, 2011) are critical for each of their corresponding sortase activities. When two other residues (Leu263 and Thr265) in this motif were changed to Ala, the effect on the enzyme activity was minimal (Fig. 3). Regarding whether these two residues are important for sortase activity, there are no mutagenesis data available for comparison in other pilus-related sortases. However, in the nonpilus-related SrtA, the corresponding L181A mutation has modest effect on catalytic efficiency, while T183A mutation resulted in a

1200-fold decrease in kcat relative to wild-type SrtA (Frankel et al., 2007). Because our polymerization assay only indicates the presence or the absence of activity, not the rate of the enzymatic activity, quantitative methods

need to be developed to address the effect of these mutations more precisely. To this end, our dot-blot Palbociclib concentration results did show that there are less FimP selleck compound components on the surface of T265A mutant than on the surface of the wild-type strain (Fig. S1). It has been proposed that sortases use a catalytic triad composed of His-Cys-Arg during the catalytic process (Table 3). The His204 residue is most likely the His residue in the catalytic triad. The His 204 residue is located 6 Å from the Cys 266 SG atom (Persson, 2011). The H204A mutation effect is consistent with what has been reported about other histidine residues located in the catalytic triads. For instance, in pilus-related sortases, its counterparts His 131in SrtC-1 of S. pneumoniae and His157 in SrtC1 of Group

B Streptococcus were essential for pilus fiber formation in both organisms (Manzano et al., 2009; Cozzi et al., 2011). In the nonpilus-related SrtA from S. aureus, His120 residue at a similar location in relation to the essential Cys184 residue is also critical for the catalytic process (Ilangovan et al., 2001; Ton-That et al., 2002). However, the catalytic function of this critical histidine residue is still a subject of debate. It is speculated that the His residue, because it is being positively charged, might contribute to the electrostatic environment essential for the catalytic activity (Zong et al., 2004). Although the newly published crystal structure (Persson, 2011) showed that Arg275 is part of the His-Cys-Arg catalytic triad, our results Isoconazole indicate that this Arginine residue is not important for the SrtC1 activity in A. oris T14V. In contrast, its counterparts Arg202 in SrtC-1 of S. pneumoniae and Arg228 in SrtC1 of Group B Streptococcus are essential for the activity of the corresponding sortases (Manzano et al., 2009; Cozzi et al., 2011). Even in the nonpilus-related sortase SrtA, the Arginine 197 residue was identified to be important for the enzyme’s activity(Frankel et al., 2007). However, in SrtA, the Arg197 residue is 13 amino acids away from the essential Cys194 residue instead of the nine-amino acid distance between the arginine and cysteine residues in the SrtC catalytic triads.

, 2008). This value is significantly lower than the values typically found for other bacteria (−180 to −200 mV). Compounds interfering with the proton motive force,

such as uncouplers or ionophores, proved Palbociclib mouse strongly bactericidal on dormant M. tuberculosis in vitro (Rao et al., 2008), demonstrating that the proton motive force is an essential element of life under dormant conditions. It is an open question as to which enzyme is mainly responsible for the maintenance of the proton motive force during dormancy. Conceivable candidates for this task are nitrate reductase, whose activity is upregulated in the dormant state, or succinate dehydrogenase operating in reverse as a fumarate reductase (Schnorpfeil et al., 2001; Wayne & Sohaskey, 2001; Cox & Cook, 2007; Rao et al., 2008). In contrast, NDH-2, the predominant route for oxidation of NADH and for fueling of electrons into the respiratory chain in the dormant state (Rao et

al., 2008), does not translocate protons. The role of this enzyme may instead be to provide redox balance, as phenothiazine inhibition AZD1152-HQPA supplier of NDH-2 resulted in elevated cellular NADH concentrations (Rao et al., 2008). Furthermore, in contrast to the situation found in most bacteria, mycobacterial ATP synthase apparently cannot efficiently invert its function to pump protons across the membrane: ATP synthase from Mycobacterium phlei showed only a very low activity in ATP hydrolysis (Higashi et al., 1975), specific inhibition of ATP synthase in replicating and dormant M. smegmatis did not decrease the proton motive force (Koul et al., 2008) and membrane vesicles of Mycobacterium

bovis BCG were not able to establish a proton motive force Phosphoglycerate kinase using ATP (A.C. Haagsma & D. Bald, unpublished data). These results indicate that in dormant mycobacteria, ATP synthase is active in the production of ATP, which may provide the energy required for residual biosynthesis activity. ATP synthesis activity may also facilitate a continuous electron flow through the respiratory chain, and in this way, contribute to redox balance. Inhibition of either NADH oxidation or ATP synthesis or collapse of the proton motive force leads to killing of M. tuberculosis (Rao et al., 2008, see also Fig. 1). The respiratory chain of M. tuberculosis may show special adaptations for survival under dormant conditions and/or low proton motive forces. The activity of ATP synthase significantly depends on the proton motive force, with considerable variation between different organisms (Kaim & Dimroth, 1999). ATP synthase of M. tuberculosis may turn out to be active at lower membrane potential as compared with most bacteria or mitochondria. The molecular basis for this variation between species is obscure, although a role for the intrinsic inhibitory subunit ɛ and for the oligomeric, proton-translocating subunit c has been implied (Turina et al., 2006, see also Fig. 2). In the alkaliphilic Bacillus sp.

By manipulating the expression of possible downstream effectors of Dlx1, neuropilin-2 and p21-activated kinase 3, we provided evidence for the involvement of these two signaling molecules in Dlx1-dependent regulation of dendritic differentiation. Our experimental data support the idea that Dlx1 expression in developing interneurons specifically U0126 suppresses two important downstream regulators, leading to the characteristic morphology of Dlx1-expressing interneurons with less branched dendrites and few dendritic spines. “
“The diuretic bumetanide,

which acts by blocking the Na–K–Cl cotransporter (NKCC), is widely used to inhibit neuronal NKCC1, particularly when NKCC1 expression is abnormally increased in brain diseases such as epilepsy. However, bumetanide poorly penetrates into the brain and, in rodents, is rapidly eliminated because of extensive oxidation of its N-butyl sidechain, reducing the translational value of rodent experiments. Inhibition of oxidation by piperonyl butoxide (PBO) has previously been reported to increase the half-life and diuretic activity of bumetanide in rats. Here we studied whether inhibition of bumetanide metabolism by PBO also increases brain levels of bumetanide in rats, and whether this alters pharmacodynamic effects in the kindling model of epilepsy. Furthermore, we studied the effects Torin 1 purchase of PBO in mice. Mice eliminated bumetanide less rapidly than rats

(elimination half-life 47 min vs. 13 min). Pretreatment with PBO increased the half-life in mice to average values (70 min) previously determined in humans, and markedly elevated brain Phosphoribosylglycinamide formyltransferase levels of bumetanide. In rats, the increase in plasma and brain levels of bumetanide by PBO was less marked than in mice. PBO significantly increased the diuretic activity of bumetanide in rats and, less effectively, in mice. In epileptic mice, bumetanide (with PBO) did not suppress spontaneous seizures. In the rat kindling model, bumetanide (with or without PBO) did not exert anticonvulsant effects on fully kindled seizures, but dose-dependently altered kindling

development. These data indicate that PBO offers a simple means to enhance the translational properties of rodent experiments with bumetanide, particularly when using mice. “
“Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (htt) gene. Neuropathology is most severe in the striatum and cerebral cortex. As mutant htt is ubiquitously expressed, it has not been possible to establish clear structure-to-function relationships for the clinical aspects. In the present study, we have injected recombinant adeno-associated viral vectors of serotype 5 (rAAV5) expressing an 853-amino-acid fragment of htt with either 79 (mutant) or 18 (wild-type) glutamines (Q) in the dorsal striatum of neonatal rats to achieve expression of htt in the forebrain.

DRPs were identified in 20% of prescription items analysed (n = 172), affecting 38% patients (n = 155). Bureaucratic interventions concerning product availability and payment issues accounted for 55% and affected 11% of the prescription items analysed. The remaining 45% of DRPs concerned clinical and patient issues and affected 9% of prescription items. This study has shown that the secondary–primary interface is problematic with respect to DRPs. Although pharmacists Kinase Inhibitor Library supplier are in a position to identify and act on these DRPs, access to basic patient notes such as a discharge summary and including

pharmacists in the communication between secondary and primary providers should assist in achieving seamless care for the patient and help to identify

and prevent DRPs. “
“Objectives  To describe hospital pharmacy involvement in medication management in Ireland, both generally and at points of transfer of care, and to gain a broad perspective of the hospital pharmacy workforce. Methods  A survey of all adult, acute, public hospitals with an accident and emergency (A&E) department (n = 36), using a semi-structured telephone interview. Key findings  There was a 97% (n = 35) response rate. The majority (n = 25, CP-690550 molecular weight 71.4%) of hospitals reported delivery of a clinical pharmacy service. On admission, pharmacists were involved in taking or verifying medication histories in a minority (n = 15, 42.9%) of hospitals, while few (n = 6, Tau-protein kinase 17.1%) deployed staff to the A&E/acute medical admissions unit. On discharge, the majority (n = 30, 85.7%) did not supply any take-out medication, a minority (n = 5, 14.3%) checked the discharge prescription, 51.4% (n = 18) counselled patients, 42.9% (n = 15) provided medication compliance charts and one hospital (2.9%) communicated with the patient’s community

pharmacy. The number of staff employed in the pharmacy department in each hospital was not proportionate to the number of inpatient beds, nor the volume of admissions from A&E. There were differences identified in service delivery between hospitals of different type: urban hospitals with a high volume of admissions from A&E were more likely to deliver clinical pharmacy. Conclusions  The frequency and consistency of delivering pharmacy services to facilitate medication reconciliation at admission and discharge could be improved. Workforce constraints may inhibit service expansion. Development of national standards of practice may help to eliminate variation between hospitals and support service development. “
“Objective  The mini Peer Assessment Tool (mini-PAT) for pharmacists was introduced in 2006 as a formative method of assessing junior hospital pharmacists in the workplace and is the first widespread application of multi-source feedback (MSF) specifically within a pharmacy setting.

, 2009), pH (Gould & Lennarz, 1970; http://www.selleckchem.com/products/FK-506-(Tacrolimus).html Minnikin & Abdolrahimzadeh, 1974), temperature and the presence of organic solvents (Ramos et al., 2002; Bernal et al., 2007). The major phospholipid in logarithmic-phase staphylococcal cells is phosphatidylglycerol (PG).

PG is converted to cardiolipin (CL) during cell growth, and it constitutes 30% of the cell membrane in stationary-phase cells (Short & White, 1971). CL, which possesses four acyl groups and carries two negative charges (Schlame, 2008), can stabilize liposomes against osmotic stress (Nagamachi et al., 1992). In 1970s, biochemical studies indicated that CL was induced under conditions of high salt. Recently, we reported that CL is dispensable for growth under high salinity, but is essential for long-term survival under high salt conditions, suggesting that membrane composition needs to be modulated to adapt to conditions of high salinity (Tsai et al., 2011). In S. aureus, two CL synthase genes, cls1 and cls2, are responsible for CL synthesis (Koprivnjak et al., 2011; Tsai et al., 2011). A previous molecular genetic study indicated that cls2 encodes the major CL synthase that is responsible for CL accumulation under both normal and high salt conditions. In

contrast, the absence of cls1 had no significant effect on CL accumulation under the experimental conditions employed (Tsai et al., 2011). In addition, the cls1 mutant exhibited no difference from the wild type (WT) in any of the tested phenotypes, including growth rate, salt resistance and L-form generation (Tsai et al., 2011). These results raised the question find more why S. aureus has cls1 in addition to the housekeeping gene cls2. Koprivnjak et al. (2011), and we found that CL synthesis by cls1 is responsive to stress: CL production in a cls2 mutant was

induced during culture in high salt (15% and 25% NaCl), at a moderately low pH (pH 5.0), under anaerobic conditions (Tsai et al., GABA Receptor 2011), and during phagocytosis by polymorphonuclear leucocytes (Koprivnjak et al., 2011). In the present study, we aimed to clarify the stress responsive role of cls1, and we explored the conditions under which cls1, but not cls2, is exclusively responsible for CL synthesis. We used the FASTA search algorithm to examine the genomes of 30 bacteria whose genome projects have been completed. Cls homologues were downloaded from the KEGG database (Kanehisa et al., 2002). The amino acid sequences of the Cls homologues obtained from our FASTA search were aligned using the clustalx program (Jeanmougin et al., 1998). The alignment was used for phylogenic analysis with the protdist and neighbour programs of the phylip 3.6 package (Retief, 2000). The phylogenic tree was inferred by the neighbour-joining method (Saitou & Nei, 1987) and tested by 100 replications of bootstrap analysis, which was carried out using the seqboot and consense programs and visualized using the treeview program (Page, 1996). The S.

Secondly, <40% of the patients had nadir CD4 counts of ≥200 cells/μL, suggesting that most of the vaccine recipients in this study had moderate to severe immunosuppression caused by HIV infection. Therefore, the results may not be generalizable to vaccine recipients whose nadir CD4 cell find more counts are significantly higher. Thirdly, the vaccine schedule consisted of a single dose of 23-valent

PPV, which is different from many other vaccination studies in HIV-infected patients in which booster vaccination was administered 1–2 months after the first dose. The short observation periods of these studies did not allow determination of whether a two-dose vaccination schedule may enhance or prolong immunogenicity to PPV. Lastly, we did not use clinical disease as an endpoint in this serological study. Therefore, we were not able to determine whether the rapid decline of antibody responses is associated with increased risk for invasive pneumococcal infection during the 5-year follow-up period, although we only observed one case of pneumococcal pneumonia among our patients over the 5-year study period (data not shown). In conclusion, our study suggests that, despite continued increases in CD4 cell counts after HAART, the serological responses of HIV-infected patients receiving 23-valent PPV

declined significantly over the 5-year follow-up period, especially in those who had CD4 counts <100 cells/μL at vaccination and who failed to achieve virological suppression. Earlier revaccination may be needed RXDX-106 research buy to maintain better antibody responses in patients with moderate immunosuppression despite HAART. The authors would like to thank the National Science Council, Taiwan for financial support (grants NSC 93-2314-B-002-086 and 94-2314-B-002-14). Conflict of Interest: All authors, none to declare. Table S1. Proportions of HIV-infected patients who developed significant antibody responses to serotypes 14. 19F, and 23F in the 6th month, 1st year, 2nd year, 3rd year, 4th year, and 5th year after receiving 23-valent polysaccharide pneumococcal vaccine. Table S2. Univariate analysis of factors associated Isotretinoin with 2-fold or greater

increase of antibody responses to any serotype in the 1st year following 23-valent polysaccharide pneumococcal vaccination. Table S3. Univariate analysis of factors associated with 2-fold or greater increase of antibody responses to any serotype in the 2nd year following 23-valent polysaccharide pneumococcal vaccination. Table S4. Univariate analysis of factor associated with 2-fold or greater increase of antibody responses to any serotype in the 3rd year following 23-valent polysaccharide pneumococcal vaccination. Table S5. Univariate analysis of factors associated with 2-fold or greater increase of antibody responses to any serotype in the 4th year following 23-valent polysaccharide pneumococcal vaccination. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors.

, 2008) with Alexa Fluor 546-labeled phalloidin (Invitrogen) (1 : 200 dilution in BSP) for 1 h, washed twice with BSP and then mounted on a glass slide using mounting solution with 4′,6-diamidino-2-phenylindole. Once the slides were dry, coverslips were sealed using clear nail polish, and images were captured using green and red filters on an Olympus IX70 inverted fluorescence microscope equipped with a DP70 digital camera. The images were merged using imagej software (National Institute of Health). In our previous study (Puttamreddy et al., 2010), a mini-Tn5 transposon insertion library was constructed in E. coli O157:H7 strain EDL933

and 51 distinct genes/intergenic regions were identified to be involved either directly or indirectly Pembrolizumab in vivo in biofilm formation. All of the 51 biofilm-negative mutants showed reduced biofilm formation in a quantitative biofilm assay at P<0.05. To test whether biofilms on different surfaces may require different gene products, we subjected all 51 Bnp mutants to a quantitative biofilm test on polystyrene, polypropylene, polyvinyl chloride and glass. There was no statistical difference in the quantity of biofilms produced on any of the surfaces tested (Supporting Information, Fig. S1). To analyze the Enzalutamide cell line role of biofilm formation of E.

coli O157:H7 in adherence to T84 (human colonic epithelial) and HEp2 (human laryngeal epithelial) cells, wild type and Bnp mutants were tested for adherence in an in vitro adherence assay by both microscopic and quantitative analysis. We also constructed eae and esp deletion mutations as controls for potential adhesin–biofilm interactions.

Additionally, we tested a biofilm-positive transposon mutant (M1) as a control for nonspecific transposon effects on cellular adherence. The quantitative adherence assay (significance P<0.05) showed that all 51 Bnp mutants lost their adherence to both T84 and HEp2 cells after a 90-min infection when compared with wild type (Fig. 1, Table S1). This was also true for the eae and espAB deletion mutants as expected (Fig. 1, Table S1) because both of these genes have been shown previously to be important to cellular adherence (Yu & Kaper, 1992; Ebel et al., 1998). For microscopic analysis, all of the bacterial strains were transformed with a green fluorescent protein-expressing plasmid, pISM31. pheromone Escherichia coli O157:H7 EDL933 wild type adhered to both cell types while all of the 51 Bnp mutants failed to adhere. A biofilm-positive mini-Tn5Km2 mutant of E. coli O157:H7 EDL933 (M1) showed no significant loss in either biofilm formation or adherence when compared with the wild type (Figs 2 and 3, also see Fig. S2 for a higher magnification of wild-type adherence to the two cell types). This eliminates the possibility of a nonspecific effect between mini-Tn5Km2 insertions and loss of adherence. To identify whether loss of adherence leads to a loss of biofilm phenotype, deletions in eae and espAB, both well-known adhesins (Jerse et al.

We excluded conference abstracts because the STROBE and CONSORT criteria were designed to evaluate published manuscripts AZD1208 concentration and abstracts lack the necessary data required for evaluation.[9, 10] Lastly, if the pharmacist participated in the study intervention, but the research was not designed to examine the HIV pharmacist’s contribution, the study was excluded. In these types of studies, the pharmacist’s involvement was often limited to antiretroviral dispensing only or dispensing directly observed therapy only. The authors considered several tools

to assess thoroughness of reporting in manuscripts and opted to apply STROBE criteria to observational studies and CONSORT criteria to randomized studies.[9, 10] Criteria were rated as present (yes), absent (no) or not applicable to the study. Compound criteria, which included multiple assessments, were separated for consistency of evaluation. Authors held a preliminary discussion of each criterion in the STROBE and CONSORT checklists to guide AUY-922 the initial interpretation. A small list of additional criteria deemed important by the authors and

relevant to studies of HIV pharmacists were assessed separately from STROBE or CONSORT criteria. These included concordance of the declared study design with Cochrane classifications, description of HIV pharmacist training or prior experience and evaluation

of key outcomes measures such as adherence, CD4+ cell count and HIV-1 viral load.[6] Each study was independently reviewed by two authors (JC/PS or JC/BD) for presence or absence of the required STROBE, CONSORT or additional criteria. Inter-reviewer agreement on the criteria evaluated for each study was assessed using an unweighted kappa statistic, calculated for each study using STATA version 12.0 (StataCorp, College Tacrolimus (FK506) Station, TX, USA).[11] If the two primary reviewers had different ratings (present versus absent versus not applicable) on a particular criterion within a manuscript, the reviewers met to see if the disagreement could be resolved through discussion. In the seven instances that a disagreement could not be resolved through discussion, a third author was asked to review the study and provide final input. Descriptive statistics were used to calculate the frequency at which studies satisfied various criteria and the overall proportion of criteria that each study satisfied. The criterion inclusion rate was summed across all observational studies and divided by 19, or summed across all randomized studies and divided by three, to obtain an average inclusion rate. Of the initial 1545 citations, 1477 were discarded after abstract review because they were duplicate or irrelevant. The remaining 68 articles were reviewed by two authors (PS/JC).

, 2009) on December 2010 were downloaded. The 16S rRNA gene sequences from each group were aligned using clc Workbench 4.2 (CLC bio, Aarhus, Denmark). The Pseudomonas and Burkholderia 16S rRNA gene sequence contains three hyper variable regions (HVR) and several minor variable regions (Moore et al., 1996; Baker et al., 2003). The HVR is the candidate spot to detect sequence variation from genus to species level, whereas conserved regions flanking the variable regions

as well as inside the alignments for the two microbial groups were manually checked to locate the optimal sequences for primers Fluorouracil nmr and probes. The specificity of all possible primer and probe sequences was tested in the RDP probe match software. Furthermore, in silico validation of selected primers and probes was carried out in clc 4.2 and Amplify 3X software. The dual-labelled probes were designed with a fluorophore (6-carboxyfluorescein/FAM) and a quencher (Black Hole Quencher BHQ I) linked to the 5′ and the 3′ ends, respectively. The characteristics of the two qPCR assays developed in this study are summarized in Table 1. To verify that the primers were suitable for studies of intra-genus diversity, an in silico analysis was performed in which the internal sequence variation between the forward and reverse primers

was tested. The regions between the primers (possible amplicons) were recovered from alignment of the entire 16S RNA gene (for INK 128 cost all 116 and 55 type sequences), and partial alignments were conducted (clc 4.2.). The partial alignments Histone demethylase were checked for suitable internal base variation, and phylogenetic neighbour-joining trees were constructed [SplitsTree (Huson & Bryant, 2006)] to verify possible species separation. All qPCRs were performed using 25 μL reactions on the Mx3000 (Stratagene, Cedar Creek, TX). The qPCR program and the reagents concentrations were identical in all SYBR Green I assay reactions consisting of 1× of Brilliant SYBR Green

QPCR Master Mix (Stratagene), 385 nM of forward primer and reverse primer and 2 μL sample DNA. The qPCR conditions were 10 min at 95 °C followed by 40 cycles of 95 °C for 30 s and 1 min at 60 °C ended by a dissociation curve segment. Fluorescent measurements were taken at the end of every merged annealing/extension steps. In the hydrolysis probe assay, the reactions contained the following: 1× TaqMan Environmental Master Mix 2.0 (Applied Biosystems, Warrington, UK), 770 nM forward primer and reverse primer, 100 nM probe and 2 μL sample DNA. The qPCR program consisted of 10 min at 95 °C, followed by 45 cycles at 95 °C for 30 s, and 1 min at 60 °C (merged annealing/extension steps). For validation, the data trend from the developed qPCR assays was compared with a 16S eubacterial qPCR assay (see Table 1 for primer details; Fierer et al., 2005).

, 2001), as well as line drawings of airplanes during fear conditioning (Hamm et al., 2003). In contrast, pulvinar damage impairs rapid processing of visual threat in humans (Ward et al., 2005). A recent this website neurophysiological study reported that monkey pulvinar neurons differentially respond to various emotional expressions in photos of humans (Maior et al., 2010). This subcortical pathway, comprising the superior colliculus, pulvinar and amygdala, is also implicated in rapid processing of facial information, including gaze direction (Johnson, 2005). Newborn babies with an immature cortical system preferentially orient toward faces

with direct gaze and schematic face-like patterns (Johnson et al., 1991). Although this suggests pulvinar LY2606368 purchase involvement in processing of facial and face-like stimuli, previous neurophysiological studies used only moving dots, gratings or simple patches. Consequently, evidence that pulvinar neurons process facial stimuli has been lacking. In the present study, we investigated neuronal responses to these stimuli in the monkey pulvinar. Two adult (one female and one male) macaque monkeys (Macaca fuscata), weighing 7.2–9.5 kg, were used in this experiment. Each monkey was individually housed with food available ad libitum. The monkeys were deprived of water and received juice as a reward during

training and recording sessions. Supplemental water and vegetables were given after each day’s session. To assess the monkeys’ health, their weight was routinely monitored. The monkeys were treated in strict compliance with the United States Public Health Service Policy on Human Care and Use of Laboratory Animals, the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the Guidelines for the Care and Use of Laboratory Animals of the University of Toyama. The study had been approved by the Committee for Animal Experiments and Ethics at the University L-NAME HCl of Toyama. The monkey sat in a monkey chair 68 cm away from the center of a 19-inch computer display for behavioral tasks during the training and recording sessions in a

shielded room. The CRT monitor was set so that its center was on the same horizontal plane as the monkey’s eyes. The monkey chair was equipped with a responding button, which was positioned so that the monkey could easily manipulate it. An infrared charge-coupled device camera for eye-movement monitoring was firmly attached to the chair by a steel rod. During training and recording sessions, the monkey’s eye position was monitored with 33-ms time resolution by an eye-monitoring system (Matsuda, 1996). The juice reward was accessible to the monkey through a small spout controlled by an electromagnetic valve. A PsyScope system (Carnegie Mellon University, Pittsburgh, PA, USA) controlled the electromagnetic valve and sound signal, as well as the timing of outputs to the CRT monitor.