Our novel likelihood method, which was robust to realistic simula

Our novel likelihood method, which was robust to realistic simulation parameters, was tested on Drosophila nuclear pore proteins, which form a complex with well-documented physical interactions. The method revealed significantly correlated evolution learn more between nuclear pore proteins, where members of a stable subcomplex showed stronger correlations compared with those proteins that interact transiently. Furthermore, our likelihood approach was better able to detect correlated evolution among closely related species than previous methods. Hence, these sequence-based methods are a complementary approach for detecting correlated evolution and could be applied genome-wide

to provide candidate protein-protein GSI-IX supplier interactions and functional group assignments using just coding sequences.”
“Current spindle models explain “anaphase A” (movement of chromosomes to the poles) in terms of a motility system based solely on microtubules (MTs) and that functions in a manner unique to mitosis. We find both these propositions unlikely.

An evolutionary perspective suggests that when the spindle evolved, it should have come to share not only components (e.g., microtubules) of the interphase cell but also the primitive motility systems available, including those using actin and myosin. Other systems also came to be involved in the additional types of motility that now accompany mitosis in extant spindles. The resultant functional redundancy built reliability into this critical and complex process. Such multiple mechanisms are also confusing to those who seek to understand how chromosomes move. Narrowing this commentary down to just anaphase A, we argue that the spindle matrix participates with MTs in anaphase A and that this matrix may

contain actin and myosin. The diatom spindle illustrates how such a system could function. This matrix may be motile and work in association with the MT cytoskeleton, as it does with the actin cytoskeleton during cell ruffling and amoeboid movement. Instead of pulling the chromosome polewards, the kinetochore fibre’s role might be to slow polewards movement to buy GW4869 allow correct chromosome attachment to the spindle. Perhaps the earliest eukaryotic cell was a cytoplast organised around a radial MT cytoskeleton. For cell division, it separated into two cytoplasts via a spindle of overlapping MTs. Cytokinesis was actin-based cleavage. As chromosomes evolved into individual entities, their interaction with the dividing cytoplast developed into attachment of the kinetochore to radial (cytoplast) MTs. We believe it most likely that cytoplasmic motility systems participated in these events.”
“Photodissociation of (ICN)(2) dimer from 265 to 270 nm are studied using time-of-flight mass spectrometry combined with velocity imaging technique.

53Ga0 47As base, and a 75-nm-thick In0 53Ga0 47As collector The

53Ga0.47As base, and a 75-nm-thick In0.53Ga0.47As collector. The emitter enables fabrication of a 15-nm-thick ledge structure simply by wet etching the n(+)-InGaAs

emitter. The emitter mesa and base metal were scaled down to 0.25 and 0.3 mu m, respectively. The fabricated HBT with a 0.25-mu m emitter provides a current gain of 62 at a collector current density, J(c), of 10 mA/mu m(2). With the thin ledge structure, the current gain is virtually independent of emitter size and emitter-base spacing. The HBT also exhibits an f(t) of 442 GHz and an f(max) of 214 GHz at a J(c) of 12 mA/mu m(2). The results of bias-temperature stress tests show that base and collector currents are stable up to 1042 h at a J(c) of 5 mA/mu m(2). (C) 2010 The Japan Society of Applied Physics”
“We Stem Cell Compound Library manufacturer have succeeded in synthesizing organic biradical crystals of m-Ph-V-2 [= 1,3-bis-(1,5-diphenylverdazyl-3-yl)benzene]. The intra and intermolecular interactions, which are deduced

from the molecular packing in the crystal, are considered to form an alternating double chain. We evaluated the intramolecular ferromagnetic ( FM) interaction from an analysis of the magnetic susceptibility of isolated m-Ph-V-2 molecules. We analyzed the magnetic susceptibility and magnetization curves of the crystals by the quantum Monte Carlo method and successfully explained these CX-6258 solubility dmso properties using an S = 1/2 FM alternating double chain model, which consists of antiferromagnetically coupled FM alternating chains. In addition, the magnetic susceptibility and specific heat showed anomalous behavior at T-N = 1.9 K, which indicates the magnetic phase transition to an antiferromagnetically ordered state.”
“Increasing life expectancy and PSA testing has increased the number of men over the age of seventy-five presenting for investigation of potential prostate malignancies. Prostatic biopsies provide diagnostic information; however, they are invasive and may not alter

management decisions. Therefore, this study aimed to investigate whether prostate biopsies in this age group were justified. All men aged 75 years and older who underwent prostatic biopsies between January 2010 and November 2011 at Bedford Hospital were identified Cell Cycle inhibitor and the indication for the biopsies, histopathological results and subsequent management plan investigated. One hundred and thirty-eight (138) prostatic biopsies were undertaken and malignancies identified in 60/138 (43 %) cases. Prebiopsy PSA and examination findings had a poor positive predictive value of 54 %. Fifty-five out of sixty (92 %) cancers were classified as high or medium risk disease with 30/60 (50 %) patients commencing radiotherapy treatment with curative intent. In selected patients aged 75 years or over, prostatic biopsies provide important diagnostic information which directly impacts on clinical decisions, supporting their use in this age group.

We hypothesize that this lack of effect of SLE on MCS may be due

We hypothesize that this lack of effect of SLE on MCS may be due to disease-coping

mechanisms interplaying with cultural factors unique to the Gullah. Lupus (2012) 21, 563-569.”
“Textural, rheological and microstructural properties of frankfurters made with 20% pork backfat, 20% canola or 20% canola-olive (3:1) oils, including rice bran (RB) and walnut extract (WE) as macronutrients (2.5%) were investigated. Textural parameters, including hardness, gumminess and rupture-force, were highly (P<0.05) influenced by the fat-oil composition. selleck chemicals llc Addition of RB or WE in vegetable oil emulsions improved textural consistency (P<0.05). However, RB addition reduced gelling capacity, suggesting antagonistic interactions between fiber and oil droplets. Vegetable oil addition favored gel network formation, and, when combined with WE, showed the highest improvement of gel elasticity. These textural and gelling properties were corroborated by frankfurter micrographs, which revealed interactions between vegetable oils, RB, or WE with protein matrix and fat globules affecting these parameters. The results suggest that functional plant-derived ingredients can be valuable to the modification of frankfurter formulations for improved nutrition AG-881 and as well as textural quality. (C) 2012 Elsevier

Ltd. All rights reserved.”
“Objective: To evaluate the association between Apgar scores of less than seven at five minutes (AS(5min) < 7) and antenatal factors and postnatal outcomes. Methods: A retrospective cohort and case-control study of 27,252 consecutive term newborns in a low risk obstetrical population between January 2003 and December 2010. Maternal and infant databases were reviewed from all cases with AS(5min) < 7 (n = 121; 0.4%) and

363 cases with AS(5min) >= 7 at 5 minutes who were randomly Selleckchem CHIR 99021 selected by a computer program. The main outcomes were neonatal death, newborn respiratory distress, need for orotracheal intubation and neonatal intensive care unit (NICU), and hypoxic-ischemic-encephalopathy. Results: After multiple regression analysis, repeated late decelerations on cardiotocography (OR: 2.4; 95% CI: 1.4-4.1) and prolonged second stage of labor (OR: 3.3; 95% CI: 1.3-8.3) were associated with AS(5min) < 7, as well as neonatal respiratory distress (OR: 3.0; 95% CI: 1.3-6.9), orotracheal intubation (OR: 2.5; 95% CI: 1.2-4.8), need for NICU (OR: 9.5; 95% CI: 6.7-16.8), and hypoxic-ischemic-encephalopathy (OR: 14.1; 95% CI: 3.6-54.7). No other antenatal factors were associated with AS(5min) < 7 (p > 0.05). Conclusion: Repeated late decelerations and prolonged second stage of labor in the low-risk population are predictors of AS(5min) < 7, a situation associated with increased risk of neonatal respiratory distress, need for mechanical ventilatory support and NICU, and hypoxic-ischemic-encephalopathy.”
“We describe a new immunity mechanism that protects actively replicating/transposing Mu from self-integration.

However, its mechanism had to be clarified We performed re-se

However, its mechanism had to be clarified.\n\nWe performed re-sequencing and genome-wide variation analysis of 7302R using ABT-737 the Solexa sequencing technology. With the genomic sequence of the indica cultivar 9311 as reference, 307 627 SNPs, 57 372 InDels, and 3 096 SVs were identified in the 7302R genome. The 7302R-specific variations were investigated via the synteny analysis of all the SNPs of 7302R with those of the previous sequenced none-IPA-type lines IR24, MH63, and SH527. Moreover, we found 178 168 7302R-specific SNPs across the whole genome and 30 239 SNPs in the predicted mRNA regions,

among which 8 517 were Non-syn CDS. In addition, 263 large-effect SNPs that were expected to affect the integrity of encoded proteins were identified from the 7302R-specific SNPs. SNPs of several important previously

cloned rice genes were also identified by aligning the 7302R sequence with other sequence lines.\n\nOur results provided several candidates account for the IPA phenotype of 7302R. These results therefore lay the groundwork for long-term efforts to uncover important genes and alleles for rice plant architecture Apoptosis Compound Library construction, also offer useful data resources for future genetic and genomic studies in rice.”
“We explored the perception and receptivity of elderly people regarding the introduction of an intelligent videomonitoring system (IVS) at home. Using a mixed methods design, 25 elderly people with a history of falls completed a structured interview (two questionnaires). In the year preceding the interview, 72% of the participants fell as many as seven times. Open-ended questions (qualitative data) were used to supplement the quantitative data. A content analysis (qualitative data) and a descriptive analysis (quantitative data) were carried out. The participants were 84% favourable or partially favourable STI571 mw to technologies which ensured

home security and 96% favourable or partially favourable to the IVS. About half (48%) said that they would use it. The other participants did not wish to use it unless they had been left to live alone or if their health condition worsened. Thus the living conditions of the elderly appear to influence their perception and receptivity regarding the acceptance and use of an IVS.”
“The manuscript describes the synthesis of novel amide tethered 7-chloroquinoline chalcone and 7-chloroquinoline-ferrocenylchalcone bifunctional hybrids and their evaluation as antimalarial agents against W2 resistant strain of Plasmodium falciparum. The antiplasmodial activity of 7-chloroquinoline-ferrocenylchalcones was found to be less than their corresponding simple chalcone conjugates.

94) Results Age and relationship length were significantl

94).\n\nResults.\n\nAge and relationship length were significantly negatively associated with self-reported ejaculation latency time. selleck Frequency of different kinds of sexual behavior generally had a positive association with self-reported ejaculation latency time, as

had different modes of achieving ejaculation.\n\nConclusions.\n\nThe findings highlight the need for more extensive studies on and increased knowledge of different aspects of ejaculatory function before a valid and suitable definition for premature ejaculation can be formulated. Jern P, Santtila P, Johansson A, Varjonen M, Witting K, von der Pahlen B, and Sandnabba K. Subjectively measured ejaculation latency time and its association with different sexual activities while controlling for age and relationship length. J Sex Med 2009;6:2568-2578.”
“The safe Geneticin research buy transfer (handoff) of responsibility for patient care from one physician to another requires that health care facilities have rigorous sign-out systems and that physicians develop effective communication skills. In 2007 and 2008, to improve the spoken and written sign-out practices of the 25 interns at Allegheny General Hospital (Pittsburgh, Pennsylvania), the authors designed and administered Likert scale surveys about training in and satisfaction

with current sign-out practices; directly observed and evaluated interns performing spoken sign-outs; assessed and graded interns’ sign-out sheets; and compared sign-out sheets with patient records to evaluate their accuracy. On the basis of their findings, the authors developed a new curriculum with didactic and interactive components to target

intern-level and system-level problems. The curriculum emphasized the importance of complete and accurate sign-outs, provided examples of good and poor sign-outs, and assigned interns to work in small groups to practice sign-out skills and receive feedback from peers and program leaders. Reevaluation of interns two months after curriculum implementation revealed not only better performance on each of the seven items evaluated for spoken sign-out but also substantial improvement in the completeness of sign-out sheets and the accuracy of reporting of identification data, code status, and medications data. The curriculum was well received by interns, and GSK3326595 order it helped them develop skills required by the Accreditation Council for Graduate Medical Education, including competencies in communication, practice-based learning, and systems-based practice.”
“What is technology transfer and what does it need to succeed? Various factors concerning the scientist, the academic institution, a fresh entrepreneur or an existing company, government policies and the environment contribute to greater efficiency in transferring technologies from academia to industry. These factors are discussed here with reference to the situation in the US and India.

Case presentation: We present a case of intra-abdominal absce

\n\nCase presentation: We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment.\n\nConclusion: In the advancing era of molecular therapy of solid tumours,

sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance.”
“Background Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis were reported to be involved in the pathogenesis of several diseases. In a recent study, it was reported that the ER stress pathway was activated in the Autophagy inhibitor mw lungs of lipopolysaccharide

(LPS)-treated mice. It was also found that the C/EBP homologous protein (CHOP), an apoptosis-related molecule, played a key role in LPS-induced lung damage. The aim of this study was to verify whether LPS could activate the ER stress response in airway epithelial cells and which molecule was involved in the pathway. This study was also aimed at finding new reagents to protect the airway epithelial cells during LPS injury.\n\nMethods ER stress markers were observed in LPS-incubated NCI-H292 cells. SiRNA-MUC5AC was transfected into NCI-H292 cells. The effects of dexamethasone and erythromycin were observed in LPS-induced NCI-H292 cells.\n\nResults LPS incubation increased the expression of ER stress markers at the protein and mRNA levels. The knockout of MUC5AC in cells attenuated the increase in ER FK866 stress markers after incubation with LPS. Dexamethasone and erythromycin decreased caspase-3 activity in LPS-induced NCI-H292 cells.\n\nConclusions LPS may activate ER stress through the overexpression of MUC5AC. Dexamethasone may protect human airway epithelial cells against ER stress-related apoptosis by attenuating

the overload of MUC5AC. Chin Med J 2011;124(1):38-44″
“A mild, efficient, and highly GSK2245840 mouse regio- and stereoselective method for the methoxy and ethoxy bromination of olefins has been developed using NH4Br as a bromine source and Oxone as an oxidant. Various kinds of olefins (aromatic, linear, and cyclic olefins) afforded the corresponding alkoxy brominated products in moderate to excellent yields. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resources: Full experimental and spectral details.]“
“Caregiving for a person with dementia can lead to physical and psychological morbidity. Technology-driven interventions hold the promise of convenient, low-cost methods of delivering psychosocial interventions. This systematic review examined the efficacy of technology-driven interventions for caregivers of persons with dementia.

Results: Forty-three

\n\nResults: Forty-three E7438 patients had missense changes (group A), and 14 patients had nonsense, splice-site, or frame-shifting mutations in the RS1 gene (group B). The mean best-corrected visual acuity was better in group A than in group B (0.34 and 0.21, respectively). Fundus examination revealed foveal schisis in approximately half of both groups. The bright-flash dark-adapted (DA) ERG (11.0 candela. sec. m(-2)) waveform was electronegative

in 62% of group A eyes and 100% of group B eyes. The photopic 30-Hz flicker ERG was delayed in all group B eyes and all except 6 group A eyes. On-Off ERG b-waves were subnormal in 39% of group A and 89% of group B eyes; d-waves were delayed in 14 eyes (group A = 10, group

B = 4). S-cone ERGs were abnormal in 50% of both groups. The PERG was abnormal in 88% of group A and 100% of group B eyes. A spoke-wheel pattern of high and low intensity was the most common FAF abnormality observed. The SB203580 cell line OCT showed intraretinal schitic cavities in the majority of eyes.\n\nConclusions: There is profound phenotypic variability in patients with XLRS. Most patients have DA bright-flash ERGs with a low b:a ratio in keeping with inner retinal dysfunction. Generalized cone system dysfunction is common and associated with an abnormal On-response and less frequent additional Off-response involvement. Nonsense, splice-site, or frame-shifting mutations in RS1 consistently caused electronegative bright-flash ERG, delayed flicker response, and abnormal PERG; missense mutations result in a wider range of ERG abnormalities.”
“Background: Apolipoprotein E allele epsilon 4 (apoE4) is a strong risk factor for developing Alzheimer’s disease Liproxstatin-1 order (AD). Secreted apoE has a critical function in redistributing lipids among central nervous system cells to maintain normal lipid homeostasis. In addition, previous reports have shown that

apoE4 is cleaved by a protease in neurons to generate apoE4(1-272) fragment, which is associated with neurofibrillary tanglelike structures and mitochondria, causing mitochondrial dysfunction. However, it still remains unclear how the apoE fragment associates with mitochondria and induces mitochondrial dysfunction.\n\nResults: To clarify the molecular mechanism, we carried out experiments to identify intracellular apoE-binding molecules and their functions in modulating mitochondria function. Here, we found that apoE4 binds to ubiquinol cytochrome c reductase core protein 2 (UQCRC2) and cytochrome C1, both of which are components of mitochondrial respiratory complex III, and cytochrome c oxidase subunit 4 isoform I (COX IV I), which is a component of complex IV, in Neuro-2a cells. Interestingly, these proteins associated with apoE4(1-272) more strongly than intact apoE4(1-299).

In the outpatient group DNA scores were higher in patients with c

In the outpatient group DNA scores were higher in patients with cancer and inflammatory bowel disease compared to those with no abnormalities detected, diverticular disease and small polyps (P<0.001 for PicoGreen assay; P=0.002 for real-time PCR). The sensitivity and specificity of the quantitative DNA test (PicoGreen assay; cut-off point 3.0 mu g/ml) for detecting serious

colorectal conditions were 1.00 and 0.74, respectively. In the group with confirmed tumours, the GDC-941 PicoGreen assay performed better for distal colorectal cancer (sensitivity 0.83; specificity 0.76) compared with proximal colon malignancies (sensitivity 0.57; specificity 0.76). It can be concluded that the proposed technique of direct collection of exfoliated cells from the surface of human rectal mucosa provides abundant cellular material suitable for diagnostic and research applications. Further refinement of the quantitative

DNA test may lead to a new approach for colorectal cancer early detection and screening.”
“It has been proposed that perceptual decision making involves a task-difficulty component, which detects perceptual uncertainty and guides allocation of attentional resources. It is thought to take place immediately after the early extraction of sensory information and is specifically reflected in a positive component of the event related potentials, peaking at similar to 220 ms after stimulus onset. However, in the check details previous research, neural processes associated with the monitoring of overall task difficulty were confounded by those associated with the increased sensory processing PXD101 in vivo demands as a result of adding noise to the stimuli. Here we dissociated

the effect of phase noise on sensory processing and overall decision difficulty using a face gender categorization task. Task difficulty was manipulated either by adding noise to the stimuli or by adjusting the female/male characteristics of the face images. We found that it is the presence of noise and not the increased overall task difficulty that affects the electrophysiological responses in the first 300 ms following stimulus onset in humans. Furthermore, we also showed that processing of phase-randomized as compared to intact faces is associated with increased fMRI responses in the lateral occipital cortex. These results revealed that noise-induced modulation of the early electrophysiological responses reflects increased visual cortical processing demands and thus failed to provide support for a task-difficulty component taking place between the early sensory processing and the later sensory accumulation stages of perceptual decision making.”
“Background: The goal of this study was to investigate the movement of contraction-relaxation effects on isolated human blood vessel samples by the actions of amlodipine (CAS 88150-42-9), cerebrocrast (CAS 118790-71-9), diltiazem (CAS 42399-41-7), and a benzimidazole derivative.

The loss of the colonic CaSR increased the number of ACF/cm(2) in

The loss of the colonic CaSR increased the number of ACF/cm(2) in response to ATM/ATR inhibitor AOM injection, suggesting colonic CaSR may mediate the chemoprotective effect of increased dietary calcium against colorectal cancer observed in humans. Laboratory Investigation (2013) 93, 520-527; doi:10.1038/labinvest.2013.51; published

online 1 April 2013″
“Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n = 3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas Bromosporine cell line (GBMs) by single-voxel MRS (n = 3) and MRSI (n = 9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 +/- 0.85 mu mol/g water, 1.5-fold higher than in control mouse brain (p < 0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 +/- 0.58 and 4.57 +/- 1.15 h, respectively. MRSI

maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T1 contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact bloodbrain Daporinad manufacturer barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors

invisible to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright (c) 2012 John Wiley & Sons, Ltd.”
“Polyamides (PAs) containing fluorene, oxy-ether, and diphenyl-silane moieties in the repeating unit were synthesized in > 85% yield by direct polycondesation between a diamine and four dicarboxylic acids. Alternatively, one PA was synthesized from an acid dichloride. The diamine 4-[4-[9-[4-(4-aminophenoxy)-3-methyl-phenyl]fluoren-9-yl]-2-methyl-phenoxy]aniline (3) was obtained from the corresponding dinitro compound, which was synthesized by nucleophilic aromatic halogen displacement from p-chloronitrobenzene and 9,9-bis (4-hydroxy-3-methyl-phenyl)fluorene (1). Monomers and polymers were characterized by FTIR and (1)H, (13)C, and (29)Si-NMR spectroscopy and the results were in agreement with the proposed structures. PAs showed inherent viscosity values between 0.14 and 0.43 dL/g, indicative of low molecular weight species, probably of oligomeric nature.

05) This study indicated that addition of Fe-Gly could obviously

05). This study indicated that addition of Fe-Gly could obviously modify antioxidant status of broiler chickens, and moreover, improve growth performance and immune function partially. (C) 2015 Elsevier B.V. All rights reserved.”
“The progressive restriction of cell fate during lineage differentiation is a poorly understood phenomenon despite its ubiquity selleck chemicals in multicellular organisms. We recently used a cell fusion assay to define a mode of epigenetic silencing that we termed “occlusion”, wherein affected genes are silenced by cis-acting chromatin mechanisms irrespective of whether trans-acting transcriptional activators are present. We hypothesized that occlusion of lineage-inappropriate

genes could contribute to cell fate restriction. Here, we test this hypothesis by introducing bacterial artificial chromosomes (BACs), which are devoid of chromatin modifications necessary for occlusion, selleck into mouse fibroblasts. We found that BAC transgenes corresponding to occluded endogenous genes are expressed

in most cases, whereas BAC transgenes corresponding to silent but non-occluded endogenous genes are not expressed. This indicates that the cellular milieu in trans supports the expression of most occluded genes in fibroblasts, and that the silent state of these genes is solely the consequence of occlusion in cis. For the BAC corresponding to the occluded myogenic master regulator Myf5, expression of the Myf5 transgene on the BAC triggered fibroblasts to acquire a muscle-like phenotype. These results provide compelling evidence for a critical role of gene occlusion in cell fate restriction.”
“Antipsychotic drugs are the mainstay pharmacotherapy for schizophrenia and related psychiatric disorders. While the metabolic pathways of antipsychotic drugs have been well defined, the role of drug transporters in the disposition and effects of antipsychotic drugs has not been systematically explored. P-glycoprotein has ubiquitous expression in brain endothelial cells

and plays a protective role by effluxing ABT737 substrates for elimination and by limiting their accumulation in the central nervous system. Risperidone and several other antipsychotic drugs are substrates of P-glycoprotein. Increased antipsychotic drug entry into the brain via blockade of the P-glycoprotein transporter may facilitate the amount of available drug to its targets, particularly dopamine receptors. By increasing available antipsychotic drug concentrations, P-glycoprotein inhibition offers a novel means of enhanced drug delivery. This study evaluated whether selective P-glycoprotein transporter inhibition would increase the effects of risperidone on relevant indices of behaviour (catalepsy and locomotion) and neurochemistry (dopamine release and metabolism as measured by in-vivo microdialysis). We administered the P-glycoprotein inhibitor, PSC 833 (100 mg/kg p.o.), to rats prior to administration of risperidone at varying doses (0.01-4.0 mg/kg s.c.).