investigated BCM induced apoptosis and HK migration in a scratch wound model [20]. In agreement with that study, S. aureus BCM induced apoptosis in HKs while PCM did not induce a significant amount of apoptosis. BCM mediated induction of apoptosis is discussed in detail in [20]. This striking dissimilarity between PCM and BCM would undoubtedly have substantial impacts on several aspects of wound healing. Cytokine production induced by PCM and BCM were normalized to adherent non-apoptotic HKs.

Another important observation is the trend of causes of trauma during the three years of the study. The 17.76% decrease in road-related injuries demonstrates that primary and secondary prevention programs for car, motorcycle, pedestrian, cycling accidents have obtained appreciable results. On the contrary many efforts need to be made for trauma prevention in houses, particularly of falls ARS-1620 ic50 in old women

living at home. The design of a new Trauma System must take into account these data: the new challenge will be the need to treat an EX 527 molecular weight increasing number of serious injuries in elderly people, with all the problems of concomitant illnesses, complications, prolonged ICU and hospital LOS, increased costs of healthcare and need of complex rehabilitation programs for the social reinstatement. On the other hand, pediatric cases are less than 200 per year in ten millions inhabitants and injured children need to be centralized in few highly specialised centres. The low number of trauma due to violence underlines a significant difference in trauma epidemiology between Europe and overseas Countries. In Lombardia only 2.06% of serious trauma (where the cause has been formally indicated) were consequence of assaults (both penetrating or blunt) and this amount is sharply lower than North America [28]. However, media reports of stabbing and shootings and anecdotal evidence based on presentations to the emergency

MAPK inhibitor departments support the idea that interpersonal violence is on the rise, particularly between immigrates from Asia and Africa, as also observed in other countries [29]. Finally time distribution of hospital trauma deaths demonstrated that acute and early deaths regarded principally road-related injuries, trauma at workplace and assaults or self-inflicted violence. On the contrary, late deaths increased in victims of domestic SPTLC1 trauma. Differences in age between

victims with acute-early deaths and victims of late deaths suggest that young patients demise has been related in the acute – early phase to the severity of injuries, while elderly people died principally for related complications [30]. These observations are consistent with the results obtained also in the national trauma deaths study [8]. A late mortality close to 40%, mostly related to domestic trauma in elderly, is a substantial change and may impact significantly costs of trauma care. Notwithstanding the highest mortality, a reduced rate of ICU admission has been observed in patients older than 74. Although the datum was not available, this may suggest use of resources weighted on functional recovery possibilities. Again, this observation outlines the need of further studies to define protocols of care in this category of patients. Funding of trauma system In Italy, as in many other Countries, public or private hospitals are reimbursed using the DRG system.

We attempted to find and include spacer sequences from CRISPR repeat motifs not known to be present in Streptococcus, including repeat motifs found in species of Gemella, Veillonella, Leptotrichia, and Kingella, but their presence was not uniform on the skin (data not shown). Because of the error rate of Ion Torrent

sequencing [36], we took additional precautions to reduce sequencing error biases in our analysis of CRISPR spacers. Each CRISPR-bearing read was trimmed according MDV3100 to quality scores, and was removed if it had significant homopolymer tracts. We specifically removed any CRISPR-bearing reads from the analysis that did not match the known consensus repeat motifs, as those reads were more likely to contain sequencing errors. The combination of these techniques reduced the error rate from approximately 1% to an estimated 0.001 and 0.002% for SGI and SGII CRISPR spacers, respectively. Our previous studies of CRISPR repertoires in humans had been performed using conventional Sanger sequencing, however we now have extended our analysis using next-generation sequencing techniques. The primary benefit of the current technique was that we were able to achieve greater sampling depth, which allowed for more robust comparisons of skin and salivary CRISPRs with fewer unsampled spacers. Our data on shared

CRISPR spacers between skin and saliva revealed several qualities about CRISPRs on human body surfaces: 1) fewer spacers GSK1120212 datasheet were shared between subjects than within subjects, suggesting

that CRISPR repertoires were individual specific, 2) the Selleck Capmatinib substantial persistence of spacers, suggesting that the bacteria harboring them were conserved over the time period studied, and 3) the level of shared spacers between skin and saliva in individual subjects (Figure 1 and Additional file 2: Figure S2), which raises the possibility that skin-derived bacteria may have encountered viruses with similar sequences to those in the mouth. While it is possible that some of the spacers were acquired through independent means [10], the substantial levels Edoxaban of shared spacers between skin and saliva suggests some vertical or horizontal acquisitions. Despite our inability to reconstruct many CRISPR loci using this short-read technology, our finding that many spacers from previously sequenced S. thermophilus isolates were present in this cohort suggests that those loci may be present in this study with their spacer content and order intact. Because the location of the CRISPR loci in our subjects was variable, we were unable investigate them robustly by PCR amplification using their flanking regions, followed by Sanger sequencing. We initially hypothesized that there would be large groups of spacers specific to saliva and specific to skin that would be unique to each body surface.

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this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. Conflicts of interest None. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. U.S. Department of Health and Human Services (2004) Bone health and osteoporosis: a report of the surgeon general. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General 2. Looker AC, Orwoll ES, Johnston CC Jr et al (1997) Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 12:1761–1768CrossRef 3. Burge R, Dawson-Hughes B, CFTRinh-172 solubility dmso Solomon DH et al (2007) Incidence and economic burden of osteoporosis-related fractures Idasanutlin research buy in the United States, 2005–2025. J Bone Miner Res 22:465–475CrossRefPubMed 4. Nelson HD, Helfand M, Woolf SH et al (2002) Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 137:529–541PubMed 5. BAY 63-2521 price Nguyen TV, Eisman JA, Kelly PJ et al (1996) Risk factors for osteoporotic fractures

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