06 0 59-1 88 0 85         Surgery (complete vs non complete) 52 0

06 0.59-1.88 0.85         Surgery (complete vs non complete) 52 0.29 0.15-.058 4.97 E-07 51 0.43 0.19-0.94 0.034 Complete clinical remission (Yes vs No) 51 0.22 0.11-0.45 3.65 E-05 51 0.33 0.15-0.74 0.007 CA-125 (normal vs >normal) 44 1.87 0.84-4.16 0.12         Treatment (CCA vs HDC) 52 2.44 1.14-5.25 0.02 51 2.31 1.06-5.04 0.036 PFS, progression-free

survival; N, number of cases with data available; 95CI, 95% confidence interval; HR, hazard ratio; OMS, performance status; CCA, conventional chemotherapy alone; HDC, high-dose chemotherapy. We then explored the impact of chemotherapy regimen on OS according to the two factors independently associated ACP-196 cost with a PFS improvement induced by HDC (young age and FIGO stage IIIc). We could ABT-737 solubility dmso observe that HDC plus HSCS significantly improved survival only when age was under 50 years, but not in stage IIIc patients (Figure 4). Median overall survival was highly increased in young patients treated with HDC (54.6 months) when compared to conventional therapy alone (36 months), (p=0.05). Effect of HDC according to FIGO stage IIIc was less important and non significant: median OS was 53.9 months in the HDC subset versus 41.3 months in the CCA subset (p=0.11). Figure 4 Overall survival after conventional chemotherapy alone (black) or

plus high dose chemotherapy (grey). (A) In patients under 50 years of age (n=52) median OS was 36 months in the CCA subset versus 54.6 months in the HDC subset; (B) in stage IIIc cases (n=129) median OS was 42 months in the CCA subset versus 49.5 months in the HDC subset; + censored data. It is worth to note that the prognostic value of HDC was not modified by the initial response to treatment. HDC improved survival in young patients whatever the response to initial therapy was: median PFS was 5 months for CCA vs. 15 months

for HDC in patients with residual disease after treatment; and 38 months for CCA whereas it had not been reached after a follow-up of 47 months in the HDC group for cases with initial CCR and CA-125 normalization. Discussion Even though HDC plus HSCS cannot be considered as a standard of care for all AOC patients, results from this monocentric comparative FER retrospective study including 163 patients suggest that it may be beneficial to young patients. In women under 50 years of age, addition of HDC to platinum/taxane-based chemotherapy improves not only PFS (p=0.02), but also OS (median of 54.6 months versus 36 months with conventional therapy alone, p=0.05). Despite advances in chemotherapy and multidisciplinary management of ovarian carcinomas, the prognosis of patients with advanced stages (FIGO III/IV) remains poor. Median PFS and OS of our cohort treated with a platinum/taxane combination alone (18.1 and 41.3 months, respectively) were similar to those of phase III pivotal studies: 18 and 38 months [10], and 19.4 and 48.7 months [6] with cisplatin and paclitaxel; 20.7 and 57.4 months for carboplatin and paclitaxel [6].

Like all other human malignancies, prostate cancer cells escape a

Like all other human malignancies, prostate cancer cells escape apoptotic death through highly efficient pathways involving multiple mechanisms [6, 7]. X-linked inhibitor of apoptosis protein-associated factor-1 (XAF1) was first identified as an interacting protein of X-linked inhibitor of apoptosis (XIAP) [8]. XIAP suppresses apoptotic cell death by binding to caspases and inhibiting their functions. XAF1 antagonizes XIAP activities, thereby promoting apoptosis [9]. XAF1 can dramatically sensitize cancer cells to apoptotic triggers

such as TRAIL, etoposide treatments 5-fluorouracil [10], H2O2, c-irradiation, ultraviolet [11], and tumour necrosis factor-α, which are independent of its interaction with XIAP [12]. XAF1 is therefore believed to play an important role in the major apoptosis-related pathways. XAF1 also serves as a candidate tumour suppressor gene. Loss of XAF1 has been observed in a variety BIX 1294 ic50 of cancer cell

lines and human cancers [13–16]. However, little is yet known about its potential selleck inhibitor implication in prostate cancer. So far, there have been no effective therapeutic measures for the treatment of hormone refractory prostate cancer. Treatment with somatostatin may therefore be a possible therapeutic alternative to chemotherapy in hormone refractory prostate cancer patients. Somatostatin, originally identified as a neuropeptide inhibiting growth hormone release more than 30 years ago, is widely present in central and peripheral human cells/tissues including prostate. Somatostatin has been shown to exert a potent anti-tumour action by affecting tumour cell proliferation, apoptosis, angiogenesis and the host’s immune response [17–21]. Octreotide is an analogue of somatostatin and has been used in clinical practice since data emerged in the 1980 s confirming its ability to palliate carcinoid syndrome

[22]. Our previous results have shown that somatostatin may affect the mitochondria Oxaprozin of LNCaP and DU145 cells in a way that eventually triggers mitochondrial-mediated apoptosis and exert its effects on prostate cancer cells via MAPK pathway and by regulating the activities of phosphotyrosine phosphatases [23]. In the current study, we examined XAF1 mRNA and protein expression in four cell lines, and determined regulatory effects of somatostatin and Octreotide on XAF1 expression in prostate cancer cell lines. We found that somatostatin and Octreotide up-regulated XAF1 mRNA and protein expression in prostate cancer cell lines. The enhanced XAF1 expression by somatostatin indicates a promising strategy for prostate cancer therapy. Materials and methods Cell lines and cell culture A human prostate epithelial cell line (RWPE-1) and prostate cancer cell lines (LNCaP, DU145 and PC3) were used and were obtained from the American Type Culture Collection (ATCC). LNCaP, DU145 and PC3 were maintained in RPMI-1640 medium supplemented with 10% foetal bovine serum (FBS).

GLPG0259 free base is poorly soluble in aqueous media, and its so

GLPG0259 free base is poorly soluble in aqueous media, and its solubility decreases with increasing pH (<0.01 mg/mL at pH 7). Two approaches were developed in parallel to overcome this low solubility and to improve compound bioavailability after dosing in a solid dosage form. The first approach was a salt screening, AZD5363 which resulted in the selection of the fumarate salt for further formulation development work. The water solubility of

the GLPG0259 fumarate salt, as compared with that of the free base, was increased to 1.9–2.7 mg/mL. The impact of the improvement in solubility was confirmed in a comparative bioavailability study in fasted dogs. In that study, GLPG0259 fumarate salt (suspension in 20% [w/v] hydroxypropyl-ß–cyclodextrin, pH 3, or as crystalline powder in capsule form) resulted in plasma exposure similar to that of GLPG0259 free base in suspension in 20% acidified hydroxypropyl-ß–cyclodextrin, but 4-fold higher plasma exposure than that of GLPG0259 free-base crystalline powder in capsule form (data not shown). In humans, administration of GLPG0259 fumarate salt as a crystalline powder in capsule form leads to 50% lower bioavailability than that of GLPG0259 free base

given as a solution in 40% (w/v) hydroxypropyl-ß–cyclodextrin, pH 3 (study 3). The lower performance of the fumarate capsule in humans than in dogs is explained by the higher percentage of hydroxypropyl-ß–cyclodextrin (40% versus 20%) in the liquid formulation, which enhances GLPG0259 free-base solubility. Bafilomycin A1 mouse Concomitant food intake with the solid

dosage form Sitaxentan prevents this decrease in bioavailability by increasing the solubility further. The second approach was the improvement of GLPG0259 solubility by physical modifications of the drug substance – in particular, the development of solid dispersion formulations with GLPG0259 free base in an amorphous form homogenously dispersed in a polymer matrix. The free-base solid dispersion as a powder or pellets filled into capsules was tested in fasted dogs, and both solid dispersion formulations showed GLPG0259 plasma exposure similar to that of the fumarate salt as a crystalline powder in capsule form. Similar results were obtained in humans (study 4). In the Biopharmaceutical Classification System, drugs are classified according to measurements of solubility and permeability.[20] Regarding GLPG0259, it is a poorly soluble compound, with solubility that decreases with increased pH. The absorption of GLPG0259 was not measured in vivo in humans (there are no data after intravenous dosing), but its permeability assessed using the well established in vitro system, based on the human adenocarcinoma cell line Caco-2, was good, with an apparent permeability coefficient (Papp) of 12.4 10-6 cm/s and limited efflux (Papp B2A/Papp A2B = 2).

Curr Opin Infect Dis 16:129–134PubMedCrossRef Murphy TF, Brauer A

Curr Opin Infect Dis 16:129–134PubMedCrossRef Murphy TF, Brauer AL, Sethi S, Kilian M, Cai X, U0126 supplier Lesse AJ (2007) Haemophilus haemolyticus: a human respiratory tract commensal to be distinguished from Haemophilus influenzae. J Infect Dis 195:81–89PubMedCrossRef Musk DJ, Hergenrother PJ (2006) Chemical countermeasures for the control of bacterial biofilms: effective compounds and promising targets. Curr Med Chem 13:2163–2177PubMedCrossRef National Committee for Clinical Laboratory Standards (2000) Approved standard: M2-A7. Performance standards for antimicrobial disk susceptibility tests, 7th ed. National Committee

for Clinical Laboratory Standards, Wayne, Pennsylvania 19087-1898, USA National Committee

for Clinical Laboratory Standards (2004) Quality control for commercially prepared microbiological culture media; approved standard—third edition. NCCLS document M22-A3. NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA Oancea S (2010) An overview of conventional and alternative strategies for developing new antibacterial agents. Acta Chim Slov 57:630–642PubMed Pillai A, Mitchell selleck inhibitor JL, Hill SL, Stockley RA (2000) A case of Haemophilus parainfluenzae pneumonia. Thorax 55:623–624PubMedCrossRef Pitucha M, Mazur L, Kosikowska U, Pachuta-Stec A, Malm A, Popiołek Ł, Rzączyńska Z (2010) Synthesis, structure and antibacterial evaluation of new N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamides. Heteroat Chem 21:215–221 Prakash Clostridium perfringens alpha toxin B, Veeregowda BM, Krishnappa G (2003) Biofilms: a survival strategy of bacteria. Curr Sci India 85:1299–1307 Raffa RB, Iannuzzo

JR, Levine DR, Saeid KK, Schwartz RC, Sucic NT, Terleckyj OD, Young JM (2005) Bacterial communication (quorum sensing) via ligands and receptors: a novel pharmacologic target for the design of antibiotic drugs. J Pharmacol Exp Ther 312:417–423PubMedCrossRef Raoult D, Drancourt M, Gallais H, Casanova P (1987) Haemophilus parainfluenzae meningitis in an adult with an inherited deficiency of the seventh component of complement. Arch Intern Med 417:2214CrossRef Reece RJ, Maxwell A (1991) DNA gyrase: structure and function. Crit Rev Biochem Mol 26:335–375CrossRef Rele M, Giles M, Daley AJ (2006) Invasive Haemophilus parainfluenzae maternal-infant infections: an Australasian perspective and case report. Aust N Z J Obstet Gynaecol 46:258–260PubMedCrossRef Rennie R, Gordon T, Yaschuk Y, Tomlin P, Kibsey P, Albritton W (1992) Laboratory and clinical evaluations of media for the primary isolation of Haemophilus species. J Clin Microbiol 30:1917–1921PubMedCentralPubMed Sanclement JA, Webster P, Thomas J, Ramadan HH (2005) Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis.

54 Sulakvelidze A, Morris JG: Bacteriophages as therapeutic agen

54. Sulakvelidze A, Morris JG: Bacteriophages as therapeutic agents. Ann Med 2001, 33:507–509.PubMedCrossRef 55. Ritz HL, Kirkland JJ, Bond GG, Warner EK, Petty GP: Association of high levels

of serum antibody to staphylococcal toxic shock antigen with nasal Z-VAD-FMK nmr carriage of toxic shock antigen producing strains of Staphylococcus aureus . Infect Immun 1984, 43:954–958. 56. Kaliner MA: Human nasal respiratory secretions and host defense. Am Rev Respir Dis 1991, 144:S52–S56.PubMed 57. Rigby KM, DeLeo FR: Neutrophils in innate host defense against Staphylococcus aureus infections. Semin Immunopath 2012, 34(2):237–259. Competing interests The authors declare that they have no competing interests. Authors’ contributions SC, SK: Conceived and designed the experiments; PG: Performed the experiments; SC, SK: Analyzed the data; SC, SK: Wrote the paper. All authors read and approved the final manuscript.”
“Background The essential trace elemental selenium (Se) is the 34th element on the periodic selleck kinase inhibitor table and plays a fundamental role in human health [1]. Se is involved in several major metabolic pathways,

such as thyroid hormone metabolism, antioxidant defense systems and immune function [2]. In humans, selenium has navigated a narrow range from dietary deficiency (<40 μg per day) to toxic levels (>400 μg per day) [3]. Selenium toxicity in humans has been reported in the Chinese provinces Hubei and Shaanxi and in Indian Punjab, where Se levels in locally produced foods were found to be very high (750–4990 μg per person and day) [4]. The variation of Se status in humans both related to either Se excess or deficiency largely depends on the diet consisting of various crops, GNAT2 vegetables, fruits and meat [1]. Therefore, it is essential to understand the factors controlling the dynamic distribution of Se in the environment. Microorganisms

are involved in the transformation of selenium from one oxidation state to another [5-7]. A few studies reported that bacteria oxidized selenium to Se(IV) and Se(VI) in soils [8,9]. The formation of volatile methylated selenium species was also studied in several bacteria [5,7,10]. In addition, numerous bacteria were shown to reduce Se(VI)/Se(IV) to elemental Se, visible as red-colored nano-selenium [11-16]. Se(IV)-reducing bacteria generate red-colored elemental selenium nanoparticles (SeNPs) either under aerobic or under anaerobic conditions. Anaerobic Se(IV)-reducing bacteria encompass Thauera selenatis [17], Aeromonas salmonicida [18] and purple non-sulfur bacteria [14]. Aerobic bacteria involved in Se(IV) reduction include diverse species such as Rhizobium sp. B1 [19], Stenotrophomonas maltophilia SeITE02 [11], Pseudomonas sp. CA5 [13], Duganella sp. and Agrobacterium sp. [20]. However, the exact mechanism of selenium metabolism and reduction is still far from being elucidated.

Appl Phys Lett 1998,73(7):918–920 CrossRef 10 Jo SH, Huang ZP, T

Appl Phys Lett 1998,73(7):918–920.CrossRef 10. Jo SH, Huang ZP, Tu Y, Carnahan DL, Wang DZ: Effect of length and spacing of vertically aligned carbon nanotubes on field emission properties. Appl Phys Lett 2003,82(20):3520–3522.CrossRef 11. Jha A, Banerjee D, Chattopadhyay KK: Improved field emission from amorphous carbon

nanotubes by surface functionalization with stearic acid. Carbon 2011,49(4):1272–1278.CrossRef ABT263 12. Hazra KS, Gigras T, Misra DS: Tailoring the electrostatic screening effect during field emission from hollow multiwalled carbon nanotube pillars. Appl Phys Lett 2011,98(12):123116.CrossRef 13. Zhang YA, Wu CX, Lin JY, Lin ZX, Guo TL: An improved planar-gate triode with CNTs field emitters by CHIR-99021 clinical trial electrophoretic deposition. Appl Surf Sci 2011,257(8):3259–3264.CrossRef 14. Sanborn G, Turano S, Collins P, Ready WJ: A thin film triode type carbon nanotube field emission cathode. Appl Phys A 2013,110(1):99–104.CrossRef 15. Chen G, Neupane S, Li W, Chen L, Zhang J: An increase in the field emission from vertically aligned multiwalled carbon nanotubes caused by NH 3 plasma treatment. Carbon 2013, 52:468–475.CrossRef 16. Futaba DN, Kimura H, Zhao B, Yamada T, Kurachi H, Uemura S, Hata K: Carbon nanotube loop arrays for low-operational

power, high uniformity field emission with long-term stability. Carbon 2012,50(8):2796–2803.CrossRef 17. Pandey A, Prasad A, Moscatello JP, Engelhard M, Wang C, Yap YK: Very stable electron field emission from strontium titanate coated carbon nanotube matrices with low emission thresholds. ACS Nano 2013,7(1):117–125.CrossRef 18. Bonard BJ, Weiss N, Kind H, Stöckli T, Forró L, Kern

K: Tuning the field emission properties of patterned carbon nanotube films. Adv Mater 2001,13(3):184–188.CrossRef 19. Dolbec R, Irissou E, Chaker M, Guay D, Rosei F, El Khakani MA: Growth dynamics of pulsed laser deposited Pt nanoparticles on highly oriented pyrolitic graphite substrates. Phys Rev B 2004,70(20):201406.CrossRef 20. Aïssa B, Therriault D, El Khakani MA: On-substrate growth of single-walled carbon nanotube networks by an “all-laser” processing route. Carbon 2011,49(8):2795–2808.CrossRef 21. Collazo R, Schlesser R, Sitar Z: Role of adsorbates in field emission from nanotubes. Diam Relat Mater 2002, 211:769–773.CrossRef 22. Bower C, Zhu W, Jin Idoxuridine S, Zhou O: Plasma-induced alignment of carbon nanotubes. Appl Phys Lett 2000,77(6):830–832.CrossRef 23. Fowler RH, Nordheim L: Electron emission in intense electric fields. Proc Roy Soc A Math Phys Char 1926,119(781):173–181.CrossRef 24. Ago H, Kugler T, Cacialli F, Salaneck WR, Shaffer MSP, Windle AH, Friend RH: Work functions and surface functional groups of multiwall carbon nanotubes. J Phys Chem B 1999,103(38):8116–8121.CrossRef 25. Su W, Leung T, Chan C: Work function of single-walled and multiwalled carbon nanotubes: first-principles study. Phys Rev B 2007,76(23):235413.CrossRef 26.

Values are presented as means ± standard deviation (n = 36) * vs

Values are presented as means ± standard deviation (n = 36). * vs. rest, P < 0.001; # vs. After-exercise, P < 0.01. Glycogen concentrations in the tissues The glycogen concentration in the liver did not differ between the groups at any of the time points Everolimus cost (Figure 4A). Furthermore, the glycogen concentration in the white gastrocnemius muscle tissue did not differ between the groups at the rest and immediately post-exercise time points; however, this variable was significantly higher in the SP group than in the CON group at the recovery period time point (1 h post-exercise; Figure 4B). In contrast, no

significant between-group differences were observed in the red gastrocnemius muscle tissue (Figure 4C). Figure 4 Changes in the glycogen levels during exercise and after 1 h of exercise. CON: distilled water LGK-974 with training, SP: silk peptide-treated with training. A, liver; B, white gastrocnemius muscle tissue; and C, red gastrocnemius muscle tissue at rest, after exercise, and recovery in the CON and SP groups. Values are presented as means ± standard deviations (n = 36). * vs. rest, P < 0.01; # vs. rest and after-exercise, P < 0.05; $ vs. recovery in CON, P < 0.001; ¶ vs.

after-exercise, P < 0.05. Discussion The present study demonstrated that a 2-week regimen of silk peptide (SP) treatment and endurance training could increase the max, whereas endurance training alone had no similar effect. Rebamipide A 2-week period of SP treatment also increased fat oxidation during the initial phase of exercise in exercised mice. In human studies, the max test during

graded treadmill exercise is the most commonly used endurance performance measurement [20, 21]. In the present study, max was not changed in the CON group after the 2-week training. Our previous study demonstrated that max was significantly increased by 4 week-training which the intensity was the same with the present study training protocol [16]. Thus, the duration (2 weeks) and/or intensity (75% of VO2 max) seem not to be enough to increase the endurance capacity in the present study. On the other hand, the max was significantly increased after a 2-week period of SP treatment when compared with the same metric before training. A previous study reported that a 30-day SP treatment regimen (800 mg/kg body weight daily) and swimming exercise training increased the maximum swimming time of mice by reducing exercise-induced tissue injuries and energy depletion [13]. In addition, a 44-day SP treatment regimen led to an increased maximum swimming time and decrease in the levels of muscle tissue damage markers such as creatine kinase, aspartate aminotransferase, and lactate dehydrogenase in a dose-dependent (50, 160, and 500 mg/kg) manner after forced swimming exercises [12]. Therefore, it seems that SP treatment can increase the exercise capacity regardless of the type of exercise.

e , misclassification does not depend on cohort), the study resul

e., misclassification does not depend on cohort), the study results for the measure of nonvertebral sites and for vertebral sites are likely more attenuated by misclassification than results at the hip. In conclusion, for this large

observational study of more than 200,000 bisphosphonate patients, the apparent differences in the baseline incidence of hip fractures among the alendronate, risedronate, and ibandronate cohorts likely reflect differences in the risk profile of patients prescribed each bisphosphonate. Statistical adjustments could not account for these differences and therefore the design of epidemiological studies should be SCH772984 mouse given careful consideration to account for these differences. Relative to the baseline fracture incidence, the longitudinal analyses indicated that alendronate and risedronate decreased nonvertebral and hip fractures over time, whereas ibandronate did not. All three bisphosphonates decreased vertebral fractures. The reductions Tyrosine Kinase Inhibitor Library cell assay observed in fracture incidence over time within each cohort suggest that the effectiveness

of each bisphosphonate in clinical practice has been consistent with their efficacies demonstrated in randomized controlled trials. Acknowledgement Funding by The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and sanofi-aventis). Conflicts of interest Dr. Abelson reports receiving consulting fees from sanofi-aventis, Procter & Gamble, Novartis; serving on speaker’s bureaus for Amgen, Procter & Gamble, Roche, Novartis, and sanofi-aventis. Dr. Gold reports receiving consulting or advisory committee fees from Amgen, Eli Lilly, GlaxoSmithKline, Merck, Procter & Gamble, Roche, sanofi-aventis; serving on

Glycogen branching enzyme speaker’s bureaus for Amgen, Eli Lilly, GlaxoSmithKline, Procter & Gamble, Roche, and sanofi-aventis. Dr. Thomas reports receiving consulting or advisory committee fees from Amgen, Daïchi-Sankyo, Ipsen, Lilly, MSD, Novartis, Procter & Gamble, Roche/GlaxoSmithKline, sanofi-aventis, and Servier; grant support from Lilly, MSD, Nicomed, Novartis, Procter & Gamble, sanofi-aventis, and Servier. Dr. Lange is an employee of Procter & Gamble. 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. Avorn J (2007) In defense of pharmacoepidemiology—embracing the yin and yang of drug research. N Engl J Med 357:2219–2221CrossRefPubMed 2. Perreault S, Dragomir A, Blais L et al (2008) Population-based study of the effectiveness of bone-specific drugs in reducing the risk of osteoporotic fracture. Pharmacoepidemiol Drug Saf 17:248–259CrossRefPubMed 3. Langsetmo LA, Morin S, Richards JB et al (2009) Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women. Osteoporos Int 20:283–290CrossRefPubMed 4.

Analysis of microarray images was carried out applying the ImaGen

Analysis of microarray images was carried out applying the ImaGene 6.0 software (BioDiscovery) as described previously [42]. Lowess normalization and significance test (fdr) were performed with the EMMA software [60]. M-values (log2 experiment/control ratio), P-values (t test) and A-values were also calculated with EMMA. The M-value represents the logarithmic ratio between both channels. The A-value represents the logarithm of the combined intensities of both channels. The microarray Caspase inhibitor results were verified for specific genes

by quantitative reverse transcription-PCR using a QuantiTect SYBR Green reverse transcription-PCR kit (QIAGEN, Hildesheim, Germany) according to the manufacturer’s instructions. Filtering find more and clustering analysis of the microarray data K-means

clustering analysis of the microarray time-course data was performed with the aid of the Genesis software [62]. After normalization, only genes with approximately threefold change in expression (M-value of ≥ 1.4 or ≤ -1.4) in at least one point of time in the wild type microarrays were considered for clustering analysis. Genes that did not present an evaluable expression value for at least 5 of the 6 points of time (missing values on the microarray flagged as empty spots) were not considered. K-means clustering was used for distributing differentially regulated genes into 6 groups, both with the wild type and with the rpoH1 mutant microarray data. Quantitative RT-PCR analyses Reverse transcription

was performed using Superscript II reverse transcriptase (Invitrogen) with random hexamers as primers. RNA samples were tested for two time points, 10 and 60 minutes after pH shock. Real-time PCRs were run on an Opticon system (BioRad) using the FastStart DNA MasterPLUS SYBRGreen I kit (Roche) according to the manufacturer’s instructions. The housekeeping gene rkpK was used as a reference for normalization. The sequences of the primers used are available at http://​www.​cebitec.​uni-bielefeld.​de/​groups/​brf/​software/​gendb_​info/​. Three independent cultures were analyzed, as GPX6 well as three technical replicates, for each time point. Microarray data accession numbers The entire set of microarray data has been deposited in the ArrayLims database [63]. Acknowledgements We thank Victoria Gödde, Manuela Meyer and Eva Schulte-Berndt for providing outstanding technical help. This work was supported by a scholarship from the NRW Graduate School in Bioinformatics and Genome Research, funded by the Ministry of Innovation, Science, Research and Technology of the state of North Rhine-Westphalia, Germany. Electronic supplementary material Additional file 1: Complementation of rpoH1 mutation.

Blunt JW, Copp BR, Hu W-P, Munro MHG, Northcote PT, Prinsep MR: M

Blunt JW, Copp BR, Hu W-P, Munro MHG, Northcote PT, Prinsep MR: Marine natural products. Nat Prod Rep 2008, 25:35–94.CrossRefPubMed 2. Tan LT: Bioactive natural products from marine cyanobacteria for drug discovery. Phytochem 2007, 68:954–979.CrossRef 3. Tidgewell K, Clark BR, Gerwick WH: The natural products chemistry of cyanobacteria. Comprehensive Natural Products Chemistry Pergamon DAPT in vitro Press, in press. 4. Chang Z, Flatt P, Gerwick WH, Nguyen V-A, Willis CL, Sherman DH: The barbamide biosynthetic gene cluster: A novel cyanobacterial system of mixed polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) origin involving an unusual trichloroleucyl

starter unit. Gene 2002, 296:235–247.CrossRefPubMed 5. Chang Z, Sitachitta N, Rossi JV, Roberts MA, Flatt PM, Jia J,

Sherman DH, Gerwick WH: Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula. J Nat Prod 2004, 67:1356–1367.CrossRefPubMed 6. Edwards DJ, Marquez BL, Nogle LM, McPhail K, Goeger DE, Roberts MA, Gerwick WH: Structure and biosynthesis of the jamaicamides, Protein Tyrosine Kinase inhibitor new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem Biol 2004, 11:817–833.CrossRefPubMed 7. Gu L, Geders TW, Wang B, Gerwick WH, Håkansson K, Smith JL, Sherman DH: GNAT-like strategy for polyketide chain initiation. Science 2007, 318:970–974.CrossRefPubMed 8. Cragg GM,

Newman DJ, Snader KM: Natural products in drug discovery and development: The United States National Cancer Institute Role. Phytochemicals in Human Health Protection, Nutrition, and Plant Defense (Edited by: Romeo JT). New York: Kluwer Academic/Plenum Publishers 1999, 1–29. 9. Suyama TL, Gerwick WH: Stereospecific total synthesis of somocystinamide A. Org Lett 2008, 10:4449–4452.CrossRefPubMed 10. Pfeifer BA, Wang CCC, Walsh CT, Khosla C: Biosynthesis of yersiniabactin, a complex polyketide-nonribosomal peptide, using Escherichia coli as a heterologous host. Appl Environ Microbiol 2003, 69:6698–6702.CrossRefPubMed 11. Schmidt EW, Nelson JT, Rasko DA, Sudek S, Eisen JA, Haygood MG, Ravel J: Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni , the cyanobacterial symbiont of Lissoclinum patella. Proc Natl Acad Sci enough USA 2005, 102:7315–7320.CrossRefPubMed 12. Watanabe K, Hotta K, Praseuth AP, Koketsu K, Migita A, Boddy CN, Wang CCC, Oguri H, Oikawa H: Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nat Chem Biol 2006, 2:423–428.CrossRefPubMed 13. Wilkinson B, Micklefield J: Mining and engineering natural-product biosynthetic pathways. Nat Chem Biol 2007, 3:379–386.CrossRefPubMed 14. Galm U, Shen B: Expression of biosynthetic gene clusters in heterologous hosts for natural product production and combinatorial biosynthesis. Exp Op Drug Discov 2006, 1:409–437.CrossRef 15.