These responses were initially predicted by clustering analysis, as these mutants fall into clusters being predicted involvements in blue light signalling (clusters I, II, IV and V) and those predictions involving blue, red and far-red light signalling (clusters III). These putative components of light signalling in Xcc included three HKs, four GGDEF-characterized

proteins and selleck four hybrid HKs. Motility is an important characteristic for infection in a number of plant pathogenic species (Swings et al., 1993); thus, we tested whether PAS proteins participate in the development of motility in the Xcc in response to variable light conditions. Five of 33 mutants showed significantly modified motility responses to light (Fig. 3). Among them, DLT4313 was increased, and DLT0728, DLT0818 and DLT1965 were decreased in blue light. DLT1036 exhibited decreased motility in blue, red, far-red or white light. These results partially agreed with the results of clustering analysis (Fig. 1c), in which the protein altered in DLT0728 was associated with cluster IV and was a putative blue light–signalling component. Selleckchem STI571 We cultured cabbage infected with Xcc strains under two levels of light intensity. The light intensity reaching into

a leaf was initially estimated in a light transmission assay, which indicated that a light intensity of 4512 and 593 lux reached the middle of a leaf exposed to light sources of 12 000 and 2000 lux, respectively (Fig. S2). The results of Xcc strains are shown in Fig. S3. We also tested rescue strains of three mutants, DLT1036, DLT 2324 and DLT3829. In assays of Xcc strains infecting cabbage, four mutants (DLT3829, DLT1036, DLT2324 and DLT1476) had an effect on light-condition-dependent shifts in bacterial virulence. Leaf-lesion photographs of the four mutants are shown in Fig. 4a (strong light) and 4b (weak light), and the mutants showed different changes in lesion length

(LL) in strong/weak light or between the two light intensities, as shown in Fig. 4c. The relative lesion rate (RLR) values of the four mutants were significantly different from Etomidate wild-type Xcc 8004 (Fig. 4d). The tests of complementary strains are shown in Fig. S4, in which the virulence of pLC1036, pLC2324 and pLC3829 were partially rescued in comparison with either LL or RLR. In addition, three of the four mutants have been shown to be GGDEF-characterized proteins involved in virulence under natural light (Ryan et al., 2007). These data strongly suggest that these PAS proteins are light-signalling components that are vital for Xcc pathogenesis. Some of the PAS proteins in Xcc may have roles as intermediates in photo-signalling pathways other than light sensing, and some of those involved in light signalling may not have phenotypes that could be observed in our screen. Previous studies have suggested that PAS domains sense light, and the subsequent functions result in various responses, for example, a PAS domain can be activated in blue light to regulate B.

, 2010). http://www.selleckchem.com/products/AP24534.html However, only two sequences of small plasmids from Arthrobacter species are deposited in GenBank database. The plasmid pA3 (AJ131246) is 2205 bp in length and harbours five hypothetical open reading frames (ORF). The second plasmid (pRE117-2, FQ311476) is 8528 bp in length, and 13 ORFs are predicted, two of them encode putative mobilization proteins (Monnet et al., 2010). Recently, Miteva et al. (2008) have described the cryptic plasmid p54 (1950 bp), which harbours seven ORFs, few of which sharing similarities with proteins of known function. However, the nucleotide sequence is not publicly available. To date, a few vectors for the bacteria of Arthrobacter genus have been

created. Two hybrid plasmids Alisertib supplier have been developed using the ori sequence of pCG100 from Corynebacterium glutamicum (Shaw & Hartley, 1988; Sandu et al., 2005) and pBL100 from Brevibacterium lactofermentum (Shaw and Hartley, 1988).

One vector has been constructed on the basis of pULRS8 from Brevibacterium lactofermentum (Morikawa et al., 1994). The pART2 and pART3 vectors can be applied for both constitutive and nicotine-inducible gene expression as well as for promoter screening by GFP fusion (Sandu et al., 2005) or production of MalE-fused hybrid proteins (Kolkenbrock & Fetzner, 2010). All above-mentioned E. coli–Arthrobacter shuttle vectors are developed from cryptic plasmids of phylogenetically related species. Recently, the hybrid vector ifoxetine pSVJ21 has been constructed

based on the cryptic plasmid p54 from Arthrobacter sp. (Miteva et al., 2008). This paper reports on characterization of a small cryptic plasmid pPRH (5.0 kb) from Arthrobacter rhombi PRH1 strain and describes the pPRH-derived hybrid vectors, which replicates in both Arthrobacter and Rhodococcus species as well as in E. coli. One of the vectors has been successfully applied for functional screening of 2-hydroxypyridine catabolism encoding genes from Arthrobacter sp. PY22, using a nonconventional host. The bacterial strains and plasmids are listed in Table 1. Arthrobacter and Rhodococcus spp. strains were cultivated at 30 °C on nutrient agar (NA) (Oxoid) plates or in nutrient broth (Oxoid) aerobically. When necessary, antibiotics were added to the media: ampicillin (50 μg mL−1), chloramphenicol (10–20 μg mL−1), kanamycin (40–60 μg mL−1 and tetracycline (10–40 μg mL−1). Cloning and DNA manipulations were performed as described by Maniatis et al. (1982). Plasmid DNA from Rhodococcus and Arthrobacter cells was isolated by alkaline lysis method following the incubation with lysozyme (10 mg mL−1) for 30 min. Escherichia coli and Arthrobacter (Rhodococcus) cells were prepared for electroporation by the method of Sharma & Schimke (1996) and Gartemann & Eichenlaub (2001), respectively. A restriction analysis of the pPRH plasmid was carried out using single and double digestions. The DNA fragments were subcloned in pTZ57R.

4 million inhabitants (6.5%) to 1,943,000 per 16.3 million inhabitants (11.9%). This increase largely

reflects travel to the Arab region (305,000 travelers in 1995 vs 968,000 in 2006), including its popular destinations of Turkey (99,000 vs 593,000) and Egypt (26,000 vs 203,000). The number of Dutch travelers to Latin America also showed an annual increase (from 164,000 in 1995 to 378,000 in 2006) particularly for the Caribbean (from 93,000 to 225,000). Travel to Sub-Saharan Africa and Asia fluctuated; the median annual number of travelers was 87,000 and 387,000, respectively. Table 2 shows the region-specific trends in attack rates for hepatitis A, typhoid fever, and shigellosis among Dutch travelers to developing countries. Overall, the attack rate per 100,000 SAHA HDAC mw such travelers declined for hepatitis A from 22.3 to 5.5, for typhoid fever from 5.6 to 1.0, and for shigellosis from 26.8 to 8.4. Among travelers to Latin America, attack rates significantly declined for hepatitis and shigellosis; for typhoid fever, attack rates were low and remained stable. In this region, the Caribbean had the lowest median attack rates; the median typhoid Belnacasan fever rate was even 0.0. As compared to the other regions, attack rates among travelers in Latin America and the Caribbean were generally

low. For Sub-Saharan Africa, attack rates for all three diseases were high and fluctuated without showing a decrease. Median rates among travelers to Western/Middle

Africa were all higher than among travelers to Eastern/Southern Africa, where the median typhoid fever rate was even 0.0. For the Arab region, attack rates for all three diseases declined significantly. In particular, for the popular tourist destinations of Turkey and Egypt, attack rates dropped substantially. The median typhoid fever rate for Turkey was very low. For Asia, attack rates for Amisulpride hepatitis A fluctuated without showing a decrease; for typhoid fever and shigellosis attack rates declined significantly. Median rates for the Indian subcontinent remained high, especially for typhoid fever. As compared to all other world regions, median rates for Thailand/Malaysia were the lowest. Figure 1 shows the trends in HDI, SI, and WSI, respectively. Indices increased for all regions studied. The HDI for all regions increased from 0.622 in 1995 to 0.679 in 2005 (+5.7%) (not shown in Figure 1). Egypt had the biggest increase: 9.5%. Sub-Saharan Africa had the smallest increase: 2.3%. During the study period, HDI levels for Latin America, Turkey, and Thailand/Malaysia were the highest; HDI levels for Sub-Saharan Africa and South Asia were the lowest. The SI for all regions increased from 0.452 in 1995 to 0.539 in 2006 (+8.6%) (not shown in Figure 1). Egypt had the biggest increase: 11.0%. Turkey had the smallest increase: 2.0%.

, 2011). Integrons

are DNA platforms selleck compound that capture exogenous gene cassettes containing open reading frames (ORFs) and assemble them under the control of a promoter that ensures gene functionality. They are composed of three elements: a gene (intI) encoding an integrase belonging to the tyrosine-recombinase family; a primary recombination site (attI); and an outward-orientated promoter (Pc) that directs transcription of the captured genes (Mazel, 2006). These assembling platforms have a major role in the spread of genes and have been described in Antarctic environments. Several ORFs, homologous to putative or hypothetical transposases, transcription elongation factors, alkylmercury lyase, transcription regulators, penicillin-binding protein, integrases, recombinase/topoisomerase and many unknown proteins, have been described (Stokes et al., 2001; Berlemont et al., 2011). Because integrons are widespread in bacterial populations, it is clear that the pool of ORFs represents a genomic resource for bacterial adaptation because

they are ready for mobilization, reshuffling, and expression of genes. Genomic islands (GIs) are genetic elements, usually acquired by HGT, that also play a major role in microbial evolution and have been found in cold-adapted bacteria. A new bacteriocin biosynthetic cluster PARP inhibitor was located in a GI of Carnobacterium sp. AT7 (Voget Nintedanib (BIBF 1120) et al., 2011). Interestingly, Ayub et al. (2007) found a GI containing polybetahydroxyalkanoate (PHA) biosynthetic genes, numerous mobile elements, an integrase, insertion sequences, a bacterial group II intron, a complete

Type I protein secretion system, and IncP plasmid-related proteins in a mosaic distribution structure, in the Antarctic Pseudomonas sp. 14-3. PHA has a role in stress alleviation, mainly environmental stress. PHA is a carbon and energy storage compound that is accumulated during suboptimal growth conditions, and their degraded elements can be used rapidly for numerous metabolic needs, enhancing fitness during stressful environmental conditions (Kadouri et al., 2005). Taken together, these results support the idea that horizontal transfer of pha genes is a mechanism of adaptability in the Antarctic environment. On the basis of its microbial diversity and extreme environmental conditions, the Antarctic continent has been described as a genomic resource for the identification of novel molecules, in particular cold-active enzymes, for biotechnological uses. These cold-active enzymes have high activities at low temperatures, and this enables their application in certain industrial processes that can be performed at room or tap water temperature, thus allowing energy savings.

Almost 70% desired greater inter-professional contact in the care of their patients with asthma. The strengths of this study include the high response rate, the high internal consistency

of responses, as indicated by the Cronbach’s signaling pathway alpha coefficient, and the high factor loadings for each of the identified factors. The sample was representative based on current national labour force data[33] (Table 2), and the sample size was adequate for factor analysis and reliability analysis. The limitations of the study were associated with the convenience sampling method, and the lack of qualitative research in the development of the questionnaire, which was based on current asthma management guidelines, the literature and expert opinion. Few published studies have explored pharmacists’ perceptions of their role in asthma management. Research in this area has primarily focused on structured community pharmacy-based asthma programmes;[11,15,17,21–23] however, for the average community pharmacist, neither national[26] nor international[27,28] asthma management guidelines articulate the optimal scope of their role in asthma care. Therefore, exploring the pharmacists’ own perceptions

was considered important for future programme implementation and sustainability. In so doing, this study showed that pharmacists viewed their role in TSA HDAC asthma management along three broad areas, consistent with current asthma management approaches outlined in national[26] and international guidelines:[27,28] medication use, patient self-management and asthma control. While 92% of participants indicated that their role was associated with counselling about ‘medication use’, far fewer believed in a role associated with patient self-management

and asthma control, and only 48% perceived an extended role encompassing all Ergoloid three areas of asthma management. These results are consistent with the more ‘recognised’ role of the pharmacist: that is, medication related in view of their therapeutic knowledge and expertise. Not surprisingly, regional pharmacists perceived a broader role for community pharmacists compared with their metropolitan counterparts. This could relate to the shortages of medical practitioners and large distances in regional areas necessitating all healthcare professionals to take on broader roles in healthcare.[34] This potentially suggests that regional pharmacists may present the ideal target group to implement new asthma management programmes in community pharmacy. When it comes to embracing a broader perspective of their role, a comprehensive study in the UK indicated that community pharmacists believed it was essential to extend their role.[35] This was driven by a dissatisfaction of a role restricted to dispensing medications and satisfaction with taking on a more patient-centred approach.

For this, 10-mL samples were harvested, centrifuged, microfiltered (0.45-μm pore size), and then concentrated by ultrafiltration using 15-mL ultracentrifuge filter devices with a cut-off of 10 kDa (Comitini et al., 2004b). The trials were carried out in duplicate. After fermentation, the main undesired compounds http://www.selleckchem.com/products/Everolimus(RAD001).html produced by D. bruxellensis, as acetic acid (volatile acidity) and 4-ethyl phenol, were determined. The volatile acidity was determined by steam distillation following the procedures of the European Community (EC, 2000), and

4-ethyl phenol concentrations (vinyl phenols) were measured according to the protocol described by Chatonnet et al. (2006), using a GC-flame ionization detector. An anova was applied to the experimental data. The values of means were analysed using the software superanova

version 1.1 for Mac OS 9.1. The significant differences were determined by Duncan tests and the results were considered significant if the associated P value was <0.01. Our previous studies have shown that Kwkt production is enhanced by the presence of yeast extract and organic nitrogen compounds in the growth medium (data not shown). However, to avoid high-molecular-mass compounds in the supernatant and to facilitate the purification of Kwkt, we used SSM in the present study as a new substrate for K. wickerhamii growth and Kwkt production. As expected, the use of SSM resulted in a limited amount of total protein and a reduced killer

activity in comparison this website Edoxaban with a richer media (Comitini et al., 2004a). Ultrafiltration procedures provided a concentration of 153-fold that from the culture broth, with a preliminary partial purification Kwkt (Table 1). Purified Kwkt was obtained after the DEAE-Sepharose Fast-Flow anion-exchange step. The 7-mL (75 mM) NaCl fraction from the elution contained the Kwkt killer activity, and the purification of the Kwkt protein was increased to 5005-fold, with a recovery of 4.2% (Table 1). Figure 1, lane (1), shows the purified profile of Kwkt with silver staining following SDS-PAGE, with an apparent molecular mass of 72 kDa, as eluted from the anion-exchange chromatography and reconcentrated 20-fold after a second step of ultrafiltration. Treatment of the purified Kwkt protein with endoglycosidase H did not show any reduction in the molecular mass of purified Kwkt [Fig. 1b, lanes (3), (4); positive control, lanes (1), (2)], demonstrating that Kwkt is a protein without a glycosyl portion. As previously shown using partially purified Kwkt (Comitini et al., 2004a) over the duration of the must microfermentations, the biomass evolution of S. cerevisiae selected wine strain (EC1118) showed typical kinetics and did not appear to be influenced by the presence of either the D. bruxellensis or the Kwkt (data not shown).

Also included are some observations on a positive contribution to reduced length of stay for people with diabetes in hospital, and low incidences of prescription and management errors in the first National Diabetes Inpatient Audit in 2009. Specifically between 2005 and 2007 the average length of stay in days for all patients whose diagnosis included diabetes fell from 9.39

to 3.76 days despite the total number of patients increasing from 507 to 633 over the same quarter each year. The inpatient team provided almost 1000 visits to patients with diabetes in the first six months of each year 2008 and 2009, and at the first National Diabetes Inpatient Audit had only 5% prescription errors and 3% management errors (versus 19% and 14% respectively nationally) with 100% appropriate blood glucose testing. We suggest that a dedicated inpatient diabetes care team raises the quality of care

for patients and enhances 17-AAG datasheet patient and professional education; we also suggest that audit standards should be developed for inpatient Selleckchem Trametinib diabetes care and assessed in future national audits. Copyright © 2011 John Wiley & Sons. “
“Liraglutide is not predominantly eliminated by renal excretion. We assessed its safety and efficacy among patients with mild and moderate renal impairment. Patients from a nationwide audit of liraglutide (1.2mg) use were divided according to pre-treatment renal function calculated by the Cockcroft-Gault formula. Adverse events, liraglutide discontinuation and changes in HbA1c, weight, systolic blood pressure and serum creatinine were compared between groups of different pre-treatment renal function. As compared with patients with normal renal function (n=1446), patients with mild renal Methocarbamol impairment (n=288) and moderate renal impairment (n=57) were equally likely to report gastrointestinal side effects (adjusted OR 1.11 [95% CI 0.80–1.54] and 0.67 [95% CI 0.31–1.48]), respectively, but more frequently stopped liraglutide due to gastrointestinal side effects (adjusted OR 2.32 [95% CI 1.45–3.74] and 2.37 [95% CI 0.97–5.81]), respectively. Minor hypoglycaemia and

acute renal failure were uncommonly reported and were not more frequent among patients with renal impairment. Patients remaining on treatment in all three groups achieved significant HbA1c and weight reduction at six months (between 11 to 12mmol/mol [1.0 to 1.1%] and -3.6 to -3.8kg). No effect of renal function was seen influencing the degree of HbA1c and weight reduction. Liraglutide treatment was associated with a small reduction in serum creatinine among patients with renal impairment. We concluded that liraglutide was safe, efficacious but more frequently discontinued among patients with mild renal impairment. More data are needed to establish its safety among patients with moderate or more significant renal impairment. Copyright © 2013 John Wiley & Sons.

[21-24] Moreover and to the best of our knowledge, there has never been a published case of HKI-272 ic50 a travel-related death in a healthy person who has received appropriate PrEP in an industrialized country rather than a developing country.[32] If using the same principle as that used for animal handlers, many of these travel-related rabies deaths could have been prevented

with adequate PrEP using a WHO- recommended regime without necessarily receiving appropriate rabies PEP. Thus, providing rabies PrEP may do more than simplify the post-exposure management of the exposed traveler. Using animal bites and rabies exposure as an illustration, we can see that the assessment of travel-related risk and uncertainty is a complex process requiring effective risk communication between the provider and traveler. The pre-travel encounter should start with a “risk conversation.” More effort needs to be directed to this core function of travel medicine practice, but research find more such as that by Rossi and Genton is a good

start.[8] The author states that he has no conflicts of interest to declare. “
“Background. Travelers with diabetes mellitus to developing countries are thought to have symptomatic infectious diseases more often and longer than travelers without diabetes. Evidence for this is needed. This study evaluates whether travelers with diabetes are at increased risk of symptomatic infectious diseases. Methods. A prospective study was performed between October 2003 and February 2008 among adult medication-dependent travelers with diabetes, with their healthy travel companions without diabetes serving as matched controls. Thus, travelers with diabetes and controls were assumed to have comparable exposure to infection. Data on symptoms of infectious diseases were recorded by using L-NAME HCl a structured diary. Results. Among 70 travelers with insulin-dependent

diabetes, the incidence of travel-related diarrhea was 0.99 per person-month, and the median number of symptomatic days 1.54 per month. For their 70 controls, figures were 0.74 and 1.57, respectively (p > 0.05). Among 82 travelers with non-insulin-dependent diabetes, incidence was 0.75, and the median number of symptomatic days was 1.68. For their 82 controls, figures were 0.70 and 1.68, respectively (p > 0.05). As for other symptoms, no significant travel-related differences were found. Only 17% of travelers with diabetes suffering from diarrhea used their stand-by antibiotics. Conclusions. Medication-dependent travelers with diabetes traveling to developing countries do not have symptomatic infectious diseases more often or longer than travelers without diabetes.

Dr John Walsh has no conflict of interests to declare. Dr Ed Wilkins has received lecture and consultancy fees from Abbott, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp and Dohme and Pfizer. Dr Alan Winston has received lecture fees from Janssen and his department has received research grants from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Pfizer, Roche and ViiV. Dr Mike Youle has received lecture and consultancy fees from Abbott

and Gilead. “
“BHIVA revised and updated the Association’s guideline development manual Regorafenib nmr in 2011 [1]. BHIVA has adopted the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for the assessment, evaluation and grading of evidence and the development of recommendations [2,3]. 1A Strong recommendation. High-quality evidence. Benefits clearly outweigh risk and burdens, or vice versa. Consistent evidence from well-performed, randomized, controlled trials or overwhelming evidence of some other form. Further research is unlikely to change our confidence in the estimate of benefit and risk. Strong recommendations, can apply to most patients

in most circumstances without reservation. Clinicians should follow a strong recommendation ABT-737 nmr unless there is a clear rationale for an alternative approach. 1B Strong recommendation. Moderate-quality evidence. Benefits clearly outweigh risk and burdens, or vice versa. Evidence from randomized, controlled trials with important limitations (inconsistent results, methods flaws, indirect or imprecise), or very strong evidence of some other research design. Further research may impact on our confidence in the estimate of benefit and risk. Strong recommendation

and applies to most patients. Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative Histamine H2 receptor approach is present. 1C Strong recommendation. Low-quality evidence. Benefits appear to outweigh risk and burdens, or vice versa. Evidence from observational studies, unsystematic clinical experience, or from randomized, controlled trials with serious flaws. Any estimate of effect is uncertain. Strong recommendation, and applies to most patients. Some of the evidence base supporting the recommendation is, however, of low quality. 1D Strong recommendation. Very low-quality evidence. Benefits appear to outweigh risk and burdens, or vice versa. Evidence limited to case studies. Strong recommendation based mainly on case studies and expert judgement. 2A Weak recommendation. High-quality evidence. Benefits closely balanced with risks and burdens. Consistent evidence from well-performed randomized, controlled trials or overwhelming evidence of some other form. Further research is unlikely to change our confidence in the estimate of benefit and risk.

Depending on the growth substrate, different O-demethylases are induced in Acetobacterium dehalogenans. A vanillate- and a veratrol-O-demethylase of this organism have been described earlier. The methyltransferase I (MT I), a component of this enzyme system, catalyzes the ether cleavage and the transfer of the methyl group to a super-reduced corrinoid bound to a protein. GKT137831 manufacturer The MT I of the vanillate- and veratrol-O-demethylase (MT Ivan and MT Iver) were found to be zinc-containing enzymes. By site-directed mutagenesis, putative zinc ligands were identified, from which the following unique zinc-binding motifs were derived: E-X14-E-X20-H for MT Ivan and D-X27-C-X39-C for MT Iver. Phenyl

methyl ethers are natural components of lignin and are formed upon lignin degradation by fungi. The methyl groups of the phenyl methyl ethers can be utilized as growth this website substrates by different acetogenic bacteria such as Acetobacterium dehalogenans, Acetobacterium woodii, Holophaga foetida, Moorella thermoacetica and Sporomusa ovata (Bache & Pfennig, 1981; Daniel et al., 1991; Traunecker

et al., 1991; Kasmi et al., 1994; Stupperich et al., 1996; Kaufmann et al., 1997; Kreft & Schink, 1997). The cleavage of the ether bond and the transfer of the methyl group to tetrahydrofolate are catalyzed by the O-demethylase enzyme system (Kaufmann et al., 1997; Engelmann et al., 2001; Naidu & Ragsdale, 2001). For A. dehalogenans, two O-demethylases have been described. They consist of two

methyltransferases (MT I and MT II), a corrinoid protein (CP) and an activating enzyme (AE) per enzyme system (Kaufmann et al., 1997; Engelmann et al., 2001). MT I mediates the cleavage of the ether bond and the transfer of the methyl group to the super-reduced corrinoid cofactor of CP. CP is subsequently demethylated by the second methyltransferase MT II and the methyl group is transferred to tetrahydrofolate. The methyl group of methyltetrahyrofolate is further oxidized to CO2 or converted to the methyl group of acetate (Drake et al., 2006). For the methylation of CP, the cobalamin cofactor has to be in its super-reduced form. Because Quisqualic acid of the negative redox potential of the cob(II)alamin/cob(I)alamin couple in CP ([CoI]/[CoII]≤550 mV; Siebert et al., 2005), inadvertent oxidation of the cofactor may occur, which leads to the formation of the inactive cob(II)alamin. Therefore, an AE (RACE protein; Schilhabel et al., 2009) is required that reduces the cob(II)alamin cofactor of CP to the super-reduced form in an ATP-dependent reaction. During the course of the activation, AE increases the redox potential of the corrinoid (Schilhabel et al., 2009). Acetobacterium dehalogenans induces different O-demethylase systems depending on the growth substrate of the organism (Kaufmann et al., 1997; Kaufmann et al., 1998; Engelmann et al., 2001). Two O-demethylase systems have been characterized so far, designated vanillate- and veratrol-O-demethylase (Kaufmann et al.