2-mm pores) and washed with water and then acetone. The CNTs were then dispersed in 5 mL of N,N-dimethylformamide using an ultrasonic bath and precipitated again with acetone, filtered,

and washed with acetone. Finally, the CNTs were treated with diluted NaOH solution (30 min in the ultrasonic bath), filtered, washed with water followed by acetone, and dried. Figure 1 Functionalization of SWCNTs. Preparation of the modified electrode Firstly, a PB film was electropolymerized at the Pt electrode surface in an unstirred fresh 2 mM K3Fe(CN)6 + 2 mM FeCl3. 6H2O in 0.1 M KCl + 1 mM HCl aqueous solution by cyclic voltammetry in the potential range of −0.2 to 1.0 V at a scan rate of 0.1 V s−1. Different amounts of the functionalized nanotubes VE-822 purchase (usually 1 mg/mL)

were dispersed in bidistilled water by sonication for 1 h. The selected amount of GOx (1 mg/mL) was then added to the CNTs solution. Afterwards, pyrrole was added (at a concentration of 0.5 M) to the GOx and SWCNTs-PhSO3 − mixture, and the electropolymerization was performed at current densities of 0.1, 0.2, or 0.5 mA cm−2 for different times. The electropolymerization was carried out at pH 7.4. After the electropolymerization, the composite film (PPY/GOx/SWCNTs-PhSO3 −/PB) was subjected to overoxidation by cycling the potential from −0.2 to 1 V for 50 cycles at 0.1 V s−1 in a phosphate BMN 673 manufacturer buffer solution at pH 7.4. For comparison, PPY/GOx/SWCNTs-PhSO3 −, PPY/GOx/PB, and PPY/GOx films have been also obtained. Results and discussion PB-modified electrodes PAK5 have been synthesized by the simple and versatile electrochemical method proposed by Itaya et al. [10] based on the reduction of a ferric-ferricyanide solution as described in the ‘Methods’ section. The procedure can be adopted with different

electrode materials (platinum, gold, and glassy carbon), and a high stability of the layer deposited through successive cycling was demonstrated [10]. The typical cyclic selleck screening library voltammogram recorded during PB film electrosynthesis, as described in the Methods section, is shown in Figure 2. Two sets of peaks can be observed in cyclic voltammetry recordings for PB/Pt-modified electrodes synthesis which correspond to the reduction and oxidation of PB to Prussian white (E 1/2 = 0.2 V) and to Berlin green (E 1/2 = 0.9 V), respectively. Figure 2 Cyclic voltammograms of Prussian blue film electrosynthesis at Pt electrode. Then the pyrrole electropolymerization was carried out galvanostatically at PB/Pt electrode surface. The electropolymerization was performed in 0.1 M phosphate buffer solution at a pH of 7.4, above the isoelectric point of the glucose oxidase, in order to provide an overall negative charge so that the glucose oxidase can electrostatically attach to the PPY backbone. The overoxidation of enzyme-doped PPY electrodes leads to a loss of the PPY electroactivity and to an enhanced sensitivity and selectivity to glucose.

By considering the size of

savannah Africa from the lion’s perspective, we can assess how much of it remains in large, relatively intact areas, not yet heavily modified by human influence. Clearly, smaller areas will still support less complete sets of species. Our first objective of estimating this area is important for Screening Library three reasons. (a) We provide an assessment of an ecosystem rich in biodiversity—much as one might assess the current extent of tropical moist forests, for example. (b) Discussions of how much land is set aside for protection of specified ecosystems are particularly important as nations evaluate the 2010 targets under the Convention on Biological Diversity (Jenkins and Joppa 2009). As we define them, African savannahs extend beyond protected areas into areas with low human impact. The question is: how

much do savannahs extend beyond the borders of protected areas? The answer certainly includes areas with other land uses, including hunting zones that comprise a selleck chemicals significant share of the lion’s range in Africa. (c) Some protected areas may be too small or their managers unable to stem the threats to them to retain lions or other wide-ranging species (Henschel et al. 2010). At continental scales, whether protected areas actually protect biodiversity is generally assessed by measures such as the retention of forest cover (Joppa et al. 2008) or the management of anthropogenic fires (Adeney et al. 2009). Much of the savannah zone is a fire climax (Bond and van Wilgen 1996). However, such methods do not permit direct evaluations of the protected areas’ effectiveness in conserving biodiversity. For African savannahs, the presence of large mammals, such as lions, permits such direct assessments Adenosine in ways unavailable for

ecosystems with less conspicuous fauna sensitive to human impacts. Our second objective of compiling estimates of all free-ranging lion populations throughout Africa builds from three previous continent-wide population assessments: Chardonnet (2002), Bauer and Van Der Merwe (2004), and the WCS and IUCN-organised range-wide priority setting exercises held in 2005 and 2006 (IUCN 2006a, b). Those reports rightly generated considerable efforts to improve population estimates across Africa. However, a recent meeting of the African Lion Working Group in Etosha, Namibia, suggested that these regional lion conservation strategies had a poor follow-up and needed an urgent update (see Final Communiqué from the 2nd African Lion Working Group meeting http://​www.​largecarnivoresa​frica.​com/​wp-content/​uploads/​ALWG-Etosha-public-statement.​pdf). This need is particularly acute: there is evidence of rapidly declining populations of many large mammals in West and Epigenetics Compound Library Central Africa and in East Africa (Craigie et al. 2010; Henschel et al. 2010), as well as some parts of Southern Africa.

) brood galleries using a regression model. J Appl Entomol 133:402–409CrossRef Podlaski R, Borkowski A (2009b)

Estimating stem infestation density of Pityokteines curvidens (Germ.) on windfalls: a statistical approach. J Pest Sci 82:357–365CrossRef Ripley BD (1981) Spatial statistics. Wiley, New YorkCrossRef Schelhaas MJ, Nabuurs GJ, Schuck A (2003) Natural disturbances in the European forests in the 19th and 20th centuries. Glob Change Biol 9:1620–1633CrossRef Schröter H (1999) Ausbreitung des Borkenkäferbefalls in Bannwäldern Baden-Württembergs. In: Wulf A, Berendes KH (eds) Forstschutzprobleme in Nationalparken und Naturschutzgebieten. Biol Bundesanst Land-Forstw, Mitt 362, Berlin, pp 63–79 Seidl R, Rammer W, Jäger D, Lexer MJ (2008) Impact of bark beetle disturbance (Ips typographus) on timber production and carbon learn more APO866 manufacturer sequestration in different management strategies under climate change. For Ecol Manag 256:209–220CrossRef Seidl R, Schelhaas MJ, Lindner M, Lexer MJ (2009) Modelling bark beetle disturbances in a large scale forest scenario model to assess climate change impacts and evaluate adaptive management strategies. Reg Environ Change 9:101–119CrossRef Simberloff D (1998) Flagships, umbrellas, and keystones: is single species management

passé in the landscape era? Biol Conserv 83:247–257CrossRef StatSoft (2004) Statistica, version 6.1. StatSoft, Inc., Tulsa Sun X, Yang Q, Sweeney JD, Gao C (2006) A review: chemical ecology of Ips typographus (Coleoptera,

Scolytidae). J For Res 17:65–70CrossRef Thompson SK (2002) Sampling. Wiley, Selleck Regorafenib New York Wermelinger B (2004) Ecology and management of the spruce bark beetle Ips typographus—a review of recent research. For Ecol Manag 202:67–82CrossRef Wermelinger B, Duelli P, Obrist MK (2002) Dynamics of saproxylic beetles (Coleoptera) in PRIMA-1MET windthrow areas in alpine spruce forests. For Snow Lansc Res 77:133–148 Wichmann L, Ravn HP (2001) The spread of Ips typographus (L.) (Coleoptera, Scolytidae) attacks following heavy windthrow in Denmark, analysed using GIS. For Ecol Manag 148:31–39CrossRef Wolfram S (2003) The mathematica book. Wolfram Media/Cambridge University Press, Cambridge Yamaoka Y, Wingfield MJ, Takahashi I, Solheim H (1997) Ophiostomatoid fungi associated with the spruce bark beetle Ips typographus f. aponicus in Japan. Mycol Res 101:1215–1227CrossRef”
“Introduction Effective conservation requires the separation of biodiversity from the factors threatening it (Hayward 2009a). Achieving this has resulted in well known conservation successes, including the Californian condor Gymnogyps californianus, which has increased from 6 to 130 wild individuals following the cessation of persecution, a reduction in lead poisoning and captive breeding (BirdLife International 2009).

In addition to the photographs shown in this News Report for the 2011 conference, the

readers will find other photographs, especially of the selleck chemical soccer game at: http://​sergei.​physics.​purdue.​edu:​7925/​Gordon and of others at http://​www.​life.​illinois.​edu/​govindjee/​g/​Photo/​Gordon2011.​html. To name just one example of the many exciting scientific presentations, we mention the 1.9 Å atomic level structure of Photosystem II, particularly of the Mn4CaO5 (H2O)4 LCZ696 complex (Umena et al. (2011) Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å. Nature 473: 55–60). The plenary lecture by Jian-Ren Shen (Okayama University, Japan, Fig. 3) was followed by a presentation by Johannes Messinger (Umeå University, Sweden, Fig. 3). These talks resulted in a highly thought-provoking and exciting informal discussion on Photosystem II, particularly of the mechanism of oxygen evolution (some of the key players are pictured in Fig. 3). Fig. 3 Photosystem Aurora Kinase inhibitor II researchers engaged in thought-provoking discussions at the Gordon Research Conference on Photosynthesis. Top row (left to right) Jian-Ren Shen (Japan), William (Bill) Rutherford (UK), Ron Pace (Australia).

Bottom row (left) Gennady Ananyev, Charles (Chuck) Dismukes (his picture is included although he was physically not there, but he was there in spirit, and through three of his students, who attended the conference, not shown) and Nikolai Lebedev (all of them from USA); (middle) Johannes Messinger (Sweden); (right, top) Junko Yano (USA); (right, bottom) Robert (Rob) Burnap (USA) Another highlight of the 2011 Gordon Research Conference on Photosynthesis was the session on biofuels,

which was led by Alison Smith (University of Cambridge, Fig. 4). Through presentations by Nanette Boyle (University of California, Los Angeles), Willem (Wim) Vermaas (Arizona State University, Fig. 4), Anastasios (Tasso) Melis (University of California, Berkeley, Fig. 4), and Ursula Goodenough (Washington University, Fig. 4), multiple approaches for utilizing energy from photosynthesis for our own energy needs were discussed. This section was followed by an exciting and inspiring Dynein lecture by Donald (Don) R. Ort (USDA Agriculture Research Station, Urbana, IL) on “Photosynthetic efficiency: limits and opportunities.” We refer interested readers to a recent highly relevant review coauthored by many of the conference’s attendees (Blankenship et al. (2011) Comparing photosynthetic and photovoltaic efficiencies and recognizing the potential for improvement. Science 332:805–809). Fig. 4 The growing field of biofuels was well represented at the 2011 Gordon Research Conference on Photosynthesis. Clockwise from top left Sabeeha Merchant (USA), Alison Smith (UK) & Ursula Goodenough (USA), Anastasios (Tasso) Melis (USA), Willem (Wim) Vermaas (USA), and Robert (Bob) Blankenship (USA) No Gordon Research Conference on Photosynthesis would be complete without the annual soccer match.

This variation ranged from 10 to 24 sequence types at a gene, including null alleles, indicating rather high variation among L. johnsonii strains. Phylogenetic analyses The variation data at SSR loci and conserved hypothetical genes were used in two separate analyses to infer

the genetic relationships Tideglusib among L. johnsonii isolates. SSR analysis: The phylogenetic analysis divided the 47 L. johnsonii isolates into 29 different SSR types, revealing high discrimination. The resulting dendrogram presented three main clusters (Figure 2A), one composed of chicken and turkey isolates, the second of human isolates and the third of identical mouse isolates together with strains isolated from the caracal feces and the owl pellet (LJ_184, LJ_188, LJ_16 and LJ_252). Note that the owl pellet isolates might be related to the mouse isolates, as it might have originated from the owl’s prey (a mouse), rather than from the owl’s upper GIT. The isolates from other diverse BTK inhibitor libraries origins were MAPK inhibitor spread out along the dendrogram. Among them, isolates from Psammomys (LJ_9-7) and silkworm (LJ_4-4), two unrelated host species, are undistinguished according to the typing results. This might be due to their common isolation location, thus additional sampling should clarify the phylogeny clustering of L. johnsonii isolates from these two host species. The genetic distances within strains from each of the three groups were significantly low (average

genetic distance of 0.25 ± 0.11, 0.27 ± 0.25 and 0.11 ± 0.12 for chicken, human and mouse clusters, respectively) compared to the high genetic distances observed between isolates from the tested group and the remaining isolates (average genetic distance of 0.65 ± 0.18, 0.87 ± 0.10 and 0.64 ± 0.12 for chicken, human and mouse clusters, respectively). Figure 2 Genetic relationships among  L. johnsonii  isolates. Dendograms are based on variation data of: (A) 47

isolates at 11 SSR loci based on 57 polymorphic points (11 loci times the number of alleles in each locus); (B) sequence of 46 isolates at three conserved hypothetical genes. Both dendrograms were constructed by UPGMA cluster analysis. Samples from: chickens – ▲, turkeys – △, humans – • and mice – ▽ are indicated. All the isolation sources of the tested L. johnsonii strains are indicated Cediranib (AZD2171) at Table 1. MLST analysis: phylogenetic analysis of the sequences at the three conserved hypothetical genes separated the 46 typable L. johnsonii isolates into 28 sequence types (Figure 2B). Three clear clusters were obtained, paralleling the SSR analysis, with the exception of strain NCC 1741. In general, the two genetic analyses similarly separated L. johnsonii isolates into three groups (Figure 2A, 2B). The clusters included strains with a common isolation host: various lines of chicken and turkey, humans, and laboratory mouse lines, while the isolates originating from other diverse sources were dispersed along the dendrograms.

The study also indicated that several factors contributed to sexual function problems. Those who received aromatase inhibitors were more likely to experience more sexual function problems compared to those who received tamoxifien but in both group body image GSK1838705A research buy was the most

contributing factor to sexual dysfunction [3]. These findings suggest that the impact of breast cancer on sexuality is much more complex than women simply losing their breasts or receiving different treatment modalities. Studies have shown that disrupted sexual functioning or unsatisfactory sexual life was related to poorer quality of life at younger age, treatment with chemotherapy, total mastectomy, emotional distress consequent on an unsatisfactory sexual life, and difficulties with partners because of sexual relationships [4–8]. This latter factor was further examined and recently a French study found that ‘no sexual activity’ or ‘sexual dissatisfaction’ among breast cancer patients were associated with the feeling of emotional

separation in the couple or of partner’s fear of sexual intercourse [9]. Emilee et al. [10] in a review of sexuality after breast cancer highlighted the issue of ‘women’s intrapsychic’ experience of changes to sexuality. They argued this experience includes a fear of loss of fertility, negative body image, feelings of

sexual unattractiveness, loss of femininity, depression and anxiety, as well as alterations to a sense of sexual MI-503 molecular weight self. Then they concluded that sexuality in the context of breast cancer could not be conceptualized the physical body separately from women’s intrapsychic experience. With any interpretations sexual functioning seems important area that needs more attention, especially for younger breast cancer survivors. It is argued G protein-coupled receptor kinase that younger survivors may need interventions that specifically target their needs related to menopausal symptoms and problems with relationships, sexual functioning and body image [11]. There is evidence that the quality of sexual life in breast cancer survivors could be improved with the sexual life reframing program focusing on the physical, psychological, and relational aspects of sexual health elements at couples rather than survivors only and if delivered earlier and for a longer period [12]. No study so far has reported on prevalence of sexual function among Iranian breast cancer patients. Breast cancer patients in Iran are usually younger that their western counterparts [13] and thus might report different experiences. In addition women in Islamic countries such as Iran usually have some reservations in talking about and reporting sexual problems or seeking processional help [14].

PubMedCrossRef 11. Slater H, Alvarez-Morales A, Barber CE, Daniels MJ, Dow JM: A two-component system involving an HD-GYP domain protein links cell-cell signaling to pathogenicity gene expression in Xanthomonas campestris . Mol Microbiol 2000, 38:986–1003.PubMedCrossRef 12. Ryan RP, Fouhy Y, Lucey JF, Crossman LC, Spiro S, He YW, Zhang LH, Heeb S, Cámara M, Williams P, Dow JM: Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. Proc Natl Acad Sci USA 2006, 103:6712–6717.PubMedCrossRef 13. Tao F, He YW, Wu DH, Swarup S, Zhang LH: The cyclic nucleotide monophosphate

domain AZD1390 order of Xanthomonas campestris global regulator Clp defines a new class of cyclic di-GMP effectors. J Bacteriol 2010,192(4):1020–1029.PubMedCrossRef 14. He YW, Ng AY, Xu M, Lin K, Wang LH, Dong YH, Zhang LH: Xanthomonas campestris cell-cell communication involves a putative nucleotide receptor protein Clp and a hierarchical signalling network. Mol Microbiol 2007, 64:281–292.PubMedCrossRef Cilengitide molecular weight 15. Chatterjee S, Sonti

RV: rpfF mutants of Xanthomonas oryzae pv. oryzae are deficient for virulence and growth under low iron conditions. Mol Plant-Microbe Interact 2002, 15:463–471.PubMedCrossRef 16. Chatterjee S, Wistrom C, Lindow SE: A cell-cell signaling sensor is required for virulence and insect transmission of Xylella fastidiosa . Proc Natl Acad Sci USA 2008, 105:2670–2675.PubMedCrossRef 17. Huang TP, Wong AC: A cAMP receptor protein regulated cell-cell communication system mediates expression of a FecA homologue in Stenotrophomonas maltophilia . Appl Environ Microbiol 2007, 73:5034–5040.PubMedCrossRef 18. Shen Y, Ronald P: Molecular determinants of disease and resistance in interactions of Xanthomonas oryzae pv. oryzae and rice. Microbes Infect 2002,4(13):1361–1367.PubMedCrossRef 19. Ray SK, Rajeshwari R, Sonti RV: Mutants of Xanthomonas oryzae pv. oryzae deficient in general secretory pathway are virulence deficient and unable to secrete xylanase. Mol Plant-Microbe Interact 2000, 13:394–401.PubMedCrossRef 20. Köplin R, Arnold W, Hötte B, Simon R, Wang G, Pühler A: Genetics

of xanthan production in Xanthomonas campestris: the xanA and xanB gene are involved in UDP-glucose and GDP-mannose Dapagliflozin biosynthesis. J Bacteriol 1992, 174:191–199.PubMed 21. Hu J, Qian W, He C: The Xanthomonas oryzae pv. oryzae eglXoB endoglucanase gene is required for virulence to rice. FEMS Microbiol Lett 2007, 269:273–279.PubMedCrossRef 22. Rajeshwari R, Jha G, Sonti RV: Role of an in planta expressed xylanase of Xanthomonas oryzae pv. oryzae in promoting virulence on rice. Mol Plant-Microbe Interact 2005, 18:830–837.PubMedCrossRef 23. Jha G, Rajeshwari R, Sonti RV: Functional interplay between two Xanthomonas oryzae pv. oryzae secretion systems in modulating virulence on rice. Mol Plant-Microbe Interact 2007, 20:31–40.PubMedCrossRef 24.

9)], the SabR-His6 proteins were specifically eluted from the resin with 4 ml elution buffer [20 mM Tris base, 500 mM NaCl, 250 mM imidazole, 5 % glycerol (pH 7.9)] and concentrated to about 20 μg μl-1 by ultrafiltration (Millipore membrane, 3 kDa cut-off size) according to the protocol provided by the manufacturer. Protein purity was determined

by Coomassie brilliant blue staining after SDS-PAGE on a 12 % polyacrylamide gel. The purified protein was stored in 5 % glycerol at -70°C. Electrophoretic mobility-shift assays (EMSAs) The EMSAs were performed as described previously [37]. The primers were labeled with T4 DNA polynucleotide kinase and the DNA fragments used for [γ-32P]-labeled probes were amplified by PCR, and then purified by using

PCR purification kit (Qiagen). For EMSAs with SabR-His6, the sanG probes were generated by PCR using primers EG0-F, EG1-F, EG2-F, EG3-F and EG0-R, EG1-R, SCH772984 concentration EG2-R, EG3-R, which were uniquely labeled at its 5′ end with [γ-32P]-ATP using T4 polynucleotide kinase respectively. The sabR, sanF and sanNO probes were generated by PCR using unlabeled primers ER-F, EF-F, ENO-F and the radiolabeled ABT-263 in vitro primers ER-R, EF-R and ENO-R, respectively. During the EMSA, the [γ-32P]-labeled DNA probe (1000 cpm) was incubated individually with varying quantities of SabR-His6 at 25°C for 25 min in a buffer containing 1 μg of poly-(dI-dC) (Sigma), 20 mM Tris-base (pH 7.5), 1 mM DTT, 10 mM MgCl2, Dimethyl sulfoxide 0.5 μg calf BSA μl-1 and 5 % glycerol in a total volume of 20 μl. After incubation, protein-DNA complex and free DNA were separated by electrophoresis on non-denaturing 4.5 % polyacrylamide gels with a running buffer containing 45 mM Tris-HCl (pH 8.0), 45 mM boric acid and 1 mM EDTA at 10 V cm-1 and 4°C. Gels were dried and exposed to Biomax radiographic film (Kodak). As controls, unlabeled probe (25-fold, 50-fold, 75-fold, 100-fold, 150-fold, 175-fold and 200-fold specific competitor or 25-fold, 50-fold, 100-fold and 200-fold non-specific competitor) and labeled probe were mixed with SabR-His6 and incubated for 25 min at 25°C. The resulting DNA-protein complexes were then subjected

to electrophoresis and autoradiography as described above. In order to quantify all probes, the probe DNA concentration was detected by ultraviolet spectrophotometer at the wavelength of 260 nm. DNase 1 footprinting To characterize the SabR-binding sites upstream region of sanG, a DNA fragment was amplified by PCR with the labeled primer EG1-F. The footprinting reaction mixture contained 30,000 cpm of [γ-32P]-labeled DNA probe, 6 ng to 0.3 μg of SabR-His6, 2.5 μg of poly-(dI-dC) (Sigma) and 20 mM Tris-base (pH 7.5), 1 mM DTT, 10 mM MgCl2, 0.5 μg calf BSA μl-1 and 5 % (v/v) glycerol in a total volume of 50 μl. After incubation of the mixture at 25°C for 25 min, 5.5 μl RQ1 RNase-free DNase Buffer and 0.1 U DNase 1 were added to the above reaction and the mixture was incubated for 1 min.

strain PCC 73102 a strain lacking a bidirectional

enzyme. Appl Environ Microbiol 1997, 63:1801–1807.PubMed 49. Sambrook J, Russell DW: Molecular Cloning: A Laboratory Manual New York, Cold Spring Harbor Laboratory Press 2001. 50. Thompson J, Higgins D, Gibson T: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choices. Nucleic Acids Res 1994, 22:4673–4680.PubMedCrossRef 51. Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001, 29:e45.PubMedCrossRef Authors’ contributions DF and FP Torin 2 purchase performed the experimental work, PMF contributed to the discussion of this manuscript, MVM coordinated the Real-time PCR studies, PT conceived and coordinated this work and the manuscript. All authors read and approved the final manuscript.”
“Background The genus Brucella comprises Gram-negative bacteria that are the etiological agents of brucellosis, a zoonosis that represents one of the most important worldwide disease affecting animals and

humans, especially in the Mediterranean areas [1, 2]. The disease can be transmitted to humans directly by contact with infected animals or indirectly by contaminated dairy products. Brucella infections can cause chronic debilitating diseases in humans with the involvement of multiple organs and low mortality while in the domesticated animals can lead to reproductive failure Pifithrin-�� mw with subsequent

economic loss. Six classically species are recognized within the genus Brucella: Brucella abortus (7 biovars), Brucella melitensis (3 biovars), Brucella suis (5 biovars), Brucella ovis, Brucella canis, and Brucella neotomae [3]. Isolation and characterization of novel different Brucella strains from a wide variety wildlife species from terrestrial and marine mammals, recently classified as three additional species, B. ceti (cetaceans) B. pinnipedialis and B. microti underline the importance of wildlife as reservoir for zoonotic brucellosis [4, 3-mercaptopyruvate sulfurtransferase 5]. In addition, Brucella spp. represent potential biological warfare agents due to the high contagious rates for humans and animals [6, 7]. Therefore it is very important to have a strain typing epidemiological tool for source trace back in outbreaks of infection. Characterization of Brucella at species and biovar level can be performed by differential microbiological approaches used for phenotyping [8]. However, these biotyping methods are time consuming and potentially hazardous for laboratory personnel. In addition, the limited variation among some species and biovars may result in conflicting data and complicate interpretation [9, 1]. Biotyping methods are not therefore suitable for epidemiological tracking where a more accurate identification is necessary. Thus, genetic characterization using molecular DNA technology has been investigated and several molecular techniques for subtyping have been proposed.

In general, compounds containing a substituent at phenyl ring electro-attracting atom (Cl) or group (CF3) exhibited higher experimental pK a values than unsubstituted ones. In addition, the replacement of arylpiperazine fragment with tetrahydroisoquinoline in respective compounds ICG-001 clinical trial caused increase of pK a values. The experimental pK a values are in range from 7.55 to 11.08, the detail data are presented in Table 1. The ranges of predicted pK a values of Pallas program are listed in Table 1. Unfortunately, the used program predicted no similar values to experimental pK a and could not diversify the acid–base properties of closely related compounds. In order to obtain more detailed

relationships between acid–base properties Tipifarnib ic50 of investigated compounds and the affinity of tested compounds to SERT, QSAR studies were undertaken. It was found linear correlation between affinities for SERT (pK i) and experimental pK a values (Fig. 1) but ratio of determination was moderate (R 2 = 0.48 for sublibraries 1 and R 2 = 0.38 for sublibraries 2). Fig. 1 Correlation between pK a values and pKi SERT of compounds 1–7 (left) and 13–22 (right) Summarizing,

two compounds 3 and 6 (derivatives of imidazo[2,1-f]purine-2,4-dione) are potent dual ligands for SERT and 5-HT1A receptor (pK i > 7.5) and were classified to the further pharmacological studies. The obtained results confirm that the applied potentiometric method is useful in characterization below of the acid–base properties of closely related compounds contrary to values of pK a predicted by Pallas program. There is no correlation between values of pK a predicted by Pallas program and experimental. The moderate correlation between activity for

SERT and pK a, indicating that acid–base properties are one of the important factors, which could influent and modify the activity for SERT. 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 Adell A, Castro E, Celada P, Bortolozzi A, Pazos A, Artigas F (2005) Strategies for producing faster acting antidepressants. Drug Discov Ther 10:578–585CrossRef Artigas F, Romero L, de Montigny C, Blier P (1996) Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci 19:378–383PubMedCrossRef Ballesteros J, Callodo LF (2004) Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomized controlled trials. J Affect Disord 79:137–147PubMedCrossRef Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function.