This observation was used to define a series of risk groups based

This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of 41 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined GDC-0449 mouse by ISS II or III and 41 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months. Leukemia (2012) 26, 349-355; doi:10.1038/leu.2011.204; published online 12

August 2011″
“Children selleck compound with specific reading impairment may have subtle deficits in speech perception related to difficulties in phonological processing. The aim of this study was to examine brain oscillatory activity related to phonological processing in the context of auditory sentence comprehension using magnetoencephalography to better understand these deficits.

Good and poor readers, 16-18 years of age, were tested on speech perception of sentence-terminal incongruent words that were phonologically manipulated to be similar or dissimilar to corresponding congruent target words. Functional coupling between regions was measured using phase-locking values (PLVs). Gamma-band (30-45 Hz) PLV between auditory cortex and superior temporal sulcus in the right hemisphere was differentially

modulated in the two groups by the degree of phonological contrast between the congruent and the incongruent target words in the latency range associated with semantic processing. Specifically, the PLV was larger in the phonologically similar than in the phonologically dissimilar condition in the good readers. This pattern was reversed in the poor readers, whose lower PLV in the phonologically similar condition may be indicative of the impaired phonological coding abilities of the group, and consequent vulnerability under perceptually demanding conditions. Overall, the results support the role of gamma oscillations in spoken language processing. NeuroReport 23:851-856 (C) 2012 Wolters Kluwer Health vertical bar Lippincott BAY 63-2521 in vitro Williams & Wilkins.”
“Using voxel-based (VBA) and region-of-interest (ROI) diffusion tensor imaging (DTI) analyses, we examined white matter (WM) organization in seven children with dyslexia and six age-matched controls. Both methods demonstrated reduced fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF) and abnormal orientation in the right SLF in dyslexics. Application of this complementary dual DTI approach to dyslexia, which included novel analyses of fiber orientation, demonstrates its usefulness for analyzing mild and complex WM abnormalities. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Enlargement was defined as a z score of greater than 1 96 from th

Enlargement was defined as a z score of greater than 1.96 from the predicted value.

Results: The autograft and native aortic dimensions increased significantly from baseline to the intermediate follow-up and continued to increase to the final follow-up. The proportion of patients with enlarged autografts and proximal ascending aortas was 13% and 16% at baseline, increasing to 33% (P = .006) and 44% (P = .0014), respectively, at the end of follow-up. Enlargement of the aorta at the final follow-up was related to larger baseline pulmonary autograft dimensions but not to native bicuspid valve or the

need to downsize the aortic root.

Conclusions: Pulmonary autograft dilatation is common after the Ross procedure Blebbistatin molecular weight in adults. The dilatation progresses over time and is often accompanied by dilatation of the native aorta. (J Thorac Cardiovasc Surg 2011;142:634-40)”
“The check details increasing number of bacterial strains that are resistant to available pharmaceutical compounds is a vital issue for public health. Innovative approaches will be required to improve the methods for both diagnosis and destruction of these organisms.

Here, we consider the possible role that can be played by technologies based on gold nanoparticles. Gold nanoparticles generally are considered to be biologically inert but can be engineered to possess chemical or photothermal functionality. A growing body of research is devoted to the potential use of these nanoparticles in the diagnosis and treatment of bacterial infections. The results are both promising and intriguing, and suggest a range of new strategies to identify, target or destroy pathogenic organisms.”
“Background: New techniques for diagnosing hereditary haemochromatosis (HHC) have become available alongside traditional I-BET151 tests such as liver biopsy and serum iron studies.

Aim: To evaluate DNA tests in people suspected of having haemochromatosis at clinical presentation compared to liver biopsy, and in family members

of those diagnosed with haemochromatosis compared to phenotypic iron studies in UK.

Methods: Decision analytic models were constructed to compare the costs and consequences of the diagnostic strategies for a hypothetical cohort of people with suspected haemochromatosis. For each strategy, the number of cases of haemochromatosis identified and treated and the resources used were estimated.

Results: For diagnostic strategies in people suspected clinically of having haemochromatosis, the DNA strategy is cost saving compared to liver biopsy (cost saved per case detected, (sic) 123) and continues to be so across all ranges of parameters. For family testing, the DNA strategy is cost saving for the offspring of the proband but not for siblings.

“Objective: For patients with aortic root pathology and ao

“Objective: For patients with aortic root pathology and aortic valve regurgitation, aortic valve replacement is problematic because no durable bioprosthesis exists, and mechanical valves require lifetime anticoagulation. This study sought to assess outcomes of combined aortic

valve and root repair, including comparison with matched bioprosthesis aortic valve replacement.

Methods: From November 1990 to January 2005, 366 patients underwent modified David reimplantation (n = 72), root remodeling (n = 72), or valve repair with sinotubular junction tailoring (n = 222). Active follow-up was 99% complete, with a mean of 5.6 +/- 4.0 years (maximum 17 years); follow-up for vital status averaged 8.5 +/- 3.6 years (maximum 19 years). Propensity-adjusted models were developed for fair comparison of outcomes.

Results: Thirty-day and 5-, 10-, and 15-year survivals were 98%, 86%, 74%, and 58%, respectively, similar Ralimetinib nmr to that of the US matched population and better than that after bioprosthesis aortic valve

replacement. Propensity-score adjusted survival was similar across procedures (P > .3). Freedom from reoperation at 30 days and 5 and 10 years was 99%, 92%, and 89%, respectively, and was similar across procedures (P >.3) after propensity-dscore adjustment. Patients with tricuspid aortic valves were more likely to be free of reoperation than those with bicuspid valves at 10 years (93% vs 77%, P = .002), equivalent to bioprosthesis aortic valve replacement and superior after 12 years. Bioprostheses increasingly deteriorated after 7 years, and hazard functions for reoperation crossed at 7 years.

Conclusions: Blasticidin S price Valve preservation (rather than replacement) and matching root procedures have excellent early and long-term results, with increasing survival benefit at 7 years and fewer reoperations by 12 years. We recommend this procedure for experienced surgical teams. (J Thorac Cardiovasc Surg 2011;142:1491-8)”
“Decline of cognitive function KU55933 with age may be due, in part, to hormonal changes and it has been hypothesized

that higher levels of endogenous sex hormones preserve brain function. The aim of this prospective cohort study was to determine the relative contribution of endogenous sex hormones to cognitive decline in a population-based sample of 242 elderly men aged 73-91 at baseline. Endogenous sex hormone levels were measured at baseline and participants underwent a cognitive assessment at baseline and at follow-up after 4 years. Higher estradiol (total and bioavailable) and estrone levels were associated with an increased risk of cognitive decline in elderly men independent of age, cardiovascular risk factors, atherosclerosis, and APOE genotype. These findings do not support the hypotheses that higher levels of endogenous sex hormones preserve brain function. (C) 2008 Elsevier Ltd. All rights reserved.

healthy aging, and in the pathophysiologies of Parkinson’s diseas

healthy aging, and in the pathophysiologies of Parkinson’s disease and schizophrenia.”
“Objective: Mast cells (MCs) are inflammatory cells present in atherosclerotic

lesions and neovascularized tissues. Recently, MCs were shown to modulate abdominal aortic aneurysm (AAA) formation in a mouse model. Progression of aneurysmatic disease process may also depend on intraluminal thrombus and neovascularization of the aneurysm wall. Here we investigated the relationship between MCs and inflammation, neovascularization, and the presence of intraluminal thrombus in human AAA.

Methods and Results: Specimens from AAAs and normal control aortas were analyzed with basic histology, immunohistochemical staining, and quantitative real-time polymerase chain reaction (PCR). Double immunostainings with endothelial cell markers CD31/CD34 and MC tryptase showed that, in contrast to histologically normal aorta, MCs in AAA were abundant in the media, but absent from the intima. Medial MCs and (CD31/CD34)(+) neovessels increased significantly Stattic concentration in AAA compared with normal aorta (P < .0001 for both), and the highest densities of neovessels and MCs were observed in the media of thrombus-covered

AAA samples. Also, the proportional thickness of aortic wall penetrated by the neovessels was significantly higher in the AAA samples (P < .0001), and the neovascularized area correlated with the density of medial MCs (P < .0001). In histologic analysis, the medial MCs were mainly located adjacent to the stern cell factor (SCF)(+) medial neovessels. Real-time PCR analysis also showed that mRNA levels of genes associated with neovascularization (vascular endothelial growth factor [VEGF], FLT1, VE-cadherin, CD31), and MCs (tryptase, chymase, cathepsin G) were higher in AAA samples than in controls. Demonstration of adhered platelets by CD42b staining and lack of endothelial cell (CD31/CD34) staining in the luminal surface of

AAA specimens suggest endothelial erosion VE-821 datasheet of the aneurysm walls.

Conclusions: The results support participation of MCs in the pathogenesis of AAA, particularly regarding neovascularization of aortic wall. (J Vasc Surg 2009;50:388-96.)”
“Action potentials (APs) provide the primary means of rapid information transfer in the nervous systems. Where exactly these signals are initiated in neurons has been a basic question in neurobiology and the subject of extensive study. Converging lines of evidence indicate that APs are initiated in a discrete and highly specialized portion of the axon-the axon initial segment (AIS). The authors review key aspects of the organization and function of the AIS and focus on recent work that has provided important insights into its electrical signaling properties.

The side-chain conformation of the proposed catalytic residue, Hi

The side-chain conformation of the proposed catalytic residue, His144, changes upon complex formation. Lineweaver-Burk plots indicate that the inhibitor binds competitively with respect to NADH, and uncompetitively with respect to crotonoyl coenzyme A. We propose that the primary basis of the inhibitory activity is competition with NADH for binding to FabK, which is the first step of the two-step ping-pong catalytic

“p53 missense mutations observed in human cancers are often associated with an increased level of p53 protein in the tumour. Using mouse models, Terzian et al. recently showed that this accumulation of mutant p53 protein is CX-5461 supplier not associated with specific properties of the protein itself but instead depends on the endogenous genetic

background of the tumours and on two important genes, mouse double minute 2 (Mdm2) and the cyclin kinase inhibitor p16(INK4a). Mice expressing mutant p53 in the absence of Mdm2 display more aggressive metastatic tumours. In light of these observations, targeting the MDM2-p53 interaction for therapy of human cancer could be more complicated than previously anticipated.”
“Purpose: To evaluate the usefulness of [F-18]-6-fluorodopamine ([F-18]-DA) and [F-18]-L-6-fluoro-3,4-dihydroxyphenylalanine ([F-18-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression

of the norepinephrine transporter (NET) and vesicular monoamine transporters I and 2 (VMAT1 and VMAT2), all important for [F-18]-DA and [F-18]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse.

Methods: SUVmax values Electron transport chain were calculated from [F-18]-DA and [F-18]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated.

Results: [F-18]-DA detected less metastatic lesions compared to [F-18]-DOPA. TLR values for liver metastases were 2.26-2.71 for [F-18]-DOPA and 1.83-2.83 for [F-18]-DA. A limited uptake of [F-18]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [F-18]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [F-18]-DA’s high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [F-18]-DOPA was found to utilize only VMAT2.

Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [F-18]-DOPA had overall better sensitivity than [F-18]-DA for the detection of metastases.

Methods and Results: The investigation strategy consisted of the

Methods and Results: The investigation strategy consisted of the combination of yeast cultivation, selection of the isolated yeasts based on the amplification of internal transcribed spacer 2 using a fluorescence-labelled primer (f-ITS-PCR) and a final identification step based on amplification and sequencing of the ITS1-5.8S rDNA-ITS2

region of the selected yeasts. By this three-step approach, it was possible to screen 433 yeasts isolates that belonged to 13 different species.

Conclusions: The f-ITS-PCR allowed the unambiguous differentiation of all isolated yeast species that produced their typical f-ITS-PCR profile.

Significance and Impact of the Study: This is one of few reports that treat the yeast diversity in Slovakian

wines and in two varieties largely cultivated in Central AR-13324 nmr Europe. The three-step approach permitted the rapid and reliable identification of isolated yeasts. The f-ITS-PCR with its good discrimination power can represent a suitable molecular tool for the selection of yeast members recovered from food or other environments.”
“Environmental enrichment (EE) has long been exploited to investigate the influence of the environment on brain structure and function. Robust morphological and functional effects elicited by EE at the neuronal level have been reported to be accompanied by improvements in cognitive performance. Recently, EE has been shown to accelerate

the development of the visual system and to enhance visual-cortex plasticity in adulthood. These new findings highlight the potential of EE as a promising non-invasive strategy to ameliorate deficits in the maturation of the nervous system and to promote recovery of normal sensory functions in pathological conditions affecting the adult brain.”
“We studied Selleckchem Evofosfamide how physical and instructed embedding of features in gestalts affects perceptual selection. Four ovals on the horizontal midline were either unconnected or pairwise connected by circles, forming ears of left and right heads (gestalts). Relevant to responding was the position of one colored oval, either within its pair or relative to fixation (“”object-based”" or “”fixation-based”" instruction). Responses were faster under fixation- than object-based instruction, less so with gestalts. Previously reported increases of N1 when evoked by features within objects were replicated for fixation-based instruction only. There was no effect of instruction on N2pc. However P1 increased under the adequate instruction, object-based for gestalts, fixation-based for unconnected items, which presumably indicated how foci of attention were set by expecting specific stimuli under instructions that specified how to bind these stimuli to objects.

“Objective: Use of single-dose antibiotic prophylaxis is a

“Objective: Use of single-dose antibiotic prophylaxis is associated with reduced antibiotic resistance, lower costs, and fewer problems with drug toxicity and superinfections. We tested the hypothesis that single doses of cefazolin are as effective as a 24-hour regimen of cefazolin in preventing surgical site infections in adults undergoing cardiac procedures.

Methods: This random, prospective, clinical study included 838 adult patients undergoing elective coronary artery bypass grafting, valve operations, or both. These patients

were randomly given a single dose of cefazolin (2 g) or a 24-hour treatment (2-g initial dose, followed by 1 g every 8 hours). Investigators blinded to selleck products the drug regimen diagnosed wound infections according to Centers for Disease Control and Prevention criteria. Patient clinical and demographic characteristics were noted, with follow-up for 12 postoperative months. The primary objective was to compare the incidence of surgical infections between groups up to 12 months postoperatively.

Results: A total of 419 patients received single-dose cefazolin, and

another 419 received the selleck chemical 24-hour treatment. Surgical site infection occurred in 35 (8.3%) patients receiving single doses and 15 (3.6%) patients administered the 24-hour treatment (P = .004). We identified no differences between groups for mortality or duration of hospitalization (preoperative hospitalization, intensive care unit stay, and hospitalization after surgical intervention). The microorganisms isolated showed a similar distribution in both groups. The

germs isolated were gram-positive cocci in 86% of the surgical site infections.

Conclusions: Single-dose cefazolin used as antibiotic prophylaxis ISRIB purchase in cardiac surgery is associated with a higher surgical site infection rate than the 24-hour, multiple-dose cefazolin regimen.”
“Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate gamma-aminobutyric-acid-type-A (GABA(A)R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (sigma 1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitive-line (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the delta-subunit of GABA(A), but not of sigma 1R mRNA, in FSL rats compared to SD rats. The delta-subunit controls the sensitivity of the GABA(A)R to the neurosteroid.

The deregulated pathways identified are likely to be critical to

The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder, thereby providing new targets for therapeutic intervention. Leukemia (2010) 24, 756-764; doi: 10.1038/leu.2010.31; published online 11 March 2010″
“The volatile organic compound 2,2,4-trimethylpentane (TMP, “”isooctane”") is a constituent of gasoline for which the current health effects data are insufficient to permit the US Environmental Protection Agency to conduct a risk assessment. The potential neurological impairment from acute inhalation exposure to IMP was evaluated in adult male Long-Evans rats URMC-099 solubility dmso using both electrophysiological

and behavioral assessments. Visual evoked potentials (VEPs) were recorded from rats viewing modulated visual patterns (0.16 cycles per degree visual angle (cpd), 60% contrast, 4.55 Hz appear/disappear). Rats (n = 7-10/dose) were exposed to IMP vapors in concentrations learn more of 0, 500, or 1000 ppm for 60-min. A VEP was recorded before exposure and at 10 min intervals during exposure and also for 60 min after exposure terminated.

The spectral amplitude of the frequency-double component (F2) was significantly reduced after exposure to IMP. In behavioral assessments, rats (n = 14) performed an appetitively motivated visual signal detection task while breathing 0, 500, 1500, 1000, 2000, or 2500 ppm IMP for 62 min. Slight reductions in accuracy of performance were observed at the 2500 ppm concentration. Concentrations of TMP in the Entinostat order brain were estimated using a physiologically based pharmacokinetic (PBPK) model to be less than 0.2 mM after 62 min at 2500 ppm. Together these data demonstrate that TMP, like other volatile organic substances, impairs neurological function during acute inhalation

exposure and that the small magnitude of the observed effects is consistent with the low concentrations of this hydrocarbon that were estimated to reach the CNS. Published by Elsevier Inc.”
“Active influx of imatinib in chronic myeloid leukemia (CML) cells is mediated by the organic cation transporter 1 (OCT-1). Functional activity of OCT-1 (OCT-1 Activity) in mononuclear cells is an excellent predictor of molecular response over the first 24 months of imatinib therapy for chronic phase patients. CML progenitor cells are less sensitive to imatinib-induced apoptosis and are likely contributors to disease persistence. We investigated whether alterations in the expression and function of OCT-1 have a role in imatinib resistance in progenitors. We found the intracellular uptake and retention (IUR) of imatinib, OCT-1 Activity and OCT-1 mRNA expression are all significantly lower in CML CD34+ cells compared with mature CD34- cells (P<0.001). However, no differences in IUR or OCT-1 Activity were observed between these subsets in healthy donors.

Methods: Flow rates in major vessels and tensions from small pulm

Methods: Flow rates in major vessels and tensions from small pulmonary arteries from the left and right lower lobes were determined

48 hours after creation of an end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta.

Results: Anastomoses increased flow through the left lower lobe pulmonary artery from 194 +/- 6 to 452 +/- 18 mL/min immediately after anastomosis to 756 +/- 19 mL/min by Go6983 ic50 the time of harvest (n = 88, P < .05). Flow rates in main pulmonary arteries from hosts with anastomoses were lower (557 +/- 26 vs 1033 +/- 244 mL/min), whereas aortic root flows were not different from control values (1370 +/- 53 vs 1120 +/- 111 mL/min; P = .07). Wet/dry weights of both lungs and aortic flow rates were proportional to shunt flow rates. Pulmonary artery rings harvested from the right (unshunted) lobes of high-flow hosts exhibited increased reactivity to the thromboxane agonist U46619 and phenylephrine relative to those of left pulmonary arteries from the same animal or those of control hosts.

Conclusions: Our studies are the first to identify enhanced reactivity of pulmonary arteries in a lung contralateral AG-120 to a localized high-output shunt between an aorta and pulmonary artery. These observations suggest that patients with localized systemic-to-pulmonary shunt could exhibit modified vascular tone in remote pulmonary arteries. (J Thorac Cardiovasc Surg 2011;141:407-12)”
“The regulator

of G protein signaling 9-2 (RGS9-2) is a constituent of G protein-coupled receptor (GPCR) macromolecular complexes with a major role in regulation of GPCR activity in the central nervous system. Previous in situ hybridization and Western blot studies revealed that RGS9-2 is expressed in the superficial dorsal horn of the spinal cord. In the present study, we monitored

tail withdrawal latencies to noxious thermal stimuli and performed in vitro whole-cell patch clamp electrophysiological recordings from neurons in lamina II of the spinal dorsal horn to examine the role of RGS9-2 in the dorsal horn of the spinal cord in nociceptive behaviours and opiate mediated modulation of synaptic transmission. Our findings obtained AZD9291 datasheet from RGS9 knockout mice indicate that the lack of RGS9-2 protein decreases sensitivity to thermal stimuli and to the analgesic actions of morphine in the tail immersion paradigm. This modulatory role of RGS9-2 on opiate-mediated responses was further supported by electrophysiological studies showing that hyperpolarization of neurons in lamina II of the spinal dorsal horn evoked by application of DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin, a mu opioid receptor agonist) was diminished in RGS9 knockout mice. The results indicate that RGS9-2 enhances the effect of morphine and may play a crucial role in opiate-mediated analgesic mechanisms at the level of the spinal cord. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

c-Met was found to be overexpressed in 73 2% of patients (186/254

c-Met was found to be overexpressed in 73.2% of patients (186/254) and was significantly associated with overexpression of p-AKT (P = 0.0274), p-GSK3 (P = 0.0047) and Ki-67 (P = 0.0012). Interestingly, c-Met overexpression was significantly more common in the germinal center subtype of DLBCL, as compared with activated B cell subtype (P = 0.0002). Overexpression of c-Met in DLBCL was significantly associated with better survival (P = 0.0028) and remained significant in multivariate analysis with international prognostic index, thereby confirming c-Met as independent prognostic marker for better outcome in DLBCL. In vitro pharmacological c-Met inhibition and siRNA targeted against c-Met triggered caspase-dependent

apoptosis. These findings provide evidence that c-Met is an independent prognostic marker for better check details outcome in Middle Eastern DLBCL. This data also enlightens the fact that c-Met through AKT kinase has a critical role in carcinogenesis of DLBCL, and strongly suggest E7080 that targeting c-Met may have therapeutic value in treatment of DLBCL. Laboratory Investigation (2010) 90, 1346-1356; doi:10.1038/labinvest.2010.108; published online 7 June 2010″
“Morphine is a widely used analgesic in humans that is associated with multiple untoward effects, such as addiction and physical

dependence. In rodent models, morphine also induces locomotor activity. These effects likely involve functionally selective mechanisms. Indeed, G protein-coupled receptor desensitization and adaptor protein beta-arrestin 2 (beta arr2) through its interaction with the m-opioid receptor regulates the analgesic but not the rewarding properties of morphine. However, beta arr2 is also required for morphine-induced locomotor activity in mice, but the exact cellular and molecular mechanisms that mediate this arrestin-dependent behavior are not understood. In this study, we show that beta arr2 is required for morphine-induced

locomotor activity in a dopamine D1 receptor (D1R)-dependent manner and that a beta arr2/phospho-ERK (beta arr2/pERK) signaling complex may mediate this behavior. Systemic administration of SL327, an MEK inhibitor, inhibits morphine-induced locomotion in wild-type mice in a dose-dependent manner. Acute morphine administration to mice promotes the formation of a beta arr2/pERK signaling complex. Morphine-induced locomotor activity and formation of the beta arr2/pERK signaling complex is blunted in D1R knockout (D1-KO) mice and is presumably independent of D2 dopamine receptors. However, D1Rs are not required for morphine-induced reward as D1-KO mice show the same conditioned place preference for morphine as do control mice. Taken together, these results suggest a potential role for a D1R-dependent beta arr2/pERK signaling complex in selectively mediating the locomotor-stimulating but not the rewarding properties of morphine.