Standing out among the remaining genes are a number involved in the regulation of vacuolar pH, including 10 of 14 V-ATPase subunits and 2 membrane proteins required for V-ATPase assembly. This set of data strongly implicated vacuolar pH in the mechanism of action of dhMotC and led to the demonstration that dhMotC prevents vacuolar acidification. This effect is likely a consequence of inhibition of sphingosine/ceramide synthesis by dhMotC, since

sphingolipids containing long-chain fatty acids Selleckchem INCB018424 are known to be necessary for V-ATPase activity [44]. Chemical-genetic synthetic lethality also revealed a large number of genes involved in vacuolar assembly and intracellular transport. Further experiments showed that dhMotC indeed inhibits the delivery of internalized FM4-64 to the vacuole as well as fluid phase endocytosis. This effect is also likely a downstream consequence of inhibition of sphingolipid synthesis since sphingolipids are important for protein trafficking [45] and endocytosis is blocked upon interruption of de novo sphingolipid biosynthesis [46]. Defects

in vacuolar acidification and endocytosis caused by dhMotC occur in ρ 0 cells and are therefore independent of effects on mitochondria. Interestingly, motuporamines also inhibited lysosome acidification and intracellular trafficking after endocytosis in cancer cells, demonstrating the capaCity of this approach to predict targets in human cells. These results also provide insight into the mechanism by which dhMotC inhibits cancer cell LY2157299 nmr invasion. EGF signaling plays an important role in cell migration [47]. Stimulation of cultured cancer cells with EGF increases invasion and motility and modulates cell adhesion to extracellular matrix components in vitro [48] and in vivo [49]. Overexpression of EGFR causes why increased intravasation and lung metastasis from tumors implanted in the mammary fat pad, and cells

overexpressing EGFR are more motile in vivo than adjacent cells not overexpressing EGFR [50]. By interfering with vesicle-mediated trafficking of EGFR, motuporamines considerably reduce plasma membrane-associated EGFR, and consequently its ability to control cancer cell migration. In summary, this study demonstrates the value of using chemical genomics approaches in Saccharomyces cerevisiae to understand the mechanism of action of biologically active chemicals that may have human therapeutic value. However, reliance on a single genome-wide approach may often provide an incomplete picture of the mechanism of action of drugs. Different chemical genomics screens can provide complementary information and their combined use is probably necessary to provide a comprehensive understanding of the spectrum of different cellular effects a drug can have on cells. Methods Yeast strains, plasmids and growth conditions The haploid set of viable yeast deletion mutants (mat_alpha_041902) was purchased from Invitrogen.

Acknowledgments This work was supported in part by co-funding from the National Breast Cancer Foundation and Cancer Australia 543400 (K. Sherman), NIH grants R01 CA104979, R01 CA158019, RO1 HG01766, ACS TURSG 02-227, the Fox Chase Cancer Center Behavioral Raf inhibitor Research Core Facility P30 CA06927, Department of Defense grant DAMD 17-01-01-1-0238 (S. Miller), and the Komen Foundation grant POP00-000657 and “Women at Risk” (now) within New York-Presbyterian Hospital/Columbia University Medical Center (S. Sheinfeld Gorin). Conflict of interest Kerry Sherman, Suzanne Miller, Laura-Kate Shaw, Karen Cavanagh, and Sherri Sheinfeld Gorin declare that they have no conflict of interest. Compliance with ethical guidelines

This article does not contain

any studies with human or animal subjects performed by the any of the authors. This review paper complies with the current laws of Australia and the USA. References Armstrong K, Micco E, Carney A, Stopfer J, Putt M (2005) Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA 293(14):1729–1736. doi:10.​1001/​jama.​293.​14.​1729 Bouchard L, Blancquaert I, Eisinger F, Foulkes WD, Evans G, Sobol H, Julian-Reynier C (2004) Prevention and genetic testing for breast cancer: variations in medical decisions. Soc Sci Med 58(6):1085–1096PubMedCrossRef Selleckchem Fulvestrant Bowen D, Hickman KM, Powers D (1997) Importance of psychological variables in understanding risk perceptions and breast cancer screening of African American women. Womens Health 3(3–4):227–242PubMed Cancer Institute NSW (2013a) Information for people and families with a BRCA2 gene fault (mutation). Cancer Institute NSW. https://​www.​eviq.​org.​au/​Protocol/​tabid/​66/​categoryid/​441/​id/​765/​Information+for+​people+and+famil​ies+with+a+BRCA2​+gene+fault+%28mutation%29.​aspx. Accessed 20 Nov 2012 Cancer Institute NSW (2013b) Information for people and families with a faulty BRCA1 gene (mutation). Cancer Institute NSW. https://​www.​eviq.​org.​au/​Protocol/​tabid/​66/​categoryid/​441/​id/​764/​Information+for+​people+and+famil​ies+with+a+fault​y+BRCA1+gene+%28mutation%29.​aspx.

Accessed 2 Nov 2012 Charles S, Kessler L, Stopfer JE, Domchek S, Halbert CH (2006) Satisfaction Thymidylate synthase with genetic counseling for BRCA1 and BRCA2 mutations among African American women. Patient Educ Couns 63(1–2):196–204PubMedCrossRef Donovan KA, Tucker DC (2000) Knowledge about genetic risk for breast cancer and perceptions of genetic testing in a sociodemographically diverse sample. J Behav Med 23(1):15–36PubMedCrossRef Durfy SJ, Bowen DJ, McTiernan A, Sporleder J, Burke W (1999) Attitudes and interest in genetic testing for breast and ovarian cancer susceptibility in diverse groups of women in western Washington. Cancer Epidemiol Biomarkers Prev 8(4 Pt 2):369–375PubMed Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers.

These yeast species with enhanced biological control efficacy have emerged as a potential alternative to the this website conventional fungicide treatment. Considering the various importance and applications of the two species, there is a need for the development of accurate and reliable method to identify and distinctly discriminate the closely related species. Current methods of yeast identification, mostly in clinical practice, are mainly based on the conventional and rapidly evolving commercial phenotypic and biochemical methods. However, such methods are often unreliable for

accurate identification of closely related yeast species [13, 27]. According to recent studies, M. guilliermondii and M. caribbica are extremely difficult to differentiate by the phenotypic methods [28–31]. We also faced similar problem during differentiation of yeast isolates from soibum, an indigenous BIBW2992 manufacturer fermented bamboo shoot product of North East India (Additional file 1: Table S1). The widely used API 20 C AUX yeast identification system and sequencing of large subunit (LSU) rRNA gene D1/D2

domain failed to give proper species-level taxonomic assignment to these isolates (Additional file 1: Tables S2 and S3). Moreover, the phylogenetic tree reconstructed from the publicly available D1/D2 sequences of different strains of M. guilliermondii and M. caribbica failed to discriminate the two species (Additional file 2: Figure S1). Several attempts have been made using molecular approaches such as DNA base composition, electrophoretic karyotyping [6, 32], multi locus sequence typing (MLST) [3], multi Tenofovir ic50 locus enzyme electrophoresis (MLEE), randomly amplified polymorphic DNA (RAPD) [4], sequencing of internal transcribed spacer (ITS) [28, 30], intergenic spacer restriction fragment length polymorphism (IGS-RFLP) [29] and RFLP of housekeeping genes such as riboflavin synthetase gene RIBO[17] in order to resolve

the misidentification. Some recent studies have claimed that the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) is advantageous over previous approaches for reliable identification of clinically important NAC and non-Candida yeast species [28, 31, 33, 34]. Unfortunately, MALDI-TOF-MS requires reference spectra of accurately identified closely related strains otherwise the results may be erroneous. On the other hand, the sequence-based studies have considered the ITS1-5.8S-ITS2 region as universal DNA barcode for yeast identification [35] and the RFLP of ITS1-5.8S-ITS2 region has successfully separated the closely related species in the genera Candida and Pichia[36, 37]. Therefore, in this study, we targeted the ITS1-5.8S-ITS2 region to develop a simple RFLP method for accurate taxonomic assignment of M. guilliermondii and M. caribbica. With this background, the aim of the present study was (i) to perform in silico prediction of restriction enzymes to discriminate M.

e. rim, shave) mandibulectomy, which entails resecting

the cortical plate of bone adjacent to the tumour. Instead when there is evidence of bone invasion the standard procedure is represented by the segmental mandibulectomy. To date, three patterns of mandibular invasion, by squamous carcinoma has been distinguished: the most common is the erosive pattern, characterized by well-defined U-shaped excavation of the mandibular cortex with/without an involvement of the medullary bone, which radiologically appears as a well-defined Etoposide chemical structure radiolucent lesions without spicules bone; a second pattern is represented by the effects due to an infiltrative mass selleck chemical which radiologically

appears as an ill-defined and irregular lesion [13, 14]. Finally, another, more unusual pattern of the mandible’s invasion is characterized by neoplastic vascular embolization with cortical integrity [15]. Squamous cell carcinoma spreads along the surface mucosa and the submucosal soft tissue until it approaches ginigival where the tumour may come into contact with the mandible’s periosteoum. The dental sockets represent the mandible’s entry way in dentate patients; the tumour cells migrate into the occlusal surface of the alveolus in the edentulous patients and enter the mandible via dental pits [15–17]. Panoramic X-ray (OPG) [18], CT scans, MRI and CT-PET [19, 20] represent the imaging techniques for early assessment of the mandibular invasion. OPG efficacy in evidencing early mandibular invasion ranges between 60% and 64%, suffering from an Etomidate high rate of false negative results [18]. MDCT scans with Dentascan may offer an excellent technique for the evaluation of bone erosion

from squamous cell carcinoma with a sensitivity of 95% and specificity of 79%, as reported in a recent work [18]. On the other hand, MRI is generally considered superior to MDCT in the evaluation of the medullary bone space invasion. However, the diagnostic accuracy of MDCT and MRI in detecting mandibular invasion varies widely, depending on the researchers [5, 7, 21]. Our results showed higher sensitivity of MRI compared to MDCT although any statistically significant difference was reported probably because of our small study population. In accordance to us, Van den Brekel et al. [12] assessed mandible’s invasion on 29 patients and found that MRI compare to MDCT had the higher sensitivity (94%), but lower specificity (73%). A previous study on the evaluation of the tongue and floor-of-the-mouth tumours by Crecco et al. [6] reported an accuracy of MRI in the evaluation of the mandibular invasion of 93%, while recently, Bolzoni et al.

coli core enzyme saturated with E. chaffeensis recombinant σ70 subunit (Figure 7). Figure 6 Transcriptional analysis of recombinant E. chaffeensis -σ 70 using pRG198 transcriptional template. C, transcription products by E. coli core enzyme alone; σ70, transcription products by the recombinant E. chaffeensis σ70 protein; N, transcription products by purified E. chaffeensis RNAP; C + σ70, transcription products by by E. coli core enzyme saturated with recombinant

E. chaffeensis σ70; N + σ70, transcription products by native purified enzyme saturated with recombinant E. chaffeensis-σ70. Figure 7 Transcription of pRG198 with varying potassium acetate concentrations showing transcription by E. chaffeensis RNAP TSA HDAC research buy saturated with the recombinant σ 70 and ABT-263 clinical trial by E. coli core RNAP reconstituted with recombinant σ 70 . Modulation of E. chaffeensis RNAP activity by whole-cell protein We evaluated the effect of E. chaffeensis whole-cell protein lysate, prepared from the bacteria grown in macrophage cell line, on transcription of p28-Omp14 and p28-Omp19 constructs using the native purified enzyme. The resulting

transcripts were analyzed by two independent methods; densitometry of radiolabeled transcripts and the Taq-Man probe-based, real-time RT-PCR. These analyses showed enhanced transcriptional activity in the presence of 4 μg of E. chaffeensis whole-cell lysate. Densitometric analysis revealed a 1.8-fold increase in transcriptional signal for the p28-Omp14 promoter construct and a 2.1-fold increase for p28-Omp19 construct

(Table 2). Addition of the same amount of protein yielded a Phloretin similar fold increases when transcription was assessed with E. coli core enzyme saturated with E. chaffeensis recombinant σ70. No transcription occurred with the addition of whole-cell lysate alone in the absence of an enzyme, a potential source of E. chaffeensis RNAP. Similarly, the addition of boiled lysate did not cause any change in transcriptional signals. Quantitation by real-time RT-PCR for the calculation of fold increase in transcription in the presence of E. chaffeensis whole-cell protein lysate was carried out as described previously [30, 31]. Transcription of p28-Omp19 construct with purified E. chaffeensis RNAP, as quantified by real-time RT-PCR, showed a 2.24 fold enhancement in the presence of 4 μg of the protein lysate, whereas transcription of p28-Omp14 promoter construct resulted in a 1.81 fold-enhancement (Table 2), indicating a higher degree of agreement between the data generated by densitometric and real-time RT-PCR methods of quantitation (Table 2). Table 2 Effect of macrophage-culture grown E.

Authors’ contributions All named authors conceived the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved

the final manuscript.”
“Introduction Acute myeloid leukemia (AML), also known as acute nonlymphocytic leukemia (ANLL), is the most common acute leukemia mostly affecting adults, characterized by the rapid growth of abnormal white blood cells in the bone marrow and impaired production of normal blood cells. The mechanisms for AML genesis are still rarely understood. Evidence suggests that radiation, smoking, obesity and exposure to chemical carcinogens are considered as its possible risk factors [1]. Nevertheless, Pifithrin-�� AML only develops in

a small proportion of people exposed to these environmental and lifestyle risk factors, TSA HDAC indicating that the host genetic background might play a critical role in its genesis. Several genetic polymorphisms have been determined as possible risk factors for leukemia by meta-analyses. Variations of GSTM1, GSTT1, MTHFR C677T and XRCC1 Arg399Gln have been indicated to raise leukemia susceptibility [2–4]. Nevertheless, polymorphic MTR A2756G has been shown to decrease acute leukemia risk [5]. Therefore, different genetic polymorphisms might exert different effects on leukemia risk. Nevertheless, only a few gene polymorphisms associated with leukemia susceptibility have been identified to date. Recent evidence indicates that carcinogen-metabolizing genes might play critical roles in determining individual susceptibility to cancers [6]. Susceptibility to cancer is determined by the activation of enzymes involved in carcinogen activation or deactivation. Polymorphisms in these genes encoding the enzymes, possibly by altering their functions, might increase or decrease carcinogen activation/detoxification

and modulate DNA repair process. Cytochrome P450 (CYP) enzymes catalyze Phase I metabolism reaction. Cytochrome P450 1A1 (CYP1A1) is a member of the CYP family that participates in the metabolism of xenobiotics and endogenous compounds, particularly polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene in smoke [7]. A commonly studied single nucleotide polymorphism (SNP) in the CYP1A1 gene has been indicated to associate with cancer susceptibility. Akt inhibitor The SNP locates at nucleotide 3801 in the 3’ non-coding region containing a single T to C base substitution that results in a polymorphic restriction site for the MspI enzyme (MspI or CYP1A1*2A polymorphism, rs4646903). The MspI restriction site polymorphism results in three genotypes: a predominant homozygous m1 allele without the MspI site (type A, TT), the heterozygote (type B, TC) and a homozygous rare m2 allele with the MspI site (type C, CC) [8]. Published studies devoted to the relationship between CYP1A1 MspI polymorphism and AML risk have generated controversial results.

A possible selleck chemicals llc caveat of this supposition is that there was also a difference in achieved Hb levels between dialysis patients in Japan and those in the other DOPPS countries. However, the Japanese Society for Dialysis Therapy explained the difference between Japan and other

countries by timing of blood collection and patient position at blood collection. Blood sampling for studies of Hb levels is performed at the beginning of the week in Japan, whereas it is generally performed on the middle day of the week in the other countries [62]. This difference in sampling time could affect the rate of weight gain and plasma volume. In addition, the supine position at blood collection may further decrease the Hb values in Japan, whereas the majority of patients in the other countries undergo MHD in a sitting position on a chair-bed. Further investigation is needed to clarify the cause underlying the differences in ferritin and Hb levels between EPZ-6438 manufacturer dialysis patients in Japan and other countries. Conclusion It has long been recognized that the most

common cause of incomplete ESA response is limited iron availability, and that iron supplementation may improve the response to ESA. Increased blood loss is inherent to the condition of hemodialysis patients. Therefore, the use of IV iron is frequently indicated to maintain iron balance. However, there is no convincing evidence that IV iron supply improves patient survival although FID is a major cause of ESA hyporesponsiveness which itself is tightly associated with the poor outcomes of anemic patients with CKD. The discovery of hepcidin has considerably PD184352 (CI-1040) improved our understanding of the regulation of iron metabolism and related disorders. It has also profoundly changed our view of iron supplementation. When hepcidin concentrations are high, FPN is internalized, iron is trapped in macrophages, DMT1 is degraded, and iron absorption in the intestine is minimal.

Based on the close correlation between ferritin and hepcidin, iron administration should increase hepcidin levels, which in turn should not only reduce the release of iron and its transport from the RES (storage tissues) but also decrease iron absorption from the gut. These effects are consistent with findings in ACD patients as well as in those with FID. We suggest that physicians be cautious in prescribing IV iron in patients with FID, even if the immediate effect is an improvement in the anemia management of iron-replete MHD patients. No long-term safety data exist with respect to the effects of prolonged IV iron therapy on hard patient outcomes. Large randomized prospective cohort studies are needed to answer the question of whether a better MHD patient survival is achieved with less ESA and more IV iron or more ESA and less IV iron.

Figure 4 TNF-α augments endocytosis Cabozantinib order of P. gingivalis through PI3K pathways. A PI3K inhibitor suppressed TNF-a-augmented invasion of P. gingivalis in Ca9-22 cells. Ca9-22 cells were preincubated with wortmannin (Wort, 300 nM) at 37°C for 3 h and were then incubated with TNF-α. Viable P. gingivalis in the cells was determined as described in Methods. (Means ± standard deviations [SD] [n = 3]). ††, P < 0.01 versus control + TNF-α (−); **, P < 0.01 versus control + TNF-α (+). Figure 5 TNF-α augments invasion of P. gingivalis through NF-kB and MAPK pathways. (A) JNK and

p38 inhibitors blocked TNF-a-augmented invasion of P. gingivalis in Ca9-22 cells. Confluent Ca9-22 cells were preincubated with MAP kinase inhibitors (p38 inhibitor (SB203580, 5 μM), JNK inhibitor (SP600125, 1 μM ) and ERK inhibitor (PD98059, 5 μM)) at 37°C

for 1 h and were then incubated with TNF-α. Viable P. gingivalis in the cells was determined as described in Methods. (Means ± standard deviations [SD] [n = 3]). ††, P < 0.01 versus control + TNF-α MK-2206 price (−); **, P < 0.01 versus control + TNF-α (+). (B) NF-κB inhibitor suppressed TNF-α-augmented invasion of P. gingivalis in Ca9-22 cells. Ca9-22 cells were preincubated with an NF-κB inhibitor (PDTC, 5 μM) at 37°C for 1 h and were then incubated with TNF-α. Viable P. gingivalis in the cells was determined as described in Methods. (Means ± standard deviations [SD] [n = 3]). ††, P < 0.01 versus control + TNF-α (−); **, P < 0.01 versus control + TNF-α (+). ICAM-1 mediates invasion of P. gingivalis Expression of ICAM-1 is required for invasion of some bacteria in KB cells [36]. To determine whether ICAM-1 affects P. ginigvalis invasion into cells, we first examined co-localization of P. gingivalis with ICAM-1 in cells. Ca9-22 cells were incubated with P. gingivalis, and localization of ICAM-1 and P. ginigvalis in the cells was observed by a confocal laser scanning microscope. ICAM-1 strongly expressed around the cell surface was partially co-localized with P. gingivalis in

the cells (Figure 6A). We also examined the expression of ICAM-1 in TNF-α-treated Ca9-22 cells. Ca9-22 cells were treated with or without TNF-α for 3 h. The cells were lysed and expression ID-8 of ICAM-1 was analyzed by Western blotting. ICAM-1 was expressed in Ca9-22 cells without TNF-α stimulation (Figure 6B). However, TNF-α increased the expression of ICAM-1 in the cells. We next examined whether ICAM-1 is associated with invasion of P. gingivalis into the cells. Ca9-22 cells were treated with TNF-α for 3 h, incubated with an anti-ICAM-1 antibody or a control IgG antibody for an additional 2 h, and then incubated with P. gingivalis. Anti-ICAM-1 antibody suppressed invasion of P. gingivalis in the cells with or without TNF-α pretreatment (Figure 6C). In contrast, P. gingivalis invasion was not prevented by control IgG. These results suggest that ICAM-1 is partially associated with invasion of P. gingivalis into Ca9-22 cells.

Phys Rev B 2006, 73:045314.CrossRef 16. Galperin M, Ratner MA, Nitzan A: Raman scattering in current-carrying molecular junctions. J Chem Phys 2009, 130:144109.CrossRef 17. Persson BNJ, Baratoff A: Theory of photon emission in electron tunneling to metallic particles. Phys Rev Lett 1992, 68:3224.CrossRef 18. Tian G, Luo Y: Electroluminescence of molecules in a scanning tunneling microscope: role of tunneling electrons and surface plasmons. Phys

Rev B 2011, 84:205419.CrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions KM and MS conceived the idea, designed the study, analyzed the data, Atezolizumab and drafted the manuscript. HK supervised and gave suggestions on the study. All authors read and approved the final manuscript.”
“Background Transparent electronics is an advanced technology concerning the creation of invisible electronic devices. To realize transparent electronic and optoelectronic devices, transparent conducting oxides (TCOs) have been widely check details utilized [1–3]. Zinc oxide (ZnO) is an n-type semiconductor with a large binding energy of 60 meV and a wide bandgap of 3.3 eV. Doped ZnO thin films are promising alternatives to replace indium-tin oxide (ITO) thin films as TCOs due to the former’s stable electrical and optical properties. The low resistivity

of ZnO-based thin films arises from the presence of oxygen vacancies and zinc interstitials [4]. Aluminum (Al) [5], gallium (Ga) [6], and indium (In) [7, 8] have been widely studied as dopants to enhance the n-type conductivity of ZnO-based thin films. ZnO-based TCO materials have numerous potential applications in electronic and optoelectronic devices, such as solar cells [9], light-emitting diodes [10], blue laser diodes [11], and flat-panel displays [12]. Trivalent cation-doped ZnO thin films present good electrical conductivity and transparency over the visible spectrum. In the past, Chung et al.

investigated the properties of Ti-doped ZnO thin films with different TiO2 concentrations and reported that the lowest resistivity of TZO thin films was achieved when the Ti concentration was 1.34 mol% [13]. Lin et al. studied the effect of substrate temperature on the properties Buspirone HCl of TZO thin films by simultaneous radio frequency (RF) and DC magnetron sputtering [14]. Wang et al. examined the effects of substrate temperature and hydrogen plasma treatment on the characteristics of TZO thin films [15]. Nickel oxide (NiO) is a p-type semiconductor TCO material with a wide range of applications: it has been used in transparent conductive films [16] and electrochromic devices [17] and as a functional layer material in chemical sensors [18]. NiO has a wide bandgap of 3.6 to 4.0 eV at room temperature; hence, a NiO thin film is also transparent in the range of visible light [19].

In other words, if there is a single effector Nutlin-3a in vivo and there are no subpopulations with different sensitivities, the relative length of the two branches of the response only depends on dosage,

not on time, which impedes the progressive predominance of one branch over the other, as can be seen in the response to nisin (Figure 2). It is difficult to specify a priori the characteristics of an effector able to produce a hormetic response in a given organism. Thus, phenol was selected for comparison because three features suggest its adequacy for this purpose: 1) it can be considered a single effector, as the weakly acidic character of its hydroxylic hydrogen makes only a negligible proportion of the ionic form in the assay conditions; 2) it is a well known, vigorous and not very specific antiseptic; 3) phenols are obligatory steps in the biodegradation of the aromatic hydrocarbons, a process which is initiated in many organisms by an active enzyme induction with a detoxifying role. The response obtained with C. piscicola (Figure 5), a stable stimulatory branch at low doses that did not progress over time at the expense of the inhibitory branch, is solid MAPK inhibitor evidence in favour of a hormetic phenomenon. Conclusions The responses of L. mesenteroides to nisin and

C. piscicola to pediocin showed variation over time, which generated anomalous DR profiles far from the simple sigmoid model. Some of these profiles were of the biphasic type with two branches of opposite sign, a characteristic that is usually attributed to a hormetic phenomenon. Our results show, however, that the combination of the kinetic model of microbial growth and the probabilistic model of DR relationships can generate time series with very different profiles, including all the anomalies detected in practice. In a complementary way, the dynamic model developed satisfactorily fits the most remarkable trends of the experimental time

succession of responses, when we accept that the microbial populations assayed contain-or develop during the exposure time-subpopulations with different sensitivity Mannose-binding protein-associated serine protease to bacteriocins. Therefore, although the biphasic profiles can be derived from a genuinely hormetic response, they can also arise when two effectors act on a bimodal-sensitive population [14, 15], or, as in the cases studied here, when a single effector acts on a unimodal-sensitive population. Any of these suppositions can be accurately described by means of a subtractive degenerate model (see Appendix), but to distinguish among them requires identification of the underlying mechanism. Toxicodynamic evidence in favour of the hormetic hypothesis could be the stability in the time of the dose intervals which define the two branches of the curve, as in the response of C. piscicola to phenol.