This finding was not surprising, as higher expression levels of m

This finding was not surprising, as higher expression levels of mexB and mexD are to be expected in mexR or nfxB mutants (Dumas et al., 2006). The nature of the specific beneficial adaptive mechanisms in the tolerant bacterial population is under investigation in our lab. To gain insight into the effect of inactivation of genes involved in the GO system on CP-868596 concentration the global gene expression, we studied the transcriptional changes produced by inactivation of the two genes. The inactivation of both mutY and mutM caused significant changes (more than twofold and P-value < 0.05 compared with PAO1) in six genes (Table 4). Remarkable was the up-regulation of pfpI whose product has been shown to have a protective role against

DNA damage caused by the oxidative stress (Rodriguez-Rojas & Blazquez, 2009). This can be considered a compensatory mechanism for the protection of the DNA in PAOMY-Mgm with impaired repair of the DNA oxidative damage. Interestingly, the most significantly down regulated gene was PA5148 involved in iron FDA-approved Drug Library mw trafficking. The modified expression of pfpI and PA5148 expression in PAOMY-Mgm compared with PAO1 was confirmed using RT-PCR, which showed up-regulation of pfpI (9 ± 2.3-fold) and down-regulation of PA5148 (4.04 ± 2.7-fold). Complementation of PAOMY-Mgm,

which showed high expression levels of pfpI and low expression levels of PA5148 compared with PAO1 with wild-type mutM or mutY, reduced the level of pfpI up-regulation to 6 ± 2.4-fold and 4.6 ± 2.4-fold, respectively and the level of PA5148 down-regulation to 1.6 ± 0.09-fold and 2.1 ± 0.25-fold, respectively. Pseudomonas aeruginosa, which colonizes and persists within the highly ROS-rich CF airways has to protect itself against the mutagenic effect of ROS and it uses the GO system, consisting of MutT, MutY and MutM to prevent or eliminate the oxidized form of guanine, which is a mutagenic lesion. Homologue proteins are present in other microorganisms as well as in eukaryotic cells. Inactivation

of each of the three genes encoding for the respective proteins led to various degree of increase in the spontaneous MF with mutants in mutY and mutM exhibiting a moderate and weak mutator phenotype (increase in MF < 20 times the MF of PAO1) (Mandsberg et al., Molecular motor 2009; Morero & Argarana, 2009; Sanders et al., 2009). In the present study, we show for the first time that the mutY and mutM double mutant (PAOMY-Mgm) showed a strong mutator phenotype providing evidence for the cooperation of MutM and MutY to prevent mutagenesis in P. aeruginosa, in a similar manner as in E. coli (Michaels et al., 1992; Tajiri et al., 1995). It has been shown that hypermutability plays an important role in the adaptive evolution of P. aeruginosa in the CF lung (Mena et al., 2008), and it has been demonstrated that mutator populations are amplified by hitchhiking with adaptive mutations. The selective pressure exerted by antibiotics plays an important role in the adaptive process of P.

4–6 In addition, the three antimalarials are characterized by ver

4–6 In addition, the three antimalarials are characterized by very different dosing regimens: At+Pro and Dxy are taken on a daily basis before, during, and after traveling, whereas Mfl is taken weekly; At+Pro and Dxy must be taken 1 to 2 days prior to travel, compared with at least 1 week (preferably 2–3 wk) for Mfl; and after return Dxy and Mfl must be taken for 4 weeks post-travel, compared with 1 week for At+Pro.7 These variations in side-effect profile and dosing convenience may impact the adherence

behavior of travelers taking these medications. Other factors such as travelers’ beliefs about malaria and antimalarial medication and previous experience of taking antimalarials may also be important. Data Paclitaxel price on the impact of travelers’ beliefs or choice of antimalarial on adherence behavior are limited, especially in the UK, and no studies have compared At+Pro with Dxy.5,8–10 There is, therefore, a need for further research to provide HCPs with the information they need if they are to promote adherence to antimalarial medication. This observational study examines two areas related to antimalarial use: the adherence behavior of travelers from the UK to crPF malarious zones, who were prescribed a recommended antimalarial (primary objective),

and the factors influencing selection of the antimalarial from the perspective of the prescriber and traveler. The results of this study should better equip HCPs to provide information and advice to travelers when prescribing antimalarials. This study was a noninterventional, observational study conducted in travel clinics in England and Scotland Bioactive Compound Library cell assay between December 2004 and April 2006, to assess the adherence behavior of individuals prescribed a licensed antimalarial at a travel clinic for a trip to a crPF malarious zone. Eleven clinics participated from London, Manchester, Glasgow, Cambridge, Bristol, and Edinburgh: six Medical Advisory Services for Travelers Abroad (MASTA) travel clinics, four Nomad travel clinics and the Royal Free Hospital travel clinic. The study was approved by Cambridge Local Research Farnesyltransferase Ethics

Committee and informed consent was obtained from all participants. The investigators in this study were mostly nurse practitioners responsible for the selection and supply of antimalarials under a system of patient group directions (PGD).11 All individuals having a naturally occurring consultation with a participating practitioner requesting antimalarial protection for travel to crPF malarious zones were considered for participation in the study once a decision to prescribe an antimalarial had been made as per routine practice. Treatment choice was solely at the discretion of the traveler and practitioner. To be eligible, travelers had to be at least 18 years of age and to have been prescribed or supplied under PGD an antimalarial medication as a result of planned travel for a duration of 28 days or less.

After Incubation for one week at 30 °C, colonies were isolated an

After Incubation for one week at 30 °C, colonies were isolated and further analysed. Southern blot analysis was performed with bacterial genomic DNA, extracted with the GenElute Bacterial Genomic DNA Kit (Sigma-Aldrich) and EcoRI digested. Detection on nylon membranes (Roche, Mannheim, Germany) was carried

out using the DIG High Prime DNA Labelling and Detection Starter Kit II (Roche) according to the manufacturer’s instructions. A 1109-bp PCR fragment of the transposon sequence was amplified using specific primers (forward primer Tnp FP01 and reverse primer Tnp RP01; Table 1) and labelled with digoxigenin provided with the kit. Labelling, hybridization and chemiluminescence detection were performed according to the manufacturer’s instructions. PCR was performed using the primer

pair Tnp FP01/Tnp RP01 for detection of the transposon in the genomic DNA of putative transposon mutants. The presence Erismodegib in vivo of the plasmid pBBR1MCS-2 GFP was tested by PCR using the primer pair MCS-2 RP01/MCS-2 FP01 and taq-polymerase under standard conditions: denaturing DNA for 30 s at 94 °C, annealing Gefitinib cost of the primers for 1 min at 58 °C and elongation for 2 min at 72 °C. These steps were repeated for 30 cycles and the results were analysed on a 1% agarose gel. For colony PCR, clones were isolated with a sterile pipette tip and heated to 95 °C for 10 min. Five microlitres were used as template in a standard PCR reaction. All 2600 mutants were tested for the presence of a flagellum, using mouse flagellum-binding monoclonal antibody CSD11. This antibody has been raised against complete A. felis by Mr William Bibb at the Centers for Disease Control and Prevention and in preliminary tests turned out to specifically recognize the Afipia flagella. To validate the transposon mutant bank, we chose to screen for the Resminostat presence of flagella because flagella are known to be virulence factors in other bacteria, they are easy to detect and they require numerous gene products for their production, secretion and assembly. For

screening, the clones were grown in 300 μL BYE medium containing 50 μg kanamycin sulphate mL−1 in 96-well format. During the incubation for 1 week, bacteria had sedimented and 10 μL of each pellet was spotted onto nitrocellulose. Filters were air-dried, nonspecific protein-binding sites were blocked with 5% fat-free milk powder in PBS-T overnight and filters were incubated with CSD11 antibody solution (CSD11 hybridoma supernatant fivefold diluted in PBS-T+5% milk powder). Three washes with PBS-T were followed by incubation with horseradish peroxidase-coupled anti-mouse antibody and development of the blot with ECL substrate. Nucleotide sequencing was performed by GATC (Konstanz, Germany). The primer for determination of the nucleotide sequence adjacent to the transposon insertion site was KAN-2 FP01 (Table 1). Oligonucleotides were provided by Thermo Scientific (Ulm, Germany).

It was concluded that elevated TrrA expression was consistent wit

It was concluded that elevated TrrA expression was consistent with an activated thioredoxin (Trx) system and that cross talk between the GSH and Trx dependent was evident in the absence of glrA. Moreover, depleted H2O2 levels in A. nidulansΔglrA were due to the observed elevation in catalase B and cytochrome c peroxidase levels. Significant upregulation

of an elongation factor 1β (ElfA; 2.5-fold) and a glutathione s-transferase (GstB; 2.6-fold) was also observed in A. nidulansΔglrA. Relevantly, orthologues of both of these proteins had previously been shown to be present and upregulated in response to oxidative stress in A. fumigatus (Burns et al., 2005; Carberry et al., 2006). Thön et al. Barasertib chemical structure (2010) observed that the deletion of hapC, a component of the transcriptional regulator AnCF that senses the cellular redox status and coordinates the oxidative stress response, resulted in an impaired oxidative stress response. Characterization of the A. nidulansΔhapC proteome

identified upregulation of a range of redox-active proteins including thioredoxin, peroxiredoxin A and glutathione, compared with the wild type. Pusztahelyi et al. (2011) investigated the A. nidulans proteome, compared with transcriptomic alterations, during long-term exposure to menadione to further exploit the power of comparative proteomics for cellular redox investigations. Lessing et al. (2007) Trichostatin A used comparative proteomics to explore ifenprodil the effect of H2O2 on, and the deletion of a potential transcription factor Afyap1, involved in the oxidative stress response, from A. fumigatus. Differential gel electrophoresis (DIGE) analysis, followed by MALDI-ToF/ToF MS identified 27 and 17 proteins, respectively, whose expression was up- and downregulated (>1.5-fold cut-off) following A. fumigatus exposure to H2O2 (2 mM). Predominant among upregulated proteins were the Allergen Asp f3 (× 10-fold), a mitochondrial

peroxredoxin, Prx1 (× 3.7) and Cu,Zn superoxide dismutase (SOD; × 1.2–2.7). The authors proposed that given the classification of Asp f3 and Prx-1 as thioredoxin peroxidases, an elevation in thioredoxin system activity in response to oxidative stress is of significant importance in A. fumigatus. The altered expression of a range of metabolic enzymes was also evident and some proteins appeared in more than one gel spot, at identical Mr, but with an altered pI and amount. Lessing and colleagues speculated that this was due to either posttranslational modification or isoenzyme occurrence; either way, it revealed a type of information that can only be derived from proteomic, and not microarray, expression analyses. Of three unclassified proteins, or UFPs, the expression of two was downregulated (an NAD-dependent dehydrogenase and a UGP-1 protein), while one, a GMC oxidoreductase, was significantly upregulated (× 6.2).

An enrichment culture, which could completely degrade 100 mg L−1

An enrichment culture, which could completely degrade 100 mg L−1 FE within 7 days was acquired by PD-0332991 chemical structure continuous enrichment (Fig. 1a). Several strains capable of transforming FE to FA were isolated on MSM plates containing 100 mg L−1 FE as the sole carbon source, but they all were incapable of completely degrading FE. We studied the degradation of FA, CDHB and HPP by the enrichment culture, and the results are shown in Fig. 1b–d. The enrichment culture demonstrated complete degradation of 50 mg L−1 FA, CDHB and HPP within 5 days. However, no single strain isolated from the LB plates and MSM plates

could degrade FA, CDHB and HPP. This indicates that the microorganisms capable of degrading FA, CDHB and HPP were in the enrichment culture and complete degradation of FE needs the interaction of a variety of microorganisms. Such phenomenon was also observed in the degradation of other environmental pollutants. Complete degradation of dimethyl isophthalate (DMI) requires the biochemical cooperation between strains Klebsiella oxytoca Sc and Methylobacterium mesophilicum Sr (Li et al., 2005; Li & Gu, 2007). Several strains capable of metabolising FE to FA were isolated on MSM plates. Strain T1 was selected for further investigation because of its high degradation rate and relatively rapid growth. The 16S rRNA gene sequence of strain T1 demonstrated similarity to the 16S rRNA gene sequence from members of the genus JQ1 mw Rhodococcus, the

degree of similarity attained was 100% with R. qingshengii djl-6 T (DQ090961) and 99% with R. baikonurensis GTC1041T (AB071951), respectively. The dendrogram illustrating the Carnitine palmitoyltransferase II results of 16S rRNA gene analysis is presented in Fig. 2. There are many reports about degradation of environmental pollutants by Rhodococcus. R. phenolicus is capable of degrading chlorobenzene, dichlorobenzene and phenol (Rehfuss & Urban, 2005). Rhodococcus sp. strain djl-6 is capable of degrading carbendazim (Xu et al., 2006b). R. opacus SAO101 is capable of degrading p-nitrophenol and a novel p-nitrophenol degradation gene cluster has been identified from this strain (Kitagawa et al., 2004). However, this is the first report of

Rhodococcus sp. degrading FE. Rhodococci are ubiquitous and numerous in soil and able to survive under extremely harsh conditions (Shao et al., 1995). These features make them ideal candidates for bioremediation of contaminated environments. The time course of FE degradation by strain T1 is presented in Fig. 3a. Strain T1 was capable of rapid degradation of FE with more than 80% FE being degraded within 8 h. After 8 h, the degradation rate began to decline, and 94% FE had been degraded 24 h after inoculation. The initial and final cell densities in the cultures were 3.15 × 107 and 1.08 × 108 cells mL−1, respectively. These results indicate that strain T1 could use FE as the sole carbon source for growth. Only one metabolite (Rt = 2.9 min) was detected by HPLC analysis.

“To explore whether oral impacts on daily performances are

“To explore whether oral impacts on daily performances are related to recent use of dental services among children and whether oral impacts on specific daily performances are more strongly related to recent use of dental services. Data from a cross-sectional survey, including 805

11–12-year-old children attending four randomly selected schools in Lima (Peru), were used. The child version of the oral impacts on daily performances (Child-OIDP) was used to assess prevalence, intensity, and extent of oral impacts. Use of dental services was assessed by self-reports of last dental visit and reason for the visit. Associations of the prevalence, intensity, and extent of oral impacts with use FK506 ic50 of dental services were tested in logistic regression models. Children with oral impacts were 1.99 (95% CI: 1.17–3.37) times more likely to have used dental services recently than their counterparts. selleck chemicals The intensity and extent of oral impacts were linearly associated with children’s use of dental services. Difficulties in

eating were the only type of oral impacts on daily performances associated with use of dental services, independent of children’s demographic characteristics, and impacts on other performances. Oral impacts on daily performances were related to recent use of dental services among these schoolchildren. “
“International Journal of Paediatric Dentistry 2011; 21: 284–288 Background.  The distribution of the attachment of the maxillary labial frenum in the children of different ethnic backgrounds has not been studied extensively. Aim.  The purpose of this cross-sectional study was to examine the prevalence of the various types of maxillary labial frenum attachment in the children of different ethnic backgrounds. Design.  Children (aged 1–18) attending a public health clinic in Chloroambucil Lavrion, Greece, were clinically examined for maxillary frenum attachment location. Demographic information was recorded. Parents provided written informed consent. Results.  The examined children were 226, with mean (±standard deviation) age of 8.5 ± 3.0 years. They were of Greek (51%), Albanian (20%), Turkish (12%),

and Afghan (11%) descent. The prevalence of the maxillary labial frenum attachment was mucosal (10.2%), gingival (41.6%), papillary (22.1%), and papillary penetrating (26.1%). Frenum attachment differed significantly by age (P = 0.001). The age of children with mucosal- or gingival-type frenum was significantly greater than the age of children with papillary penetrating–type frenum. Frenum attachment did not differ by gender or ethnic background (P ≥ 0.20). Conclusions.  The results of this study suggest that, in children, ethnic background and gender are not associated with maxillary labial frenum attachment type, whereas age is strongly associated. “
“The capacity to overcome social disadvantages and maintain oral health through psychosocial processes remains poorly understood in children.

2,100 It is well documented that high altitude expeditions may el

2,100 It is well documented that high altitude expeditions may elicit alterations in both emotional and cognitive

functioning. These changes are likely due to the cumulative effects of hypoxia, high altitude deterioration, physical exhaustion, fluid and electrolyte disturbances, and preexisting psychological morbidity.106,107 Cultural and interpersonal challenges are additional stressors likely to be encountered on a high altitude sojourn. Ryn documented profound psychological changes in a large portion of a cohort of healthy Polish mountaineers traveling in the Andes. With increasing altitude, the symptoms progressed from neurasthenic syndrome to cyclothymic disorder to acute psychotic disturbances.106 New onset anxiety disorders or exacerbations of diagnosed anxiety are also common at altitude and are thought to predispose people to AMS.106–110 Safety, positive group interactions, and success at mountain travel demand a high degree of skill, cognitive flexibility, and emotional control. While at altitude, dramatic changes in a traveler’s psychiatric status should be considered a medical emergency and supervised descent should follow without delay.105 Patients with preexisting psychiatric disorders

should undergo careful psychiatric assessment prior to embarking on a high altitude sojourn. Patients taking psychotropic drugs should ensure that they are compliant with their prescribed medication at high altitude. Pregnant women Selleckchem Lenvatinib are not believed to be at increased risk of altitude-related illness. However, hypoxic conditions have the potential to compromise the uteroplacental circulation and cause placental hypoxia.111,112 The fetal circulation is further

compromised when the mother exerts herself and the skeletal muscle competition for blood supply increases.15 Susceptibility to dehydration increases as a result of the additive effects of pregnancy and altitude-related hyperventilation.14 Women staying at altitudes over 2,500 m for weeks to months have an increased rate of antenatal complications including bleeding,14 hypertension,113,114 preeclampsia,112,113,115 abruptio placentae,14,116 preterm labor,117 intrauterine mortality,115,116 and intrauterine growth retardation.112–116,118–120 Isolation from medical care and the potential for physical trauma inherent in many outdoor pursuits Inositol monophosphatase 1 present additional challenges. Pregnant women are also more prone to serious complications of certain travel-related infections and may be limited in their treatment options.14 According to a recent consensus statement, travel to high altitude is contraindicated in the first trimester of pregnancy in women at increased risk of spontaneous abortion. Beyond the first trimester, low risk pregnant women can safely enjoy short sojourns up to 2,500 m. Moderate physical exertion at these altitudes is acceptable following 2 to 3 days of acclimatization.

No cases of rash illness including rubella, measles, or varicella

No cases of rash illness including rubella, measles, or varicella were detected in passengers of this ship based on passive surveillance measures. The BCHD estimated a total cost of $67,000 spent on vaccinations, TAM Receptor inhibitor supplies, and health department staff time (ie, excluding CDC and cruise line staff time) to interrupt transmission (Florida Department of Health, unpublished data, 2006). Although this outbreak occurred in 2006, CDC continued to receive reports of these VPD on cruise ships arriving at US ports; for example, during May 2006 to December 2010, 2 confirmed rubella cases and 1 suspect measles case, all among crew members, were reported to CDC (CDC, unpublished

data, 2010). Cruise travel continues to gain popularity, with a 7.2% annual average passenger growth rate in the North American cruise industry since 1990.[10] In 2009, 9.4 million of PLX3397 datasheet the 13.4 million cruise ship voyages worldwide were made by persons who resided in the United States, where Florida had the busiest ports.[10] Despite high levels of immunity to measles, rubella, and varicella among US residents,[11] clusters of some of these VPD on cruise ships originating

in the United States continue to occur.[3, 12] These clusters are often associated with the introduction and spread of VPD among susceptible crew members from countries with differing epidemiology of disease (ie, varicella), with low immunization rates, or that have not introduced or just recently introduced the vaccine and have ongoing disease transmission. The semi-enclosed, densely populated environment of cruise ships has been documented to facilitate

person-to-person transmission of communicable diseases, including VPD such as rubella and varicella.[3, 12, 13] The clusters of VPD on this cruise ship resulted from an imported case of rubella from the Philippines, an imported case of measles from Ukraine, and a varicella GNAT2 case of unknown source country, demonstrating the potential for exposure to diseases during cruise travel, which may be more common in developing countries without routine vaccination programs or continuing endemic transmission.[3, 4] The outbreak was confined to crew members, of whom less than 1% had proof of immunity to measles and rubella. Similarly, in a previous rubella outbreak investigation on cruise ships, approximately 85% of 366 crew members tested were born outside the United States (representing 50 countries), and 75% lacked proof of immunity to rubella. A serosurvey showed 4% of (366) crew members were acutely infected and 7% were susceptible to rubella.[3] Of 3,643 passengers surveyed 75% were US-born, 33% were of childbearing age, and 0.8% were pregnant. As with the investigation described in this report, although the immune status of passengers was not known, no transmission was detected among them.

Assessment of CSF HIV RNA, CSF HIV genotropism and genotyping of

Assessment of CSF HIV RNA, CSF HIV genotropism and genotyping of CSF HIV RNA. In subjects with detectable CSF HIV RNA, modifications to ART

should be based on plasma and CSF genotypic and genotropism results. Several published randomized controlled studies, assessing both intensification of ART with a new ARV agent [25] and with adjunctive therapies [26-29] have been published. Unfortunately, none of these studies describe improvements in cognition subsequent to the study interventions. Without evidence-based interventions, the Writing Group outlines below a best practice approach based on the current literature. As HIV-associated NC disorders are a diagnosis of exclusion, re-evaluation of subjects with ongoing NC impairment despite ART for confounding conditions, with expert input from other clinical specialties such as psychiatry, neurology and neuropsychology, is recommended and, where possible, input from an buy GDC-0068 HIV neurology service. Assessment of CSF HIV RNA, CSF HIV genotropism and genotypic analysis of CSF RNA may be useful tools in the management of subjects with ongoing NC for the following reasons. First, data from cohorts of untreated HIV-positive subjects would suggest CSF HIV RNA to be greater in subjects with HIV-associated dementia and cognitive decline [30, 31] and therefore suppression of CSF HIV RNA may be beneficial for cognitive function. Secondly, in subjects with ongoing NC impairment, higher degrees of genetic diversity between HIV viral strains in the CSF and plasma compartment may exist [32], even in subjects with undetectable plasma HIV RNA [33]. Therefore, assessment for CSF HIV resistance may be worthwhile

to tailor ART. We recommend patients with HIVAN start ART immediately irrespective of CD4 cell count (1C). We recommend patients with end-stage kidney disease who are suitable candidates for renal transplantation start ART irrespective of CD4 cell count (1C). Proportion of patients with HIVAN started on ART within 2 weeks of diagnosis Protein kinase N1 of CKD. The use of ART has been associated with a decline in the incidence of HIVAN in HIV cohort studies [1], with renal histological improvement in case reports [2, 3], and with delayed progression to end-stage kidney disease in case series [4, 5]. In the UK, most HIVAN cases are encountered in patients with advanced immunodeficiency who were not previously known to be HIV positive, or who disengaged from care or who declined ART [6]. HIVAN is rare in patients with CD4 cell counts >350 cells/μL or with undetectable HIV RNA levels [7].

This was done by first binning the spikes of all neurons at 100 m

This was done by first binning the spikes of all neurons at 100 ms. Binning spikes at 100 ms removes high-frequency oscillations, and thus correlations seen in the plots are low-frequency correlations. This was a similar analysis as was used in Goard & Dan (2009). We then used the MATLAB routine corrcoef to compute the correlation coefficient for a subset of 80 neurons taken from all layers (20 neurons per layer) in RF1 and RF2 across trials in both the control and the stimulated cases. To see how attention, mAChR stimulation and BF stimulation changed correlations between cells, in Figs 8 and 9 we plot the excitatory–excitatory, excitatory–inhibitory and inhibitory–inhibitory correlations for the six


conditions discussed above (indicated selleck inhibitor by the row name). For each of the nine subplots in Figs 8 and 9, the non-control condition is plotted on the y-axis against the control condition, plotted on the x-axis. Each scatter point corresponds to the correlation value computed under both the non-control (y-axis) and control (x-axis) conditions. Thus, a scatter point above the line y = x indicates an increase in correlation in the non-control condition. A scatter point below the line y = x indicates a decrease in correlation in the non-control condition. Black and blue scatter points are used for RF1 and RF2, respectively. Red and green crosses indicate the center of mass of the scatter points for RF1 and RF2, respectively, and the size of the crosses is 20 times the standard error of the mean (SEM) of the center of mass. We first

analysed the between-cell correlations during BF stimulation. A similar study was find more performed experimentally on rats by Goard & Dan (2009). In their study, the BF was periodically stimulated (similar to Rebamipide ours) while showing the rats a natural movie. They found that during periods of BF stimulation, the neurons in V1 became decorrelated. In addition, they showed that this correlation is mediated by muscarinic receptors. As can be seen in the bottom row of Fig. 8, when we stimulated the BF, excitatory–inhibitory and inhibitory–inhibitory correlations in both RF1 and RF2 decreased, while excitatory–excitatory correlations remained unchanged. Our result suggests that the decorrelation reported by Goard and Dan was primarily mediated by inhibitory neurons. For the mAChR in RF1 case (middle row of Fig. 8), we also see a decrease in between-cell correlations, indicating that the decrease in correlations is further mediated by mAChRs. We also applied top-down attentional signals to our cortical columns and saw how this affected between-cell correlations with and without mAChR and BF stimulation (Fig. 9). Attentional modulation is classically known to increase firing rates in a particular subset of neurons in order to bias these neurons so they win out in competition against other groups (Desimone & Duncan, 1995).