In the transmission equilibrium test and haplotype analysis, we f

In the transmission equilibrium test and haplotype analysis, we found a statistically significant association between microsatellites and Korean ASDs. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.”
“Bacterial lipopolysaccharide (LPS) association with their connate receptor TLR4 triggers Type I interferon signaling cascade through its MyD88 independent downstream. Compared to plethora of reported empirical data on both

TLR4 and Type check details I interferon pathways, there is no known model to decipher crosstalk mechanisms between these two crucial innate immune pathogen activated pathways regulating vital transcriptional factors such as nuclear factor-kappa B (NF kappa B), IFINI beta, the interferon-stimulated gene factor-3 (ISGF3) and an important cancer drug target protein kinase-R (PKR). Innate immune system is based on a sensitive

balance of intricate interactions. In elucidating these interactions, in silico integration of pathways has great potential. Attempts confined to single pathway may not be effective in truly addressing source of real systems behavior. This is the first report combining toll-like receptor-4 (TLR4) and interferon JPH203 beta (IFN beta) pathways in a single in silico model, analyzing their interactions, pinpointing the source of delay in PKR late phase activity and limiting the transcription of IFN and PKR by using a method including an statistical physics technique in reaction equations. The model quite successfully recapitulates published interferon regulatory factor-3 (IRF3) and IFNI beta data from mouse macrophages and PKR data from mouse embryonic fibroblast

cell lines. The simulations end up with an estimate of IRF3, IFN beta, ISGF3 dose dependent profiles mimicking nonlinear dose response characteristic of the system. Involvement of concomitant PKR selleck products downstream can unravel elusive mechanisms in specific profiles like NF kappa B regulation. (C) 2012 Elsevier Ltd. All rights reserved.”
“The influence of genetic variants of FACL4 on individual cognitive ability was examined in a random sample of 213 boys and 224 girls. Both conventional genetic methods and analysis of variance were applied in this study. We found no significant relationship between FACL4 and cognitive function. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“In this paper, we propose and discuss a possible mechanism, which, via continuous mutations and evolution, eventually enables HIV to break from immune control. In order to investigate this mechanism, we employ a simple mathematical model, which describes the relationship between evolving HIV and the specific CTL response and explicitly takes into consideration the role of CD4(+)T cells (helper T cells) in the activation of the CTL response.

Methods: The phosphorylation level of Src, Akt and eNOS was asses

Methods: The phosphorylation level of Src, Akt and eNOS was assessed by Western blot analysis, the formation of reactive oxygen species by dihydroethidine staining and the level of eNOS Ser1177 phosphorylation by immunohistochemical staining in sections of coronary arteries. Results: HEDS-induced endothelium-dependent relaxations were strongly reduced by N omega-nitro-L-arginine, an eNOS inhibitor, and by its combination with charybdotoxin plus apamin, inhibitors of endothelium-derived hyperpolarizing factor-mediated responses. These relaxations were markedly reduced by MnTMPyP (a membrane-permeant

mimetic of superoxide dismutase), polyethylene glycol catalase (PEG-catalase; a membrane-permeant analog of catalase), and by wortmannin (an inhibitor of PI3-kinase). HEDS-induced sustained phosphorylation of Akt and eNOS LY2109761 supplier in endothelial cells was PP2 mw abolished by MnIMPyP, PEG-catalase and wortmannin. Oral administration of HEDS induced a significant decrease of mean arterial pressure in spontaneously hypertensive rats. Conclusion: These

findings indicate that HEDS caused endothelium-dependent relaxations of coronary artery rings through the redox-sensitive activation of the endothelial PI3-kinase/Akt pathway leading to the subsequent activation of eNOS by phosphorylation. HEDS also has antihypertensive properties. Copyright (C) 2012 S. Karger PLX-4720 datasheet AG, Basel”
“BACKGROUND: The fiber dissection technique provides unique 3-dimensional anatomic knowledge of the white matter.

OBJECTIVE: To examine the optic radiation anatomy and its important relationship with the temporal

stem and to discuss its findings in relation to the approaches to temporal lobe lesions.

METHODS: We studied 40 cerebral hemispheres of 20 brains that had been fixed in formalin solution for 40 days. After removal of the arachnoid membrane, the hemispheres were frozen, and the Klingler technique was used for dissection under magnification. Stereoscopic 3-dimensional images of the dissection were obtained for illustration.

RESULTS: The optic radiations are located deep within the superior and middle temporal gyri, always above the inferior temporal sulcus. The mean distance between the cortical surface and the lateral edge of the optic radiation was 21 mm. Its fibers are divided into 3 bundles after their origin. The mean distance between the anterior tip of the temporal horn and the Meyer loop was 4.5 mm, between the temporal pole and the anterior border of the Meyer loop was 28.4 mm, and between the limen insulae and the Meyer loop was 10.7 mm. The mean distance between the lateral geniculate body and the lateral margin of the central bundle of the optic radiation was 17.4 mm.

Kinematics and electromyographic data were recorded in two groups

Kinematics and electromyographic data were recorded in two groups of adolescents (11-13 and 14-16 years of age) and a group of adults. Age and gender effects were tested. During voluntary PCI-32765 molecular weight unloading, the postural forearm stabilisation in adolescents was still different from the adult one, suggesting that further improvement of the postural forearm stabilisation must take place after the age of 16. No differences occur in the two adolescent groups. Moreover, girls presented a better stabilisation of the postural forearm than boys, indicating an earlier refinement of anticipatory postural control. The decrease of activity over postural

flexors, which ensure postural stabilisation, appeared later in adolescents with respect to adults. Delayed timing adjustments and increased variability SRT2104 clinical trial could reflect intense developmental processes underlain by an intense period of CNS maturation during adolescence. We discuss the role of brain maturation in the refinement of sensori-motor representations and the update of body schema. (c) 2012 IBRO. Published by Elsevier

Ltd. All rights reserved.”
“Purpose: Medical malpractice indemnity payments continue to rise, resulting in increased insurance premiums. We reviewed closed malpractice claims pertaining to endourological procedures with the goal of helping urologists mitigate their risk of lawsuit.

Materials and Methods: All closed malpractice claims from 2005 to 2010 pertaining to endourological procedures filed against urologists insured by the Medical Liability Mutual Insurance Company of New York were examined. Claims selleck products were reviewed for plaintiff demographics, medical history, operative details,

alleged complication, clinical outcome and lawsuit disposition.

Results: A total of 25 closed claims involved endourological operations and of these cases 10 were closed with an indemnity payment. The average payout was $346,722 (range $25,000 to $995,000). Of the plaintiffs 16 were women and mean plaintiff age was 51.4 years. Cystoscopy with ureteral stent placement/exchange resulted in 13 lawsuits, ureteroscopic lithotripsy 8, percutaneous stone extraction 2 and shock wave lithotripsy 2. There were 17 malpractice suits brought for alleged operative complications. Failure to arrange adequate followup was implicated in 4 cases. Error in diagnosis and delay in treatment was alleged in 3 claims.

Conclusions: Urologists are not immune to the current medical malpractice crisis. Endourology and urological oncology generate the greatest number of lawsuits against urologists. Most malpractice claims involving endourological procedures result from urolithiasis and alleged technical errors. Therefore, careful attention to surgical technique is essential during stone procedures to reduce the risk of malpractice litigation.

5-fold-higher survival rate than in the HD5 group Furthermore, t

5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher

antiviral potency against HIV-1 over parental HD5 in vitro. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way Selleckchem Poziotinib to search for potent antiviral drugs based on natural antimicrobial peptides.”
“Restricted and repetitive behaviors (RRBs) are a core feature of autism spectrum disorders. They constitute a major barrier to learning and social adaptation, but research on their definition, cause, and capacity for change has been relatively neglected. The last decade of research has selleck chemicals brought new measurement techniques that have improved the description of RRBs. Research has also identified distinctive subtypes of RRBs in autism spectrum disorders. Research on potential causal origins and immediate triggers for RRBs is still at an early stage. However, promising new ideas and evidence are emerging from neurobiology

and developmental psychology that identify neural adaptation, lack of environmental stimulation, arousal, and adaptive functions as key factors for the onset and maintenance of RRBs. Further research is needed to understand how these factors interact with each other to create and sustain atypical levels of RRB. The literature indicates that RRBs have the potential

to spontaneously reduce across time, and this is enhanced for those with increased age and cognitive and language ability. Research on interventions is sparse. Pharmacological treatments can be helpful in some children but have adverse side effects. Behavioral intervention methods provide the better intervention option with positive effects, but a more systematic and targeted approach is urgently needed. Evidence suggests that we will learn best from the last decade of research by taking a developmental perspective, by directing future research toward subtypes of RRBs, and by implementing early intervention targeted to improve RRBs before these behaviors become entrenched.”
“SAMHD1 is a viral restriction factor expressed in dendritic cells and other cells, inhibiting infection by cell-free human immunodeficiency virus type 1 (HIV-1) particles. SAMHD1 depletes the intracellular pool of deoxynucleoside triphosphates, thus impairing HIV-1 reverse transcription and productive infection in noncycling cells. The Vpx protein from HIV-2 or simian immunodeficiency virus (SIVsm/SIVmac) antagonizes the effect of SAMHD1 by triggering its degradation. A large part of HIV-1 spread occurs through direct contacts between infected cells and bystander target cells. Here, we asked whether SAMHD1 impairs direct HIV-1 transmission from infected T lymphocytes to monocyte-derived dendritic cells (MDDCs).

Following extensive analysis of a large set of microsatellite/sho

Following extensive analysis of a large set of microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel comprising 13 STR markers was established with the aim to optimally meet the specific requirements of quantitative chimerism analysis. Based on highly stringent selection criteria, the EUC panel provides multiple informative markers in any transplant setting. The standardized STR-PCR tests permit detection of donor-or recipient-derived cells at a sensitivity ranging between buy DAPT 0.8 and 1.6%. Moreover, the EUC assay facilitates accurate

and reproducible quantification of donor and recipient hematopoietic cells. Wide use of the European-harmonized protocol for

chimerism analysis presented CH5183284 manufacturer will provide a basis for optimal diagnostic support and timely treatment decisions.”
“Recent evidence suggests a role for the dynorphin/kappa-opioid receptor (KOR) system in the expression of stress-induced behaviors. Wistar Kyoto (WKY) rats exhibit increased depression-like and anxiety-like responses in behavioral tests compared to other strains and may be a model of comorbid depression and anxiety characterized by increased activity within the dynorphin/KOR system. Though KOR antagonists produce antidepressant-like effects in WKY rats, their effects in tests of anxiety-like behavior have not been examined in the WKY strain.

The aim of the current study was to investigate the effects of the KOR antagonist 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide hydrochloride (DIPPA) on the behavior of WKY rats and Sprague Dawley (SD) rats in tests of anxiety-like behavior.

The novelty-induced hypophagia and defensive burying tests were used to measure anxiety-like behavior in WKY and SD rats and determine the effects of DIPPA on anxiety-like behavior in both strains.

WKY rats displayed greater amounts of anxiety-like behavior compared to SD rats. DIPPA produced anxiolytic-like effects in both tests in both strains.

WKY rats

display more anxiety-like behavior at baseline compared to SD rats, and DIPPA produced anxiolytic-like effects in both WKY and SD rats. These findings support previous research suggesting that KOR antagonists possess anxiolytic-like properties and may potentially represent a novel class of treatments for mood disorders.”
“The t(8;21) translocation fuses the DNA-binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML).

Prolonged NPV-BHG712 treatment resulted in increased albuminuria

Prolonged NPV-BHG712 treatment resulted in increased albuminuria and dysregulated mesangial recovery. Additionally, NPV-BHG712 inhibited capillary repair by intussusceptive angiogenesis (an alternative to sprouting angiogenesis), indicating a previously unrecognized role of podocytes in regulating intussusceptive vessel splitting. Thus, our results identify EphB4 signaling as a pathway allowing podocytes to survive transient capillary collapse during glomerular disease.”
“Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is amultifaceted protein that

is involved in numerous Nec-1s in vitro processes including glycolysis, translational silencing, transcriptional regulation of specific genes, and acting as a nitric oxide sensor. The precise mechanism on how GAPDH is targeted to these different roles is unclear but believed to involve specific posttranslational modification to the protein. Numerous studies have demonstrated this website that GAPDH is a target for tyrosine nitration. However, the site of modification and the molecular consequence have not been defined. Rabbit GAPDH with a reversibly protected catalytic cysteine was nitrated in vitro with tetranitromethane, resulting in complete loss of GAPDH catalytic activity. Nitration was estimated as 0.32 mol of nitrotyrosine residue per mole of GAPDH. Mass

spectrometry analysis of nitrated GAPDH indicated that Tyr311 and Tyr317 were the sole sites of nitration. The X-ray crystal structure revealed that the distances between Tyr311 and Tyr317 and the cofactor nicotinamide adenine dinucleotide (NAD(+)) were less than 7.2 and 3.7 angstrom, respectively, implying that nitration

of these two residues may affect NAD(+) binding. This possibility was assessed using an NAD(+) binding assay, which showed that nitrated GAPDH was incapable of binding NAD(+). Selisistat datasheet Thus, these results strongly suggest that Tyr311 and Tyr317 nitration prohibits NAD(+) binding, leading to the loss of catalytic activity.”

In October 2010, nearly 10 months after a devastating earthquake, Haiti was stricken by epidemic cholera. Within days after detection, the Ministry of Public Health and Population established a National Cholera Surveillance System (NCSS).


The NCSS used a modified World Health Organization case definition for cholera that included acute watery diarrhea, with or without vomiting, in persons of all ages residing in an area in which at least one case of Vibrio cholerae O1 infection had been confirmed by culture.


Within 29 days after the first report, cases of V. cholerae O1 (serotype Ogawa, biotype El Tor) were confirmed in all 10 administrative departments (similar to states or provinces) in Haiti. Through October 20, 2012, the public health ministry reported 604,634 cases of infection, 329,697 hospitalizations, and 7436 deaths from cholera and isolated V. cholerae O1 from 1675 of 2703 stool specimens tested (62.0%).

73 +/- 0 68 mu mol/min (by a factor of 6 3) (p < 0 05) in SHR

73 +/- 0.68 mu mol/min (by a factor of 6.3) (p < 0.05) in SHR and WKY, respectively, thus confirming the presence of exaggerated natriuresis in SHR. FELi rose to 34 +/- 4 and 29 +/- 2 (p < 0.05) and C-Na/C-Li rose to 3.0 +/- 0.8 and 2.0 +/- 0.6 (p < 0.05) in SHR and WKY, respectively, demonstrating that Na reabsorption in both the proximal and the distal nephron was involved. Additional experiments showed that giving the rats saline instead of water to drink for four days prior to the clearance measurement led to a remarkable increase

in the natriuretic response to volume expansion. There was a close correlation between the peak increase in FENa and the logarithmic values of the baseline FENa values. In conclusion, the study confirms the LDK378 presence of an exaggerated natriuresis in response to volume expansion in conscious SHR rats compared to WKY rats, and that the renal response to acute volume expansion is related to the baseline sodium excretion.”
“Background. In the operating room and at the ICU, Rotational thromboelastometry (ROTEM (R)) and multiple platelet function analyzer (Multiplate (R)) Selisistat are frequently performed

on arterial blood samples while known reference ranges refer to venous blood only. To evaluate whether there are clinical important differences between parameters measured in arterial and venous blood, we performed a prospective study in patients undergoing orthopedic surgery. Methods. Arterial and venous blood samples were drawn simultaneously after line insertion (T0), intraoperatively (T1), at the end of surgery (T2) and the INTEM (R), EXTEM (R) and FIBTEM (R) ROTEM assays, as well as the ASPI (R), ADP (R) and TRAP (R) assays were performed in arterial and venous samples using the ROTEM (R) and the Multiplate (R) device, respectively. Results. After informed consent, 52 patients were enrolled and data of 50 patients remained for final analysis. Venous and arterial measurement results correlated significantly with a coefficient

of 0.519-0.977. At the three measurement points only a few statistically significant deviations were detected for some of the ROTEM (R) and Multiplate (R) parameters. The magnitude of differences was small and most likely without clinical relevance. PP2 price Pathological conditions were detected with similar frequency regardless of the sampling site. Only Multiplate (R) TRAP at T0 indicated low platelet aggregation more frequently in venous than in arterial samples (p = 0.0455); however, values were only narrow below reference range. Conclusion. The observed differences between arterial and venous results were within the range of variability of the methods reported for venous blood. Pathological values that might be clinically relevant could be detected at similar rates regardless of the sampling site.”

e , strains with the gE gene) and the other group of primers was

e., strains with the gE gene) and the other group of primers was designed to detect both PRV gE-vaccine and wild-type strains (i.e., strains with the gG gene and with or without the gE gene). After amplification by Bst enzyme JPH203 concentration at a constant temperature of 65 degrees C, a laddering of bright products was visible following electrophoresis on a 2% agarose gel. LAMP was 100-1000-fold more sensitive than the standard PCR. The assay was specific in that it did not amplify other porcine viruses including porcine

parvovirus, porcine circovirus type 1, porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, classical swine fever virus, swine transmissible gastroenteritis coronavirus, and porcine epidemic diarrhea virus. Because of this website its sensitivity, specificity, and simplicity, the LAMP assay could be a useful method for early and rapid differentiation of swine vaccinated with PRV gE-deleted vaccine from swine infected with wild virus. (C) 2010 Elsevier B.V. All rights reserved.”

Cigarette smoking is associated with emphysema and radiographic interstitial

lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known.


We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression

to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema.


Interstitial Belinostat cell line lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P < 0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P < 0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P < 0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity < 80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P < 0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P < 0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P < 0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking.

(C) 2011 Elsevier Ltd All rights reserved “
“Recognition sy

(C) 2011 Elsevier Ltd. All rights reserved.”
“Recognition systems play a key role in a range of biological processes, including mate choice, immune defence and altruistic behaviour. Social insects provide an excellent model for studying recognition systems because workers need to discriminate between nestmates and non-nestmates, enabling them to direct altruistic behaviour towards closer kin and to repel potential invaders. However, the level of aggression directed learn more towards conspecific intruders can vary enormously, even among workers within the same colony. This is usually

attributed to differences in the aggression thresholds of individuals or to workers having different roles within the colony. Recent evidence from the weaver ant Oecophylla

smaragdina suggests that this does not tell the whole story. Here I propose a new model for nestmate recognition based on a vector template derived from both the individual’s Epigenetic Reader Domain inhibitor innate odour and the shared colony odour. This model accounts for the recent findings concerning weaver ants, and also provides an alternative explanation for why the level of aggression expressed by a colony decreases as the diversity within the colony increases, even when odour is well-mixed. The model makes additional predictions that are easily tested, and represents a significant advance in our conceptualisation of recognition systems. (C) 2010 Elsevier Ltd. All rights reserved.”
“Supraoptic nucleus (SON) neurons secrete either oxytocin or vasopressin into the bloodstream from their axon terminals in the posterior pituitary gland. SON neurons are powerfully inhibited by the classical p-opioid receptor agonist, morphine. Oxytocin neurons develop morphine dependence when chronically exposed to this opiate, and undergo robust withdrawal excitation when morphine is subsequently acutely antagonized by naloxone. Morphine withdrawal excitation Urease is evident as an increased firing rate and

is associated with an increased post-spike excitability that is consistent with the expression of an enhanced post-spike afterdepolarization (ADP) during withdrawal. Here, we used sharp electrode recording from SON neurons in hypothalamic explants from morphine naive and morphine treated rats to determine the effects of morphine on the ADP, and to test the hypothesis that morphine withdrawal increases ADP amplitude in SON neurons. Acute morphine administration (0.05-5.0 mu M) caused a dose-dependent hyperpolarization of SON neurons that was reversed by concomitant administration of 10 mu M naloxone, or by washout of morphine; counter-intuitively, acute exposure to 5 mu M morphine increased ADP amplitude by 78 +/- 11% (mean +/- SEM).

Low doses of N/OFQ and NOP receptor antagonists promoted movement

Low doses of N/OFQ and NOP receptor antagonists promoted movement whereas higher doses inhibited it. Motor facilitation was selectively prevented by raclopride while motor inhibition was prevented by amisulpride. Amisulpride also attenuated the hypolocomotion induced by the D2/D3 receptor agonist pramipexole and dopamine precursor L-3,4-dihydroxyphenylalanine, whereas raclopride (and S33084) worsened it. To dissect out the contribution of pre- and postsynaptic D2

receptors, mice lacking the D2 receptor (D2R(-/-)) or its long isoform (D2L(-/-) )were used. Motor facilitation induced by N/OFQ and NOP receptor antagonists was lost in D2R-/- and D2L-/- mice whereas motor inhibition induced by NOP receptor antagonists (and pramipexole) was lost in D2R(-/-) but preserved in D2L(-/-) mice. N/OFQ-induced hypolocomotion

was observed in both genotypes. We demonstrate that motor GSK3326595 actions of NOP receptor ligands rely on the modulation of endogenous Givinostat purchase dopamine. Motor facilitation induced by NOP receptor antagonists as well as low dose N/OFQ is mediated through D2L postsynaptic receptors whereas motor inhibition observed with higher doses of N/OFQ occurs by direct inhibition of mesencephalic DA neurons. Motor inhibition seen with high doses of NOP receptor antagonists appears to be mediated through the D2 presynaptic autoreceptors. These data confirm that endogenous N/OFQ is a powerful modulator of dopamine transmission in vivo and that the effects of NOP receptor antagonists

on motor function reflect the blockade Ispinesib manufacturer of this endogenous N/OFQ tone. (C) 2013 Elsevier Ltd. All rights reserved.”
“Tobacco withdrawal is characterized by a negative mood state and relatively mild somatic symptoms. Increased noradrenergic transmission has been reported to play an important role in opioid withdrawal, but little is known about the role of noradrenergic transmission in nicotine withdrawal.

The aim of these experiments was to investigate the effects of prazosin, clonidine, and propranolol on the negative mood state and somatic signs associated with nicotine withdrawal in rats.

A discrete-trial intracranial self-stimulation procedure was used to assess the negative affective state of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function.

In all the experiments, the nicotinic acetylcholine receptor antagonist mecamylamine (3 mg/kg) elevated the brain reward thresholds of the nicotine-treated rats and did not affect those of the control rats. The alpha 1-adrenergic receptor antagonist prazosin (0.0625 and 0.125 mg/kg) dose-dependently attenuated the elevations in brain reward thresholds associated with precipitated nicotine withdrawal. The alpha 2-adrenergic receptor agonist clonidine (10-40 mu g/kg) and the nonselective beta-adrenergic receptor antagonist propranolol (2.