Therefore, the choice of lipids alone is not sufficient for optim

Therefore, the choice of lipids alone is not sufficient for optimal DNA delivery, and the morphology of the complexes is essential. Figure 2 Proposed model showing cross-sections of extruded DOTAP: Chol liposomes (BIVs) interacting with nucleic acids. Nucleic acids adsorb onto a BIV via electrostatic interactions. Attraction of a second BIV to this complex results in further charge neutralization. … Figure 3 Proposed model showing cross-sections of an extruded DOTAP:Chol

liposome (BIV) interacting with adenovirus. Adenovirus interacts with a BIV causing negative curvature and wrapping around the virus particle. 4. Optimal Lipids and Liposome Morphology: Effects on Gene Delivery Inhibitors,research,lifescience,medical and Expression Choosing Inhibitors,research,lifescience,medical the best cationic lipids and neutral lipids are also essential for producing the optimal in vivo formulation. For example, using our novel manual extrusion procedure does not produce BIVs using the cationic lipid dimethyldioctadecylammonium bromide (DDAB). Furthermore, DOTAP is biodegradable, whereas DDAB is not biodegradable. Use of biodegradable lipids is preferred for use in humans. Inhibitors,research,lifescience,medical Furthermore, only DOTAP and not DDAB containing liposomes produced highly efficient gene expression in vivo [1]. DDAB did not produce

BIVs and was unable to encapsulate nucleic acids. Apparently, DDAB and DOTAP containing SUVs produce similar efficiency of gene delivery in vivo; however, these SUVs are not as efficient as BIV DOTAP:Chol [1]. In addition, use of L-α dioleoyl phosphatidylethanolamine (DOPE) as a neutral lipid creates liposomes that cannot

wrap or encapsulate nucleic acids. Several investigators have reported efficient transfection of cells in culture using DOPE in liposomal formulations. Inhibitors,research,lifescience,medical However, our data showed that Inhibitors,research,lifescience,medical formulations consisting of DOPE were not efficient for producing gene expression in vivo [1]. Investigators must also consider the source and lot variability of certain lipids purchased from companies. For example, different lots of natural check details cholesterol from the same vendor can vary dramatically and will affect the formulation of liposomes. We use synthetic cholesterol instead of natural cholesterol that is purified from the wool of sheep. Synthetic cholesterol is required by the Food and Drug Administration for use in producing therapeutics for injection into humans. Our BIV formulations are also stable for a few years as liquid suspensions. Freeze-dried Ketanserin formulations can also be made that are stable indefinitely even at room temperature. Stability of liposomes and liposomal complexes is also essential particularly for the commercial development of human therapeutics. 5. Liposome Encapsulation, Flexibility, and Optimal Colloidal Suspensions A common belief is that artificial vehicles must be 100nm or smaller to be effective for systemic delivery. However, this belief is most likely true only for large, inflexible delivery vehicles.

Cognitive dysfunctions are directly correlated with Aβ oligomers

Cognitive dysfunctions are Libraries directly correlated with Aβ oligomers in Tg2576 mice, which start at around 6 months old and are stable until 14 months old [29]. Thus, we first evaluated cognitive NVP-AUY922 concentration functions in both non-tg (n = 18) and Tg2576 mice (n = 24) at the age of 12 months. After the behavioral test, mice were divided into two groups to be treated with rSeV-LacZ or rSeV-Aβ. There is no difference between the two groups in behavioral scores at the age of 12 months. To evaluate the effect of vaccine treatment, each group (rSeV-LacZ-treated non-tg mice, n = 9; rSeV-Aβ-treated non-tg mice, n = 9; rSeV-LacZ-treated

Tg2576 mice, n = 10; rSeV-Aβ-treated Tg2576 mice, n = 14) was subjected to behavioral tests at the age of 15 months. All tests were done according to the methods described previously [30]. 24 h after 10 min-training session following 3 day-habituation, each mouse was placed back into the same box in which one of the familiar objects used during training was replaced with a novel one. The animals

were then allowed to Staurosporine explore freely for 10 min and the time spent exploring each object was recorded. The exploratory preference (%), a ratio of the amount of time spent exploring any one of the two objects (training session) or the novel object (retention session) over the total time spent exploring both objects was used to measure cognitive function. Each mouse was placed at the center of the apparatus and allowed

to move freely through the maze during an 8-min session, and the series of arm entries was recorded visually. Alternation was defined as successive entry into the three arms on overlapping triplet sets. The % alternation was calculated as the ratio of actual alternations to the possible alternations (defined as the number of arm entries minus two) multiplied by 100. The Morris water maze test was conducted in a circular pool (1.2 m in diameter) with a hidden platform (7 cm in diameter) filled with water at a temperature of 22 ± 1 °C. The mice were given two trials Bay 11-7085 (one block) for 10 consecutive days during which the platform was left in the same position. The time and distance taken to reach to the escape platform (escape latency and distance moved) was determined in each trial by using the Etho Vision system (Brainscience Co. Ltd., Osaka, Japan). Three hours after the last training trial, the platform was removed, and mice were allowed for 60 s to search the removed platform. For measuring basal levels of freezing response (preconditioning phase), mice were individually placed in a neutral cage for 1 min, and then in the conditioning cage for 2 min. For conditioning, mice were placed in the cage, and an 80 dB tone was delivered for 15 s. During the last 5 s of the tone stimulus, a foot shock of 0.

24 The MADRS6

includes the corresponding HAM-D6 items A

24 The MADRS6

includes the corresponding HAM-D6 items. A major pitfall in a microanalysis of the HAM-D is the use of factor analysis to test Faravelli’ s assumptions. A comprehensive review by Bagby et al7 has shown that factor analysis as used from 1980 to 2003 in many psychometric analyses of the HAM-D has identified quite different factor scores. As discussed elsewhere,32 the clinimetric analysis of a rating scale should indicate to what extent the total score is a sufficient statistic by considering both the individual items of the scale and the population under examination. When trying to define the ABT199 antidepressant effect of a drug, Prien and Le vine33 concluded that a greater improvement in Inhibitors,research,lifescience,medical total HAM-D scores does not necessarily indicate antidepressant action (“… assume that a group treated with an experimental Inhibitors,research,lifescience,medical drug shows significantly more improvement than a group treated with placebo on the factors of anxiety, somatization or sleep disturbances and no significant change on other factors. These changes, by themselves, should not qualify the drug as an antidepressant…”33). Another major pitfall to be considered is the use of several depression scales in the same trial

without clearly indicating a priori which of them has been determined to be the the primary measure of antidepressant Inhibitors,research,lifescience,medical effect. To avoid this problem, a researcher should always use the specific items of depression, Inhibitors,research,lifescience,medical eg, the HAM-D6 or the MADRS6, as the primary efficacy measure. When determining clinically significant antidepressant effect, it is recommended to use standardized effect size statistics.34 These statistics examine the reduction of rating scale scores from baseline to end point (mean scores) for both active drug and placebo in relation to the pooled standard deviation Inhibitors,research,lifescience,medical of the two treatments. Thus, if the baseline score is 24 for both treatments, but the change score is 14 for the active drug while it is 10 for the placebo, and if the pooled standard deviation is 8, then the effect size is 4/8 or 0.50. In clinical trials with antidepressants an effect size of 0.40

or higher is considered a clinically significant response criterion.35 This equals a 20% advantage of the active drug over placebo by using either a global impression score of very much and much response36 or a 50% reduction in baseline rating scores on the HAM-D.23 Illustrating antidepressant effect, as shown in (Figure 1)., is yet another difficult 17-DMAG (Alvespimycin) HCl area. Because both groups of patients, ie, on active drug treatment as well as on placebo treatment, exceed 100 subjects, a small statistically significant difference will be found. In the example illustrated in (Figure 2)., it is obvious that the effect of escitalopram is of clinical significance (effect size >0.40) in depressed patients after only 4 weeks. Figure 1. A typical illustration from a placebo-controlled trial with a new potential antidepressant.

Because the values of minimum bactericidal concentration (MBC) an

Because the values of minimum bactericidal concentration (MBC) and MIC are usually very similar,31 it can be logically assumed that the above-mentioned plant extracts and oils have a bactericidal effect on Gram-negative bacteria, especially against Proteus spp. and K. pneumoniae. The Probit Analysis (table 4) revealed that the minimum concentrations of the essential oils that could inhibit 50% of the various bacteria were T. syriacus

Boiss. for E. coli O157H7 (7.85 µl/ml), O. syriacum. L. for Proteus spp. and Y. enterocolitica (1.12 and 1.59 µl/ml, respectively), and S. aromaticum for K. pneumoniae (1.33 µl/ml). Ooi et al.32 reported that Cinnamomum verum shows excellent activities against E. coli and Proteus vulgaris. Preuss et al.33 Inhibitors,research,lifescience,medical found that origanum essential oil proves cidal to E. coli and K. pneumoniae.

In addition, Barbosa et al.34 found that the MIC90 of Origanum vulgare essential oil is 0.46% (v/v) against E. coli. López et al.35 found that 8-10% Inhibitors,research,lifescience,medical (v/v) concentrations of Origanum vulgare essential oil can completely inhibit the growth of E. coli and other Gram-negative bacteria. Elsewhere, Mkaddem et al.36 reported that Mentha essential oils are very active against K. pneumoniae Inhibitors,research,lifescience,medical bacteria, whereas they are less effective against E. coli. Furthermore, Mentha longifolia oil is thought to exhibit an antimicrobial activity against some Gram-positive bacteria such as Streptococcus mutans and Staphylococcus Inhibitors,research,lifescience,medical aureus, but without affecting Pseudomonas aeruginosa.37 Since the antibacterial effectiveness of medicinal plants varies dramatically depending on the phytochemical characteristics of plant families and subfamilies, it is not surprising to note the difference in this efficacy even when using samples taken from the same plant, but from two different regions.38 Our Inhibitors,research,lifescience,medical results reveal that the cephalosporins were the most effective antibiotics against almost all the studied bacteria, and only

Ciprofloxacin, one of the fluoroquinolones group, was effective against these bacteria. Conclusion O. syriacum. L., T. syriacus Boiss., S. aromaticum L., C. zeylanicum L., J. foetidissima Astemizole Wild, A. sativum L., and M. fragrans Houtt. oils and L. nobilis L. extract were the most effective plant extracts against the Gram-negative bacteria studied in this work. These plant extracts could be a potential source of new antibacterial agents. Further and more specific studies, in vivo, are recommended to determine the efficacy of these essential oils in the treatment of gram-negative bacterial infections. Acknowledgment The Cyclopamine chemical structure authors would like to thank the Director General of the Atomic Energy Commission of Syria (AECS) and the head of the Department of Molecular Biology and Biotechnology for their support. Conflict of Interest: None declared.
Background: Application of follicular fluid (FF) and platelet-activating factor (PAF) in artificial insemination improves sperm motility.

Pulsed ultrasound exposures (sonications) were performed in the

Pulsed ultrasound exposures (sonications) were performed in the brains of rabbits

under monitoring by MRI. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using staining for ischemic neurons and TUNEL staining for apoptosis. Tiny regions of extravasated red blood cells scattered around the sonicated locations, indicated capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence of apoptosis or ischemia. The authors found that ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic Inhibitors,research,lifescience,medical or apoptotic death to neurons [63]. The method Inhibitors,research,lifescience,medical could find application in the delivery of large therapeutic molecules that do not normally permeate the BBB. Herceptin

(trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, was delivered locally and noninvasively into the mouse central nervous system Inhibitors,research,lifescience,medical through the blood-brain barrier under image guidance by using an MRI-guided focused ultrasound. The amount of herceptin delivered to the target tissue was selleck chemicals correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. The method could be used to treat breast cancer metastases to the brain [64]. It was further shown that dopamine D(4) receptor-targeting antibody could

also be delivered using the same technique Inhibitors,research,lifescience,medical in the brain [65, 66]. Delivery of small molecules can also be enhanced with the use of HIFU cavitation disruption of the BBB. Treat et al. demonstrated relatively high concentrations of doxorubicin in the brain with minimal healthy tissue damage effects. The authors observed that doxorubicin accumulation in nontargeted contralateral Inhibitors,research,lifescience,medical brain tissue remained significantly lower. MRI signal enhancement in the sonicated region correlated strongly with tissue doxorubicin concentration, suggesting that contrast-enhanced MRI could perhaps indicate drug penetration during image-guided interventions [67]. Konofagou and coworkers assessed the spatial permeability of the BBB-opened science region using dynamic contrast-enhanced MRI (DCE-MRI) in mice. The authors processed DCE-MR images using the general kinetic model and the reference region model. Permeability maps were generated and the Ktrans (the transfer rate constant from the intravascular system to the extracellular extravascular space) values were calculated for a predefined volume of interest in the sonicated and the control area for each mouse. The results demonstrated that Ktrans in the BBB-opened region was at least two orders of magnitude higher when compared to the contralateral (control) side [68].

Another limitation is that we did not investigate the intake of v

Another limitation is that we did not investigate the intake of vegetables since this information was not covered by the questionnaires used in the survey. We also highlight the fact that information on physical activity was also self-reported, which may lead to overestimation. The criterion

used to define alcohol intake was highly sensitive, as the prevalence of adolescents who ingested alcohol on a daily basis was very low. Finally, the use of a cut-off point RAD001 molecular weight to analyze the risk factor score may be Modulators controversial. However, we analyzed the chance to present one more risk factor, through ordinal analyses, and the results were similar (data not shown). Studies investigating the clustering of risk factors for chronic conditions vary greatly as to the sets of factors under study, which makes comparisons between different studies difficult. It should be noted that biological risk factors (high arterial selleck pressure, hypercholesterolemia, among others) are at the core of most CNCD risk factor clustering studies, especially those focusing on cardiovascular disease. In the present study, however, we placed greater emphasis on behavioral

risk factors, given the evidence that lifestyle variables have a greater tendency to cluster and are potentially modifiable (Schuit et al., 2002). We highlight the important clustering effect for smoking and alcohol intake found in the present study. This finding underscores the importance of educating adolescents as to the importance of avoiding such behaviors, since one behavior Ketanserin leads to the other, as well as to the intake of heavier drugs. We also demonstrate the clustering of these both behaviors

(smoking and alcohol) with low fruit intake among girls and with physical inactivity among boys. Special attention should be given to adolescents from poorer families, since this group was more vulnerable to displaying three or more risk factors for CNCDs. Our results may have important implications in terms of health policy and practice given that the high prevalence of multiple CNCD risk factors underscore the importance of interventions aimed at their reduction. Adolescence is a period in which lifestyle habits are being formed and consolidated. Many of the behaviors acquired during adolescence tend to remain through to adult life, with important implications for adult health. Given that behavioral risk factors such as those investigated in the present study are potentially modifiable, identifying subgroups that are at higher risk of simultaneously displaying multiple factors is of extreme importance if we wish to reduce propensity to chronic diseases in adult life. None. “
“Most readers of a certain age will be familiar with the murder of Nicole Brown Simpson and Ronald Goldman, and the events that followed. Ms Simpson’s ex-husband, former professional athlete O.J.

Paclitaxel Paclitaxel was originally isolated from the bark of th

Paclitaxel Paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia. Its

chemical structure was determined in 1971, and its mechanism of action was elucidated in 1979 (33). Paclitaxel is an anti-microtubule agent that irreversibly binds specifically to the subunit of the protein tubulin and promotes the assembly of microtubules. The stabilization of microtubules prevents normal mitotic spindle formation and Inhibitors,research,lifescience,medical function. This disruption of normal spindle function, which is the primary mechanism of action of paclitaxel (34),(35) ultimately results in chromosome breakage and inhibition of cell replication and migration. Therefore, paclitaxel inhibits cell replication by blocking cells in the late G2 and/or M phases of the cell cycle(35). Another important mechanism of action of paclitaxel includes induction of apoptosis via binding to and subsequently blocking the function of the apoptosis inhibitor-protein, bcl-2. Inhibitors,research,lifescience,medical Pharmacokinetics studies with paclitaxel have demonstrated that its distribution is a biphasic process, with values for α and β half-lives

of approximately 20 minutes and 6 hours, respectively (33). True nonlinear pharmacokinetics may have important clinical implications, particularly in regards to dose modification, because a small Estrogen antagonist increase in drug exposure and hence toxicity (33). More than 90% of the time, paclitaxel Inhibitors,research,lifescience,medical binds to plasma proteins. Approximately 71% of an administered dose of paclitaxel is excreted in the stool via Inhibitors,research,lifescience,medical the enterohepatic circulation (33). Renal clearance is minimal, accounting for 14% of the administered dose(33). In humans, paclitaxel is metabolized by cytochrome P-450 (CP-450) mixed-function oxidases. Specifically, either isoenzymes CYP2C8 and CYP3A4 of CP-450 will metabolize paclitaxel to hydroxylated 3′ phydroxypaclitaxel Inhibitors,research,lifescience,medical (minor) and 6α-hydroxyplacitaxel (major), as well as to other forms of dihydroxylated metabolites. Paclitaxel

is typically administered intravenously at a dose of 135-175 mg/m2 every 21 days (33),(36). Docetaxel While paclitaxel is a natural product, docetaxel is a semi-synthetic product. Docetaxel inhibits microtubule disassembly and promotes microtubule stabilization, leading to disruption of microtubule-mediated cellular function during cell division, cell cycle arrest at G2/M transition, and cell death (37). Like paclitaxel, docetaxel induces the activation of several molecular pathways mafosfamide leading to cellular apoptosis by disorganizing the microtubule structure (38). However, another proposed mechanism of action of docetaxel is related to its effect on phospholipase-D (PLD) (38). PLD has been implicated in several physiological processes, such as membrane trafficking, cytoskeletal reorganization, cell proliferation, differentiation, survival, and apoptosis (38). Pharmacokinetics studies with docetaxel have demonstrated a linear pharmacokinetic behavior with a 3-compartment model.

In total,

a cohort of 291 susceptibles was included to ev

HBsAg and HBV infection showed a higher prevalence in males before 55 years (Fig. 3). In total,

a cohort of 291 susceptibles was included to evaluate the HBV incidence: 75 in Dhiba (hyperendemic region) and 216 in Rogba (hypo-endemic region). At baseline FDA-approved Drug Library screening in 1996, they were seronegative for all markers and they were retested for HBV infection markers 3 years later. They did not receive any HBV vaccine between the 2 tests. Out of the total sample of the cohort, 15 in Dhiba and 6 in Rogba seroconverted corresponding to a cumulative incidence during 3 years of 20.0% CI95% [10.95–29.05%] and 2.8% CI95% [0.60–5.00%] in Dhiba and Rogba, respectively, leading to a mean annual incidence of infection of 6.67% CI95% [3.65–9.70%] and 0.93% CI95% [0.20–1.67%] in these two villages (p < 10−3). The first part of the analysis is related to the study of environmental, demographic

and behavioural risk factors at the individual level. Bivariate analysis revealed that Libraries education level, past history of scarification, needle practices in the Primary Care Centre (PCC), gender, existence of sanitation in the house, and family scarification practices were significantly associated with HBV infection and chronic carriage find more (Table 2). By multivariate analysis, family scarification practices, needle practices in the PCC and gender were significantly associated with anti-Hbc positivity (AOR equal to 2.15 CI95% [1.85–2.49], 1.64 CI95% [1.36–1.97] and 1.26 CI95% [1.12–1.42], respectively). The same risk factors were found for HBsAg positivity (AOR equal to 2.36 CI95% [1.60–3.00],

1.85 CI95% [1.24–2.77] and 1.53 CI95% [1.23–1.90], respectively) and chronic carriage (AOR equal to 2.85 CI95% [2.10–3.86], 2.37 CI95% [1.33–4.19] and 1.37 CI95% [1.02–1.83], Ketanserin respectively). Lack of sewage in the house was found to be protective against anti-HBc (AOR equal to 0.49 CI95% [0.37–0.65]), and HBsAg positivity (AOR equal to 0.08 CI95% [0.02–0.31]). No significant association between HBV subgroups and household size was noted (Table 3). The second part of the analysis attempted to assess the importance of transmission within the family as a risk factor to acquire infection for the individual. We concentrated on the study of non-sexual close contact risks. Therefore, we evaluated the risk of HBV infection of the individual due to: (i) HBV chronic carrier mother, (ii) HBV chronic carrier brother/sisters(s), and (iii) and HBV chronic carrier father. Individuals having a carrier mother are about three times more likely to be anti-HBc positive (AOR = 2.97 CI95% [1.86–4.75]), 10 times more likely to be HBsAg positive (AOR = 10.64 CI95% [6.23–17.82]) and six times more likely to be chronic carriers (AOR = 5.65 CI95% [3.09–10.33]). Those having HBV chronic carrier brother(s) or sister(s) are at high risk of HBV infection (AOR equal to 11.60 [8.35–16.12] for anti-HBc and 13.61 CI95% [8.78–21.07] for HBsAg) and chronic carriage (AOR = 24.73 CI95% [13.56–45.12]).

In addition, the effects of drug noncompliance and EPS can both m

In addition, the effects of drug noncompliance and EPS can both mimic true treatment resistance.137,138 At least a 1- to 2-year course of persistent symptoms should also be considered as one of the criteria for treatment BYL719 resistance in schizophrenia,

because of the waxing and waning course of this illness. The most widely accepted current criteria for treatment resistance in schizophrenia were first used by Kane et al.127 These criteria, modified for clinical use, are as follows: Persistent positive psychotic symptoms (item score ≥ 4) on Inhibitors,research,lifescience,medical at least two of four positive symptom items on the BPRS: hallucinatory behavior, suspiciousness, unusual thought content, or conceptual disorganization. Current presence of at least a moderately severe illness as rated by the total BPRS (score ≥45 on the 18item scale) and a score of ≥4 on the Clinical Global

Impression (CGI) scale. Persistence of illness: no period of good social and/or occupational functioning within the last Inhibitors,research,lifescience,medical 5 years. Drug-refractory condition defined as at least two periods of treatment in the preceding 5 years with appropriate doses of conventional or SGAs, each without clinically significant symptom relief. The rates for two retrospective drug trial failures have been found Inhibitors,research,lifescience,medical to be similar to the rates for three when screening for treatment resistance; this fact is now widely accepted.138 People Inhibitors,research,lifescience,medical not responsive to two adequate antipsychotic trials (one retrospective and one prospective) have less than a 7% chance of responding to another trial.139 The Food and Drug Administration (FDA) guidelines for clozapine, as reflected in the product labeling for clozapine,140 also states that people should fail to respond to two separate trials of antipsychotics, before being treated with clozapine. It is generally recognized that Inhibitors,research,lifescience,medical a 4- to 6-week period (rather than strictly a 6-wcck one) is adequate for a treatment trial of an antipsychotic.141 Dosages of >400 mg/day of chlorpromazine

have been shown to be adequate to block 80% to 90% of dopamine receptors (thought to be the target of this drug action).142 Higher doses produce no direct therapeutic benefit, even in patients not Thiamine-diphosphate kinase responsive to therapy, and do not have greater efficacy in acute treatment than lower doses.143-145 Therefore, two 4- to 6-weck trials of 400 to 600 mg/day chlorpromazine or a chlorpromazine equivalent are now accepted as a standard for an adequate trial.138,146 Until the arrival of standardized criteria for defining treatment resistance, research into the neurobiological nature of the problem had been scant.147 Recently, however, with the use of more objective criteria, some consistent findings have been seen. There is a relative paucity of data in this area and more research needs to be done.

The SOA between prime and target was 300 msec The use of a shor

The SOA between prime and target was 300 msec. The use of a short SOA between

prime and target (300 msec) ensures to reduce the risk of semantic expectancies (i.e., creation of a mental list of potential associates). The intertrial interval (ITI) separating the single trials varied between 2000 msec and 2000 msec plus one repetition time (TR; here TR = 2.37 sec) to increase the sampling rate of the blood oxygenation level-dependent (BOLD) response (Josephs et al. 1997). The stimuli were presented visually via projection to a mirror directly above the participant’s head at eye level. The experimental procedure was programmed Inhibitors,research,lifescience,medical using the software presentation (Neurobehavioral Systems, Figure 1 Timing (in milliseconds) used in each experimental trial of Experiment 1 (semantic categorization [SC]) and Experiment 2 (silently SRT1720 clinical trial thinking about a word’s meaning [SilTh]). Critically, Experiments 1 and Inhibitors,research,lifescience,medical 2 differed with respect to the linguistic task. However, a linguistic task involving a binary decision was used in Experiment 1 (i.e., semantic categorization), a linguistic “task” that did not require a binary decision was used in Experiment 2 (i.e., silently thinking about a word’s meaning). Experiment 1: semantic categorization Participants were asked to decide whether Inhibitors,research,lifescience,medical each

item presented in capital letters (i.e., the second word of each trial) was natural or manmade (i.e., semantic categorization). For the symbol pairs, participants indicated whether the series of symbols were identical or different. Participants responded using their left hand. Half of the participants (n = 9) used the forefinger for the response “natural” and the Inhibitors,research,lifescience,medical middle finger for the response “manmade” and the other half (n = 9) used the reversed pattern. The first session was preceded by a short practice session of 12 items

before scanning started. Inhibitors,research,lifescience,medical Practice was repeated until participants responded without errors. Experiment 2: silently thinking about a word’s meaning In the related, unrelated, neutral, and filler conditions, the trial timing was identical to the one used in Experiment 1 except for the presentation duration of the target Dichloromethane dehalogenase word. The written target word was presented in capital letters for 300 msec followed by a blank screen for 1500 msec. The same timing was applied for the presentation of symbol pairs. As in Experiment 1, the prime word was replaced by a blank screen for 200 msec in the neutral and symbol trials. All other parameters (i.e., SOA, variable ITI) and the software used for stimulus presentation were equivalent to Experiment 1. In Experiment 2, inspired by Chee et al. (2003), participants were instructed to read each uppercase target-word silently and to think of its meaning (i.e., deeply process its semantic properties). Participants performed the semantic processing from the onset of the target until the next trial started.