Ann Oncol 2001, 12:1127–1131 PubMedCrossRef 26 Srinivasan R, Gil

Ann Oncol 2001, 12:1127–1131.PubMedCrossRef 26. Srinivasan R, Gillett CE, Barnes DM, Gullick WJ: Nuclear expression of the c-erbB-4/HER-4 growth factor receptor

in invasive breast cancers. Cancer Res 2000, 60:1483–1487.PubMed 27. Haugen DR, Akslen LA, Varhaug JE, Lillehaug JR: Expression of c-erbB-3 and c-erbB-4 proteins in papillary thyroid carcinomas. Cancer Res 1996, 56:1184–1188.PubMed 28. Prickett TD, Agrawal NS, Wei X, Yates KE, Lin JC, Wunderlich JR, Cronin JC, Cruz P, Rosenberg SA, Samuels Y: Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet 2009, 41:1127–1132.PubMedCentralPubMedCrossRef 29. Kurppa K, Elenius K: Mutated ERBB4: a novel drug target in metastatic melanoma? Pigment Cell Melanoma Res 2009, 22:708–710.PubMedCrossRef selleckchem 30. Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS: Human embryonic stem cells express a unique set of microRNAs. Dev Biol 2004, 270:488–498.PubMedCrossRef 31. Selleckchem S3I-201 Bourguignon LY, Wong

G, Earle C, Chen L: Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression KPT-8602 leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem 2012, 287:32800–32824.PubMedCrossRef 32. Murray MJ, check Saini HK, van Dongen S, Palmer RD, Muralidhar B, Pett MR, Piipari M, Thornton CM, Nicholson JC, Enright AJ, Coleman N: The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression. Mol Cancer 2010, 9:290.PubMedCentralPubMedCrossRef 33. Wang L, Yao J, Shi X, Hu L, Li Z, Song T, Huang C: MicroRNA-302b suppresses cell proliferation by targeting EGFR in human hepatocellular carcinoma SMMC-7721 cells. BMC Cancer 2013, 13:448.PubMedCentralPubMedCrossRef 34. Fabbri M, Ivan M, Cimmino A, Negrini M, Calin GA: Regulatory mechanisms of microRNAs

involvement in cancer. Expert Opin Biol Ther 2007, 7:1009–1019.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions MZ, LZ and QY constructed the manuscript. MZ, LZ and QY were responsible for clinical data and evaluated clinical data; formed analysis of relation between clinical data and survival data. QY, SZ and WY carried out intro experiments. ZL, CH, QW, and JW reviewed the manuscript. All authors read and approval the final manuscript.”
“Background c-Jun NH2-terminal kinases (JNKs) are strongly activated by a variety of stressful cellular environments, such as chemotherapy and oxidative stress, and induce growth inhibition or cell death [1, 2].

One of these techniques is based on the sequencing of Variable Nu

One of these techniques is based on the sequencing of Variable Number Tandem Repeat (VNTR) loci, which detect polymorphisms in tandem repeats in a given genome and have been important to obtain informative MGCD0103 supplier markers [20, 21]. VNTRs were implemented P005091 more than a decade ago to characterize

highly monomorphic human and animal pathogens such as Mycobacterium tuberculosis [22, 23], Bacillus anthracis [24] and Staphylococcus aureus [25]. More recently, VNTRs have been implemented to analyze the population genetics and diversity of plant pathogens such as Xylella fastidiosa [26], Xanthomonas citri pv. citri [27], Ralstonia solanacearum [28], and the bacterial rice pathogen Xanthomonas oryzae pv. oryzicola [29]. VNTRs have allowed to uncover variability that was not detected using other

molecular markers [30, 31]. An additional advantage of VNTRs compared to other typing techniques is the reduction in costs, which is given by the following factors: first of all, a DNA extraction procedure is often not required because VNTRs can be easily amplified from bacterial colonies. Secondly, the amplification check details and detection does not require specialized equipment and reagents [21]. Finally, the reduction in the sequencing cost allows the analyses of a higher number of loci and samples, with at a reasonably low cost [17, 19]. All these advantages make VNTRs promising molecular markers to study populations of Xam when cost is a limiting factor and when the access to especialized laboratory equipment is restricted. The aim of this study was to evaluate the diversity of current Xam populations in the Eastern Plains of Colombia using two types of neutral molecular

markers. The Eastern Plains is the second most important region for cassava cultivation in Colombia. In contrast to the Caribbean cassava fields, Eastern Astemizole Plains fields are considerably small and their growers are not commercially allied for trading of their produce. In this study, we isolated strains from cassava fields located at the provinces of Meta and Casanare, located at the Eastern Plains of Colombia, from 2011 to 2012. The collected isolates were typed using both AFLPs and VNTRs markers. This study highlights the usefulness of VNTR markers for characterizing populations of Xam. This study provides an updated distribution of distinct populations of Xam in the Eastern Plains of Colombia. Methods Sampling and bacterial isolation Cassava crops in the Meta and Casanare provinces of Colombia were sampled from 2011 to 2012 (Figure  1). In Meta, local fields at La Libertad, Granada and Fuente de Oro were visited during 2011. In Casanare, fields near Orocué were sampled in 2012. Sampling was conducted in diagonal transects in three to four fields in each location. Leaves with characteristic CBB symptoms were collected for bacterial isolation.

‡‡ Good, better, bad and worse refer to the comparisons between t

‡‡ Good, better, bad and worse refer to the comparisons between treatments in terms of their clinical risks and benefits. ††† Good reference standards are independent of the test, and applied blindly or objectively to applied to all patients. Poor reference

standards are haphazardly applied, but still independent of the test. Use of a Blasticidin S supplier non-independent reference standard (where the ‘test’ is included in the ‘reference’, or where the ‘testing’ affects the ‘reference’) implies a level 4 study. †††† Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value treatments are as good and more expensive, or worse and

the equally or more expensive. ** Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects information and trawls the data (e.g. using a regression analysis) to find which factors are ‘significant’. *** By poor Epoxomicin concentration quality prognostic cohort study we mean one in which sampling was biased in favour of patients who already had the target outcome, or the measurement of outcomes was accomplished in <80% of study patients, or outcomes were determined in an unblinded, non-objective way, or there was no correction for confounding factors. **** Good follow-up in a differential diagnosis study is >80%,

with Alectinib solubility dmso adequate time for alternative diagnoses to emerge (for example 1-6 months acute, 1 – 5 years chronic) Table 3 Grading system for ranking recommendations in clinical guidelines Grade of recommendation   A Good evidence to support a recommendation for use B Moderate evidence to support a recommendation for use C Poor evidence to support a recommendation, or the effect may not exceed the adverse effects and/or inconvenience (toxicity, interaction between drugs and cost) D Moderate evidence to support a recommendation against use E Good evidence to support a recommendation against use Results – Definition, risk factors, natural history and diagnosis Patients with ASBO treated nonsurgically have shorter hospital stay, however they have an higher recurrence rate, shorter time to re-admission, although the risk of new surgically treated Pritelivir cost episodes of ASBO is the same.

Strain B represented the most common haplotype,

comprisin

Strain B represented the most common haplotype,

comprising 18 R. salmoninarum isolates from Atlantic salmon and rainbow trout farmed in Scotland and Norway over a period of more than 20 years. Strain B was one of five closely related strains (A, B, C, D, E) differing from each other at a single locus. Figure 1 Relationship among the observed haplotypes described in Table 2 . Group 1 includes haplotypes A to L and Group 2 includes haplotypes M to Q. Bootstrap values indicate the level of support for clusters if higher than 50%. Group 2 represents R. salmoninarum isolates obtained uniquely from Atlantic salmon originating from Scotland and Norway. These isolates differed from group 1 at loci BKD396 and BKD1935. A moderately supported cluster within group 2, comprising VE822 strains O-Q, represented isolates exclusively from wild Atlantic salmon, including the Dee disease isolates NCIMB 1114 and 1116 associated with first occurrence of BKD in Scotland. Similar clustering of R. salmoninarum isolates see more into two main groups was achieved using the eBURST algorithm based on either 16 or 6 polymorphic loci (Figure 2A,B). Using 16 polymorphic loci, a large radial cluster of 7 closely related haplotypes (A-G) was defined. Haplotype B was assigned as the most parsimonious “founder” of this group. Group 2 haplotypes

occurred as a single pair O/P find more representing the Dee disease isolates and three singletons (L,M,N). Using eBURST, a loss in resolving GPX6 power of the genotyping system was observed when the number of polymorphic loci included was reduced to 6 (Figure 2B). Figure 2 eBURST diagram of R. salmoninarum population derived from the allelic variation in (A) 16 polymorphic loci or (B) 6 polymorphic loci. The present VNTR

typing scheme was also applied to investigate whether Scottish R. salmoninarum isolates can be distinguished from isolates originating from Norway. Within group 1, some association with country of origin was observed for haplotypes A, C, and G, uniquely obtained from Scottish aquaculture, while haplotype E represented R. salmoninarum from Norway. On the contrary, the most common haplotype B contained isolates obtained from aquaculture establishments in both countries. Discussion The present study describes development and application of a VNTR typing system for R. salmoninarum, a bacterium affecting salmonid aquaculture worldwide and discusses the potential implications for disease management. In comparison to other genotyping methods used to study R. salmoninarum such as RAPD, tDNA-ILPs [20–23], multilocus VNTR typing offers a considerable improvement. Using a combination of sixteen VNTRs, 17 different haplotypes can be identified among 41 R. salmoninarum isolates. The discriminatory power of the present combined VNTR scheme was high, characterized by HGDI index of 0.81, indicating that two unrelated isolates will on 81% of occasions fall into different haplotypes.

e , supersaturation, for example, after rainfall) typically limit

e., supersaturation, for example, after rainfall) typically limits CO2 diffusion into the cells, also resulting in the inhibition of photosynthesis. The CO2-exchange mechanism in Apatococcus, and most probably also in alpine BSC algae, likely mirrors the adaptations of alpine BSC algae that exist in a terrestrial

environment. Ecophysiological studies of many plants indicate that photosynthesis and respiration exhibit different responses when dehydrated, and that photosynthesis is less tolerant than respiration to many environmental stresses. An explanation of the different susceptibility of the two physiological processes may be related to the structural properties of chloroplasts and mitochondria. While chloroplasts easily swell or shrink depending on intracellular water content, with consequences for the thylakoid fine structure, PDGFR inhibitor functionally this website the location of the photosynthetic electron transport chain affects the mitochondrial cristae ultrastructure less (Kirst 1990). Physiological constraints caused by dehydration in BSC green algae were mainly LY411575 investigated in relation to photosynthesis (see above), and hence far less is known about molecular and cell biological changes that accompany water loss. Structural

and ultrastructural features of alpine biological soil crust algae Limited data on the structure and ultrastructure of alpine BSC algae are available. This scarcity of information is most likely due to the limited availability of taxonomically characterized algae from these habitats (e.g., Tschaikner et al. 2007, 2008; Holzinger et al. 2011; Karsten and Holzinger 2012). Characterization of whole soil crusts has been attempted by scanning electron microscopy (e.g., Hoppert et al. 2004; Büdel 2005). Microscopic observation of desiccated cells has been recently achieved for K. crenulatum (Fig. 4b; Holzinger et al.

2011). Additionally, water loss has been generated by exposure to hyperosmotic solutions in Klebsormidium (Fig. 4c, d; Kaplan et al. 2012). Ultrastructural changes as a consequence of desiccation have been reported earlier in field-collected Klebsormidium Oxalosuccinic acid (Morison and Sheath 1985) and another crust-forming green alga, Zygogonium (Hoppert et al. 2004; Holzinger et al. 2010), as well as in alpine BSC algae and alpine algae from semi-terrestrial habitats (Holzinger et al. 2011; Karsten et al. 2010; Karsten and Holzinger 2012; Aigner et al. 2013; Kaplan et al. 2012, 2013). In these algae the basic organelles such as the nucleus, chloroplast and mitochondria remain intact upon desiccation, and the cytoplasm appears extremely condensed (Fig. 5a, b). Elementary differences were found in the cell walls of these genera. While in Klebsormidium the secondary walls remain flexible and have a good capacity to follow the shrinkage process (Holzinger et al. 2011; Karsten and Holzinger 2012), the cell walls of Zygogonium are thick and inflexible (Holzinger et al. 2010).

psychrophilum by qPCR Data seem thus to suggest a high prevalenc

psychrophilum by qPCR. Data seem thus to suggest a high prevalence of the pathogen in 2009, with a regression in 2010, but this is most likely a consequence of the different sampling strategies adopted in the two XAV-939 ic50 seasons. In 2009, in fact, we screened selleck screening library only fish farms in Ticino where outbreaks of F. psychrophilum occurred, whereas in 2010 all Swiss fish farms under investigation were screened independently of any outbreaks diagnosis. We also used only 15 ml water samples, whereas increasing the sample volume may also increase the probability to detect

F. psychrophilum in environmental water samples. In addition, this was only a preliminary study to test the technique and its limits in natural field conditions: the study was neither planned nor powered to allow drawing any conclusions or making any interpretations about the disease distribution. Unfortunately little is known about the pathogen in its environment and about its mode of transmission. We suggest that F. psychrophilum could be present and replicate in the tank (in both, fish and organic layer) and diffuse in the water [37], where favourable ecological conditions would allow colonization/infection of other fishes. F. psychrophilum detection by qPCR in the spleen Selleck LY2835219 of diseased and symptomless fishes suggests that the pathogen may have already been present in the spleen of

symptomless fish at densities below QL but above LOD. Marancik and Wiens [25] report similar results using their qPCR, which detected the presence of F. psychrophilum in few symptomless

carriers that had been infected with the pathogen. In contrast, no infection was recorded prior to sampling of healthy-looking fishes in our study. Thus, F. psychrophilum is apparently able to colonize and live asymptomatically in the spleen, where it is inactive until favorable environment conditions and a weakening of the fish immune system allow this opportunistic pathogen to multiply, spread in the fish and eventually in the whole fish population. During outbreaks, fish spleen harbored higher amounts of the pathogen, at concentrations markedly higher than the QL. Healthy, colonized fish may thus act C-X-C chemokine receptor type 7 (CXCR-7) as reservoirs for infection: in our opinion, this is a valid assumption, because another study has demonstrated the presence of this pathogen in eggs and ovarian fluids [38]. Further investigations, however, are needed to assess the mode of transmission and ecology of this species. qPCR detected and quantified F. psychrophilum in all 4 F. psychrophilum outbreaks investigated in this study; 13 of 15 qPCR values were higher than LOD, and in 8 cases higher than the QL. FISH could also detect all outbreaks, while culture methods could detect only 3 outbreaks and one was incorrectly recorded as negative. Changes in water temperature (e.g. a temperature variation of 4°C), oxygen availability in water, pH and conductibility could lead to a disease outbreak.

, Tokyo, Japan) and field-emission

scanning electron micr

, Tokyo, Japan) and field-emission

scanning electron microscope equipped with EDX analysis tool (FESEM; Hitachi S-7400, Hitachi Ltd., Chiyoda, Tokyo, Japan). Information about the phase and crystallinity was obtained by using Rigaku X-ray diffractometer (XRD, Rigaku Corporation, Tokyo, Japan) with Cu Kα (λ = 1.540 Å) radiation over Bragg angle ranging from 10° to 90°. Results and discussion The simplicity of the electrospinning process, the diversity www.selleckchem.com/products/Roscovitine.html of the electrospinnable materials, and the unique features of the obtained electrospun see more nanofibers provide especial interest for both of the technique and the resultant products. Various polymers have been successfully electrospun into ultrafine fibers in recent years mostly in solvent solution and some in melt form. Moreover, functional inorganic nanofibers can be produced by using sol–gel composed of metal(s) precursor(s) and proper polymer(s). In the field of metallic nanofibers, electrospinning process has a good contribution as it has been invoked to produce several pristine metallic nanofibers [18–21]. Beside the metal alkoxides, metal acetates have been widely utilized as metal precursors, as these promising salts have a good tendency for polycondensation to

form electrospinable sol-gels with the proper polymers [22]. The polycondensation reaction can be explained as follows [22]: where M is Ni. Accordingly, the prepared NiAc/PVP solution produced good morphology, AZD5582 smooth and beads-free electrospun

ADAMTS5 nanofibers, as shown in Figure 1A. Due to the polycondensation characteristic, the calcination of the prepared electrospun nanofibers did not affect the nanofibrous morphology as shown in Figure 1B. Figure 1C represents the SEM image for the synthesized NiO NPs. From Figures 1B and C, it can be concluded that the average diameters of the synthesized NFs and NPs are approximately 70 nm. Figure 1 SEM images of electrospun PVP/NiAc electrospun nanofibers (A), synthesized NiO nanofibers (B), and NPs (C). SEM images of the electrospun PVP/NiAc nanofiber mats (A) and after calcination at 700°C (B). SEM image of the synthesized NiO NPs (C). Scale bar = 200 nm. It was expected that the calcination of the prepared NiAc/PVA nanostructures in air will lead to eliminate the polymer and decompose the metallic precursor to the oxide form; this hypothesis was affirmed by using the XRD analysis. As shown in Figure 2, the XRD spectra of the synthesized NiO NPs and NFs are similar and match the standard spectra of NiO (JCPDS number 44–1159). From the obtained XRD spectra, the grain size could be estimated using Scherrer equation [23]. The determined sizes were 36 and 37 nm for the NPs and NFs, respectively. Figure 2 XRD analyses for the prepared NiO nanofibers and nanoparticles. Due to its surface oxidation properties, nickel reveals good performance as electrocatalyst. Many materials involving nickel as a component in their manufacture could be used as catalysts in fuel cells.

MFN1032 cells did not show this cell-associated hemolysis during

MFN1032 cells did not show this cell-associated hemolysis during the stationary growth phase. Previous studies have shown a negative effect of high

cell density, through a RpoS-mediated mechanisms [36] or by quorum-sensing [37], on TTSS gene expression in Pseudomonas aeruginosa. We found increased hemolytic activity in the MFN1032 gacA mutant (V1). This result suggests that the Gac two-component system is a negative regulator of cell-associated hemolytic activity. Studies on TTSS regulation in Pseudomonas aeruginosa have demonstrated that the GacA response regulator inhibits TTSS function and that, in a gacA mutant, the TTSS effector ExoS is hypersecreted [38]. Opposite, in Pseudomonas syringae, GacA is a positive regulator of the TTSS [39]. R406 cost The homology between MFN1032 genes and plant-associated TTSS genes is not in favour of a direct negative transcriptional regulation by the system Gac. To investigate the potential role of TTSS in this hemolytic process, we constructed a mutant with hrpU operon disruption, MFN1030, in which hemolytic activity was severely impaired. Hemolysis was restored in revertant MFN1031 cells, with hemolytic activity levels similar to wild type. Thus, cell-associated hemolytic activity

seems to require an intact hrpU operon. In contrast, hrpU operon disruption did not affect swimming motility, suggesting that hrpU operon is not involved in flagella biosynthesis. In MFN1030 the single homologue recombinaison Cyclooxygenase (COX) event with PME3087-hrcRST would result in, at least, a lack of HrcT protein. In Pseudomonas cichorri, an insertion of transposon in hrcT was described as sufficient to lost virulence on SCH727965 eggplant [40]. This large insertion in MFN1030 would have a polar effect on genes situated downstream this operon. In Pseudomonas fluorescens, hrcRST genes are highly conserved. Other genes of the hrpU operon, however, seem to vary considerably [22, 34]. PCR experiments based on SBW25 and KD sequences did not lead to an amplification

of any hrc genes located downstream or upstream hrcRST (data not shown). An experiment of chromosome walking should allow us to identify these genes. The hrcRST genes from Pseudomonas fluorescens MFN1032 show a high level of homology with hrcRST genes from Pseudomonas syringae, a plant pathogen. TTSS-dependent pore formation is due to the insertion of the translocation pores into host cell membranes. In Pseudomonas syringae, Hrpz psph forms pores in vitro and is exported by the TTSS. However, when introduced into learn more Yersinia enterocolitica cells, this protein is exported via the Yersinia SSTT but cannot replace YopB functions and do not cause RBC hemolysis [19]. HrpZ is unable to induce pore formation. Moreover, in the two strains of Pseudomonas fluorescens already described no hrpZ homologue was found. We tried to amplify this gene with primers design from hprZ from other pseudomonad, but without success.

First, ever since decolonisation, Asian governments have viewed t

First, ever since learn more decolonisation, Asian governments have viewed the click here customary laws of their populations with mixed feelings (Antons 2003). They symbolise a link to ancient traditions

and are important symbols for national identity, but they are also suspect because of their potential to harbour pre-modern, sectarian and even secessionist tendencies. The constitutional provisions quoted above clearly show that in most cases, the rules of customary law are subordinated and made subject to the overriding imperatives of national development policies (Antons 2009b, p. 50). Secondly, it has been pointed out that colonisation, state building and globalisation have affected customary “traditions” in many parts of the world to such an extent that they have to be rebuilt and become discursive weapons in negotiation processes rather than statements about the regularity of past practices (Chanock 2009; Zerner 1994). Chanock (2005) sees some prospects for combining what he calls “new custom” and contracts, but fears that radically divergent interests of resource users will make such compromises difficult. Traditional knowledge and access to biodiversity: The example of Indonesia Indonesia provides an example www.selleckchem.com/products/KU-55933.html of how many of these complex issues play out at the national level. The Indonesian government has recently been

involved in various disputes with Malaysia over cultural heritage and traditional cultural expressions in the form of songs,

see more handicrafts and dances (Antons 2009c; Gelling 2009). Traditional knowledge related to biodiversity, agriculture and traditional medicine has equally been the subject of cross-border disputes and “biopiracy” claims. Widely reported in the media (Antons and Antons-Sutanto 2009, pp. 382–383) were the patenting of Eurycoma longifolia, widely used in traditional medicine and known in Malaysia as Tongkat Ali and in Indonesia as Pasak Bumi (GRAIN and Kalpavriksh 2006); aborted attempts by a Japanese cosmetics manufacturer to patent compounds of traditional Indonesian medicinal plants (GRAIN 2008); the prosecution of a farmer from East Java under Law No. 12 of 1992 on Plant Cultivation Systems for selling non-certified seeds to neighbours (Jhamtani and Patria 2006); and longstanding claims about the patenting in the US of a traditional Indonesian formula for making a special type of soya bean cake (tempe) (Sardjono 2006, pp. 204–205). As in many other Asian developing countries, the role of the national government of Indonesia in the conservation and exploitation of natural resources remains strong. This strong position is enshrined in Article 33(3) of the Constitution, which provides that “the land, the waters and the natural resources within are controlled by the State and shall be used for the greatest possible welfare of the people.” It comes further to expression in two laws enacted by the Suharto government during the 1990s, Law No.

e wild type RN6390, RN6390sodA::tet, RN6390sodM::erm, RN6390sodM

e. wild type RN6390, RN6390sodA::tet, RN6390sodM::erm, RN6390sodM::erm sodA::tet), what is seen in Figure 1. Our results differ from the one presented by Hart [8], which may be attributed to the differences in types of oxidative stress generated as a result of photodynamic action versus methyl viologen-induced oxidative stress used by Hart group. Methyl viologen is believed to induce internal oxidative stress. Our previous results showed that PDI-induced oxidative stress is mainly external

[25]. In our previous work, when PpIX was washed away from the cell suspension before illumination, the photodynamic Ipatasertib effect was abolished. Thus we can speculate that oxidative stress selleck chemical associated toxicity is a result of cell wall and bacterial membrane damage, which eventually leads to loss of cell viability. We can hypothesize that in our experimental conditions we used a more complex oxidative stress generating system than that used by Hart or Foster group. It is known that during Necrostatin-1 in vivo photodynamic inactivation a number of reactive oxygen species are generated. This phenomenon is dependent on the type of photosensitizer used as well as medium conditions. For example, it was shown for fullerol c60, a recently studied photosensitizer, that depending on the medium used, either singlet oxygen alone or singlet oxygen together with superoxide

anion were produced in a phototoxic process [40]. Different species of ROS produced in various media may affect the phototoxic effect on the same strain. We can speculate that Thiamet G apart from singlet oxygen and superoxide anion, other ROS can be generated in PpIX-mediated photodynamic process, which can affect

either SodA or SodM regulatory pathways. The regulation of Sod activity in bacterial cells is very complex and yet not fully understood. Divalent metal ions, eg. Mn, Fe play a crucial role in these processes as enzyme or transcription factor regulator cofactors [16, 41, 42]. It is known that homeostasis of Mn and Fe are intertwined and most likely the manipulation of one of them greatly alters the uptake, storage and regulation of the other. It was shown that direct elemental superoxide scavenging by Mn occurs in S. aureus [12]. This effect was also clearly visible in our experimental data, where the survival rate of the double S. aureus sodAM mutant increased from 4.1 log10 units reduction in the Mn-depleted medium to 1.3 log10 units in the Mn-supplemented one (Figure 2) as a response to oxidative stress generating PDI. The comparison of the survival fraction of wild type RN6390 and sod mutants among each other as well as between conditions of Mn presence and absence in the medium explicitly indicates that Mn++ ions influence the efficacy of bacteria killing but based on our results this seems to be regardless of the Sod activity.