R.L., Buenos Aires, Argentina). Seventeen Argentinean F. poae isolates from different regions and

hosts selected at random were analysed by HPLC/FD to test NIV/DON production (Table 1). Fusarium poae isolates were cultured in Erlenmeyer flasks (250 mL) containing 25 g of long-grain rice. Ten mL of distilled water was added before autoclaving for 30 min at 121 °C, twice. Each flask was inoculated with a 3-mm diameter agar disc taken from the margin of a colony grown on SNA (Nirenberg, 1976) at 25 °C for 7 days. Flasks were shaken once a day by hand for 1 week. These cultures were incubated for 28 days at 25 °C in the dark. At the end of the incubation period, the contents of the flask Ipilimumab manufacturer were dried at 50 °C for 24 h and then stored at −20 °C until being analysed for toxin. Toxin extraction and clean-up were carried out using a modified version of that originally reported

by Cooney et al. (2001). For the detection of NIV and DON, the analysis was performed using the conditions described by Barros et al. (2008). The dried residue was dissolved in 400 μL of methanol/water (5 : 95), homogenized in a vortex mixer and injected into the HPLC system by full-loop injection technique (Hewlett Packard model 1100 pump, Palo Alto, CA and Rheodyne manual injector with a 50 μL loop; Rheodyne, Cotati, CA). The HPLC system consisted of a Hewlett Packard model 1100 pump connected to a Hewlett Packard 1100 Series variable wavelength detector and a data module Hewlett Packard Kayak XA (HP ChemStation Rev. A.06.01). GSK126 Interleukin-3 receptor Chromatographic separations were performed on a Luna™ C18 reversed-phase column (100 × 4.6 mm, 5 μM particle size) connected to a guard column SecurityGuard™ (4 × 3.0 mm) filled with the same phase. The mobile phase consisted of methanol/water (12 : 88),

at a flow rate of 1.5 mL min−1. The detector was set at 220 nm with an attenuation of 0.01 AUFS. Quantification was relative to external standards of DON and NIV (Sigma-Aldrich Co., St Louis, MO) from 1 to 4 μg mL−1 in methanol/water (5 : 95). The detection limit was 5 ng g−1 for each toxin. Fusarium poae is recognized as a more prominent member of the FHB complex (Yli-Mattila et al., 2008; Kulik & Jestoi, 2009; Stenglein, 2009). Several researchers have developed specific primer pairs for PCR assays, to have a rapid, inexpensive and relative simple technique to identify F. poae isolates of cereal samples (Parry & Nicholson, 1996; Kulik, 2008; Yli-Mattila et al., 2008). Fusarium poae isolates used in our study were found to be positive based on the specific primer pair developed by Parry & Nicholson (1996). Seventeen Argentinean isolates were analysed by HPLC/FD for production of trichothecenes and only NIV was detected (0.3–8.7 μg g−1; Table 1). This was in agreement with other studies (Vogelgsang et al., 2008a ,b; Yli-Mattila et al.

We calculated the incremental cost of the educational video intervention versus treatment as usual from a National Health Service (NHS) perspective. We applied unit costs from market prices and published sources [5]. Our main analysis is based on an HA (Band 7) conducting three tests selleck chemical per hour. In sensitivity analyses we explored the impact of using different staff and increasing the number of tests per hour. Full details of the methodology

used and results have been previously published [6]. During the pilot period there were 606 eligible admissions to the AAU. Three-quarters (456 of 606; 75.3%) of all eligible admissions were approached to participate in the study. There were no significant differences in gender, age, ethnicity, presence of HIV indicator condition [1] or length of stay between those approached and not approached. Despite often multiple attempts, over half (53.5%) of approaches failed as patients were frequently absent or too unwell. Of the 282 patients who were asked if they would be involved in JAK inhibitor the pilot project, 153 (54.3%) agreed. On introduction of the video, four patients asked to have an HIV test but did not want to watch the video, and five disclosed that they had recently been tested for HIV and therefore withdrew from further involvement. After watching the video, a further 11 patients declined to be tested: four had been tested within

the past 3 months; two had never been sexually active; two declined because of communication difficulties; one wanted to be tested in an anonymous environment and was referred to a sexual health clinic; one became unwell during the video; and one declined. In all, of the 140 patients who watched the video and had not been tested for HIV in the preceding 3 months, 93.6% (131 of 140) agreed

to a test. All patients received their results at the time of testing. There was no difference in uptake of the video or HIV test by gender, or in uptake of the Fossariinae test by age. In total, 23.0% of eligible admissions during the pilot period had a POCT, and 25.7% left the AAU knowing their HIV status, having been tested on that admission or within the preceding 3 months or having previously been diagnosed HIV positive. Three tests (2.2%; three of 135) were reactive on POCT and all were confirmed HIV positive on further laboratory testing. All three patients were seen by specialist HIV services while in-patients and remained engaged with HIV services 12 months on. Only one of the three had previously been tested for HIV, over 5 years previously. The majority of participants who completed the survey were male (58.6%), with a median age of 38.5 years. Over half (51.9%) resided in the hospital catchment area and 85.5% were from within London. In total, 42.8% were born abroad: 19 (12.5%) in Europe, 17 (11.2%) in Africa [nine (5.9%) black African] and 15 (9.9%) in Asia or the Indian subcontinent. Forty per cent (61 of 152) of participants had previously been tested for HIV; however, only 22 (14.

We calculated the incremental cost of the educational video intervention versus treatment as usual from a National Health Service (NHS) perspective. We applied unit costs from market prices and published sources [5]. Our main analysis is based on an HA (Band 7) conducting three tests HIF inhibitor per hour. In sensitivity analyses we explored the impact of using different staff and increasing the number of tests per hour. Full details of the methodology

used and results have been previously published [6]. During the pilot period there were 606 eligible admissions to the AAU. Three-quarters (456 of 606; 75.3%) of all eligible admissions were approached to participate in the study. There were no significant differences in gender, age, ethnicity, presence of HIV indicator condition [1] or length of stay between those approached and not approached. Despite often multiple attempts, over half (53.5%) of approaches failed as patients were frequently absent or too unwell. Of the 282 patients who were asked if they would be involved in AZD6244 the pilot project, 153 (54.3%) agreed. On introduction of the video, four patients asked to have an HIV test but did not want to watch the video, and five disclosed that they had recently been tested for HIV and therefore withdrew from further involvement. After watching the video, a further 11 patients declined to be tested: four had been tested within

the past 3 months; two had never been sexually active; two declined because of communication difficulties; one wanted to be tested in an anonymous environment and was referred to a sexual health clinic; one became unwell during the video; and one declined. In all, of the 140 patients who watched the video and had not been tested for HIV in the preceding 3 months, 93.6% (131 of 140) agreed

to a test. All patients received their results at the time of testing. There was no difference in uptake of the video or HIV test by gender, or in uptake of the Ribose-5-phosphate isomerase test by age. In total, 23.0% of eligible admissions during the pilot period had a POCT, and 25.7% left the AAU knowing their HIV status, having been tested on that admission or within the preceding 3 months or having previously been diagnosed HIV positive. Three tests (2.2%; three of 135) were reactive on POCT and all were confirmed HIV positive on further laboratory testing. All three patients were seen by specialist HIV services while in-patients and remained engaged with HIV services 12 months on. Only one of the three had previously been tested for HIV, over 5 years previously. The majority of participants who completed the survey were male (58.6%), with a median age of 38.5 years. Over half (51.9%) resided in the hospital catchment area and 85.5% were from within London. In total, 42.8% were born abroad: 19 (12.5%) in Europe, 17 (11.2%) in Africa [nine (5.9%) black African] and 15 (9.9%) in Asia or the Indian subcontinent. Forty per cent (61 of 152) of participants had previously been tested for HIV; however, only 22 (14.

1 μg L−1). This ability remained stable after the fungus was cultured for five generations. The other three ts PCR positive isolates only produced traces of taxol. The isolate SBU-16 (Fig. 4) was identified based on its morphological characteristics as well as ITS rDNA gene sequencing. Colonies on PCA are effuse, pale brown, and do not sporulate abundantly. The mycelium is septate and pale brown. Conidiophores are solitary, occasionally short-branched, pale brown to brown, smooth, 1–4-septate, 14–110 × 3–5.0 μm, cylindrical,

and at the apex swollen to 6–8 μm. Conidia develop singly and almost entirely through a narrow pore at the apex of each conidiophore, medium brown, oblong to oblong-ellipsoid, subtruncate at the apex, rounded or subtruncate at the base, straight or slightly curved, with 1–3 this website transverse septa, and usually distinctly constricted in the

middle, 0–3 longitudinal or oblique septa, 15–30 × 12–18 μm (av. 21.84 × 14.06 μm), L/W ratio is 1.4–2.16 (av. 2.0) dark, and thin-walled. Ascomata develop in large numbers within PCA and PDA and on the firm base of an alfalfa stem on the PCA, but they contain immature asci (Fig. 4a). Isolate SBU-16 exhibits the key morphological characters of Stemphylium, including the proliferation and swollen apical cell or region of the conidiophores (Simmons, 1967, 1969) as well as morphological characters of Stemphylium sedicola (Simmons, 2001). Percurrently proliferating conidiophores are recognized as the principal morphological characteristic that clearly distinguishes Stemphylium from two similar genera, Ulocladium and Selleckchem AZD2281 Alternaria (Wang et al., 2010). Although the

identification of Stemphylium species is based principally on morphological characteristics of conidium and conidiophores, many of these characters often overlap among species, making species determinations difficult (Leach & Aragaki, 1970). In addition, the systematic position of the isolate Inositol oxygenase SBU-16 was estimated by a sequence comparison of the ITS region with other species of the genus Stemphylium from the GenBank. Sequences of the SBU-16 in the ITS region were 530 bp. An online blast search of the ITS gene sequence of the SBU-16 isolate exhibited 99% similarity with several species of the genus Stemphylium and uncultured endophytic fungi. Evolutionary distances were calculated for a dataset that consisted of the sequences of the SBU-16 isolate and other species of the genus Stemphylium. The ITS neighbor-joining tree (Fig. 5) was reconstructed on the basis of the obtained distance matrix data. Finally, according to the evolutionary distance and morphological characters, isolate SBU-16 was identified as S. sedicola SBU-16. DNA sequence data are now commonly used to test morphological concepts and other taxonomic hypotheses (Hunter et al., 2006). The ITS DNA sequence is a widely accepted DNA marker for identifying fungi (Nguyen & Seifert, 2008).

mutans, which is one of the principle causative agents of dental caries, has to be elucidated. MicroRNAs (miRNAs) are small noncoding RNAs that are c. 22 nt long. They are found in various species of plants, animals and viruses (Bushati & Cohen, 2007), and normally act as regulators in every major cellular event through inhibitory

mechanisms (He & Hannon, 2004). It has long been known that bacteria contain noncoding small RNAs (sRNAs) that have regulatory functions, other than miRNAs (Gottesman, 2005; Waters & Storz, 2009). sRNAs are usually between 50 and 200 nt in length and have been predicted by computational searches in a variety of bacterial species (Livny & Waldor, 2007). Like miRNAs, sRNAs usually act as post-transcriptional regulators by interacting with the target mRNAs through a variety of mechanisms, including changes in RNA conformation and modulation of the stability

of the specific targets (Waters & Storz, Stem Cell Compound Library isocitrate dehydrogenase inhibitor 2009). Smaller RNAs that have size similar to miRNAs are not well understood in bacteria, although many of them may be found among sequence reads registered in the transcriptome of Escherichia coli (Dornenburg et al., 2010). Streptococcus mutans is the major causative agent of human dental caries and is considered to be the most cariogenic of all of the oral streptococci (Ajdić et al., 2002). The disease occurs when ecologically driven changes in oral biofilms are perturbed and S. mutans is mainly responsible for the formation of the oral biofilms (Burne, 1998). The genome of S. mutans has been fully sequenced and contains c. 2 Mb and 1963 ORFs (Ajdić et al., 2002). This study examined the existence of small (c. 26 nt) RNAs in S. mutans that we subsequently isolated. For this purpose, a deep sequencing (next-generation sequencing) approach was used and more

than 19 million sRNA clones were read. To differentiate these very sRNAs from the bacterial sRNAs (50–250 nt) and well-studied eukaryotic miRNAs, we suggest the term ‘miRNA-size, next small RNA’ (msRNA). Their origin and putative functional significance are discussed. Streptococcus mutans (ATCC 25175) were inoculated into brain heart infusion broth (three independent cultures) and total RNA was extracted from the cultured S. mutans after pooling using the miRNeasy Mini kit (Qiagen, CA) according to the manufacturer’s protocol. RNA was processed and used for deep sequencing by LC Sciences (Houston, TX). An sRNA library was generated from the S. mutans RNA according to Illumina’s sample preparation instructions for Illumina Genome Analyzer IIx (Ilumina Inc., San Diego, CA). The following gives a brief summary of the procedures performed. The total RNA sample was size-fractionated on a 15% Tris–borate–EDTA (TBE)–urea polyacrylamide gel. The RNA fragments of c. 15–50 nt in length were eluted and ethanol-precipitated.

The National Community Pharmacists Association asserts that independent pharmacies encourage the training of pharmacy technicians, but believes that required standards need to be differentiated based on work area. It also desires to know the financial impact of such requirements and how the standards would be implemented for special situations (e.g. technicians employed buy Sirolimus part-time). If other organizations are unanimous in the move towards standardization and accreditation, the National Community Pharmacists Association states that it will fully support

and follow the decision accordingly.[20] Although chain pharmacies encourage the continuing education of their pharmacy technicians, the idea of setting mandatory standards has raised some concerns. Chain pharmacies suggest that their sector of the profession will be most affected by changes in requirements for training due to the substantial portion of pharmacy technicians working in this sector. There are concerns that current economic factors, combined with a training mandate, could add to their overhead costs, both through possible payment of registration or certification fees, and through Torin 1 molecular weight likely wage increases sought by technicians.[20] In addition, chains have questioned whether part-time technicians and/or technicians employed in

rural areas will have adequate access to training or certification programmes, and whether the added time and expense would have a negative impact on those part-time technicians. The National

Association of Chain Drug Stores has also stated that the education and training required of pharmacy technicians is not identical across all pharmacy settings. Therefore, the overall sentiment is that state boards of pharmacy should ultimately mandate any changes.[20] The ASHP strongly supports standards and accreditation of pharmacy technicians, and this is especially true today when there is more pressure to delegate tasks to technicians so that Cytidine deaminase pharmacists can spend more time with patients. The organization posits that the immense variability in the knowledge, skills and abilities of technicians impacts the pharmacist’s comfort level with delegating non-professional responsibilities. The ASHP contends that ‘The state-by-state haphazard approach to the education and training of technicians is impossible to justify to the public. The current situation puts pharmacy at serious risk for erosion of public confidence as consumers and health officials become more aware of gaps in the qualifications within the pharmacy technician workforce.’[20] Studies performed in hospitals have demonstrated that, with appropriate training and supervision, pharmacy technicians can have a positive impact on pharmacy workload, reducing medication errors and allowing the pharmacist more time to focus on clinical aspects of the job.

[36] Baricitinib is currently in phase 3 trials for RA. VX-509 is a selective JAK3 inhibitor currently in phase 2 and 3 investigation in the treatment of RA. Phase 2 studies compared 12 weeks of VX-509 monotherapy to placebo in patients who had failed a non-biologic DMARD. A significant response based on ACR20 and DAS28-CRP was seen with VX-509 dosed above 50 mg twice daily. Serious infections were noted, including a case of tuberculosis and pneumonia. As seen with tofacitinib and JAK3 inhibition, elevations in LDL,

HDL and transaminases were reported. No effect was seen on hemoglobin, neutrophils or creatinine.[37] GLPG0634 is a selective JAK1 inhibitor. Conceptually, this might lead to anti-inflammatory effects of IL-6 reduction without the side-effect profile of JAK2 and JAK3 inhibition. A 4-week phase 2a trial was performed buy GDC-0941 on 36 RA patients comparing GLPG0634 to placebo in those with inadequate response to MTX. A statistically significant response was seen in ACR20, DAS28 and CRP. Mild decreases in neutrophils and platelets counts were reported

without see more effects on hemoglobin, LDL, creatinine or transaminases.[38] A larger phase 2a study confirmed the efficacy previously seen as well as the safety profile.[39] Phase 2b trials were scheduled to start in 2013. Spleen tyrosine kinase (Syk) is another intracellular cytoplasmic tyrosine kinase. Syk has generated interest in the rheumatology community because it is downstream

from the B cell receptor and Fc receptors, which have integral roles in immunoreceptor signaling for macrophages, neutrophils, mast cells and B cells.[40, 41] Additionally, Syk plays an important role in osteoclast development and bone remodeling, adding to its attraction as a target for inhibition in RA treatment.[42] Syk is expressed in the RA synovial tissue and mediates TNF-α-induced production of cytokines such as IL-6 and metalloproteinase.[43] Fostamatinib (R788) is a Syk inhibitor that showed superiority over placebo in attaining ACR20, ACR50, ACR70 and DAS28 responses in a phase 2a trial of patients failing MTX.[44] Calpain In a second, 6-month phase 2 trial, fostamatinib continued to show efficacy over placebo in RA patients on background MTX, with statistically significant improvements in ACR20, ACR50, ACR70 and DAS28 responses at 100 mg twice daily and 150 mg daily dosing regimens. Side-effects included diarrhea, neutropenia and transaminitis. Hypertension was also noted as an adverse event, although patients responded to anti-hypertensive therapy with subsequent normalization of blood pressure.[45] A subsequent phase 2 study of fostamatinib 100 mg twice daily in patients with an incomplete response to biologic therapy failed to demonstrate efficacy based on ACR response criteria. A difference was reported on CRP levels and magnetic resonance imaging synovitis score despite the lack of clinical response.

Adaptation to specific

signals involves methylation of the MCPs, such that increased methylation will dampen the response to the specific ligand of the MCP. There are more than 43 MCPs annotated in the V. cholerae genome (Heidelberg et al., 2000). Vibrio cholerae possess a single polar flagellum, and flagellar-mediated chemotaxis contributes to V. cholerae colonization and infectivity. Vibrio cholerae strains with counterclockwise-biased rotation of the flagellum colonize the intestine to higher levels and have a lower infectious dose than normally chemotactic bacteria (Butler & Camilli, 2004). Nonchemotactic bacteria colonize the upper small signaling pathway intestine in addition to the lower small intestine, the location where normally chemotactic V. cholerae preferentially colonize, suggesting that chemotaxis functions to avoid colonizing the upper small intestine. Vibrio Belnacasan order cholerae shed in human stool is in a transient nonchemotactic state, and this enhances the infectivity of the organism, likely contributing to the spread of cholera epidemics (Merrell et al., 2002). One of the 43 V. cholerae MCPs, McpX (VC2161), was previously identified as contributing to diminished intestinal colonization of chemotactic bacteria, because

an mcpX mutant showed enhanced colonization of the infant mouse intestine (Lee et al., 2001). In this study, we investigated the role of two proteins regulated by ToxT and predicted to be MCPs, AcfB, and TcpI, in V. cholerae intestinal colonization. We found that while the absence of either AcfB or TcpI had no noticeable effect on colonization, the absence of both led to a decrease in intestinal colonization, suggesting that these proteins may have overlapping functions that contribute to colonization. Luria broth (LB)

was used for both liquid media and agar plates. The LB was routinely supplemented with antibiotics (ampicillin at 50 μg mL−1, streptomycin at 100 μg mL−1, and chloramphenicol at 2 μg mL−1) or 0.1% arabinose as required. The motility of the bacterial strains was measured in 0.3% LB agar supplemented with appropriate antibiotics and 0.1% arabinose as required. A complete list of plasmids and oligonucleotide primers used in this study can be found in Table 1. Restriction sites used in cloning are underlined Etomidate in the oligonucleotides listed in Table 1. Splicing by the overlap extension (SOE) PCR technique (Horton et al., 1989) was used to create the ΔacfB mutation, utilizing the primers acfBMet BHI paired with ΔacfB Up, and ΔacfB down paired with acfBStop EcoRI. The ΔacfB mutation is an in-frame deletion that removes the coding sequence for aa 180–446. The ΔtcpI∷Cm mutation was created by a SOE PCR technique involving three overlapping fragments (Liu et al., 2007), utilizing primers tcpI Dn KpnI paired with ΔtcpI Up, ΔtcpI Dn paired with tcpI Up KpnI, and Uni Dn paired with Uni Up; the latter pair were used to amplify the Cmr cassette from pKEK923.

2a–c), similar to the ΔAoatg8 disruptant (Kikuma et al., 2006). The ΔAoatg13 and ΔAoatg8 disruptants exhibit decreased levels of autophagy, particularly strain ΔAoatg8, in which autophagy is completely inhibited (Kikuma et al., 2006; Kikuma & Kitamoto, 2011) (Fig. 2b), indicating that the level of autophagic activity correlates with Akt inhibitor drugs the degree of conidiation and aerial hyphal growth (Kikuma & Kitamoto, 2011). Based on the lack of aerial hyphae and conidiation in ΔAoatg1, autophagy was likely completely inhibited in ΔAoatg1. To confirm the above speculation,

we generated a ΔAoatg1 strain expressing EGFP–AoAtg8 (ΔA1EA8). We previously demonstrated that the Atg8 ortholog in A. oryzae, AoAtg8, is a useful marker for detecting autophagy in A. oryzae (Kikuma et al., 2006). When the ΔA1EA8 strain was cultured in CD + m medium (growth condition), EGFP–AoAtg8 was localized in PAS-like structures, but was also diffused in the cytoplasm (Fig. 3a). After shifting the mutant to nitrogen-deprived medium (CD − N) to induce autophagy, EGFP–AoAtg8 fluorescence was observed in PAS-like structures, but could not be detected in vacuoles (Fig. 3a). Moreover, punctate structures with larger diameters than typical PAS-like structures were observed (Fig. 3a, arrows), and no cup-shaped isolation membranes or Y-27632 ring-like structures were detected. These observations indicated that the autophagic process was completely defective in the

ΔAoatg1 disruptant. To determine whether the Cvt pathway exists in A. oryzae and to evaluate the role of AoAtg1 in this pathway, we constructed strains expressing Aspartate AoApe1, which is an A. oryzae homolog of prApe1, fused to EGFP in the wild type (WT) and ΔAoatg1 backgrounds (Ku70aApe1EG and ΔA1Ape1EG, respectively). We selected prApe1 as it has been used as marker for the visualization of the Cvt pathway in S. cerevisiae (Harding et al.,

1995). Under normal growth conditions, prApe1 oligomerizes into homo-dodecamers and is then delivered to vacuoles by autophagic machinery, where it is cleaved to form the mature peptide. When the Ku70aApe1EG and ΔA1Ape1EG strains were cultured in CD medium for 20 h at 30 °C, AoApe1–EGFP was localized to vacuoles in WT, but appeared as punctate structures in ΔA1Ape1EG (Fig. 3b). These observations indicated that the Cvt pathway was functional in A. oryzae, but was completely defective in ΔAoatg1. PAS-like structures are normally observed at the periphery of vacuoles in yeast and filamentous fungi (Shintani et al., 2002); however, in strain ΔA1EA8 expressing EGFP–AoAtg8 and strain ΔA1Ape1EG expressing AoApe1–EGFP in the ΔAoatg1 background, the punctate structures observed in the perivacuolar region of ΔAoatg1 were also localized diffusely in the cytoplasm. Therefore, we consider that the structures observed in ΔAoatg1 were not normal PAS-like structures, but aggregates of AoAtg8 or AoApe1 oligomers.

Subsequent tests revealed that amygdala-lesioned animals only expressed juice preferences if they differed in ‘sweetness’. Unlike controls, orbitofrontal cortex-lesioned and medial prefrontal cortex-lesioned animals, they were unable to display preferences between juices matched for ‘sweetness’ i.e. 5% sucrose solutions BYL719 aromatised with different essential oils. The most parsimonious explanation is that

the amygdala contributes to the expression of food preferences based on learnt cues but not those based on an innate preference for sweetness. “
“Brain histamine is involved in the regulation of the sleep–wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1-methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine-N-methyltransferase PD0325901 molecular weight in C57BL/6J mice. In the C57BL/6J strain, histamine

release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively

correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24-h periodicity was observed. Brain tissue 1-methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine-N-methyltransferase in the striatum SSR128129E and cortex did not show a 24-h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12-h periodicity. These results show that the activities of histamine-metabolizing enzymes are not under simple direct circadian regulation. The complex and non-uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness. The histaminergic system is involved in the regulation of sleep, feeding behaviour, and hibernation (Haas & Panula, 2003). Gene knockout of the key histamine-synthesizing enzyme, histidine decarboxylase (HDC), leads to alterations in the circadian rhythm of motor activity and the expression of key genes involved in the mechanism of the biological clock, i.e. Period1 and Period2, in several brain areas in mice (Abe et al., 2004).