Real-time PCR analyses showed that mRNA levels of the genes from TF1059 to TF1065 in the mutant were reduced to 14–39% of the wild-type levels (Table 2). These results suggest that the expression of the putative glycosylation-related gene cluster is under the positive control of the see more TF0022 HTCS. Based on the similarity of subdomain architectures and homology of polypeptide sequences as well as the characteristic phenotype (i.e. enhanced autoaggregation) of the mutant cells, we predict that the TF0022 protein is a GppX ortholog with an N-terminal truncation. An original single ORF may have been divided into TF0023 and TF0022 by a nonsense mutation, the two separately

translated polypeptides might functionally complement each other, or these ORFs may be cotranscribed and translated as a fusion peptide by stop codon skipping. The TF0022 disruption mutant exhibited distinct phenotypic properties compared with the wild-type strain, indicating that the TF0022 polypeptide alone maintains a certain level of functionality. Development of gene complementation techniques for T. forsythia is still in progress, and an examination of the functionality of the TF0022 protein with or without the TF0023-encoding portion will be the focus of future work. A systematic sequence analysis of the TF0023-TF0022

locus in clinical isolates may also test our prediction. We cannot exclude the possibility that the culture conditions used in this DAPT study were not suitable for full activation of this HTCS protein. Among Gram-negative oral anaerobes, the genetic loci known to affect autoaggregation

or biofilm formation include a capsular polysaccharide gene cluster in P. gingivalis W83 (Davey & Duncan, 2006), and the exopolysaccharide synthesis operon in T. forsythia ATCC 43037 (Honma et al., 2007). In the present study, we identified TF1061 glycosyltransferase as the gene product most upregulated by TF0022 and showed that the transcription of the TF1061-containing gene cluster is reduced in the TF0022 mutant. This finding may link autoaggregation of T. forsythia to the O-methylated flavonoid glycosylation rate of cell surface components regulated by the HTCS. The reduced apparent masses of two S-layer proteins in denatured gels suggest that the disruption of TF0022 caused a defect in post-translational modification of these cell surface components. One of the identified S-layer proteins, TF2663, differed in theoretical and apparent masses on the 2D-PAGE gels (152 and 80–90 kDa, respectively) and might be a short fragment of the S-layer protein resulting from an endogenous protease activity. The type of modification of the S-layer proteins that was affected is unknown, but S-layer proteins are highly glycosylated (Lee et al., 2006).

They secrete proteins such as tPAI-1, tumour necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin, resistin, and leptin [11]. An excess or deficiency of these adipokines in cases of obesity or lipoatrophy is thought to play an important

role in the development of IR, positive energy balance, endothelial dysfunction and abnormal fibrinolysis [11,22]. Serum leptin concentrations reflect body fat content and are associated with IR [11]. Increases in leptin may also be explained by so-called leptin resistance [23]. Furthermore, the increase in circulating resistin levels may reflect fat redistribution, as it has been found to correlate with the amount of visceral fat [24]. However, we did not find an association of leptin or resistin with lipodystrophy

or HOMA values, which only increased during the Selleck Selumetinib Gemcitabine chemical structure first year on HAART. This lack of an association of leptin or resistin with lipodystrophy or HOMA values may be attributable to the increase in adiponectin levels, which happened at the same time as increases in leptin levels because of a compensatory mechanism for IR [3,25]. The possibility that the follow-up time in our study was not long enough to show adipokine levels to be associated with lipodystrophy should also not be excluded. A previous report on HIV noninfected children showed that leptin and BMI values increased over the 3-year follow-up period [26], while our data show an increase in plasma leptin levels in HIV-infected children on HAART despite a lack of change in BMI. Finally, leptin regulates proinflammatory immune responses because leptin is capable of controlling TNF-α production and macrophage activation

[27]. Moreover, it appears that TNF-α SB-3CT and IL-6 are capable of stimulating adipocyte leptin production [27]. Alternatively, an increase in leptin levels might be a manifestation of a chronic activation process observed with increasing tPAI-1, an important inhibitor of fibrinolysis, which is increased in metabolic syndrome and lipodystrophy and has been shown to be an independent risk factor for cardiovascular disease [11,22]. We observed a significant increase in tPAI-1 after patients started HAART, which may be associated with dysregulation of the TNF system, decreased fibrinolysis and increased coagulability [28], and thus represent an additional risk factor for cardiovascular disease in this patient group [29]. Furthermore, we did not find a significant increase in cholesterol or triglyceride levels, and only a few children in our study had significant hyperlipidaemia during follow-up. It is possible that plasma lipid levels in the peripheral blood do not show a close correlation with chronic immune activation, metabolic disorders or endothelial disease in HIV-infected children. Adiponectin has been found to be inversely associated with components of metabolic syndrome such as obesity, IR and type II diabetes [11].

All of the chemicals and oligonucleotides were purchased from Sigma (Hamburg, Germany). Both of the strains were maintained at 4 °C on potato dextrose agar (PDA) slants in the dark. The

fungus was transferred to fresh PDA plates and incubated at 20 °C for 7–14 days for further experiments (Zhan et al., 2006). Fungal genomic DNA was isolated from 8-day-old PDA liquid cultures according to a published procedure (Jiang & Yao, 2005). The NRPS and PKS genes were screened by PCR using the primers listed in Supporting Information, Table S1 in a 50-μL reaction containing 1.5 mM MgCl2, 0.2 mM each dNTP, 0.5 μM each primer, 2.5 units Taq DNA polymerase, and the buffer provided by the manufacturer (Invitrogen, Darmstadt, Germany). The thermal cycling conditions were as follows: initial denaturation at 94 °C for FK506 price 3 min; 35 cycles of 94 °C for 45 s, 55 °C

for 30 s, and 72 °C for 2 min; and a final extension at 72 °C for 10 min. The PCR products were separated on a 1.5% agarose gel, and the bands of the expected sizes were excised and purified using the Invisorb DNA Cleanup kit (Invitek GmbH, Berlin, Germany). The purified fragments were cloned using the TOPO TA Cloning kit (Invitrogen) Sorafenib and sequenced. The libraries were constructed using the CopyControl Fosmid Library Production kit (Epicentre Biotechnologies, Madison, WI). The libraries were screened using colony PCR under the conditions described above but with gene-specific primers designed from the determined PCR products (Table S1). The fosmids were isolated from overnight cultures of Escherichia coli EPI300 clones using a Nucleobond Xtra Midi Kit, according to the manufacturer’s instructions (Macherey-Nagel, Düren, Germany). The insert size was estimated Buspirone HCl by digestion with restriction enzymes HindIII and EcoRI. The fosmids were sheared using a HydroShear DNA Shearing Device (GeneMachines, San Carlos, CA) and were cloned into an SmaI-digested pUC19 vector (Fermentas, St. Leon-Rot, Germany) for shotgun sequencing. Plasmid preparation was performed using the 96-well Robot Plasmid Isolation kit (NextTec, Leverkusen, Germany) and a Tecan Evo Freedom 150 robotic

platform (Tecan, Männedorf, Switzerland). Pair-end reads were obtained using an ABI 3730xl automatic DNA sequencer (PE Applied Biosystems, Foster City, CA). Vector clipping, sequence trimming and assembly were performed using the lasergene (DNAStar Inc.) and the staden (http://staden.sourceforge.net/) software packages. The open reading frames (ORFs) were predicted using the SeqBuilder program of the lasergene package and confirmed with a blastp search using the encoded whole protein sequences at the National Center for Biotechnology Information (NCBI). The domain assignment was first performed by aligning the protein sequences with known sequences and was confirmed by identifying the signature sequences. The NRPS adenylation domain specificity was predicted using nrpspredictor2 (Rottig et al.

FCM was performed as described previously (Feng et al., 2009), with slight modifications. Briefly, the overnight cultured 05ZYH33 cells were harvested by centrifugation.

The bacteria were Selleck MK-1775 then washed in PBS and adjusted to 108 CFU mL−1. Bacteria were incubated with rabbit anti-HtpS sera or preimmune sera for 1 h at 4 °C. Following three washes with PBS and incubation with fluorescein isothiocyanate (FITC)-conjugated goat anti-rabbit IgG (Sigma) for 1 h, the cells were fixed in 2% paraformaldehyde for 30 min, and examined using a flow cytometer (BD). The C3 deposition assay was performed as described previously (Ochs et al., 2008), with some modifications. Streptococcus suis 2 05ZYH33 was grown in TH broth to a mid-logarithmic growth phase. The bacteria were harvested by centrifugation for 2 min at BAY 57-1293 price 8000 g, washed three times with PBS and then adjusted to approximately 5 × 109 CFU mL−1. Bacterial suspension (20 μL) was incubated with 380 μL of heat-inactivated rabbit anti-HtpS sera of different concentrations (0%, 1%, 5%, 25% and 50%) at 37 °C for 30 min. Fifty percent of normal human sera or preimmune rabbit sera were used as controls. The bacteria were then washed in PBS, suspended in 20% healthy

newborns’ sera (source of complement) and incubated at 37 °C for 30 min. The bacteria were then washed three times with PBS and incubated with FITC-conjugated mouse anti-human C3 antibody (Cedarlane, Canada) at room temperature for 30 min. After washing enough three times with PBS, the percentage of FITC-positive bacteria was detected by FCM. To evaluate the bactericidal activity of the rabbit anti-HtpS sera, an in vitro whole-blood bactericidal

assay was performed as described previously (Terao et al., 2005), with some modifications. Streptococcus suis 2 05ZYH33 cells were cultured to a mid-logarithmic growth phase, and harvested by centrifugation for 2 min at 8000 g. After washing three times with PBS, the bacteria were adjusted to 1 × 105–5 × 105 CFU mL−1 with PBS. Heparinized whole blood (375 μL) from healthy humans was mixed with 20 μL of rabbit anti-HtpS sera. Preimmune sera were used as a negative control. Then, 10 μL of bacterial suspension was added to the mixture and rotated at 37 °C for 1 h. Aliquots were plated on THB agar plates and cultured at 37 °C for 48 h before the colonies on each plate were counted. The HtpS protection test was performed as described previously (Liu et al., 2009), with some modifications. Briefly, 4-week-old, SPF grade female BALB/c mice (SLAC, China) were divided into two groups (10 mice per group). Group 1 was immunized subcutaneously with approximately 25 μg of purified rHtpS protein emulsified with Freund’s complete adjuvant. After 14 and 21 days, the mice were booster immunized with the same concentration of rHtpS emulsified with Freund’s incomplete adjuvant, respectively.

) at a wavelength of A550 nm. The amount of FC absorbed into the H. pylori cells was quantified

based on the FC-standard curve and calculated per the CFU. Helicobacter pylori cell suspension (600 μL) was cultured for 24 h with various volumes of FC beads (FC concentration: 30–90 μM) in a simple-PPLO broth (15 mL) containing progesterone (30 μM), with continuous shaking under microaerobic conditions in the dark, and the CFUs were Selleck BTK inhibitor then measured. Next, an H. pylori cell suspension (600 μL) was cultured for 24 h with various concentrations of progesterone (from 10 to 30 μM) in a simple-PPLO broth (15 mL) containing FC beads (FC concentration: 500 μM) or the FC-free beads (in a similar volume), with continuous shaking under microaerobic conditions in the dark, and the CFUs were then measured. In our first experiments, we investigated the effects of the steroid hormones estradiol, androstenedione, and progesterone in inhibiting the growth of H. pylori. NSC 683864 mouse When H. pylori (approximately 105.5 CFU mL−1) was cultured for 24 h in different simple-PPLO broths (3 mL) containing single steroids at concentrations ranging from 10 to 100 μM, every steroid hormone examined exhibited inhibitory effects on the growth of H. pylori at concentrations >50 μM (Fig.

1). Estradiol appeared to act bacteriostatically on H. pylori, as the CFUs of H. pylori cultured in the presence of estradiol at the 50 and 100 μM concentrations were entirely unaltered from the baseline CFU (105.5 CFU mL−1) before the cultures (Fig. 1a). In contrast, androstenedione and progesterone Thymidylate synthase exhibited growth-inhibitory effects that were dependent on the dose against H. pylori (Fig. 1b and c). Androstenedione, however, was less potent than progesterone in inhibiting the growth of H. pylori. The CFUs of H. pylori cultured for 24 h with androstenedione at the 100 μM concentration

were slightly lower than the baseline CFU (105.5 CFU mL−1), whereas the CFUs of the organisms cultured for 24 h with progesterone at the 100 μM concentration were below the limits of detection. Thus, progesterone demonstrated the most effective anti-H. pylori action of the three steroid hormones, and it appeared that this action was bactericidal to H. pylori. This led us to investigate the antibacterial effect of progesterone on H. pylori in more detail. Progesterone has two derivatives: 17α-hydroxyprogesterone (17αPS) and 17α-hydroxyprogesterone caproate (17αPSCE). The derivatives 17αPS and 17αPSCE are modified by a hydroxyl group and an acyl group (caproic acid), respectively, at the carbon 17 position of the progesterone framework (Fig. 2). Noting this, we next examined the anti-H. pylori action of 17αPS and 17αPSCE using the simple-PPLO broth. Surprisingly, 17αPS, a natural progesterone derivative, had no influence on the growth of H. pylori.

The aim of this study was to determine whether a caries infiltrant resin material is capable of penetrating MIH-affected enamel. Ethical approval was obtained to collect extracted teeth (from private and public paediatric specialist practices), which were

then placed in 4% neutral buffered formaldehyde for at least 2 weeks, rinsed, and stored at 4°C and 100% humidity until use. Both MIH affected (n = 17) and sound (n = 3) teeth were collected. MIH lesion types (white/cream or yellow/brown) were divided as equally as possible into three groups (n = 7 per group) and the Icon® Caries infiltrant (smooth surfaces) clinical kit (DMG, Hamburg, Germany) used to apply HCl etch, ethanol, and infiltrant resin according to manufacturer instructions (standard group) [12], or with an additional step of 2 min

0.95% w/v NaOCl irrigation followed by 2 min water rinsing prior to or following etching (pre-treatment selleck chemicals llc group and mid-treatment check details group, respectively). Lesions were sectioned 24 + hrs post-curing using a water cooled diamond embedded circular saw (Minitom, Struers, Denmark) and polished with successively finer grade silicon carbide paper (600–4000 grit). Sections were examined under a light microscope (Leica L2, Wetzlar, Germany) before undergoing Vickers microhardness testing (MHT-10, Anton Paar, Austria) while hydrated (F = 0.5 N, t = 5 s). Data were obtained from captured microscope images using appropriate standards and image analysis software

(ImageJ, NIH, Bethesda, MD, USA) and entered into Excel (Microsoft Corp, Washington, USA) software for analysis. Due to the inherent variability of hardness in MIH lesions, change in hardness was determined by comparing values of infiltrated and non-infiltrated enamel as closely adjacent as possible. Descriptive statistics and ANOVA and t-tests with the critical level for significance set at P < 0.05 were undertaken using the same software. Additional sections were gold sputter coated and surfaces examined using scanning electron microscopy (SEM) at 10 kV (FEI Quanta SEM). Light microscopic examination showed significant, but erratic, infiltrant resin penetration of MIH enamel for most lesions (Fig. 1); however, however two lesions were found to be confined to the inner half of enamel, and so, no apparent infiltration had occurred. There was no statistically significant difference between either lesion type or infiltration protocols in terms of absolute or percentage depth or percentage area of penetration (Table 1). Vickers microhardness increased, relative to the immediately adjacent hypomineralised enamel, in areas where visible infiltrant penetration had occurred: 3.0 ± 1.8 GPa v 1.8 ± 1.2 GPa (control 4.4 ± 1.0 GPa). The mid-treatment NaOCl group demonstrated the greatest changes in hardness; but, this was due to one outlying sample where a 12-fold, corresponding to a 2.

The results also confirm that protein transfer across the blood–CSF barrier is developmentally and physiologically regulated. “
“Deep brain stimulation (DBS) is currently being investigated as a therapy for the treatment of depression. Despite promising results

of recent clinical trials, neural and chemical mechanisms responsible for the effects of stimulation are still unclear. In this article, we review clinical and laboratory findings on DBS for depression. Particular emphasis will be given to aspects involved in the translation of data from animal models to humans and in our findings on the potential substrates involved in the antidepressant effects of DBS in rats. “
“Although promise exists for patterns of resting-state blood oxygen level-dependent (BOLD) PD98059 functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature Natural Product Library of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi-laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two-dimensional optical imaging spectroscopy measurements of resting-state haemodynamics

that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting-state haemodynamic fluctuations taken after neural ‘events’ closely Carbachol resembled the temporal profile of stimulus-evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting-state haemodynamic fluctuations resembling the temporal profile

of stimulus-evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting-state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus-evoked neurovascular responses. “
“Ample evidence suggests that, when reactivated by a reminder, a consolidated memory may return to a labile state and needs to be stabilized again in order to persist, a process known as reconsolidation. In a previous study, performed in the crab Chasmagnathus, we found a dual role for the biogenic amine octopamine (OA) during memory consolidation. On the one hand, it was necessary for appetitive memory formation and, on the other, it had a deleterious effect on aversive memory consolidation.

88. These results were comparable to the original version. The Thai version of the HAQ is valid for assessing functional status in patients with PsA; however, its validity may be limited in patients who have ICG-001 nmr axial involvement or permanent joint damage. “
“We describe the clinical profile of elderly with primary antiphospholipid syndrome (APS). Charts of seven elderly patients diagnosed with

APS between 1996 and 2012 were retrospectively assessed. The mean age at diagnosis was 77 ± 6 years (67–84 years). Two patients had experienced frequent miscarriages. Five patients presented with deep venous thrombosis of the lower limb, one had venous thrombosis of the upper limb and brachiocephalic vein and another had a cerebral ischemic stroke. The antiphospholipid antibodies Dasatinib chemical structure tests revealed the presence of significant amounts of anticardiolipin antibodies, 12 weeks apart, twice in four patients. The antibodies to β2-glycoprotein 1 were positive twice in two patients and lupus anticoagulant in one of these. All patients were treated with heparin and long-term anti-vitamin K and thrombosis was cleared in all cases. Two patients presented with bleeding complications: hematuria and hematoma of the buttock in one patient and rectal bleeding in another case. Two elderly developed a colon cancer and lymphoma 1 year later. In this report, we report on primary APS in the elderly, to discuss its prevalence and the clinical

significance of positive antiphospholipid Dichloromethane dehalogenase antibodies in subjects over the age of 65 years. “
“Asia Pacific League of Associations for Rheumatology (APLAR) celebrated its 50th birthday last year in beautiful Bali. The South East Asia and Pacific Area League Against Rheumatism (SEAPAL), as it was called in formative days, was started with initiatives of stalwart Rheumatologists from Australia, India, Japan and New Zealand. Today it also includes rheumatology societies from central Asia, the Middle East region, the Indian subcontinent, China, Southeast and Far East Asia. A first meeting was held at Mumbai in 1968.

From this year, APLAR congress is going to be an annual event similar to the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). However, the science of rheumatology and autoimmunity in most of the APLAR countries is far from matching that of ACR and EULAR. With the economic disparities between APLAR countries in mind, this year’s theme of ‘sustainable rheumatology’ makes sense. Only relevant scientific research and quality training can realize this slogan in the higher specialty of rheumatology and immunology. There are many resourceful nations in the APLAR region; the resource-limited countries, on the other hand, have talented human resource and a goldmine of large cohorts of patients. One can very well imagine the strength of combined data from populous nations like China and India. Together, we can get there. Forming special interest groups (SIG) can go a long way in this direction.

After 1 week, the PRL2010pNZ8048 supplementation was discontinued, and after one additional week, the animals were killed. To follow PRL2010pNZ8048 colonization, fecal samples were collected periodically (on

days 0, 2, 5, 9, 12, and 15), and PRL2010pNZ8048 cell enumeration was performed by plating fecal material on MRS–Cys–Agar supplemented with chloramphenicol. After incubation at 37 °C, the identity of colonies grown on MRS supplemented with chloramphenicol was further evaluated using PCR and employing PRL2010-specific primers that target pili-encoding loci, which have been described previously (Turroni et al., 2010; Foroni et al., 2011). The inoculated bacterial population increased in number (Fig. 2), reaching a maximum of 107 CFU g−1 feces at day 5. Interestingly, following this rapid increase

Palbociclib purchase of PRL2010 cell numbers during the period of bacterial supplementation, the level of PRL2010 cells decreased to reach a plateau of approximately 105 CFU that appeared to remain stable during the full length of the post-treatment period (Fig. 2). Notably, the presence of high numbers of PRL2010pNZ8048 cells upon a period of 7 days without any supplementation with bifidobacterial cells reinforces the notion that the plasmid is stable. Altogether these data indicate that PRL2010 is capable of colonizing the intestine of mouse, which will open new avenues in the exploration of host–microbe interactions of this microorganism BAY 57-1293 manufacturer using an in vivo murine model (O’Connell Motherway et al., 2011). This study describes an optimized protocol for the transformation of bifidobacteria Histamine H2 receptor that enables the establishment of plasmid DNA into two very distantly related species, that is, B. bifidum and B. asteroides taxa, where in the

latter case it represents the first report on plasmid-mediated transformability. The transformation rates achieved were sufficiently high for cloning purposes; nonetheless, the experiments so far performed highlighted transformation efficiency of 104 CFU μg−1 which is not yet high enough for site-directed mutagenesis and for an effective selection of transformants in gene knock-out experiments (O’Connell Motherway et al., 2009). The next step will be to improve the transformation efficiency, which could be achieved by overcoming the restriction modification systems of this microorganism (O’Connell Motherway et al., 2009). Genetic tools to manipulate bifidobacteria are still largely undeveloped and represent a bottleneck in the advancing of knowledge on this important group of microorganisms. Thus, the transformation protocol and subsequent colonization model described in this study offer two important adjuncts in exploring genomic functionalities of bifidobacteria under in vitro as well as in vivo conditions. We thank GenProbio srl for the financial support of the Laboratory of Probiogenomics. This work was financially supported by a FEMS Advanced Fellowship 2011 and an IRCSET Embark postdoctoral fellowship to F.T.

This suggests that while tDCS was interfering with frequency discrimination it did not interfere with the ability to perform the task. Because DLFs were still significantly higher for the tDCS group than the sham group on Day 2, all subjects who received this treatment were contacted to complete a third day of testing without stimulation; all but one was re-tested between 48 and 109 days (median = 64 days) after the initial test day. To determine if the tDCS group’s performance returned to normal levels, it was selleck products compared with the sham group’s performance on Day 2. Fig. 3 shows DLFs (upper panel)

and response times (lower panel) for the tDCS group’s Day 3 results (n = 6) and those for the sham group’s performance on Day 2 (n = 8). Re-tested DLFs for the tDCS group were similar to those for the sham group on Day 2 (F2,24 = 4.26, P = 0.06,  = 0.49) and considerably smaller than the this group’s DLFs 1 day after stimulation (0.85 and 1.19 Hz, respectively). Response times were also similar between the tDCS group’s re-tested results and the sham group’s performance on Day 2. Contrary to expectations, anodal tDCS over auditory cortex did not accelerate rapid frequency discrimination learning, but did degrade frequency discrimination, with the mean DLF in the tDCS group about 0.8 Hz higher than that in the sham stimulation group. This degradation was still present on the testing session 1 day

after stimulation with DLFs being ~0.6 Hz higher, showing that the effects of changing cortical excitability persisted for at least 24 h after stimulation, but was not present 2–3 months following stimulation, showing that the effect Barasertib in vivo was not permanent. As response times for both groups were similar and decreased with training it is unlikely that the effect of stimulation was due to stimulation inhibiting task performance. The results overall suggest strongly that the increased DLFs for the tDCS group are a genuine perceptual degradation rather than a more general impairment Adenosine triphosphate in the ability to

perform the task. Frequency selectivity, quantified as ERB values, relies on place coding, which is thought to be one process that underlies frequency discrimination. We hypothesized that if tDCS degraded frequency discrimination by affecting place coding it would be evident in broader ERBs. Fig. 4 shows representative PTCs for the 1000- and 2000-Hz test tones during a tDCS and a sham stimulation session. As shown, the amplitude of the narrow-band noise was lower when it contained frequencies near that of the test tone. For this subject, PTCs for the 1000-Hz test tone were very similar during both tDCS and sham stimulation sessions. For the 2000-Hz test tone, the PTC was broader during tDCS than sham stimulation, showing that a wider range of noise frequencies interfered with detection of the test tone. Mean ERB values for the tDCS and sham stimulation sessions for the 1000- and 2000-Hz test tones are shown in Fig. 5.