In response to its toxicity, cells keep copper concentration under strict control allowing enough metal to be available for protein assembly but below Mdm2 antagonist damage induction threshold [4]. Current knowledge of copper homeostasis systems in bacteria has been elucidated from the study of gamma proteobacteria such as Salmonella OSI 906 enterica sv. Typhimurium [5], Shigella flexneri[6] and Escherichia coli[7]. In these organisms, the archetypical copper resistance response involves the coordinated function of four different systems: CopA/Cue, Cus, Pco and Cut, responsible for copper import, export or detoxification. A set

of copper-sensing transcriptional regulators (CueR, CusR, CusS, PcoR and PcoS) specifically modulate the expression of these genes [8]. For instance, in E. coli under aerobic conditions, CueR activates the expression of copA and cueO, encoding for a periplasmic multi-copper oxidase (MCO). CueR also induces expression of cueP, encoding for a periplasmic protein of unknown function putatively involved in copper-resistance in Salmonella[5]. While CopA pumps out Nirogacestat excess copper from the cytoplasm

to the periplasm, CueO oxidizes Cu(I) to Cu(II) in periplasm thereby reducing Cu(I) concentration [9, 10]. Under anaerobic conditions, CusR and CusS activate the transcription of the cusCBAF operon that encodes for a complex that pumps Cu(I) to the extracellular space [11]. This complex consists of the inner membrane pump CusA, the periplasmic protein CusB Etofibrate and the outer membrane protein CusC forming a channel through the periplasm. CusF has been proposed to feed the CusABC channel with copper from the periplasmic space [12]. PcoR and PcoS are transcriptional regulators for the copper-inducible expression of the pcoABCD operon [13]. pcoA encodes for a periplasmic MCO. There is no known

function for PcoB although it may function as an outer membrane protein. PcoC is a periplasmic copper carrier with two metal binding sites selective for Cu(I) or Cu(II) and has been suggested to interact with PcoD (an integral membrane protein) in copper translocation into the cytoplasm. pcoE apparently encodes for a cytoplasmic protein with a putative function as a copper scavenger. There is no information available regarding the regulation of the Cut system that involves at least six proteins: CutA, CutB, CutC, CutD, CutE, and CutF [14]. CutF and CutC have been described as involved in copper tolerance in E.coli. Since CutC is a cytoplasmic protein perhaps involved in intracellular trafficking of Cu(I), while CutF is an outer membrane protein [15], we only included CutF in our analysis Figure 1.

After 4 years of treatment, the supplemented group had a 60% lower risk of developing cancer than the placebo group [113]. However, a recent re-analysis has indicated that this inverse association between vitamin D levels and cancer incidence disappeared after adjustment for BMI and physical activity [9, 112]. In another randomised trial, the Women’s Health Initiative, no YH25448 chemical structure effect of calcium and 400 IU vitamin D/day was found on the incidence of colorectal TEW-7197 purchase or breast cancer, which were secondary outcomes [114]. However, the dose of

400 IU used in that trial may have been inadequate to raise 25(OH) vitamin D blood levels significantly, particularly after factoring in adherence levels. A recent review of randomised vitamin D supplementation trials with cancer incidence as a secondary endpoint concluded that the results were null [112]. Moreover, the recent large-scale “Cohort Consortium Vitamin D Pooling Project of Rarer Cancers” showed no evidence linking higher serum 25(OH) vitamin D levels to reduced risks of less common cancers, including endometrial, gastric, kidney, pancreatic and ovarian cancers [115]. In summary, the available evidence that vitamin D reduces cancer incidence is inconsistent and inconclusive. Randomised controlled trials assessing vitamin

D supplementation for cancer prevention are in progress. Their results are to be awaited before promoting vitamin D supplementation to reduce cancer risk. As a general conclusion, the importance of vitamin D for bone health and the prevention of osteomalacia and c-Met inhibitor osteoporosis are well recognized. More recently, vitamin D deficiency has been associated with other chronic conditions, including cardiovascular disease, autoimmune diseases and cancer. However, most evidence for the importance of vitamin D in these conditions

comes from laboratory studies and observational investigations. Suplatast tosilate Randomised controlled trials are needed to determine whether long-term supplementation with vitamin D has a favourable impact on the development or clinical course of non-skeletal diseases [116]. Bisphosphonates BPs are the mainstay in the treatment of osteoporosis and other metabolic bone diseases such as Paget’s disease, as well as in tumoural conditions such as multiple myeloma, bone metastases and cancer-induced hypercalcaemia. Their efficacy and safety have been thoroughly established on the basis of multiple large pivotal trials dealing with their main indications. Their daily use in clinical medicine since 1969 has confirmed the general conclusions of the trials. Their strong affinity for the skeleton partially explains their excellent safety profile for other systems of the body. Even at high pharmacologic doses, their bone affinity grossly precludes tissue uptake outside the skeleton.

(a) Sample A, (b) sample B, and (c) sample C. We also carried out XRD measurements for samples A and B, as shown in Figure 4a,b. Sample B exhibits no peaks because of the small Co particles and amorphous ZnO. Selleck Blasticidin S Broadened peaks of Co (002) and ZnO (002) appear in sample

A, although the Co content of sample A is lower than that of sample B according to the nominal structure of the films. This finding indicates that the distribution of Co particles is inhomogeneous in sample A. Figure 4c shows the variation of the deposition rate of ZnO film with sputtering pressure. The deposition rate decreases from 0.113 to 0.054 nm/s with an increase in sputtering Combretastatin A4 solubility dmso pressure from 0.4 to 0.8 Pa, which is attributed to the increase in collisions and the scattering of sputtered species under high processing pressure [18, 19]. In general, the surface of the ZnO film deposited at low pressure is very rough, and a ravine-like topography can form at the surface because of higher deposition rate [18, 20]. In our experiments, Co does not wet the surface of ZnO when Co deposits on the surface of ZnO. Co consequently may agglomerate into larger elongated particles in ravines because the surface energy of metallic Co (approximately 2.52 J/m2) is higher than that of ZnO (approximately 1.58 J/m2). For sample C, superparamagnetic Co particles with smaller size and larger distance

between Co particles may form because of the increase in ZnO content and higher sputtering pressure.

Figure 4 XRD patterns and variation of deposition rate with AZD1480 nmr sputtering pressure. XRD pattern of (a) sample A and (b) sample B. (c) Deposition rate of ZnO film. From the above discussions, it can be concluded that the films of samples B and C contain Co nanoparticles with different particle Immune system sizes dispersed in the ZnO matrix, and some interconnected Co particles may exist in sample A. The plane-view schematic illustrations of the three samples are shown in Figure 3. The structural, magnetic, and transport measurements strongly suggest that the MR effect in these granular films should be related to the size and spatial distribution of Co particles. In the metallic regime, the value of MR decreases with decreasing resistivity probably because of the increase in the number of interconnected Co particles. When the resistivity is less than 0.004 Ω · cm, the value of MR is almost zero. Most Co particles connect with one another and provide few opportunities for spin-polarized electron tunneling. The MR ratio is also reduced as the resistivity in the hopping regime increases, but it still remains greater than 3.7% even when resistivity reaches 3.8 Ω · cm and the volume fraction of Co calculated according to the nominal structure of Co (0.6)/ZnO (2.0) is less than 24%. This observation can be ascribed to the relatively long spin-coherence length in our material [21, 22].

This approach was largely successful in generating a coherent, integrated, holistic classification for the Hygrophoraceae that is based on nested Linnaean ranks and is phylogenetically supported. The family Hygrophoraceae is among the early diverging lineages of the Agaricales (Matheny et al. 2006; Binder et al. 2010), and it comprises a relatively click here large number of genera (26) with many

infrageneric taxa that have been proposed over the past two centuries. While the species appear to be primarily biotrophic, the genera vary in their morphology and ecology to the extent that there are few mycologists who have studied all of the genera in Hygrophoraceae. This challenge was addressed by using teams of experts to review different aspects and revise taxonomic groups, resulting in many coauthors (see attribution in Suppl. Table 3). Our sampling design of using two representatives per clade for the 4-gene backbone analysis see more was successful in providing strong backbone support throughout most of Hygrophoraceae. The Supermatrix analysis was useful for incorporating more species into the analyses though it sometimes showed lower bootstrap support for branches

and a few species and clades are oddly placed relative to other analyses despite our efforts to maintain a balanced data set. LSU and ITS analyses, alone and in combination, were especially helpful in resolving the composition Vasopressin Receptor of sections and subsections as more species are represented by sequences of one or both gene Erastin datasheet regions. Sampling short, overlapping segments of the family based on the branching orders in the backbone and Supermatrix analyses and using new alignments to limit data loss were part of that strategy. Incorporating a basal and distal member of each clade was informative and shows that most of the characters that are used to define groups do not correspond to the branching points

for the corresponding clades and are thus not synapomorphic (Table IV). The dearth of synapomorphic characters has been previously documented in the AFTOL publications on the Agaricales and Russulales (Matheny et al. 2006; Miller et al. 2006), so their absence in this study is not surprising. Some characters that are likely adaptive, such as hymenial proliferation of basidia in pachypodial structures and production of dimorphic basidiospores and basidia, appear in separate phylogenetic branches. Multiple independent origins were previously noted for other adaptive traits in the Basidiomycota, e.g.: fruit body morphology (Hibbett and Donoghue 2001; Hibbett and Binder 2002; Miller et al. 2006), ectomycorrhizal trophic habit (Bruns and Shefferson 2004), and brown rot of wood (Hibbett and Donoghue 2001).

J Am Chem Soc 2013, 135:2684–2693.CrossRef 15. Dressaire E, Bee R, Bell DC, Stone HA: Interfacial polygonal nanopatterning of stable microbubbles. Science 2008, 320:1198–1201.CrossRef 16. Zhang YX, Huang M, Hao XD, Dong M, Li XL, Huang JM: Suspended hybrid films assembled from thiol-capped gold nanoparticles. Nanoscale Res Lett 2012, 7:295–299.CrossRef 17. Wang YQ, Liang WS, Geng CY: Coalescence behavior of gold nanoparticles. Nanoscale

Res Lett 2009, 4:684.CrossRef 18. Biswas M, Dinda E, Rashid MH, Mandal TK: Correlation between catalytic activity and surface ligands of monolayer protected gold nanoparticles. J colloid interface sci 2012, 368:77–85.CrossRef 19. Wang Y, Zeiri O, Neyman A, Stellacci see more KU55933 research buy F, Weinstock IA: Nucleation and island growth of alkanethiolate ligand domains on gold nanoparticles.

ACS NANO 2012, 6:629–640.CrossRef 20. Tosoni S, Boese AD, Sauer J: Interaction between gold atoms and thio-aryl ligands on the Au(111) surface. J Phys Chem C 2011, 115:24871–24879.CrossRef 21. Zhang YX, Zeng HC: Template-free parallel one-dimensional assembly of gold nanoparticles. J Phys Chem B 2006, 110:16812–16815.CrossRef 22. Zhang YX, Zeng HC: Gold sponges prepared via hydrothermally activated self-assembly of Au nanoparticles. J Phys Chem C 2007, 111:6970–6975.CrossRef 23. Manea F, Bindoli C, Polizzi S, Lay L, Scrimin P: Expeditious synthesis of water-soluble, monolayer-protected gold nanoparticles of controlled size and monolayer composition. Langmuir 2008, 24:4120–4124.CrossRef 24. Li J, Zeng HC: Preparation of monodisperse Au/TiO 2 nanocatalysts via self-assembly. Chem Mater 2006, 18:4270–4277.CrossRef 25. Li J, Zeng HC: Nanoreactors – size tuning, functionalization, and reactivation of Au in TiO 2 nanoreactors. Angew Chem Int Ed 2005, 44:4342–4345.CrossRef Competing interests The selleckchem authors declare that they have no competing interests. Authors’ contributions ZYX synthesized the self-assembled samples and wrote the manuscript. HXD, Resminostat KM, and CRD characterized the self-assembled samples and coordinated

the experiments. All authors read and approved the final manuscript.”
“Background The synthesis of metal nanoparticles (gold, silver, palladium, copper) and their further incorporation into thin films is of great interest for applications in antibacterial coatings [1, 2], catalysis [3, 4], chemical sensors [5, 6], drug delivery [7, 8], electronics [9], photochemistry [10] or photonics [11, 12]. The wide variety of synthesis methodologies to obtain the metallic particles provide alternative ways to synthesize the nanoparticles controlling various parameters such as the shape, size, surface functionalization or interparticle distance which affect their final properties. A control of these parameters is a challenging goal, and a large number of reports have been published [13–20].

All 4 heat shock proteins (HtpG, DnaK, GroEL and PA4352) were elevated in AES-1R compared to both PAO1 and PA14. Five proteins involved in oxidative stress resistance (PA3529, AhpC, PA4880, PA2331 and KatA) were altered in AES-1R, Dactolisib in vivo with all except KatA present at increased abundance. Additional smaller functional clusters included the 3 enzymes of the arginine deiminase

pathway (ArcABC) and the ATP synthase alpha and beta subunits. We identified 2 proteins that were expressed from genes only encoded in the AES-1R genome (spots 26 and 43), and a further protein that was not contained within the PAO1 genome (spot 37). Previously hypothetical protein AES_7139 (spots 43 a-e; Figure 1) was the most abundant protein identified on the 2-DE gels of AES-1R and is present in multiple mass and pI variants. Variants exist at two masses, approximately 28 kDa and 16 kDa, with three pI variants at the higher mass (pI 5.2, 5.6, and

6.0), and two pI variants at the lower mass (pI 5.2 and 6.0). We subjected these spots to both MALDI-TOF MS peptide mass mapping and to LC-MS/MS for sequence characterization. We identified 9 peptide sequences that generated 90.8% sequence coverage for the Y27632 predicted AES-1R gene (Figure 2). All variants generated near identical MALDI-MS spectra, suggesting the unusual migratory pattern on 2-DE gels are due to folding artifacts or poorly reduced Ceramide glucosyltransferase disulfide bonds [31–33]. The AES_7139 translated gene sequence is predicted to encode a protein of 16.7 kDa and with a pI of 5.3, suggesting the higher mass variants may be homodimers or artifacts of the gel process. The sequence contains a single cysteine Bortezomib solubility dmso residue through which a disulfide could be formed, however under the reducing conditions used to conduct 2-DE, it is more likely that a gel artifact results in the spot pattern. One of the peptides sequenced by MS/MS displayed a non-tryptic N-terminus 8-GTYLFQYAQDKDYVLGVSDEQSGAK-32 (2782.4093

m/z) cleaved between Met-7 and Gly-8 that suggests either N-terminal processing, or that Met-7 is the true N-terminus. We subjected the AES_7139 protein sequence to BLAST search and showed that there is 100% amino acid sequence identity with a hypothetical protein (PA2G_05851) from P. aeruginosa PA2192 (Blastp score 311, query coverage 100%, e-value 2e-83), an isolate from a chronically infected CF patient in Boston. Other matches displayed similarity to ricin B-type lectins, suggesting the protein might be involved in carbohydrate binding. Importantly, however, no other P. aeruginosa genomes within the Swiss-Prot database contained AES_7139 homologs. Figure 2 Predicted protein sequence of a P. aeruginosa AES-1R hypothetical protein ((A); AES_7139; spot 43a-e) characterized by MALDI-MS and LC-MS/MS (B).

It is seen that the average absorption and scattering efficiencies of a nanoshell ensemble, excited at a fixed wavelength, are functions of the four parameters: Med[R], Med[H], σ R , and σ H . This poses the problem of finding, and studying the properties of, the optimal distribution parameters for which the nanoshell ensemble exhibits the maximum absorption or scattering efficiency. Results and discussions We focus on HGNs with gold permittivity described by the size-dependent model from Ref. [9], and begin by evaluating their average absorption and scattering efficiencies inside a tissue of refractive index n=1.55. Figures 1(a) and 1(b) show these efficiencies in the parametric space of Med[R] and Med[H] for

σ R =σ H =0.5 and excitation wavelength PF-01367338 cost λ=850 nm. Each dependency is seen to exhibit a distinct peak in the form of a flat plateau, which arise predominantly due to the resonant interaction of light with the localized symmetric plasmon modes of the HGNs [9]. The absorption peaks for Med[R]≈44 nm and Med[H]≈9 nm, while the scattering reaches its maximum for larger and much thicker nanoshells, with Med[R]≈54 nm and Med[H]≈26 nm. The broadness of the peaks and the associated high tolerance ARS-1620 of the nanoshell ensemble to the fabrication inaccuracies are the consequences of size distribution. Figure 1 Average

(a) absorption and (b) scattering efficiencies of an hollow-gold-nanoshell ensemble with lognormal distribution. The ensemble is excited by monochromatic light at λ=850 nm. Optimal distributions of core radius and shell thickness for maximum [(c) and (d)] absorption and [(e) and (f)] scattering efficiencies of the ensemble excited at λ=750, 850, and 950 nm. In all cases, n=1.55 and σ R =σ H =0.5. The effects of the excitation wavelength on the optimal distributions of the core radius and shell thickness are shown in Figures 1(c)– 1(f). Equal σ R and σ H (σ R =σ H =σ) correspond to the situation of similar (scalable) shapes of the two distributions. It is seen that the increase in the excitation wavelength shifts the optimal distribution f(r;μ R ,σ) towards larger radii for both absorption

[Figure PLEK2 1(c)] and scattering [Figure 1(e)]. This trend is opposite to the behavior of the optimal distributions f(h;μ H ,σ) in Figures 1(d) and 1(f), which shifts towards thinner shells with λ. Since the increase in Med[R] is larger than the reduction in Med[H], the optimal excitation of ensembles with larger HGNs require lower-frequency sources. The optimal Osimertinib geometric means of HGNs’ dimensions crucially depend on the shape of size distribution determined by the parameter σ. Figure 2 shows how the optimal distributions of R and H are transformed when σ is increased from 0.1 to 1. As expected, larger σ results in broader distributions that maximize the absorption and scattering efficiencies of the nanoshell ensemble. It also leads to the right skewness of the distributions, thus increasing the fabrication tolerance.

J Natl Cancer Inst 2005, 97:643–655.learn more PubMedCrossRef 25. Hirsch FR, Varella-Garcia M, Bunn PA Jr, Franklin WA, Dziadziuszko R, Thatcher N, Chang A, Parikh P, Pereira JR, Ciuleanu T, von Pawel J, Watkins C, Flannery A, Ellison G, Donald E, Knight L, this website Parums D, Botwood N, Holloway B: Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-smallcell lung cancer. J Clin Oncol 2006, 24:5034–5042.PubMedCrossRef

26. Italiano A, Vandenbos FB, Otto J, Mouroux J, Fontaine D, Marcy PY, Cardot N, Thyss A, Pedeutour F: Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 2006, 17:981–985.PubMedCrossRef 27. Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L, Sabatier L, Dartevelle LOXO-101 P, Taranchon E, Besse B, Validire P, Italiano A, Soria JC: Differential Expression of Biomarkers in Primary Non-small Cell Lung Cancer and Metastatic Sites. J Thorac Oncol 2009,

4:1212–1220.PubMedCrossRef 28. Badalian G, Barbai T, Rásó E, Derecskei K, Szendrôi M, Tímár J: Phenotype of Bone Metastases of Non-Small Cell Lung Cancer: Epidermal Growth Factor Receptor Expression and K-RAS Mutational Status. Pathol Oncol Res 2007, 13:99–104.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions CR and QH participated in the design

of the study, carried out the clinical and immunohistochemical data analysis; JM and LS interpreted the histological and immunohistochemical data; JL and CZ contribute with the clinical data; and QW conceived the study, interpreted the immunohistochemical data and wrote the manuscript. All authors read and approved the final manuscript.”
“Background The Tientsin Albino 2 (TA2) mouse is an inbred strain originating from the Kunming strain. It has a high incidence of spontaneous breast cancer without the need for external inducers or carcinogens. The morbidity in parous females is 84.1% within an average of 280 days after birthing a litter [1–3]. Until now, the mechanism of carcinogenesis has remained unclear. Gene expression arrays are commonly used in cancer research Adenosine triphosphate to identify differentially expressed candidate genes under two different conditions [4, 5]. The Affymetrix expression array is one of the most widely used commercially available oligonucleotide arrays and can determine the gene expression status of virtually the complete genome at the mRNA level. Genomic imprinting is an epigenetic process that marks the parental origin of a subset of genes, resulting in the silencing of specific alleles [6]. To date, more than 70 imprinted genes have been described in the mouse http://​www.​mgu.​har.​mrc.​ac.​uk/​imprinting/​imprinting.​html.

Extensive post-translational modifications are carried out during the biosynthesis of the active 34 amino acid peptide. Specifically, serine and

threonine residues in the pro-peptide region are enzymatically dehydrated to dehydroalanine and dehydrobutyrine (Dha and Dhb), respectively. Lanthionine (Lan) and β-methyllanthionine (MeLan) ring structures are CB-839 in vivo generated through the interaction of cysteine with Dha and Dhb, respectively [5–7] (Figure 1). The N-terminal domain, containing one Lan and two meLan rings (A, B, and C) is linked to the C-terminal intertwined rings (D and E) by a flexible hinge region. The antibacterial activity of nisin is exerted via a dual action through the activity of the different domains. The N-terminal domain binds to the pyrophosphate moiety of lipid II, inhibiting its transport to the developing cell wall AG-120 and therefore interfering with cell wall biosynthesis [8]. This binding also facilitates pore formation by the C-terminal domain within the cell membrane, resulting in the loss of solutes from the bacterial cell [9, 10]. Figure 1 The structure of nisin A showing the location of the N-terminal domain, containing one lanthionine and two

(β-methyl) lanthionine rings (A, B, and C) linked to the C-terminal intertwined rings (D and E) by a flexible hinge region. Post-translational modifications are highlighted as follows: dehydroalanine (Dha); dehydrobutyrine (Dhb); lanthionine (A-S-A) and (β-methyl) lanthionine (Abu-S-A). selleckchem Standard residues are represented in the single letter code. Arrow indicates location of the methionine to valine substitution

(M21V) in nisin V. As a result of their highly potent biological activities, selleck products lantibiotics have the potential to be employed as novel antimicrobials to combat medically significant bacteria and their multi-drug resistant forms [11–13]. Currently, a number of lantibiotics are under investigation for clinical use. NVB302, a semi-synthetic derivative of actagardine, is in stage I clinical trials with a view to treat infections caused by the hospital-acquired bacteria Clostridium difficile[14]. Similarly, microbisporicin (under the commercial name NAI-107), which targets several multi-drug resistant (MDR) bacteria, is in late pre-clinical trials [15]. In models of experimental infection involving mice and rats, the efficacy of microbisporicin in vivo was found to be comparable or superior to reference compounds (vancomycin and linezolid) in acute lethal infections induced with several MDR microbes, including methicillin resistant Staphylococcus aureus (MRSA), penicillin-intermediate Streptococcus pneumonia and vancomycin resistant enterococci (VRE) [16]. Another lantibiotic, mutacin 1140 (produced by Streptococcus mutans) is also undergoing pre-clinical trials [17].

Again, females show stronger intensity levels than

males, especially in the higher frequency regions S63845 datasheet (average response over all frequencies 8.0 vs. 5.6, F = 16.5, p < 0.001). When including only the large instrument categories (i.e. HS, LS, WW, BW) into the analysis, we found significant differences in DPOAE responses (F(3, 26) = 3.14, p < 0.01): High- and low-string players showed overall higher DPOAE responses than wood-wind and brass-wind players. No significant interactions were found with gender and instrument category (F = 1.2, p > 0.5). The DPOAE intensity levels also covariated with age, showing a decrease in intensity with increasing age (F = 4, p < 0.001). TEOAE and DPOAE responses significantly correlated at the same frequencies (1, 1.5, 2, 3, and 4 kHz): R 2 ranged from 0.27 to 0.45, p < 0.001. The individual relation Selleck AMN-107 between TEOAE and DPOAE responses and the pure-tone thresholds was weak. Some musicians showed (almost) normal pure-tone thresholds with surprisingly low OAE responses, while others showed poor pure tone thresholds, Emricasan in vivo but relatively high OAE responses.

Correlation coefficients between audiometric thresholds and TEOAE intensity levels at the same frequencies were significant, but low: R 2 = 0.17/0.19/0.22/0.23, p < 0.05) at 1, 2, 3, and 4 kHz, respectively. The correlation between the average TEOAE response and the average pure-tone threshold at 1, 2, 3, and 4 kHz was 0.29. Slightly higher correlations were found between the DPOAE-responses and the pure-tone thresholds: R 2 = 0.13/0.21/0.37/0.40 at 1, 2, 3, and 4 kHz, respectively and R 2 = 0.45 for the average pure-tone threshold

and average DPOAE response of 1, 2, 3, and 4 kHz. In addition to the individual data, we also investigated the OAE distributions in the audiogram categories defined above. The average TEOAE per audiogram FER category is shown in Fig. 5a, the average DPOAE in Fig. 5b. The figures illustrate that the musicians in the normal hearing category have the strongest overall TEOAE (mean = 8.04, SD = 4.6) and DPOAE (mean = 9.51, SD = 4.6) responses, while musicians in the rest category show the weakest TEOAE (mean = 3.32, SD = 5.7), and DPOAE (mean = 2.01, SD = 6.6) responses. Significant differences were also found between OAE of the normal hearing category and the other categories (i.e. N vs. NM, NP, SL, and FL, post-hoc Bonferroni, p < 0.05) Fig. 5 a Average TEOAE-intensity levels for musicians in each audiogram category b Average DPOAE-intensity levels for musicians in each audiogram category Discussion The first experimental question was whether musicians of symphony orchestras should be treated as a special group with regard to hearing, noise, and noise related hearing problems. A combination of factors puts the hearing of many professional musicians at risk: they are often subjected to intense sound levels for long periods of time, while studying, rehearsing, and performing music.