Patients who fail to respond to these measures may have the dose

Patients who fail to respond to these measures may have the dose of the EGFR inhibitor interrupted or dose

reduced. Gastrointestinal side effects including diarrhea (54%), nausea (33%), vomiting (23%), stomatitis (17%), and abdominal pain (11%) have been reported. EGFR is frequently overexpressed in gastrointestinal normal mucosa. There is evidence that EGFR is a negative regulator of chloride secretion. EGFR inhibitors could, therefore, increase chloride secretion by blocking this regulation loop and thereby inducing secretory diarrhea. Diarrhea induced by inhibitors that target the EGFR pathway can be managed easily by reducing the dose of the oral compound, which rapidly lowers the incidence and severity of diarrhea. Rarely does treatment have to be interrupted. Loperamide is a useful treatment that can decrease intestinal motility signaling pathway [49]. Like ocular complication such as conjunctivitis, hepatic as increase in Liver Function Tests, renal, hematologic

side effects including leukopenia (25%) and anemia (16%) have been reported in patients receiving cetuximab. Remarkable developments in the systemic treatment of advanced non-small-cell lung cancer have taken place over the past few years. Targeted therapies have been largely employed in patients with far advanced disease, and some of them have demonstrated consistent activity in this setting. Epidermal growth factor receptor inhibitors cause dramatic response in patients especially

with EGFR mutation. As oncology trends towards personalized therapy to reach the optimal efficacy of drug with BAY 73-4506 cost less side effect, anti EGFR and or third line TKIs have proven to be promising effective drugs in Sitaxentan lung cancer treatment as first, second and maintenance therapy which encouraging further trials in this field. Combined irreversible inhibition of EGFR revealed striking benefit compared to chemotherapy alone. The development of resistance, tumor heterogeneity, and the need to rebiopsy the tumor are all challenges that requires further study to optimize the management of patients with NSCLC. Funding: No funding sources. Competing interests: None declared. Ethical approval: Not required. “
“We have recently witnessed a remarkable progress in our understanding of molecular biology and signalling pathways of NSCLC cells which resulted in ErbB targeted therapies, ALK inhibitors and other targeted agents being now in clinical trials. However, a substantial number of NSCLC patients remain non-responsive or relapse early on these targeted therapies. Improved understanding of the functioning of ErbB receptor family have led to second generation active anti-ErbB therapies. It is clear from different preclinical and clinical studies that combined anti-ErbB therapies have a superior efficacy to single agent therapies. In future it will be essential to characterize mutations of resistance in each line of treatment.

Systems combining phosphorothioate and bridging oxygen-substituti

Systems combining phosphorothioate and bridging oxygen-substitutions (Table 3, entry 7) have demonstrated potential as therapeutics against Alzheimer’s disease owing to their metal click here ion chelation properties [47 and 48]. The use of sulfur-based analogues in the determination of mechanism has been reviewed recently [49]. Recent synthetic advances have also given (easier) access

to: azido-phosphonate dNTPs, where bridging O-atoms have been replaced by CHN3 groups (Table 3, entry 8), and these analogues can be isolated as separate diastereomers [50]; and oxymethyl analogues (CH2 insertion between O and P within anhydride linkages) for following ApnA and NpnN degradation and metabolism (Table 3, entry 9) [51]. Phosphonate NDP-sugar analogues, where the C1-oxygen of the glycosyl group has been replaced by methylene, have given insight into the mechanism of UDP-apiose/UDP-xylose synthase (Table 3,entry 10) [52], and bis-α,β-β,γ-CF2-NTPs offer sterically undemanding mimics that do not hydrolyse while maintaining comparable polarity properties to their natural NTP progenitors (Table 3,entry 11) [53]. Multi-faceted approaches

combining several experimental techniques and/or computational methods are currently giving some of the clearest pictures of phosphoryl transfer strategies. Most of these approaches have, in principle, been available for some time, however, experimental difficulties have precluded their exploitation. Synthesis selleck chemicals llc of analogues remains a substantial obstacle, with many ‘obvious’ analogues only becoming

accessible through painstaking development of challenging routes. This is particularly true of the phosphoanhydride systems. Fortunately, several groups are working towards more convenient methodologies for the preparation of phosphoesters, anhydrides and their analogues, and details of these efforts can be accessed elsewhere [55, 56•, 57, 58, 59, 60•, 61, 62, 63•, 64, 65•, 66, 67, 68•• and 69]. Heavy isotope kinetic studies have proven extremely enlightening, however, the measurement of these extremely small effects (even in best case scenarios) remains the preserve of a few specialist groups. Combinations Florfenicol of experimental approaches with computational methods are also allowing more rigorous, quantitative assessment of observed kinetic data, where interpretations of kinetic results can often be complex. In summary, synthetic methodology, in tandem with kinetic measurements and computational dissection are providing enzymologists with an enhanced toolbox for the determination of phosphoryl transfer mechanisms. Papers of particular interest, published within the period of review, have been highlighted as: • of special interest HJK was funded by a postdoctoral grant from the Jenny and Antti Wihuri Foundation. LPC was funded by a PhD studentship from EPSRC.

These mutations cause a reduction in the overall levels of methyl

These mutations cause a reduction in the overall levels of methylation on H3K27 by targeting the active site of SET-domain containing methyl transferases [45••]. The loss of H3K27 methylation is predicted

to disrupt a feedback loop that regulates the polycomb repressor complex 2 (PCR2), which then promotes the cancer state. Thus, histones can play a pivotal role CDK inhibitor in the progression of the disease state, making them potential candidates to consider for therapeutic targeting. As is evident from the large body of literature on histones and their variants, nucleosomes and their structure, and chromatin organization in vitro and in vivo, this topic is a continuously evolving chapter in the study of genomes. Despite almost 40 years of steady progress on understanding chromatin, profound open questions persist that make this field one of the most exciting to investigate. Do histone variants have different preferences for particular DNA sequences?

Do histones re-associate with the same DNA sequence after being disrupted? Is there true molecular memory at sites that are to be marked for the next cell cycle? How is such memory over-ridden when cells embark on different developmental programs? How does the vigorous compression in the mitotic chromosome physically affect the position and stability of various types of nucleosomes? When cells age or transit into resting phase, how does the proportion of histone variants and nucleosome positions change, and how do such phenomena affect the rate of gene expression, DNA repair, Thiamet G Tacrolimus datasheet remodeling and replication? All these questions await answers, which will eventually bring a more complete conceptual framework of the behaviors

used to regulate genetic accessibility by these tiny, but crucial proteins, the tricksters of the genome. Papers of particular interest, published within the period of review, have been highlighted as: • of special interest “
“Current Opinion in Genetics & Development 2014, 25:15–21 This review comes from a themed issue on Genome architecture and expression Edited by Victor Corces and David L Levens For a complete overview see the Issue and the Editorial Available online 22nd December 2013 0959-437X/$ – see front matter, © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2013.10.013 DNA is a dynamic molecule. In its relaxed state it adopts a right-handed helically coiled conformation, the detailed structure of which is dependent on the localised sequence. Winding DNA around its axis introduces supercoils increasing the free energy stored in the molecule; winding in the same direction as the helix introduces positive supercoiling whereas winding in the opposite direction generates negative supercoiling [1 and 2]. In addition to supercoiling derived from changes in DNA twist, it is also a product of the coiling or bending of the helix in space, a parameter commonly termed writhe.

No QTL was previously found on chromosomes 1DL, 4AL and 7BL in co

No QTL was previously found on chromosomes 1DL, 4AL and 7BL in common wheat, implying that the present QTL for content of A-type starch Selleck Fluorouracil granules are new. However, the QTL were not consistently detected across environments and thus other populations or materials should be used in QTL or association mapping to validate these findings. It was concluded that A-type and B-type starch granules were controlled by different genes[32]. Although the relative quantity reflects the granule size distribution and is relatively easy to estimate. Percentage volume is not a suitable parameter for direct comparison of QTL conferring

the two types of granules. Therefore, the specific diameters, numbers and weights of A-type and B-type starch granules should be examined in the future. Starch granule size and RVA parameters are important factors in determining starch function. In a previous study, RVA parameters were mapped with the same RIL population this website [31]. Compared to the previous results, Qga.caas-1DL was located near

QTL for sedimentation value and mixograph parameters and the marker for Dx5 + Dy10, where a QTL for palate, stickiness and smoothness of Chinese dry noodle was also mapped [33], indicating that these parameters are related to each other and may have pleiotropic effects on noodle quality. The QTL for both starch properties and dough tolerance may contribute to quality improvement. In addition, Batey et al. [24] mapped a QTL for peak viscosity on chromosome 7BL in the same interval as Qga.caas-7BL. Therefore, content of A-starch granules is closely related to RVA parameters. Many enzymes are involved in starch biosynthesis.

The genes for the key enzyme involved in amylose synthesis, granule-bound starch synthase I (GBSS I), were identified on chromosomes 7AS, 4AL and 7DS [34]. It was reported that partially waxy and waxy wheats had less A-type starch granules and more B-type starch granules than non-waxy wheats [35]. GBSS I was found to be responsible for the ratio of A-type to B-type starch granules [1]. In this study, however, both PH82-2 and isothipendyl Neixiang 188 have wild type Wx-A1, Wx-B1 and Wx-D1 alleles and no QTL was found at these loci. Soluble starch synthase may control starch granule size distribution in the early stage of grain filling [1]. SS III and SS IV (soluble starch synthase) genes were located on common wheat homoeologous group 1 chromosomes [36] and [37], and it was reported that SS IV affected starch granule formation in Arabidopsis thaliana [38]. In addition, the genes for ADP-glucose pyrophosphorylase low subunit, SS I and SS II, and branching enzymes (SBE I and SBE II) were located on homoeologous group 7 chromosomes [39], [40], [41] and [42]. Starch branching enzymes were associated with A-type starch granules [7].

, 2005) RNA was extracted from purified lamprey lymphocytes usin

, 2005). RNA was extracted from purified lamprey lymphocytes using Qiagen RNeasy systems (Qiagen, Valencia, CA). Total RNA was used as a template for subsequent random-primed cDNA generation (SuperScript III, Invitrogen, Grand Island, NY), followed by amplification of VLR sequences with gene specific oligonucleotides located in the signal peptide (5′-ATATGCTAGCCACCATGTGGATCAAGTGGATCGCCACGC-3′)

and stalk region (5′-ATATACCGGTTCAACGTTTCCTGCAGAGGGCG-3′) of the VLR gene. The amplified gene sequences were digested with the Nhe I and Age I restriction enzymes and cloned into the expression vector pIRESpuro2 (Invitrogen, Grand Island, NY). To generate HA/6xHis-tagged VLR antibodies and monomeric VLR antibodies we used the alternative antisense primer sequences CP-868596 order 5′- ATATACCGGTTGGGCATTTCGAGGGGCTAGTGCT-3′ and 5′- TATACCGGTTCAGGGTTTCTGGGTTGTGATCAC-3′, respectively. VLR expression constructs were transfected into 293T cells using polyethylenimine (PEI) at a ratio of 3 μg PEI:1 μg DNA as described (Reed et al., 2006). 3 days after transfection, the supernatant was harvested and used for staining of primary cells and cell lines. Alternatively, 293T cells transfected with HA/6xHis-tagged

VLR clones cells were subjected to treatment with puromycin (1 μg/ml) and supernatant from puromycin-resistant cells was used for purification of recombinant VLR proteins using Ni-NTA columns followed by elution with 150 mM imidazole. PBMCs were incubated with VLR containing supernatants from transfected 293T cells for 30 min on ice. The cells were washed 2 × with PBS/1% BSA followed PD0332991 purchase by incubation with mouse monoclonal antibody (4C4) with VLR specificity at a concentration of 6 μg/ml in PBS/1%BSA for 15 min on ice. Subsequently the cells were washed 2 × and incubated with goat anti-mouse

NADPH-cytochrome-c2 reductase PE-labeled secondary antibody. Following this step, the cells were blocked extensively in 5% normal mouse serum, stained with anti-human CD3 and CD19 monoclonal antibodies and analyzed on a FACS CyAN instrument (Dako Cytomation, Carpinteria, CA). FACS data were analyzed using FloJo software. As negative control we used the monoclonal VLR4 antibody that specifically reacts with the BclA antigen of Bacillus anthracis ( Herrin et al., 2008). Western blotting and immunoprecipitation experiments with Jurkat cells and transfected 293T cells were performed as described previously with minor modifications (Ehrhardt et al., 2005). Briefly, cells were pelleted and resuspended in lysis buffer containing 1% Nonidet P-40, 50 mM Tris·HCl (pH 7.5), 5 mM EDTA, 150 mM NaCl, and the protease inhibitors leupeptin (5 μg/ml), pepstatin (1 μg/ml), aprotinin (5 μg/ml), PMSF (40 μg/ml). The whole cell lysates were incubated with 20 μl of a 50% slurry of protein G beads (GE Biosciences) which were pre-coated with anti-HA antibody 12CA5 and the indicated monoclonal VLR antibodies.

In our series, all patients were treated with doses from a minimu

In our series, all patients were treated with doses from a minimum of 15 Gy up to 18.5 Gy and no neuropathy was observed. Three patients (19%) had Grade 3 complication as reported by the physician during followup visit: one had urethral stenosis and two others had fistulas (rectovaginal and ureter). Nonetheless, it is not easy to separate treatment-related local complications in patients with recurrent learn more tumors previously treated with surgery and radiation therapy. Previously published data from our institution described the most common type of toxicity: wound (24%), ureter (23%), and bladder (20%) complication in patients with recurrent colorectal cancer who received

HDR-IORT without DP (14). Despite the use of HDR-IORT, local failure can occur in up to 50% of patients [2] and [8]. Resection margin status has been shown to be the primary predictor of local failure. In a prior study from our institution, patients with R1 or R2 resections had a median time to local failure of 5-Fluoracil 38 vs. 63 months for patients with an R0 resection (15). Although negative

margins can be obtained microscopically in a second radical resection, in previously irradiated patients, clear margins are difficult to achieve even by the most experienced surgeons in high-volume cancer centers. The cohort of patients receiving IORT-HDR-DP was particularly high risk for positive margins as all patients had recurrent disease and previous EBRT. Yet, despite positive microscopic margins in 25% of our patients, the 2-year LC was excellent (80%), suggesting that IORT was effective as an adjuvant treatment. Given the small cohort of patients and its retrospective nature, we cannot draw definitive conclusions related to survival outcomes. Also, Verteporfin cell line owing to the lack of a control group, we cannot evaluate the real impact of HDR-IORT-DP in LC compared with regular HDR-IORT without DP. The largest single-institution experience in IOERT on recurrent colorectal cancer (n = 607) from the Mayo Clinic showed a 3-year local and distant relapse incidence of 23% and 49%, respectively (2). In their series, 37% of

the resections were R1. Interestingly, despite comparable LC rates to the Mayo Clinic series, the DM rate (69%) was higher in our cohort, potentially demonstrating more advanced disease at the time of surgery or more aggressive tumor biology in our group of patients who had tumors of other sites in addition to colorectal cancers. Local recurrence after previous EBRT also seems to be an unfavorable factor. The Mayo Clinic series reported 5-year survival of 20% in patients with recurrent colorectal cancer without prior radiation vs. 12% in previously irradiated patients (16). In our study of previously irradiated patients, the 2-year actuarial OS was 20%. DM was the major problem in our series because about two-thirds of the patients developed DM and died of disease.

The crude extract of whole midgut S levis larvae was submitted t

The crude extract of whole midgut S. levis larvae was submitted to ion exchange chromatography in DEAE-Sepharose. A large peak of inactive protein was eluted with 0.3 M NaCl. Two other peaks were eluted learn more in 1 M NaCl ( Fig. 4A). These two peaks hydrolyze Z-FR-MCA, but most of the activity was associated with the second peak. SDS-PAGE of the purified proteins

revealed a single band corresponding to each eluted peak, displaying the same molecular mass of approximately 37 kDa ( Fig. 4B). As the enzyme present in the second peak has greater activity and was more stable than the first, it was chosen for characterization. Thus, the data refer only to the major S. levis midgut cathepsin L. The successfully purified enzyme is active on Z-FR-MCA, has an optimal pH of 6 (Fig. 5). The kinetic parameters for the hydrolysis of the fluorogenic peptides Z-FR-MCA, Z-RR-MCA and Z-LR-MCA by S. levis cysteine proteinase were determined. The greatest catalytic efficiency was obtained with Z-FR-MCA with kcat/Km value of 30.0 ± 0.5 μM−1 s−1. The substrate Z-LR-MCA was hydrolyzed with a kcat/Km value of 20.0 ± 1.1 μM−1 s−1 and Z-RR-MCA substrate was resistant to hydrolysis. The kinetic data and standard deviations were calculated from at least three separate determinations. Amylase and maltase were assayed throughout the midgut to

define the sites of initial (amylase) and final (maltase) starch digestion. Cysteine proteinase buy TSA HDAC and trypsin were found to be the major and minor digestive proteinases, respectively,

in S. levis (see previous item). Hence, both proteinase activities were selected Clomifene to identify the site of initial protein digestion and that of final digestion of aminopeptidase. Optimal pH for the selected enzymes are ( Fig. 5) 6–7 for amylase, 5–6 for maltase, 8–10 for trypsin, 7–8 for aminopeptidase and 6.0 for cysteine proteinase. The selected enzymes were analyzed in the midgut contents and in the soluble and membrane-bound fraction of the midgut tissue at different sites along the midgut ( Fig. 6). Based on the data, amylase, maltase, cysteine proteinase and trypsin predominate in the luminal contents of the anterior (V1 and V2) midgut. However, trypsin also occurs in significant amounts in the tissue both as a soluble and as a membrane-bound enzyme ( Fig. 6). An aminopeptidase is found mainly in the posterior (V3 + V4) midgut as a membrane-bound enzyme ( Fig. 6). The midgut of S. levis has two cysteine proteinases, two trypsins and perhaps a negligible chymotrypsin. SDS-PAGE analysis showed purified bands of cysteine proteinases both with 37 kDa eluted at 1 M NaCl as two peaks. This elution profile suggests the presence of two isoforms of cysteine proteinase that most likely differ in their charge or isoeletric point. S. levis cathepsin L exhibits elution profile similar to human cathepsin L (EC 3.4.22.15) purified from human kidneys ( Turk, 1993). The major S.

Numerous studies mapping multiple omics dimensions to annotated p

Numerous studies mapping multiple omics dimensions to annotated pathways and cancer Belinostat cell line hallmarks support the notion that alterations work

in concert to selectively deregulate pathways and further confirm that AC and SqCC develop through distinct oncogenic pathways [11], [50], [51] and [65]. Single subtype analyses have identified several affected pathways/hallmarks including; focal adhesions, cell cycle, activation of the JAK/STAT pathway and sustainment of proliferation in AC [22] and [52] and oxidative stress response, squamous differentiation and deregulation of the PI3K pathway in SqCC [51]. Of therapeutic relevance, was the finding that ∼70% of SqCC tumors had alterations in one of the PI3K/AKT, receptor tyrosine kinase, or RAS pathways, however the optimal intervention points of these pathways are still under investigation. Work by our group comparing AC and SqCC identified 778 subtype-specific genes (altered by CNA or DNA methylation and a two-fold expression change) which were found to differentially disrupt cellular GDC-0199 supplier pathways and networks, including down-regulation of the HNF4alpha pathway in AC and disruption of histone modifying enzymes and the E2F1 transcription factor in SqCC [65].

Differential pathway activation of the cell cycle in AC, and DNA repair in SqCC, have been reported along with differences in multiple metabolic pathways [78]. With distinct patterns of genetic disruption underscoring tumor development, it is unrealistic to assume AC and SqCC would have similar responses to all chemotherapies, especially those targeting specific proteins.

Both bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF) and pemetrexed, an antifolate chemotherapy that targets thymidylate synthetase (TS) are contraindicated in SqCC due to an increased tuclazepam risk of pulmonary hemorrhage and reduced survival times, respectively [79], [80] and [81]. TS gene expression has been shown to be predictive of pemetrexed efficiency [82] and [83] and is elevated in SqCC compared to AC, providing an explanation for the reduced efficacy in these patients [81] and [84]. In silico screening of compounds capable of “reversing” gene expression signatures has been shown to identify compounds with subtype specific efficacy. For example, treatment of lung cancer cell lines with the HDAC inhibitor Trichostatin A, revealed SqCC lines were significantly more sensitive than AC lines [65]. These findings highlight the potential importance of information about the underlying biology to inform decisions regarding treatment regimes, such that treatments can be tailored to the individual to potentially improve patient response and survival.

In a previous work, we reported that low or high concentrations o

In a previous work, we reported that low or high concentrations of LPS induce differential DC activation and maturation resulting in differential T-cell activation and polarization.48 Here we show that the expression of activation CHIR-99021 ic50 and maturation markers of lp DC significantly differs in Endohi and EndoloRag1−/− mice, in E coliMUT or E coliWT and in LPSWT or LPSMUT challenged mice, respectively, according to our in vitro studies. Consistent with this, we found increased expression of TH1/TH17 cytokines in Endohi-, E coliWT-, and LPSWT-treated Rag1−/− mice, but not in the Endolo-, E coliMUT-, or LPSMUT-challenged Rag1−/− mice. Accordingly, treatment of

mice with E coliMUT resulted in increased expression of FoxP3 and treatment with LPSMUT in a reduced expression of IL-17a in the colonic lp T cells. The delivery of purified LPS or LPS by viable bacteria might result in different LPS availability at different intestinal and cellular components,49 and can contribute to the differences in the IL-17a and FoxP3 expression on treatment with LPS or viable bacteria. However, we cannot rule out that an additional factor of viable E coli might account for this effect. Currently,

it seems to be highly likely that the intestinal microbiota plays a critical role in the accumulation and functional maturation of intestinal regulatory T cells.50 We demonstrated that commensal bacterial species, depending on the structure of LPS, can induce or prevent expansion and polarization of intestinal T cells. However, as discussed by Chung et al,33 many questions remain about the causes of differential T-cell response. Fulvestrant chemical structure The different maturation states of lp DC might be induced directly by the commensal bacteria or be due to a secondary effect induced by differences in the local chemokine and cytokine milieu, possibly resulting in

a difference in the downstream T-cell proliferation. Both the administration of bacteria (E coliWT and E coliMUT) and treatment with LPSWT or LPSMUT resulted in alterations in the composition of the intestinal microbiota. Analysis of the intestinal microbiota by deep sequencing techniques implies that phylogenetic groups of bacteria like Firmucutes or Verrucomicrobia might also be involved in the regulation of the intestinal until immune homeostasis. However, additional functional studies need to clarify the biologic relevance of this finding and whether the shift of the intestinal microbiota by LPS administration is a direct effect, or represents a secondary effect due to changes in the local environment in terms of, for example, nutrition, altered cytokine and chemokine patterns, or induction of defensins. In addition, an influence of the altered intestinal microbiota, and therefore the modified endotoxicity of the intestinal microbiota on the maintenance of intestinal homeostasis or induction of inflammation, would be conceivable.

We used a similar age range used by other studies examining ‘midd

We used a similar age range used by other studies examining ‘middle age’ adults (Zysset et al., 2006, range: 45–75 years). Most importantly we used an age range similar to previous ERP studies of middle age so that the results would be comparable (Falkenstein et al., 2006, mean age 58.3, range not given; Mager et al., 2007, 41–61 years). All participants were fluent in English, had normal or corrected to normal vision and had no history of psychiatric or neurological disorders. Informed written consent was obtained from each participant and from the parent or guardian of the adolescent participants. The adults were graduate students and staff at the University of Cambridge, UK. Middle age adults were staff

at the University of Cambridge check details or employed in the Cambridge area and had completed at least 14 years of formal schooling (A Levels UK). Adolescents were students at the Hills Road 6th Form College, Cambridge, UK. The study received ethical approval from the Psychology Research Ethics Committee of the University of Cambridge. Although no measure Silmitasertib of general intelligence was administered in this study, an indication of memory ability was derived by comparing group differences in raw scores on the digit span (forward and backward) subtest of the Wechsler Adult Intelligence Scale (WAIS) III (UK). Scores on the combined digit span forwards

and backwards were not significantly different between groups [F(2,42) = 3.199, p > .05]. Stimuli PAK5 were the following English words: BLUE, RED, GREEN, YELLOW. Words could be presented in each of the following colours; blue, red, green or yellow. Stimulus presentation was pseudo-randomized whereby each subject had a different random order of stimuli presented. Participants were seated in a small room facing a 19 inch computer screen and they watched the computer screen and held a video game controller. Participants responded to the ink colour of the word by using their left and right thumbs. According to one response assignment participants pressed the left button if the ink colour was red or green. They

pressed the right button if the ink colour was yellow or blue. Response assignments were counter-balanced between participants. In the congruent condition there is no stimulus or response conflict. The semantic meaning and the correct response engage the same hand (e.g., ‘RED’ printed in red ink). In the stimulus conflict (SC) condition even though the semantic meaning and correct response are incongruent they are mapped to the same response hand thereby eliminating response conflict (e.g., the word RED printed in green ink). In the response conflict (RC) condition the printed colour is incongruent with the semantic meaning of the word (e.g., the word RED printed in blue ink) and additionally the associated responses are mapped to different response hands. This condition is considered to produce both stimulus and response conflict.