We know that

H/R is associated with a poor prognosis, met

We know that

H/R is associated with a poor prognosis, metastasis, and radio- and chemoresistance in a variety of human cancers.20 H/R can generate a mutated gene pool and set the field to select genes responsible for worse phenotypes. Managing tumor hypoxia may be an effective way to treat cancers.111 The authors thank Dr Hiromichi Hemmi for critical reading of this article. The authors also thank Mrs M. Koi and Mrs M. Garcia for editing the article. This work is supported by grants from Baylor Health Care System Foundation (No. 430538) and from NIH Grants R01-CA98572. “
“The purpose of this study was to compare prophylactic subcutaneous drainage plus subcuticular sutures versus staples for the risk of wound separation after skin closure following gynecologic malignancy surgery, Afatinib order and to investigate the risk factors of this procedure. Patients were divided into two groups: 120 patients who were treated with subcutaneous drainage plus subcuticular sutures (Suture group) and 201 patients with staples plus subcutaneous sutures (Staples group). In the Suture group, subcuticular tissue was approximated with interrupted 4-0 polydioxanone sutures, and adhesive closure strips were

used on the skin surface. A 3.3-mm closed drainage was implicated in subcutaneous tissue. In the Staples group, subcutaneous tissue was approximated with interrupted polyglactin (Vicryl, Ethicon) sutures. Baseline characteristics were not significantly different

between the two groups. Mean operation times were compatible Amoxicillin (201 vs 196 min, P = 0.16). The incidence of wound separation was less in the PD0325901 solubility dmso Suture group than in the Staples group (3/120 vs 17/201, P = 0.033). Multiple logistic regression analysis revealed that the Staples group was an independent risk factor for wound separation (odds ratio 7.34, 95% confidence interval: 1.59–33.91, P = 0.011), independent of obesity, International Federation of Gynecology and Obstetrics stages, and operation time. None of the 14 obese patients in the Suture group showed surgical wound separation. The combination of a prophylactic subcutaneous drain and subcuticular sutures reduced wound separation after skin closure following gynecologic malignancy surgery. With the information regarding risk factors established in this study, the above method provides the best results to minimize the risk, particularly in obese patients. “
“Aim:  The aim of the present study was to investigate associations between ovarian cancer survival and reproductive, gynecological and hormone factors. Material and Methods:  A prospective follow-up study was conducted in the Southeast of China. The cohort comprised 202 patients with histopathologically confirmed epithelial ovarian cancer who were enrolled during 1999–2000 and followed-up for 5 years subsequently. One hundred and ninety five (96.

The results indicated that amounts of IF1 are lower by ∼23% in th

The results indicated that amounts of IF1 are lower by ∼23% in the 30S fraction from E. coli cells coexpressing U791 ribosomes and IF1 than Natural Product Library datasheet those expressing G791 ribosomes and IF1 (Fig.

2c). The composition of ribosomal proteins in both 30S fractions was similar (Fig. 2c), indicating that the U791 mutation does not affect assembly of ribosomal proteins to 16S rRNA. Considering that the proportion of mutant 30S subunits in the 30S peak from the sucrose gradient analysis is ∼40% (data not shown here), we conclude that the U791 mutation severely inhibits IF1 binding to the 30S ribosomal subunit. Overexpression of IF1 resulted in increased ribosomal subunit association, probably by stabilizing P-site-bound initiator tRNA, which is mediated by its cooperation with IF2 and its interaction with the initiation codon of the mRNA (Hartz et al., 1990; Wu & RajBhandary, 1997; Meinnel et al., 1999). Although no clear function has been assigned to initiation factor 1, considering that IF1 is known to aid IF2 and IF3 in translational initiation and increase the rate of both subunit association

and dissociation (Grunberg-Manago et al., 1975), and that IF1 footprinting mimics A-site-bound tRNA, a local PD-166866 datasheet change in the A-site due to an increase in IF1 binding to the A-site may be transmitted to the P-site (790 loop), thus restoring the functional conformation of the P-site for initiator tRNA binding and consequent ribosomal subunit association. The crystal structures of ribosomes also support this hypothesis. The 790 loop interacts with the 900 region and the 900 region docks somewhere in the vicinity of residues at positions 1413–1418 and 1483–1487 (Cate et al., 1999; Clemons et al., 1999), which interact with Tolmetin IF1 (Carter et al., 2001). We thank Dr John W.B. Hershey for providing us with a monoclonal antibody to IF1. This research was supported by the Pioneer Research Center Program (20100002201) through the National Research Program of Korea and NRF grant (2010-0008539) funded by the Ministry of Education, Science

and Technology. “
“The limited information on the genetic differences among the 15 currently known serotypes of Actinobacillus pleuropneumoniae has significantly hampered the development of typing-based diagnostic methods and multivalent vaccines. In this study, we compared the genomic differences between A. pleuropneumoniae strains CVCC259 (serotype 1) and CVCC261 (serotype 3) by representational difference analysis. Of the eight differential DNA sequences in the CVCC259 strain and 11 differential DNA sequences in the CVCC261 strain that we identified, seven represent known virulent genes, 10 encode putative proteins, and two encode hypothetical proteins. We also investigated the distribution of these 19 sequences among the 15 serotypes, and each serotype showed a different distribution pattern. The autotransporter adhesin occurred as a novel putative virulence factor in serotypes 1, 5, 7, 8, 9, and 11.

There was no associated

history of fevers, diaphoresis, c

There was no associated

history of fevers, diaphoresis, cough, or dyspnea. His symptoms were refractory to antacids (Mylanta, Johnson & Johnson Pty Ltd) and selleck kinase inhibitor pantoprazole (Somac, Nycomed). He immigrated to Australia 8 months prior, had no previous medical or family history or allergies, and physical examination was unremarkable. Laboratory results revealed microcytic hypochromic anemia (hemoglobin concentration 112 g/L, normal 130–180 g/L; mean cell volume 74 fL, normal 80–100 fL; and mean cell hemoglobin 24 pg, normal, 27–32 pg), thrombocytosis (platelet concentration 521 × 109 L−1, normal 150–450 × 109 L−1), raised erythrocyte sedimentation rate (76 mm/h, normal 1–10 mm/h), and C-reactive protein (56 mg/L, normal <5 mg/L) suggesting an inflammatory process (albeit a normal white cell count and differential), normal renal function and electrolytes, an isolated raised alkaline phosphatase (205 U/L, normal 35–110 U/L) on liver function

panel, and a positive quantiferon gold [tuberculosis (TB) antigen 1.50 IU/mL, normal <0.35 IU/mL and mitogen 5.44 IU/mL, normal >0.50 IU/mL]. Subsequent amebic and schistosoma serology were negative. Contrast enhanced chest, abdominal, and pelvic computed tomography (CT) revealed a calcified granuloma within Pexidartinib solubility dmso the left lower lung lobe with left hilar and subcarinal foci of calcification, marked right colonic wall thickening with surrounding inflammation (Figure 1), prominent regional lymphadenopathy with one showing nodal calcification, and terminal ileal thickening. Gastroscopy revealed a 5 cm area of mucosal inflammation in the posterior wall of the antrum and prepyloric region with a cobble stone

appearance, small ulcerations, and scant mucopurulent exudates. Similar changes were noted in the pyloric channel and proximal duodenum. Multiple antral and pyloric biopsies were obtained. Colonoscopy revealed a Sinomenine cobblestone mucosa in the ascending colon that was associated with inflammation, mucopurulent exudate, and multiple large ulcers. The cecum revealed similar inflammatory and ulcerative changes, and a fistulous opening but the terminal ileum appeared normal. Similarly, multiple biopsies of the terminal ileum and ascending colon were obtained for histopathology, polymerase chain reaction (PCR), microscopy, and culture for Mycobacterium tuberculosis (MTB). Histopathological examination of gastric mucosal biopsies showed severe Helicobacter pylori-associated gastritis, whereas a nonspecific chronic inflammatory cell infiltrate was noted in colonic mucosal biopsies. The changes were not suggestive of either Crohn’s disease or mycobacterial infection. Terminal ileal biopsies did not reveal any histological abnormalities. Microscopy and PCR of right colon biopsies were negative for MTB.

[41] Where CPD was paid for by the employer, in pharmacy it seeme

[41] Where CPD was paid for by the employer, in pharmacy it seemed employers were more accepting in terms of the content and cost of the CPD. In terms of comprehending CPD, a range of issues were outlined early in the decade including the distinction between CE and CPD and generally lack of information about CPD, what it entails, how to record it and how much to record (see Table 4). There were also concerns and difficulties expressed in relation to distinct stages of CPD such

as assessing own learning needs, as well as problems identifying resources to meet the learning needs, reflection and evaluating one’s learning. Feedback from participants RAD001 supplier about one protected time scheme indicated it increased participants’ understanding of CPD.[35] In a study conducted around the middle of the decade, pharmacists in Scotland reported feeling comfortable with identification of learning needs and assessing the value of what they had learnt and with applying it to practice,[18] and a study conducted in 2006/2007 reported the main benefit of the CPD process related to pharmacists’ Natural Product Library increased understanding and use of reflection, compared to CE.[21] However, studies conducted as late as 2007 and 2008 still reported confusion over what to record, how to record it, difficulty with choosing competencies (to relate to one’s CPD) and what counted as CPD. Pharmacy technicians were

also reported to have faced uncertainty about how to record CPD.[38] Early in the decade, pharmacists expressed a consistent need for training and facilitation (see Table 5). One study providing participants the opportunity to interact with a facilitator reported it was useful in overcoming the initial CPD inertia;[35] another examining a CPD development toolkit recommended example documentation of CPD activities to be made available as a future

resource.[36] The role of the departmental head in introducing and supporting CPD was deemed vital in one study conducted mafosfamide in the middle of the decade,[23] when along similar lines another study found pharmacists relied on one another for guidance with CPD.[22] Respondents in a Scottish study conducted around 2005/2006 also needed more support for CPD[18] and a paper examining pharmacy technicians’ views around the same time discovered that technicians did not seem to have received any training on how to undertake CPD within the formal technician-training courses.[27] Motivation (lack of) was a barrier to undertaking CPD (see Table 6). In the first half of the decade some pharmacists were apathetic towards CPD, and some even viewed CPD as a ‘waste of time’, while others sought external motivation from employers and some felt mandatory CPD would act as the catalyst towards their engagement in CPD.[26] Some pharmacists queried the relevance of CPD once their career had reached a plateau.

Even though acidification is usually effective in controlling bac

Even though acidification is usually effective in controlling bacterial growth, organisms

have evolved several mechanisms directed toward survival in conditions of low pH.12 In this project, the acidified conditions caused by lime juice were insufficient to kill the pathogenic bacteria tested and should not be relied upon to adequately sterilize potentially contaminated fish. Maintenance of seafood quality is central to ensuring the safety of seafood. There is presently no way to ensure that all food is kept free from potential sources of contamination. Good manufacturing practices, involving the harvest of fish from approved areas (sewage-free harvest beds), type and size of fish caught, methods of capture and processing immediately after capture, can all decrease the rate of contamination of fishery products.9,21 Good handling practices selleck screening library guidelines are available for seafood restaurants, and they recommend the use of several refrigerating, freezing, defrosting, and storage measures to reduce the microbial spoilage of products and to improve food safety. This experiment has limitations that may restrict its applicability to travelers who consume find more cebiche. We tested only a focused number of enteric pathogens and did not evaluate other common causes of infectious

diarrhea, such as Campylobacter, Salmonella, and Shigella species. Additionally, we used high inocula in our testing that were in excess of the described infectious doses of the bacteria tested. We cannot state what the effect of cebiche preparation would be on lower bacterial doses. In summary,

conventional methods of cebiche preparation are not adequate to inactivate common pathogenic bacteria. International travelers should exercise caution when consuming uncooked seafood. Persons at particular risk (including young children, the elderly, immunocompromised persons, and pregnant women) should be encouraged to eat fully cooked seafood and to avoid buying fish or shellfish from street vendors.20,21 This work was supported by work unit number 847705 82000 25GB B0016. IRB statement: The study protocol was approved by the Naval Medical Research Center Institutional Review Board (PJT.NMRCD.2007.006) in compliance with all applicable Federal regulations governing the protection of human subjects. The views expressed in this article are those of the all authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. Dr Martin, Dr Espinosa, and Dr Maves are US military service members. This work was prepared as part of their official duties. Title 17 United States Code (USC)/Section 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 USC Section 101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties.

coli ArgDC mutant in an acid shock assay

coli ArgDC mutant in an acid shock assay. buy PF-02341066 Active AaxB was detected in four additional species: Chlamydia caviae, Chlamydia pecorum, Chlamydia psittaci, and Chlamydia muridarum. Of the C. trachomatis

serovars, only E appears to encode active enzyme. To determine when functional enzyme is present during the chlamydial developmental cycle, we utilized an anti-AaxB antibody to detect both uncleaved and cleaved enzyme throughout infection. Uncleaved enzyme production peaked around 20 h postinfection, with optimal cleavage around 44 h. While the role ArgDC plays in Chlamydia survival or virulence is unclear, our data suggest a niche-specific function. Infection with Chlamydia, a genus of Gram-negative obligate intracellular

bacteria, may result in ocular, genital, or pneumonic disease, depending on the route of entry and bacterial species/serovar. While the majority of Chlamydia species are zoonotic, infecting a wide range of mammalian and avian hosts, the Chlamydia trachomatis serovars are human-specific pathogens (Carlson et al., 2005; Rohde et al., 2010). All species undergo a unique biphasic developmental cycle transitioning between the extracellular, infectious elementary body (EB) and the intracellular, replicative form known as the reticulate body (RB; AbdelRahman & Belland, 2005). Arginine decarboxylases Epacadostat (ArgDCs), which catalyze the conversion of arginine into agmatine, are conserved in bacteria and play dual roles in acid resistance and the metabolism of polyamines such as putrescine (Tabor & Tabor, 1984; Lin et al., 1995). In bacteria such as Yersinia, functional ArgDC is required to produce biofilms, making this enzyme essential for virulence (Patel et al., 2006). Two ArgDC are encoded by Escherichia coli: the acid-inducible adiA and a constitutive speA that functions in polyamine biosynthesis (Stim & Bennett, 1993). In Chlamydia, the only known ArgDC is encoded by aaxB, which resides in an operon between the putative porin aaxA and the characterized arginine–agmatine antiporter, aaxC (Giles & Graham,

2007; Fig. 1a). Although AaxB is Florfenicol functionally equivalent to E. coli AdiA, the enzyme itself is actually a member of the pyruvoyl-dependent ArgDC (PvlArgDC) and shares more similarities with ArgDC from organisms such as Methanococcus jannaschii (Graham et al., 2002). The AaxB proteins of Chlamydia pneumoniae and C. trachomatis serovars D and L2 were previously characterized (Giles & Graham, 2007; Giles et al., 2009). All sequenced C. pneumoniae encode a 25 kDa proenzyme, which requires autocleavage between the conserved Thr52Ser53residues to produce 16 kDa α and 9 kDa β subunits. The cleaved subunits are then free to assemble into the active (αβ)3 complex. In contrast, C. trachomatis serovars D and L2 have inactivated AaxB through one of two independent mutations (Giles et al., 2009).

Phenylketonuric (PKU) and epileptic mice show altered expression

Phenylketonuric (PKU) and epileptic mice show altered expression of NIPSNAP1 in the brain. Therefore, the distribution and localization of NIPSNAP1 in rat brain was determined. Results show that NIPSNAP1 is expressed exclusively in neurons including pyramidal neurons in the cerebral cortex, Purkinje neurons in the cerebellum and motor neurons in the spinal cord. Dopaminergic neurons in midbrain and noradrenergic Anti-diabetic Compound Library neurons in the brainstem, which are affected in PKU, also express NIPSNAP1. NIPSNAP1 is found to be localized in the mitochondrial matrix and can bind dihydrolipoyl-transacylase and -transacetylase components of the BCKA and pyruvate

dehydrogenase complexes in vitro. Our data provide the first experimental evidence for a strictly neuronal expression of this mitochondrial protein in the rat nervous system. “
“Temporal order memory (memory for stimulus order) is crucial for discrimination between familiar objects and depends upon a neural circuit involving the perirhinal cortex (PRH) and medial pre-frontal cortex. This study examined the role of glutamatergic and cholinergic neurotransmission in the encoding or retrieval of temporal order memory, using a task requiring the animals to discriminate between two familiar objects presented

at different intervals. 6-Cyano-7-nitroquinoxaline (CNQX) (AMPA/kainate receptor antagonist), scopolamine (muscarinic receptor antagonist) or 2-amino-5-phosphonopentanoic acid (AP5) (N-methyl-D-aspartate Doxorubicin receptor antagonist) was administered before sample phase 2 (to be active during encoding) or before test (to be active during retrieval). Unilateral CNQX administration into the PRH and pre-limbic/infra-limbic Monoiodotyrosine cortices (PL/IL) in opposite hemispheres, i.e. to disrupt neurotransmission within the circuit, impaired encoding and retrieval. Administration of scopolamine or AP5 in the PRH–PL/IL circuit impaired encoding. Drug effects in each brain region were then investigated

separately. Intra-PRH CNQX, scopolamine or AP5 disrupted encoding, such that the animals explored the recent object significantly more than the old object. In contrast, intra-PL/IL CNQX, scopolamine or AP5 impaired memory performance such that the animals spent an equal amount of time exploring the objects. CNQX but not AP5 or scopolamine impaired retrieval. Furthermore, CNQX impaired novel object preference when infused into the PRH but not PL/IL following a 3 h delay. Thus, encoding of temporal order memory is mediated by plastic processes involving N-methyl-D-aspartate and muscarinic receptors within the PRH–PL/IL circuit, but these two regions make qualitatively different cognitive contributions to the formation of this memory process.

, 2008) In the present study, PE-related BOLD responses in the a

, 2008). In the present study, PE-related BOLD responses in the amygdala occurred in its corticomedial subregion and SN/ventral tegmental area, and the computational approach of the study further indicates that these signals are important for the updating of expectations at a later point in time. Mirroring the results obtained in rodents, our findings therefore strongly suggest a crucial role of the CM and SN/ventral tegmental area in the signalling of surprise, which is related to a later enhancement of learning. Apart from

the amygdala and the midbrain, the unsigned PE also correlated Alisertib nmr with activity in the anterior insula. This region has been shown before to be activated by salience rather than valence in associative learning (Seymour et al., 2005; Metereau & Dreher, 2012) in addition to its frequently highlighted role in signalling uncertainty and risk (Mohr et al., 2010). In a previous fMRI study, Li et al. (2011) reported

a positive correlation of amygdala activity and associability at the time of outcome. Given that the unsigned PE and associability are correlated, this result fits with the current finding of a representation of the unsigned PE in the CM at the time of outcome. Both results can be interpreted as reflecting surprise or attentional changes in response to unexpected shocks or omissions. Associability Natural Product Library research buy in the current study, however, was used to modulate the CS and not the US onset event. This approach is based on the theoretical description of associability as a property of the CS in the original PH and in the hybrid model (Pearce & Hall, 1980; Le Pelley, 2004). Furthermore, although the associability information

is in principle available as soon as the PE occurs, it only affects the update of the value when the next CS is presented. Thus, associability in the current study reflects the reliability of prior outcome expectations at the point in time, when this information is used to update current outcome expectations, whenever a new CS is presented. We observed a negative correlation between associability and brain activity in the BLA. We refer to this negative associability signal in this study as reflecting predictiveness. 4-Aminobutyrate aminotransferase Predictiveness represents a CS processing signal, which is large when prior outcome predictions are reliable and small when outcome predictions are poor. It increases during acquisition in all conditions, decreases at the beginning of the reversal stage and increases again when the reversed CS–US contingencies are learned. The finding of a predictiveness signal in the BLA ties in with the amygdala’s role in learning to predict aversive outcomes (Glascher & Buchel, 2005; Schiller et al., 2008). It further fits with the findings of a recent fMRI study reporting increased amygdala responses to predictive as compared with nonpredictive cues that received the same pairing with the US in a blocking paradigm (Eippert et al., 2012).

Gibbons et al (2000) had isolated a gene

from Salmonella

Gibbons et al. (2000) had isolated a gene

from Salmonella responsible for the introduction of a 2-hydroxyl group into a lipid-A-bound myristic acid residue. The hydroxylation reaction is catalyzed by the Fe2+/O2/α-ketoglutarate-dependent LpxO dioxygenase. Rojas-Jiménez et al. (2005) had identified a gene called olsC in R. tropici encoding an LpxO homolog responsible for the synthesis of hydroxylated OLs. Later, it was shown that OlsC is responsible for the introduction of a hydroxyl group in the C-2 position of the piggy-back fatty acid of OLs (Vences-Guzmán et al., 2011). A prediction indicates that OlsC of R. tropici CIAT899 is a water-soluble protein of 281 selleck inhibitor amino acids (Rojas-Jiménez et al., 2005). Owing to its homology to LpxO from Salmonella, it can be expected that OlsC-dependent hydroxylation of the ester-linked fatty acid will also be Fe2+/O2/α-ketoglutarate dependent. Genes encoding OlsC homologs can be found in Selleck Epigenetic inhibitor Agrobacterium vitis, Agrobacterium radiobacter, Ochrobactrum anthropi, Ochrobactrum intermedium, Aurantimonas manganoxydans, Fulvimarina pelagi, Roseomonas cervicalis, Chelativorans sp., Mycobacterium rhodesiae, and several Brucella species (Supporting

Information, Table S1). Interestingly, in the so-called classical Brucella such as Brucella ovis, Brucella suis, Brucella melitensis, or B. abortus, which are intracellular pathogens, the olsC gene is present only as pseudogene containing a frameshift mutation. As a consequence, the olsC gene is translated into two ORFs, making the gene olsC nonfunctional (Palacios-Chaves et al., 2011). In the genomes of several atypical Brucella strains such as Brucella microti, Brucella sp. BO1, or Brucella sp. BO2 which share several characteristics with the opportunistic soil pathogen Ochrobactrum, olsC genes lacking the frameshift can

be detected that are probably functional. This observation implies that organisms like Ochrobactrum, R. tropici, and nonclassical Brucella such as Brucella isolated from soil that present GPX6 both (De et al., 2008;Scholz et al., 2008a, 2008b, 2009, 2010) an intracellular and a free-living lifestyle have preserved a functional copy of olsC, whereas the classical Brucella strains that are strictly intracellular pathogens present only a nonfunctional copy of olsC (Palacios-Chaves et al., 2011). A functional OlsC might confer a selective advantage in adverse abiotic stress conditions, but might not be of use or even have a negative impact when the bacteria are inside a host. Recently, Vences-Guzmán et al. (2011) reported a more detailed study of an olsC-deficient R. tropici mutant. Strains lacking the OL hydroxylase OlsC showed a growth defect at increased temperatures (37 and 42 °C) and under acid pH conditions (4.5 and 4.0).

If this procedure revealed adjacent voxels fulfilling this condit

If this procedure revealed adjacent voxels fulfilling this condition they http://www.selleckchem.com/products/AZD6244.html were considered

for the analysis of the percentage signal change. For further quantitative analysis the newly defined ROIs based at the group-level results were then used to determine the amount of signal change for the four different search and control conditions in every session and subject. Every eye-centred ROI contained at least 7 voxels. The signal change analysis was carried out using routines provided by the software package MarsBar. The onset of the search array was defined as the onset of the analysis. The covert search related signal change was defined by taking the difference between the search-related signal and its matched control condition. By normalizing the height of the search signal by the matched Selleckchem AG-14699 control condition [Search(i) (normalized) = Search(i) – Control(i)], we controlled for the different visual and oculomotor components in the signal. Later we applied one-way anovas on the normalized signal change for covert search to verify that there is a significant difference across conditions. When the anova was positive we tested whether there was a difference between the eye-centred contralateral and ipsilateral conditions. Because these post hoc comparisons involved four t-tests, we corrected the P-value for multiple comparisons by the Bonferroni–Holm method. We also tried

to identify areas coding covert search to the contralateral space in head- or non-eye-centred FORs. We applied the same procedure mentioned above, but now examined for every hemisphere the overlap of non-eye-centred contralateral conditions excluding those voxels being activated for the non-eye-centred ipsilateral conditions. This procedure did not reveal any voxels responding preferentially to non-eye-centred contralateral shifts of attention during covert search. Further, the early and later visual regions, anterior insula

and the supplementary eye field (SEF) were identified by the contrast [sR(fC), sL(fC), sL(fR), sR(fL)] > [‘all control conditions’]. These clusters were used as ROIs, in order to assess the effect of the search conditions on the BOLD response in these regions. The 17-DMAG (Alvespimycin) HCl size of these ROIs ranged from 456 mm³ to 4840 mm³. For each ROI the mean of the percentage signal change was calculated, averaged across voxels and across repetitions of blocks, for each subject. The covert search-related signal change was defined by taking the difference between the search-related signal and its matched control condition. Student’s t-tests were used to compare the signal change between the four search conditions. To ensure that subjects were fixating properly and to detect the target of the indicative saccade, we monitored and recorded the position of the right eye of 13 subjects during the scanning sessions, using an infrared camera (SMI iViewX MRI-LR spatial resolution ≤ 0.15°, at 60 Hz).