text:
After consecutive losses, Detroit recalls AHL scoring leader Nyquist
Mar 12, 2013, 11:24 AM EDT
After dropping two straight games to the Columbus Blue Jackets, the Detroit Red Wings sent LW Tomas Tatar to AHL Grand Rapids and recalled Gustav Nyquist.
Nyquist, 23, has only appeared in two games for Detroit this season but has been a dynamic scorer at the American League level, registering 23G-37A-60PTS in 57 games for the Rapids.
He's three points clear of Syracuse's Tyler Johnson for the AHL scoring lead despite appearing in two fewer games.
Tatar, 22, has appeared in 18 games for the Wings this season, registering 4G-3A-7PTS while averaging 11:22 per night.
He scored the lone goal in Detroit's 2-1 shootout loss to Chicago on Mar. 3 but has been pointless since, going minus-1 in the last two games against Columbus while receiving just 20 total minutes.
The move to Nyquist makes sense from an offensive standpoint. Detroit has only scored 10 goals in its past seven games and has slipped to 20th in the NHL in goals per game, averaging 2.54 per contest.
- bensawesomeness - Mar 12, 2013 at 11:58 AM
this season has been brutal, injuries being the major factor to that, we still don't have Helm and who knows if Bert'll play this season, but I must say, the kids have stepped up and played some fun hockey.
Tatar, Andersson, Lashoff, Smith, Nyquist, and the backup goalie who's name skills my mind
Have all played well on this level. and give me confidence as a fan that we'll be okay over the next 3+ seasons
- datsyukdominates - Mar 12, 2013 at 12:16 PM
There are a lot of great prospects coming over from juniors and Europe next year as well (Jarnkrok, Pulkinnen, Oullett, Sproul, etc). The Wings future is bright.
- fusionix7 - Mar 12, 2013 at 1:56 PM
He better be on Datsyuk's line. Datsyuk desperately needs a shooter on his wing. I get that Babcock was using the 2nd line as a shutdown line to go against the other teams top line, but when you're only scoring a couple goals at best a game it's time to introduce some offense to that line.
Apparently he's not comfortable enough with Tatar's defense to give him a shot on Datsyuk's line despite how awful they have been offensively.
- clefty1 - Mar 12, 2013 at 3:38 PM
Abdelkater should of never been on Datsyuk's line to begin with…
- porkchopexpress1969 - Mar 12, 2013 at 5:45 PM
I read somewhere Tartar was the only choice to send down, because he can skip waivers. I think he earn a spot next year on the roster.
- clefty1 - Mar 12, 2013 at 3:35 PM
Babcock should of put Tatar on Datsyuk's line and moved Abby down to the 3rd line, Abby is a grinder and he does not belong on the top 2 lines let alone the PP plus his only goal is an empty netter. Hopefully Nyquist will not be buried on the 3rd line and he will get an opportunity next to Datsyuk.
- porkchopexpress1969 - Mar 12, 2013 at 5:46 PM
This is a great take, love Abby but no where near the 1 or 2 line.
- polegojim - Mar 13, 2013 at 5:46 PM
Yes… Abby is a fourth liner at best. Frankly, I'd rather see Tatar stay and Abby get sent down.
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Chef Kim's "White Chocolate and Apricot Sphere" floored the judges with its surprising flavors, which were all locked away in the focal point of the plate, a small orange and gold sphere. The little amber gem hid layers of citrus, apricot, lime and white chocolate components, which came together to deliver a delicious tasting experience. In addition to her dessert's excellently executed flavor profiles, Chef Kim's unique plate presentation also impressed the judges, solidifying her first place standing.
This year's second place winner was Chef Deden Putra of The Peninsula New York for his "Sea Salt Caramel Chocolate Tart." His creation featured chocolate pot de crème and sea-salt caramel, accented with a passion fruit cream and thyme ice-cream. Chef Putra's dessert impressed the judges with its well-balanced flavors and elegant plating style.
Third place in the competition was awarded to Chef Jove T. Hubbard of The James Hotel and David Burke's Primehouse. Chef Hubbard's "Strawberry Savarin" dessert showcased a bright and flavorful balance of strawberries, pistachio and lemon. His dessert's flavors were expertly balanced and elegantly plated, gaining him solid scores from the judges and his third place standing.
The Signature Plated Dessert competition brings to light both the delicate beauty of plated desserts and the talented chefs that create them. Each competitor is encouraged to craft an elegant, well-balanced dessert, as well as revolutionary creations that display their culinary flair and expertise. Pastry Live wishes to congratulate all of the winners, as well as thank each of the competitors for their professionalism, hard work and dedication.
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These authors contributed equally to this work.
Gene expression in accumbens GABA neurons from inbred rats with different drug-taking behavior
Article first published online: 1 AUG 2011
DOI: 10.1111/j.1601-183X.2011.00716.x
© 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society
Genes, Brain and Behavior
Volume 10, Issue 7, pages 778–788, October 2011
Additional Information
How to Cite
Sharp, B. M., Chen, H., Gong, S., Wu, X., Liu, Z., Hiler, K., Taylor, W. L. and Matta, S. G. (2011), Gene expression in accumbens GABA neurons from inbred rats with different drug-taking behavior. Genes, Brain and Behavior, 10: 778–788. doi: 10.1111/j.1601-183X.2011.00716.x
Publication History
- Issue published online: 9 OCT 2011
- Article first published online: 1 AUG 2011
- Accepted manuscript online: 11 JUL 2011 12:00AM EST
- Received 25 February 2011, revised 18 April 2011 and 23 May 2011, accepted for publication 1 July 2011
- Addiction;
- Fisher 344 rats;
- laser-capture microdissection;
- Lewis rats;
- nicotine;
- nucleus accumbens;
- synapse;
- transcriptome;
- ventral pallidum
Inbred Lewis and Fisher 344 rat strains differ greatly in drug self-administration; Lewis rats operantly self-administer drugs of abuse including nicotine, whereas Fisher self-administer poorly. As shown herein, operant food self-administration is similar. On the basis of their pivotal role in drug reward, we hypothesized that differences in basal gene expression in GABAergic neurons projecting from nucleus accumbens (NAcc) to ventral pallidum (VP) play a role in vulnerability to drug-taking behavior. The transcriptomes of NAcc shell-VP GABAergic neurons from these two strains were analyzed in adolescents, using a multidisciplinary approach that combined stereotaxic ionotophoretic brain microinjections, laser-capture microdissection (LCM) and microarray measurement of transcripts. Laser-capture microdissection enriched the gene transcripts detected in gamma-aminobutyric acid (GABA) neurons compared to the residual NAcc tissue: a ratio of neuron/residual >1 and false discovery rate (FDR) <5% yielded 6623 transcripts, whereas a ratio of >3 yielded 3514. Strain-dependent differences in gene expression within GABA neurons were identified; 322 vs. 60 transcripts showed 1.5-fold vs. 2-fold differences in expression (FDR < 5%). Classification by gene ontology showed that these 322 transcripts were widely distributed, without categorical enrichment. This is most consistent with a global change in GABA neuron function. Literature mining by Chilibot found 38 genes related to synaptic plasticity, signaling and gene transcription, all of which determine drug abuse; 33 genes have no known association with addiction or nicotine. In Lewis rats, upregulation of Mint-1, Cask, CamkII, Ncam1, Vsnl1, Hpcal1 and Car8 indicates that these transcripts likely contribute to altered signaling and synaptic function in NAcc GABA projection neurons to VP.
In rats, the inbred Lewis and Fisher 344 strains differ greatly in drug self-administration (SA) behavior; while Lewis rats operantly self-administer several drugs of abuse, including nicotine, Fisher rats self-administer poorly (Brower et al. 2002; Martin et al. 1999; Suzuki et al. 1988a,b). The nucleus accumbens shell (NAcc shell), located in ventral striatum, and its primary output target, the ventral pallidum (VP), are both critical to the integration and discrimination of information encoding the rewarding dimension of motivated behavior (Carlezon & Thomas 2009; Heimer & Wilson 1975; Shirayama & Chaki 2006; Smith et al. 2009). The vast majority of neurons in the NAcc are GABAergic medium spiny projection neurons (Meredith et al. 1993). The normal function of VP is essential for aspects of reward learning and to motivational 'wanting' and hedonic 'liking' (Smith et al. 2009). On the basis of their pivotal role in reward (Carlezon & Thomas 2009; Meredith et al. 1993), we hypothesized that differences in basal gene expression by these GABAergic neurons in the Lewis vs. Fisher 344 strains may contribute to drug-taking vulnerability, which for cigarette smoking is usually manifest during adolescence (Chassin et al. 1996; Dappen et al. 1996; SAMHSA 2001).
Differences in the gene expression profiles or transcriptomes between the NAcc shell-VP GABAergic neurons from these two strains were analyzed in adolescents [postnatal day 41 (PN41)]. We used a multidisciplinary approach, combining stereotaxic ionotophoretic brain microinjections, laser-capture microdissection (LCM) and microarray detection of transcript expression levels. Neuroanatomical specificity was obtained by ionotophoretic delivery of fluorogold (FG) into VP (Pieribone & Aston-Jones 1988) followed by capture of all FG+ neurons in sections from the NAcc shell by LCM. The efficacy of this approach was evaluated by measuring the ratio of gene expression for neurons compared to the remaining NAcc tissue after removal of the neurons. RNA extracted from both neurons and remaining NAcc was amplified and then analyzed by microarray. Differential gene expression by rat strain was validated for a subset of genes by real-time polymerase chain reaction (RT-PCR).
Animals and surgeries
Lewis rats were bred in the laboratory, using breeders purchased from Harlan Laboratories (Indianapolis, IN, USA). Adolescent male Lewis rats (PN35) were anesthetized with ketamine/xylazine (90 and 10 mg/kg, respectively, i.p.) and then placed in a stereotaxic frame. Fluorogold (2% in sterile saline, Fluorochrome, Englewood, CO, USA) was deposited into VP (Anterior–Posterior: −0.22, Medial–Lateral: ±2.2, Dorsal–Ventral: −8.0) bilaterally by ionotophoretic injection, using a Midgard high-voltage current source (Stoelting Co., Wood Dale, IL, USA). The current was set at +5 µA (7 seconds on, 7 seconds off, for 5 min). Micropipettes were left in place for 15 min before the scalp incision was sutured. Five days later, rats were killed, brains removed, immediately frozen, and stored at −70°C. All procedures were conducted in accordance with the NIH Guidelines Concerning the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee of the University of Tennessee.
Chronic nicotine self-administration
Rats were acclimated to a reversed 12:12 h light:dark cycle. Standard rat chow and water were provided ad libitum. Nicotine (pH = 7.2; calculated as free base) was prepared weekly in 200 U heparinized saline to deliver 50 µl i.v. of 0.03 mg/kg body weight per injection. Self-administration was performed according to our published protocol (Valentine et al. 1997). Briefly, PN38 adolescent rats received jugular cannulae under xylazine-ketamine anesthesia and were individually housed in operant chambers (Coulbourn Instruments, Whitehall, PA, USA) inside a sound-attenuating chamber. Operant chambers were equipped with two levers positioned 4 cm above the floor, and a green cue light 1 cm above each lever was illuminated when nicotine was available. Lever presses were recorded and syringe pumps controlled by computers and interfaces, using L2T2 or Graphic State software (Ver 3.01, Coulbourn Instruments). Rats were given 3 days to recover from jugular surgery, during which time they received antibiotic daily and hourly aliquots (50 µl) of 200 U heparin. At PN41, rats received 0.03 mg/kg nicotine in heparinized saline i.v. with each lever press.
One lever was randomly designated as the active lever. Pressing this lever elicited a computer-driven i.v. injection of nicotine over 0.81 seconds on a fix ratio 1 (FR1) schedule. Each injection was followed by a 7-second period during which the green cue light was extinguished and lever presses were recorded, but nicotine was not injected. Pressing the inactive lever had no programmed consequence. Rats were given access to nicotine or saline SA 23 h/day and learned to self-administer nicotine without prior training, priming or food deprivation. The final hour of the lights-on cycle was reserved for housekeeping tasks. During this interval, environmental enclosure doors were opened and green cue lights turned off; levers were not retracted, and lever press activity was not recorded nor rewarded during this period. Self-administration day 1 (SA d 1) is the first day nicotine was made available and the rats were given 10 days unlimited free access to acquire nicotine SA.
Food SA
Beginning on PN41, a separate cohort of adolescent male rats were trained on an FR1 schedule to self-administer food pellets (45 mg) during daily 2-h sessions in the same operant chambers used for nicotine SA. Animals were food deprived overnight prior to the first session. Thereafter, they received 16 g food per day.
Laser-capture microdissection
Brains were sectioned in a Leica cryostat at 10 µm, and sections were mounted onto uncharged glass slides and maintained at −20°C until dehydration. Slides were dehydrated by sequential immersion in the following: 100% methanol (3 min), 95% EtOH (2 min), 100% EtOH (1 min, twice) and xylene (5 min, twice), and then air dried (15 min). The Arcturus XT (Life Technologies, Carlsbad, CA, USA) was used to capture FG-labeled neurons. The infrared laser produced spots approximately 15 µm in diameter, which allowed consistent capture of neurons onto CapSure LCM caps (Life Technologies). Approximately 750 neurons were captured from each brain.
RNA extraction
RNA trapped in the CapSure LCM caps was extracted using the PicoPure RNA isolation kit (Life Technologies); RNA was eluted with 13 µl nuclease-free H2O. RNA quality was analyzed using Bioanalyzer (Agilent Technologies, Foster City, CA, USA). The mean value of RNA Integrity Number (RIN) was 7.9 for the 1.84 ± 2.4 ng of total RNA obtained from each rat.
RNA amplification and Affymetrix microarray
Total RNA were amplified by NuGen Ovation Pico WTA system, followed by cDNA synthesis using the WT Ovation Exon module. Ovation Biotin kits were then used to fragment and label the cDNA (Ovation reagents: NuGen Inc., San Carlos, CA, USA). The labeled cDNA was then hybridized to the Rat Gene ST 1.0 array (Affymetrix, Santa Clara, CA, USA), according to the manufacturer's protocols for whole transcriptome arrays. Microarrays were then processed on a Fluidics Station 450 and scanned by the Affymetrix GeneChip 3000 7G Scanner. Expression Console software (version 1.1.2) was used to normalize data. All microarray samples were processed by the same technician consecutively, interleaving the two strains. No batch effect was observed. The Rat Gene ST 1.0 array probe sets are generated from the Brown Norway rat genome. Therefore, false-positive differences between Lewis and Fisher rat samples may occur because of the asymmetrical expression of single nucleotide polymorphisms (SNPs) by these two strains, differentially affecting cDNA hybridization to array probe sets.
Real-time PCR
Real-time quantitative PCR of eight genes (and two reference genes Ywhaz and Sdha) was performed on the LightCycler 480 (Basel, Switzerland) using probes from the Universal Probe Library. The original unamplified RNA from each sample was used to prepare cDNA. The critical threshold (Ct) of genes of interest was normalized to the geometric mean of the two reference genes.
Data analysis
Microarray data were analyzed using the R-statistical package (Team 2010). t-Tests were used to compare the expression level of each gene from the two strains of rats and then all genes were analyzed for false discovery rate (FDR). Gene ontology analysis was conducted using DAVID Bioinformatics Resources (Huang et al. 2009). Nicotine and food SA data were analyzed using repeated-measures analysis of variance (anova), with both lever and day treated as within-subject variables. Strain was treated as a between-subject variable.
The capacity to acquire operant nicotine vs. food SA was evaluated in adolescent Lewis compared to Fisher rats. For nicotine SA, rats were housed in operant chambers and were not shaped, primed or food deprived. Three days after jugular vein surgery, nicotine was made available for 23 h per day. Figure 1 (data analyzed by repeated-measures anova) indicates that Lewis rats rapidly acquired nicotine SA, manifest by a significant increase in active lever presses in the absence of any change in the inactive lever (effect of lever on number of presses, F1,7: 18.2, P < 0.001; effect of day on active lever presses, F9,63: 2.1, P < 0.05; effect of day on inactive lever presses, F9,63: 0.8, P > 0.05). In contrast, both active and inactive lever presses by Fisher rats failed to increase over time (F9,81: 1.5, P > 0.05). The number of lever presses was different between strains (F1,16: 111.8, P < 0.001) and the interaction between lever and strain was significant (F1,15: 17.5, P < 0.001). Thus, the number of active lever presses for nicotine was different between strains (F1,16: 66.6, P < 0.001), as was the number of inactive lever presses (F1,16: 53.5, P < 0.001). The higher number of inactive lever presses in Lewis rats is likely the result of stronger locomotor activation induced by a larger amount of nicotine intake. Both strains showed a specific increase in active lever presses reinforced by food (Fisher, F1,7: 47.1, P < 0.001; Lewis, F1,5: 35.1, P < 0.001). Neither active lever presses for food (F1,12: 0.7, P = 0.41) nor inactive lever presses (F1,12: 0.7, P = 0.41) differed by strain. The similar amount of inactive lever presses reflected similar level of arousal induced by food. Hence, both strains were capable of learning the operant task, but nicotine was only reinforcing in Lewis rats, under these conditions.
Neurons projecting from NAcc shell to VP were identified by retrograde uptake of FG delivered by ionotophoresis. Figure 2 illustrates coronal sections of rat brain, identifying both NAcc shell and VP. Within VP, the central area of FG fluorescence for each of six rats is marked by an asterisk. A representative deposit of FG is shown in the inset. Within NAcc shell, the center of the distribution of retrograde-labeled FG+ neurons for each rat is shown by a green dot within the boxed area. The corresponding inset shows a representative fluorescence image of these FG+ neurons, located in ventral medial NAcc shell (20×). In this region of NAcc shell, virtually all neurons are FG+. All individual FG+ neurons were captured by LCM. Thus, this approach specifically captured a subpopulation of NAcc shell neurons that project from NAcc shell to VP, excluding neurons that project from NAcc shell to other brain regions.
Microarray analysis was used to detect the level of specific gene transcripts expressed by the transcriptome from laser-captured FG+ neurons compared to the tissue remaining in the area of NAcc shell after removal of these fluorescent neurons. A heat map of all genes was generated; Fig. 3a shows representative areas that show clustering of genes expressed at significantly greater or lesser levels in neurons vs. tissue remainder. At a ratio of neuron/remainder >1 and FDR < 5%, 6623 gene transcripts were identified in both Lewis and Fisher rats; at ratios >2.0 and >3.0, 5483 and 3514 genes, respectively, were enriched in the neuron populations from both inbred rat strains (Fig. 3b). Amongst the enriched transcripts, Table 1 shows those related to the neurotransmitter, GABA (e.g. GABA A receptor alpha 1, glutamate decarboxylase 1 and 2), and/or associated with regulation of GABA neuron-related functions (e.g. dopamine receptors D1A and D2; GABA vesicular transporter). These data indicate that LCM of individual FG+ neurons successfully enriched transcripts from GABA neurons projecting to VP. At three incremental levels of enrichment (i.e. neuron/remainder >1 to >3), the majority of these transcripts were common to both strains of rat. Nonetheless, LCM unavoidably introduces glial cells, in intimate contact with FG+ neurons, within each sample captured. For example, myelin basic protein and glial fibrillary acidic protein, standard markers for oligodendrocytes and astrocytes, respectively, were detected at neuron/remainder ratios of 2.7 and 1.5. This enrichment of glial markers indicates that targeting most of the neuronal soma for capture, by using 15-µm-diameter spot size, eliminates the ability to separate the neuronal vs. glial transcriptomes. This limitation of geometric capture by LCM of a high heterogeneous tissue was recently reported (Okaty et al. 2011).
|Gene name
|Neuron/remainder (mean of both strains)
|Neuron fluorescence intensity (mean of both strains)
|A kinase (PRKA) anchor protein (yotiao) 9
|Diazepam binding inhibitor (GABA receptor modulator acyl-Coenzyme A binding protein)
|Dopamine receptor D1A
|Dopamine receptor D2
|GABA(A) receptor-associated protein
|GABA(A) receptor-associated protein like 1
|GABA(A) receptor-associated protein like 2
|GABA(A) receptor-associated protein like 2
|Gamma-aminobutyric acid (GABA) A receptor alpha 1
|Gamma-aminobutyric acid (GABA) A receptor alpha 2
|Gamma-aminobutyric acid (GABA) A receptor alpha 4
|Gamma-aminobutyric acid (GABA) A receptor alpha 5
|Gamma-aminobutyric acid (GABA) A receptor beta 1
|Gamma-aminobutyric acid (GABA) A receptor beta 2
|Gamma-aminobutyric acid (GABA) A receptor beta 3
|Gamma-aminobutyric acid (GABA) A receptor gamma 1
|Gamma-aminobutyric acid (GABA) A receptor gamma 2
|Gamma-aminobutyric acid (GABA) A receptor gamma 3
|Gamma-aminobutyric acid (GABA) B receptor 1
|Gamma-aminobutyric acid (GABA) B receptor 2
|Glutamate decarboxylase 1
|Glutamate decarboxylase 2
|Proenkephalin 1
|Solute carrier family 32 (GABA vesicular transporter) member 1
|Solute carrier family 6 (neurotransmitter transporter GABA) member 1
|Solute carrier family 6 (neurotransmitter transporter GABA) member 11
|Synaptosomal-associated protein 25
|Syntaxin binding protein 1
Genes that were differentially expressed in Lewis vs. Fisher NAcc shell GABA neurons projecting to VP were identified. One caveat about array analysis across strains concerns the potential for false positives because of asymmetrical expression of SNPs by the two strains, differentially affecting hybridization to the array probes. Table 2 shows the total number of gene transcripts as a function of the expression ratio in Lewis compared to Fisher rats (i.e. >1.5-fold and >2-fold); total transcript number declined with the application of increasingly stringent criteria to achieve statistical significance. A total of 322 genes were differentially expressed at a Lewis vs. Fisher ratio of >1.5-fold (P < 0.05 and FDR < 5%; see Table S1). Of these, 174 gene transcripts could be mapped to biological processes, as shown in Fig. 4. Transcripts mapped across a wide range of biological processes and molecular functions, showing no specific enrichment by either biological or molecular ontology.
|Number of genes
|Lewis vs. Fisher > 1.5-fold
|t-Test P < 0.05
|Lewis vs. Fisher> twofold
|t-Test P < 0.05
The differential gene expression detected by microarray analysis was validated by PCR using the same RNA samples. Eight gene transcripts were selected for validation. By microarray analysis, it was found that the expression ratio of these transcripts in Lewis vs. Fisher rats varied by 1.5- to 2-fold (see Fig. 5). In addition, six of the eight transcripts were expressed at higher levels in Lewis rats, whereas two (i.e. A disintegrin and metalloproteinase with thrombospondin motifs 3 and Neuromedin B) transcripts were expressed at higher levels in Fisher rats. Significant strain-dependent differences were detected by PCR analysis of all eight transcripts.
Gene interactions between the 322 differentially expressed transcripts were sought using Chilibot, an established data-mining software, to analyze relationships documented in all the abstracts compiled in PubMed (Chen & Sharp 2004). We identified genes likely to determine drug abuse behavior based on their known relationships to cell signaling, synaptic plasticity, transcription, addiction and nicotine. Table 3 shows 22 genes that mapped to synaptic plasticity, 24 to signaling, 18 to transcription, 10 to addiction and 4 to nicotine. Twenty-one of 22 genes mapping to synaptic plasticity were also related to cell signaling. However, the strength of these gene relationships to signaling vs. synaptic plasticity varied in that gene × signaling interactions were based on a median of 14.5 unique publications, whereas gene × synaptic plasticity interactions were derived from a median of 3.5 publications. Only 4 of 18 genes mapped to transcription regulation were common to signaling and synaptic plasticity. Strong interactions between gene × transcription regulation were evident based on a median of 15.5 publications. Lastly, 7 of 10 genes mapped to addiction and all 4 genes mapped to nicotine were common to signaling and synaptic plasticity. Overall, 33 of the 41 genes in Table 3 have not previously been associated with addiction or nicotine. CASK (calcium/calmodulin-dependent serine protein kinase) exemplifies a gene strongly associated with all three biological processes, but not with addiction or nicotine.
|Gene symbol
|Synaptic plasticity
|Transcription regulation
|Gene name
|Adrenergic, beta, receptor kinase 1
|Abelson helper integration site 1
|Amyloid beta (A4) precursor protein-binding, family A, member 1
|Calcium/calmodulin-dependent protein kinase II delta
|Carbonic anhydrase 8
|Calcium/calmodulin-dependent serine protein kinase
|Dishevelled associated activator of morphogenesis 1
|Electron-transfer-flavoprotein, alpha polypeptide
|Glutamate receptor, ionotrophic, AMPA 4
|Growth factor receptor-bound protein 10
|Gamma-aminobutyric acid (GABA) A receptor, gamma 1
|HMG-box transcription factor 1
|Homeobox containing 1
|Hippocalcin-like 1
|Interleukin enhancer binding factor 3
|Metastasis suppressor 1
|Neural cell adhesion molecule 1
|Nuclear factor of activated T-cells, calcineurin-dependent 3
|N-myc (and STAT) interactor
|Neurexophilin 1
|Polymerase (DNA directed), epsilon 3 (p17 subunit)
|Protein phosphatase 1, regulatory (inhibitor) subunit 14A
|Peroxiredoxin 1
|Psmd7 proteasome 26S subunit, non-ATPase, 7
|Platelet-activating factor receptor
|RAD21 homolog (Schizosaccharomyces pombe)
|RPTOR independent companion of MTOR, complex 2
|RUN and FYVE domain containing 2
|Slingshot homolog 2
|Small nuclear RNA activating complex, polypeptide 2
|Secreted protein, acidic, cysteine-rich (osteonectin)
|Syntaxin binding protein 3
|Telomeric repeat binding factor (NIMA-interacting) 1
|Very low density lipoprotein receptor
|Visinin-like 1
|Zinc finger, CCHC domain containing 12
|Zinc finger protein 410
|Number of genes
|Median PubMed hits
These studies show significant rat strain-dependent differences in the transcriptomes from neuroanatomically defined sets of enriched GABA neurons that regulate the reinforcing dimension of motivated behavior. Differences in gene expression may impact the motivational function of these GABA neurons, because Lewis vs. Fisher rats differ greatly in their propensity to operantly self-administer nicotine and other drugs (Brower et al. 2002; Martin et al. 1999; Suzuki et al. 1988a,b). In contrast, acquisition of operant food SA was similar between these strains. Therefore, differential gene expression is potentially related to drug reinforcement, rather than operant learning per se.
We combined neuroanatomical identification of specific neurons labeled with FG and laser capture of individual neurons. Fluorogold was transported from VP by GABA neurons in ventral medial NAcc shell. Despite RNA yield of only 1.8 ng/rat, requiring amplification before microarray, this protocol enriched >6600 genes, including GABA-related transcripts. Strain-dependent effects on gene expression were identified; 322 vs. 60 transcripts showed 1.5-fold vs. 2-fold expression differences (FDR 5%). Polymerase chain reaction validated the expression of selected gene transcripts. The LCM method unavoidably captures glial cells in close apposition to FG+ neurons, thus affecting the specificity of the transcriptome attributed to GABA neurons.
Classification by gene ontology showed that these 322 strain-dependent transcripts lacked categorical enrichment. This wide-ranging alteration in the transcriptome from enriched NAcc GABA neurons is most consistent with a global change in neuronal function manifest throughout the cellular machinery. As literature mining by Chilibot (Chen & Sharp 2004) did not find networks amongst these genes, all 322 were analyzed for relationships to cellular processes pivotal to drug abuse (i.e. synaptic plasticity, signaling and regulation of gene transcription). Chilibot found genes with documented relationships to these three processes (Table 3). Almost all genes related to plasticity were common to signaling, whereas only 4 of 18 transcription genes were common to signaling/synaptic plasticity. Thirty-three of 38 genes related to plasticity, signaling and/or gene transcription have no association with addiction or nicotine. On the basis of novelty in the addiction literature, magnitude of the difference in strain-dependent expression and prior knowledge of protein function, the following genes are highlighted.
Mint-1 (i.e. APBA1) has a relatively large number of associations with signaling, synaptic plasticity and transcription, but only one with addiction. Mint, an adaptor protein containing isoform-specific N-terminal sequences and common PTB and PDZ domains, is found in soma, axons and dendrites of excitatory and inhibitory neurons throughout the brain (Duclos & Koenig 1995; Okamoto & Sudhof 1997; Tanahashi & Tabira 1999). Mints bind calcium channels, potentially affecting presynaptic calcium influx (Maximov & Bezprozvanny 2002; Maximov et al. 1999). Only the N-terminus of Mint-1 binds Cask (Borg et al. 1998; Butz et al. 1998), which itself is a synaptic membrane-associated guanylate kinase that interacts with membrane receptors affecting GABA release (Ho et al. 2003). Cask is associated with all three cellular processes, but not addiction/nicotine. In hippocampal interneurons, expressing high levels of Mint-1 vs. Mint-2, Mint-1 deficiency is associated with impaired regulation of GABA release (Ho et al. 2003). Therefore, in Lewis vs. Fisher rats, the release of GABA by NAcc neurons regulating VP motivational functions might be affected by increased Mint-1-Cask heterodimers, reflecting increased basal levels of both transcripts (Lewis/Fisher ratios of Mint-1 and Cask: 1.7 and 1.6, respectively).
Cask associates with synaptic vesicles through interactions with neurexins, Mints and synaptotagmin (Biederer & Sudhof 2000; Hata et al. 1993). Neurexins are presynaptic transmembrane cell-adhesion proteins (Nam & Chen 2005) involved in initiating postsynaptic specializations at glutamate and GABA synapses (Graf et al. 2004). Cask binds and phosphorylates the cytoplasmic tail of neurexin-1, which may be essential for regulation of the presynaptic cytoskeleton (Mukherjee et al. 2008). Cask kinase activity is suppressed by neuronal activity and increased by silencing synapses. Two reports suggest that inhibitory synapses may undergo silencing (Bekkers 2005; Kilman et al. 2002). In Lewis rats, the enhanced basal expression of Cask may promote phosphorylation of neurexin concomitant to the silencing of GABA synapses involving NAcc GABA projections.
In contrast to Mint-1 and Cask, Ca2+/calmodulin-dependent protein kinase IIδ (CamkIIδ) is related to all three cellular processes and addiction/nicotine. Its expression ratio in Lewis vs. Fisher NAcc GABA neurons was 1.76 (P = 0.03, FDR 5%). CamkIIδ is present throughout rat brain (Takeuchi et al. 1999). Nuclear CamkIIδ is implicated in gene transcription, exemplified by mPer1 (Nomura et al. 2003). Dopamine D2 receptors (D2R) activate CamkIIδ to increase brain-derived neurotropic factor (BDNF) (Takeuchi et al. 2002), which is required for expression of activity-dependent inhibitory synapses (Hong et al. 2008; Yamada et al. 2002). These observations and the strain-dependent differences in basal CamkIIδ expression indicate that neuronal plasticity, involving BDNF and inhibitory synapses encoding aspects of behavioral reward, may be facilitated in Lewis rats.
Table 3 shows that neural cell adhesion molecule 1 (Ncam1) has the strongest associations with signaling and synaptic plasticity and is also associated with addiction/nicotine. Its expression ratio in Lewis vs. Fisher NAcc projection neurons was 1.54 (P = 0.023, FDR 5%). Neural cell adhesion molecules mediate extracellular interactions with matrix and cells. Membrane clustering of Ncams initiate intracellular signaling cascades implicated in synaptic plasticity (Luthl et al. 1994; Maness & Schachner 2007). By direct interaction with D2R, Ncam1 promotes internalization and degradation, regulating D2R signaling (Xiao et al. 2009). Increased Ncam1 expression appears to reduce surface D2R levels, which inhibit NAcc GABA neuron activity. Across 21 strains of recombinant inbred BXD mice, D2R and Ncam expression were associated with models of ethanol preference (Hitzemann et al. 2003). In Lewis rats, increased Ncam1 expression in NAcc GABA projection neurons is likely to enhance synaptic plasticity and alter surface expression of D2R, reducing dopamine-dependent inhibition.
Visinin-like 1 (Vsnl1; aka Vilip-1) and hippocalcin-like 1 (Hpcal1) are members of the neuronal Ca2+ sensor subfamily of Vsnl proteins, which belong to the superfamily of EF-hand Ca2+ binding proteins (Braunewell & Gundelfinger 1999). Vsnl interacts with multiple intracellular signaling cascades and affects exocytosis, modulation of adenylyl cyclase activity and regulation of both ligand- and voltage-gated ion channels (Burgoyne 2007). Vsnl proteins are cytoplasmic at resting Ca2+ concentrations, and translocate to the plasma or Golgi membrane with increased intracellular Ca2+ concentration (Spilker et al. 2002). Vsnl1 has low to moderate associations with signaling and synaptic plasticity and minimal relationships to addiction/nicotine. Similarly, Hpcal1 has relatively few relationships with signaling and synaptic plasticity, and none with addiction/nicotine. The expression ratios for Vsnl1 and Hpcal1 in Lewis vs. Fisher were relatively high: 2.03 (P = 0.023, FDR 5%) and 1.75 (P = 0.043, FDR 5%), respectively. The Vsnl1 ratio was confirmed by RT-PCR.
Vsnl1 interacts directly with the alpha4 subunit of the most abundant brain nicotinic cholinergic receptor (nAChR), alpha4beta2, increasing the surface expression of functional receptors, depending on Ca2+ concentration (Zhao et al. 2009b). In contrast, alpha7-containing nAChRs elicit a calcium-dependent membrane localization of Vsnl1 (Zhao et al. 2009a). The inward Ca2+ current induced by nicotinic stimulation of alpha7 nAChRs (Berg et al. 2006) may drive the activation and membrane localization of Vsnl1 that is associated with upregulation of alpha4beta2 nAChRs. The brain-region-specific upregulation of alpha4beta2 nAChRs has been reported in rats that chronically self-administer nicotine (Moretti et al. 2010; Parker et al. 2004). Upregulation of nAChRs would likely increase neuronal sensitivity and responsiveness to nicotine (Nguyen et al. 2004). However, in NAcc GABA projection neurons, the effect of chronic nicotine exposure on the level of nAChRs is not, to our knowledge, known. Nevertheless, the twofold increased expression of Vsnl1 in Lewis vs. Fisher GABA projection neurons may contribute to the motivational effects of nicotine in Lewis rats and to their ability to acquire nicotine SA.
Carbonic anhydrase 8 (Car8) displayed the greatest difference in expression between Lewis and Fisher rats (3.36-fold; P = 0.024, FDR 5%). This was confirmed by RT-PCR. Car8, an acatalytic carbonic anhydrase, binds inositol trisphosphate [IP(3)] receptors, inhibiting binding to inositol 1,4,5-trisphosphate (Hirota et al. 2003). Thus, Car8 modulates IP(3) receptor-dependent mobilization of Ca2+ from intracellular stores, which is critical to propagation of cytosolic Ca2+ signals (Taylor & Tovey 2010). Car8 mutant mice show the essential role of Car8 in synaptogenesis and maintenance of synaptic function (Hirasawa et al. 2007). The difference in basal expression by Lewis vs. Fisher rats suggests that Car8 modulation of intracellular Ca2+ mobilization and signaling varies substantially between these inbred strains.
In summary, these studies show the feasibility of obtaining neuronal phenotype-enriched samples to ascertain strain-specific differences in gene transcript expression. On the basis of gene ontologies of 322 transcripts that differed between these two strains, there is a wide-ranging alteration in the transcriptome of GABA neurons projecting from NAcc shell to VP. This is most consistent with a global change in function. In Lewis rats, significant upregulation of Mint-1, Cask, CamkIIδ, Ncam1, Vsnl1, Hpcal1 and Car8, which participate in cellular signaling and synaptic plasticity, indicates that these gene transcripts may contribute to altered function of NAcc GABA neurons, potentially predisposing to nicotine SA in Lewis rats. However, data from a manifold of inbred strains and F1 crosses will be required to specify the potential role of individual genes.
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These studies were supported by DA-028962 (B.M.S., H.C., S.G.M.) from NIDA.
Supporting Information
Supporting Information
Additional Supporting Information may be found in the online version of this article:
Table S1: Genes differentially expressed in Lewis vs. Fisher nucleus accumbens shell GABA projection neurons.
Laser capture microdissection was used to obtain nucleus accumbens shell GABA neurons project to ventral pallidum labeled by Fluorogold. The gene expression profiles of these neurons were obtained using Affymetrix Rat Gene ST 1.0 microarrays. A total of 322 genes were differentially expressed at a Lewis vs Fisher ratio of >1.5-fold (P < 0.05 and FDR < 5%).
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Originally published August 6, 2013 at 10:24 PM | Page modified August 7, 2013 at 9:29 PM
Sloppy Mariners fall to Toronto, 7-2
Felix Hernandez gives up first-pitch homer to Jose Reyes and suffers first loss since May as Seattle commits four errors.
Seattle Times staff reporter
Felix Hernandez was talking about his own subpar outing, but he might well have been referring to the entire stinker of a night by the Mariners on Tuesday.
"I'm just going to forget about this and look at the next one,'' Hernandez said.
The Mariners' 7-2 loss to Toronto was eminently forgettable. Seattle committed four errors, leading to four unearned runs, as the M's lost for the ninth time in their last 13 games on the heels of an eight-game winning streak.
"Overall, just kind of a sloppy game, as far as overall defense,'' acting manager Robby Thompson said.
Third baseman Kyle Seager had two errors, rookie shortstop Brad Miller had one, and left fielder Raul Ibanez dribbled an off-balance throw for yet another. But Hernandez, characteristically, declined to blame his defense.
"It happens. It's baseball,'' Hernandez said. "Errors are part of the game. I made a couple of mistakes and fell behind a lot. They capitalized and scored some runs."
It had all the makings of a classic mismatch: King Felix riding a two-month surge of great pitching facing the struggling Josh Johnson, who has been battered around much of the season.
And a mismatch it was – in an unexpected direction. Johnson out-dueled Hernandez, who lost for the first time since May 25 in front of a Safeco Field crowd of 28,198 that was once again jammed with vocal Canadian supporters of the Blue Jays.
Hernandez was not sharp in this game, which was apparent literally from his very first pitch – rocketed for a home run by Jose Reyes. It was just the second time in his career Hernandez has given up a leadoff homer.
Hernandez was touched for nine hits in five innings, but the Mariners added considerably to his struggles, particularly in a nightmarish fourth. Seager booted a grounder and Miller made a wild throw to second on a force attempt, making all three runs in the inning unearned. In addition, Miller couldn't hold onto a throw by catcher Henry Blanco that appeared in time to catch Brett Lawrie attempting to steal.
It finally caught up to Hernandez, who gave up a two-run double to Emilio Bonifacio, the No. 9 hitter, and an RBI single to Reyes, all with two outs.
"When he did miss, he missed out and over the plate, and he was hit,'' Thompson said. "Even with the sloppy defense, we've seen a sharper Felix, obviously. Hey, we're all human. He still pitched a pretty good ballgame, with the sloppy defense."
Johnson, meanwhile, threw five shutout innings, quite an accomplishment in the context of his season. The two-time All-Star has hit hard times and brought a 1-6 record and 6.62 earned-run average into the game. In fact, Johnson had lost 15 of his last 17 decisions dating back to last year, and gave up 10 hits and seven runs in just 21 / 3 innings in his last start.
The Mariners' frustration continued after Johnson departed when Toronto center fielder Colby Rasmus made a leaping catch at the wall to rob Kendrys Morales of a potential home run in the sixth.
The Mariners finally got on the board in the seventh on a two-out, two-run triple by Miller off reliever Juan Perez.
Fellow rookie Nick Franklin, returning to the lineup, went 0 for 3 with a walk and two strikeouts, and is now hitless in his last 27 at-bats.
"You hope he comes right out of it, but you stick with him,'' Thompson said. "That's part of the growing pains of a young player coming up is learning how to deal with the failure of it. You go into slumps, and you've got to fight your way out of it. This is where he's got to maintain and keep grinding it out and stay positive. He'll get it back soon."
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shooting environment. The EO Tech 512 A65 1x Holographic Red Dot Sight fills the needs of all ... EOtech 512 A65 Holographic Weapon Sight combines the most popular model of holographic sight ... represent a revolutionary weapon sighting system based on advanced holographic technology. ... leader. Whatever your shooting discipline, you can make good use of the EO-Tech 512-A65 65 MOA ... Circle-Dot Holographic Sight. EOTech 512-A65-EE: 512-A65 Black Holographic Weapon Sight, 2x Alkaline AA ... with useful and versatile accessories. This holographic sight is perfect for agencies that want the best ... The EOTech red dot sight enhances target acquisition, improves accuracy, and provides more control over your...
Blade Tech Black Ice OWB Weapon Holster
such as when in a vehicle or behind a desk. Drawing from the Blade Tech BLACK ICE Weapon Holster takes less ... to accommodate after-market night sights as well as higher profile fiber optic sights. Package Contents: Blade Tech Black Ice OWB Hand Gun Holster ... The Blade Tech Black Ice OWB Hand Gun Holster has been designed to be the ideal holster for any ... shooter. This Hand Gun Holster from Blade Tech is very popular with shooting sports competitors. ... Featuring a "Full Combat Grip" the Blade Tech BLACK ICE Over the Waistband Holster was designed to give ... Re-holstering is also quick and easy. This Blade Tech Holster is a great choice for IDPA competition ... physical range of motion. For a great way to make sure your weapon is ready for action at the drop...
Starts at $51.99
EOTech 517 A65 Holographic Weapon Sight (HWS) Buttons On Left Side w/ Raised 7mm Base (517.A65/1) for M4 & M16
For a full line of EOTech Red Dot Sights and other products by EOTech on sale please visit EoTech ... This EOTech 517 A65 Holographic Weapon Sight comes with a modified Eotech 517 Holographic ... Specifications for EOTech 517 A65 Holographic Weapon Sight (HWS) Buttons On Left Side w/ Raised 7mm Base ... source. In addition it has a cantilevered base that allows one to mount a part of the Holo sight ... over standard hand guards of a M4 Rifle or an M-16 Assault Rifle. Scope Coat Covers are constructed ... of the highest quality neoprene (2, 3, 6 mm thick) laminated with nylon. Scope Coat has simple design ... safeguards that protect your Scope dings and scratches, dust, dirt, and moisture. The shock...
Eotech 553 Series A65 Holographic Weapon Sight
Battery cap tether to avoid loss in the field Package Contents: Eotech 553 A65 Holographic Weapon Sight Scope Coat Protective Cover ... The Eotech 553 A65 Holographic Weapon Sight was developed after extensive testing of various ... optical sights, and US Special Operations Command has standardized on the Eotech Holographic Weapon Sight ... A65 Holographic Weapon Sights is its holographic reticle patterns that are instantly visible in any ... The magic of EOTech Holographic 553 Weapon Sights is the edge they provide to you in close quarter ... or urban combat zones. The EOTech Holographic M553 Weapon Sight will remain fully operational even ... for Eotech 553 A65 Holographic Weapon Sight: Optics: Transmission holography - 100% parallax free...
Aimpoint Micro H-1 Red Dot Weapon Sight
Micro Red Dot H1 Weapon Sight is made with precision adjustments for windage and elevation ... Red Dot Weapon Sight - Standard Mount, 2 MOA Aimpoint 200158: Micro H-1 2 MOA LRP mount/39mm spacer ... Dot Waterproof Sight: Weight: 84g w/o mount, 105g w/ mount Technology: ACET (Advanced Circuit ... Features of AimPoint Micro Red Dot H1 Weapon Sight: Perfect for firearms or archery equipment ... To have a successful hunt, the Aimpoint H-1 Micro Red Dot Scope has been designed specifically ... sights, these red dot sights by Aimpoint can be used on any type of firearm or bow. The AimPoint ... Waterproof Sight is keyed to the sight body to absorb recoil and the 12 settings are perfect...
Starts at $606.00
EOTech 512 A65 RealTree APG HD Camouflage Holographic Weapon Sight (HWS) (M512) Standard Reticle
Holographic Weapon Sight. This tactical optical sight is perfect for agencies that want the best ... choice of a HOLOgraphic Sight ( HWS ) / EOTech Red Dot Sight a revolutionary weapon sighting system ... RedDot sight will have you on target without hesitation. Also available is the EOTech HOLOgraphic Weapon ... Red-Dot A65 Sight Kits Eotech 512-A65 Black KIT with AA Batteries and Scope Coat Cover for 512 Red ... Dot Sights Eotech 512-A65 Mossy Oak Kit with AA Batteries and Scope Coat Cover for 512 Red Dot Sights ... EOtech 512-A65 Real Tree Kit with AA Batteries and Scope Coat Cover for 512 Red Dot Sights ... etc., the Holographic Weapon Sight HWS remains fully operational , with point of aim/impact being...
Ultradot 30mm Red Dot Weapon Sight
The Ultra Dot 30mm Red Dot Pistol Scope is the most compact, lightweight and streamlined sight ... 30mm Weapon Sight comes complete with a battery, rubber eyepiece, polarizing filter, tube extension, ... on the market. This Red Dot Gun Sight from the professional product experts at Ultradot has click ... Ultradot UD30B: 30mm Red Dot Gun Sight, Black, 30mm Red Dot Gun Sight Ultradot UD30S: 30mm Red ... Dot Gun Sight, Silver, 30mm Red Dot Gun Sight Specifications for Ultra Dot Red Dot Sight - UltraDot ... of Ultra-Dot Red Dot Sight - Ultradot 30mm: Compact Lightweight Streamlined Sight Click Adjustable ... Brightness Control Package Contents: Ultra Dot 30mm Red Dot Pistol Scope Battery Rubber eyepiece...
Starts at $165.99
ATN ARES 6-4 Nightvsion Weapon Sight NVWSARS640
ATN NVWSARS640: ARES6x-4 Nightvision Weapon Sight Specifications for ATN 6x Ares NV Scope - 6-4: ... will provide the user with a rugged, easy to use and accurate night vision weapon sight. Fast infra-red ... Features of ATN 6x Ares 6-4 Night Vision Weapon Sight: Precision windage and elevation ... The ATN Ares 6-4 Night Vision Riflescope w/ 6x Magnification NVWSARS640 has been designed ... to be the perfect night vision riflescope for any nighttime shooter. This Night Vision Scope from ATN ... sensitive optics coupled with quality image tubes on the ATN Ares 6-4 NV Riflescope offer high ... and accurate are just a few of the features that the ATN 4-6 6x Ares Night Vision Scope has to offer.
ATN ARES 2-3 Nightvision Weapon Sight
ARES2x-3P Nightvision Weapon Sight Specifications for ATN Ares 2-3 2X Riflescope w/ Night Vision: Total ... and accurate night vision weapon sight. Fast infra-red sensitive optics coupled with quality image ... Nightvision Weapon Sight ATN NVWSARS23A: ARES2x-3A Nightvision Weapon Sight ATN NVWSARS23P: ... The ATN Ares 2-3 Night Vision Riflescope - 2x has been designed to provide you with the ultimate ... in night vision technology. This NV Scope from ATN will provide the user with a rugged, easy to use ... tubes of the ATN Ares 2-3 Night Vision Riflescope offers high resolution, clear images for outstanding ... of the features that the ATN 2-3 2x Ares Night Vision Riflescope have to offer. ATN NVWSARS230: ARES2x-3...
Starts at $2,924.99
ATN ARES 6-WPT Nightvsion Weapon Sight - 6x
to be the perfect night vision riflescope for any nighttime shooter. This NV Weapon Sight from ATN ... to offer. ATN NVWSARS6WP: ARES6x-WPT Nightvision Weapon Sight Specifications for ATN 6x Ares NV Scope - ... will provide the user with a rugged, easy to use and accurate night vision weapon sight. Fast infra-red ... 2 years Features of ATN 6x Ares 6-WPT Night Vision Weapon Sight: Precision windage ... The ATN Ares 6-WPT Night Vision Riflescope w/ 6x Magnification NVWSARS6WP has been designed ... sensitive optics coupled with quality image tubes on the ATN Ares 6-WPT NV Riflescope offer high ... and accurate are just a few of the features that the ATN 6-WPT 6x Ares Night Vision Scope has...
BSA Optics 30mm Bow Hunters Weapon Sight, 5 MOA Dot
making it the perfect sight for any hunting environment. BSA Optics TW30RDCP: 30mm Tactical Weapon Red ... The BSA Optics 30mm Red and Green Dot Bow Hunter Sight TW30RDCP has been designed ... to be the perfect sight for any bow hunter. This Archery Sight from BSA is great for deer, bow and turkey hunting. ... The BSA 30mm Bow Hunting Red & Green Dot 5MOA Scope is waterproof, shockproof and fogproof, ... Dot, 5 MOA Dot, Black, 30mm Specifications for BSA Illuminated Bow Hunters 5 MOA Sight - 30mm: ... Reflex Bow Hunting Sight: 30mm Waterproof, Shockproof, Fogproof Perfect for Deer and Turkey ... Hunting 5MOA Reticle Package Contents: BSA Optics 30mm Red and Green Dot Bow Hunter Sight...
ATN Night Arrow2-2I 2x Night Vision Weapon Sight
The ATN Night Arrow 2-2 Night Vision Gun Sight is a rugged Night Vision Weapon Sight that provides ... Sight one of the best commercial Night Vision Weapon Sights! Don't let the darkness hold you back ... because the sun went down. ATN NVWSNAR22I: Night Arrow2-2I 2x Night Vision Weapon Sight ATN ... NVWSNAR22J: Night Arrow2-2IA 2x Night Vision Weapon Sight ATN NVWSNAR2CI: Night Arrow2-CGTI 2x Night Vision ... Weapon Sight ATN NVWSNAR2WI: Night Arrow2-WPTI 2x Night Vision Weapon Sight ATN NVWSNAR2W0: Night ... Arrow2-WPT 2x Night Vision Weapon Sight Specifications for ATN Night Arrow 2-2 Night Vision Gun ... years Features of ATN Night Arrow 2-2 NV Weapon Sight: Light and compact design Top-notch...
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ATN ATN Night Arrow4-2I 4x Night Vision Weapon Sight
The ATN Night Arrow 4-2 Night Vision Weapon Sight is a rugged, night vision weapon sight ... and performance make the ATN Night Arrow 4-2 NV Weapon Sight is one of the best commercial night vision weapon ... sights there is! ATN NVWSNAR42I: ATN Night Arrow4-2I 4x Night Vision Weapon Sight ATN NVWSNAR42J: ... ATN Night Arrow4-2IA 4x Night Vision Weapon Sight ATN NVWSNAR4CI: ATN Night Arrow4-CGTI 4x Night ... Vision Weapon Sight ATN NVWSNAR4W0: ATN Night Arrow4-WPT 4x Night Vision Weapon Sight ATN NVWSNAR4WI: ATN ... Night Arrow4-WPTI 4x Night Vision Weapon Sight Specifications for ATN Night Arrow 4-2 Night ... Weight: 1.4 kg / 3.1 lbs Features of ATN Night Arrow 4-2 NV Weapon Sight: Light and compact...
Starts at $1,276.99
Trijicon ACOG 4x32 Illuminated Crosshair Red Dot Weapon Scope w/ Battery, .223 Ballistic Reticle & TA51 Mount
lighting. The body on the Trijicon ACOG 4x32mm Illuminated Weapon Scope, has been optimized by moving ... The Trijicon 4x32mm ACOG Red LED Crosshair .223 Ballistic Reticle Rifle Scope w/ TA51 TA02 robust ... on this Riflescope from Trijicon offers an outstanding level of reliability with a straightforward brightness ... the RMR mount forward to maximize its performance in conjunction with the ACOG. This Trijicon Gun Sight ... the Trijicon Advanced Combat Optical Gunsight - 4x32mm. TA02: Trijicon ACOG Red Dot Rifle Sight - ... Ballistic BDC Red Illuminated Gun Sight - 4x32mm: Robust engineering Enhanced user control Single AA ... .223 Ballistic Reticle Rifle Scope w/ TA51 TA02 Thumbscrew Flattop Adapter (TA51) LENSPEN (TA56) Trijicon Logo Sticker (PR15) Manual Warranty Card...
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Lucid Kill Flash for HD7 Red Dot Weapon Sights L-KF
dot sight, choose the Lucid Kill Flash for HD7 Red Dot Weapon Sight. Specifications for Lucid Red ... Designed to enhance your already amazing Lucid HD7 Red Dot Sight, the Lucid Kill Flash for HD7 Red ... Dot Sights, has been developed to reduce any lens glare or reflection. Made using in a 6061 T6 ... Dot Sight Kill Flash: Material: 6061 T6 Aluminum Finish: T3 Mil-Spec Anodized Weight: .2oz. ... Features of Lucid Kill Flash for HD7 Red Dot: Fits HD7 Lucid Red Dot Sight Add lens protection ... Durable Long lasting Package Contents: Lucid Kill Flash for HD7 Red Dot Sights...
ATN Mars4x Gen.3 Night Vision Weapon Scope
vision sights - has a new flagship - the ATN Mars4X Night Vision Weapon Scope. Inspired ... ATN Mars4x Gen.3 Night Vision Weapon Scope - the world´s largest line of professional night ... and calibrated to achieve optimum performance. ATN NVWSMRS430: Mars Night Vision Weapon Scope - ... 4x, Gen III, 64 lp/mm Specifications for ATN Mars4x Gen.3 Night Vision Weapon Scope ... Weight: 1.3kg Features of ATN Mars 4X Night Vision Weapon Scope: Powerful 4x magnification Superior ... represent the absolute latest in the world of night vision equipment. Similar to all ATN Aries ... scopes the ATN MARS features only the purest grades of heavy glass and computer-aided optical designs...
Sightmark Wolfhound 6x44 Prismatic Weapon Sight
Make your mark and hunt down your target with the Sightmark Wolfhound 6x44 Prismatic Weapon Sight ... . This riflescope from the experts at SightMark features an advanced horseshoe dot reticle ... stance. The reticle on the Sightmark Wolfhound 6x44 Prismatic Shockproof Weapon Sight w/ HS-223 Reticle ... Prismatic Shockproof Weapon Sight w/ HS-223 Reticle: Fully multi-coated optics Prismatic optical ... rifle scope is equipped with a .5 MOA central aiming point for precision long-range shooting ... Fogproof Tactical Sight gives you the speed and agility experienced shooters look for. Sightmark ... SM13026: Wolfhound 6x44 Prismatic Sight Specifications for Sightmark Wolfhound 6x44 Prismatic Fogproof...
Eotech Zombie Stopper Red Dot Holographic Sight
this Holographic Weapon Sight by the zombie research team at EoTech will help you to get the perfect ... XPS-2-Z: Zombie Stopper Red Dot Sight - Biohazard Reticle Specifications for EO-Tech XPS-2 Zombie ... breaching your perimeter. With an average of 600 hours of use at the highest setting, this Eo-Tech Red Dot ... at you. Whether fleeing from swarming hordes, or protecting your compound, the EO Tech XPS2 Red Dot ... of EOTech Zombie Stopper Holographic Bio-Hazard reticle Weapon Sight: Designed to help you survive ... Biohazard Reticle Red Dot Holographic Rifle Sight XPS-2-Z. As the virus spreads across the country ... Reflex Sight allows you to quickly acquire your target, so you can effectively stop walkers from...


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High school boys basketball: 2A state tournament capsules
The first round of the 2A state tournament gets underway Friday at Orem High School, with the eight winners advancing to the quarterfinals at the Southern Utah University in Cedar City next Thursday. Defending state champion South Sevier heads into the playoffs on a 15-game winning streak and is on a collision course with No. 1 Wasatch Academy in the semifinals.
Reigning 2A MVP Race Parsons has scored 1,996 career points, and is just a few points away from becoming the sixth player in state history to sure pass 2,000 career points.
In order of winning percentage, these are the 16 teams that qualified for the 2A boys state basketball tournament this year:
1. Wasatch Academy (21-1)
2. South Sevier (18-3)
3. Beaver (15-3)
4. South Summit (14-7)
5. Gunnison (14-7)
6. Emery (13-7)
7. Manti (13-8)
8. Enterprise (13-9)
9. Richfield (11-8)
10. Merit Academy (11-8)
11. Parowan (11-10)
12. Summit Academy (11-10)
13. San Juan (11-10)
14. Kanab (9-10)
15. North Summit (8-12)
16. Waterford (6-14)
Here's a team-by-team look at all 16 teams in the state tournament, and what to expect.
James Edward is the prep sports editor for the Deseret News. Email: email@example.com; Twitter: @dnewspreps
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Home > Arts & Events >
Critics' Pick
Lincoln Center for the Performing Arts
1 at 66th St.-Lincoln Center
Ballet dancers and opera singers have called this theater''s stage their own since it opened on April 23, 1964. Home to New York City Ballet and New York City Opera, the classically influenced, rectangular structure sits on the southeast corner of Lincoln Center for the Performing Art's airy Fountain Plaza. It comprises one of the three principal venuesthe others being the Metropolitan Opera House and Avery Fisher Hall. Designed by architect Philip Johnson, the thin vertical travertine columns and glass facade create a skeleton-like edifice that allows attendees to see into the four-story Promenade lobby that is outfitted with modern art, like Jasper John's painting Numbers. Inside the theater, up to 2,755 attendees line up for performances such as George Ballanchine's perennial The Nutcracker and Puccini's Madame Butterfly. Overhead, above five levels of balconies, a spherical chandelierthat looks more like a planet stricken with glowing mumps than a lightis suspended from the gold-paneled ceiling. To improve sound quality, a massive five million dollar, state-of-the-art acoustical reconstruction was completed in the summer of 1982, affording patrons a better, if still less-than-perfect, experience once the gold curtains part.Tours
For in-depth history, legends and architecture, take the Lincoln Center Tour for a one-hour exploration of the complex's three theaters. Book all tours in advance. Call 212-875-5350 for reservations.
An Evening with Primus and the Chocolate Factory at The Beacon Theater
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Motown: The Musical at Lunt-Fontanne Theatre
With songs from its legendary catalogue, this story of the record label and its most famous acts also features a book written by Motown founder Berry Gordy. More »


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When Pelco Products Inc. initially contracted Oklahoma City-based Dale Rogers Training Center for help with assembly work, the manufacturer constantly would shuttle loose and packaged parts to and from its Edmond facility and the vocational center in northwest Oklahoma City.
Edmond's Pelco Products Inc., Oklahoma City-based Dale Rogers' partnership is called good for business
It wasn't long before Pelco co-founder Phil Parduhn decided to dedicate a work space for Dale Rogers' clients to work on-site, alongside his other employees.
Pelco — North America's largest traffic signal hardware manufacturer — and Dale Rogers recently celebrated the 10-year anniversary of its partnership.
During the past decade, a team of about six disabled workers have assembled from 9 a.m. to 3 p.m. every weekday, together providing more than 108,000 man-hours and helping put together 4.5 million hardware kits that have been shipped to some 730 customers in all 50 states and 14 countries.
It was an easy decision for Parduhn, whose late mother was physically disabled. She suffered from rheumatoid arthritis and raised him and his sister from a wheelchair. "We'd take knitting and other things to her and she'd get things done," he said. "There was no complaining."
"We're kind of like a big ol' family," Parduhn said. "They enjoy being here, and we enjoy having them here."
Low error rates
Along with giving the disabled workers a sense of productivity and self-esteem, the arrangement is good for business, said Mark Nash, Pelco operations manager.
Pelco pays Dale Rogers' clients on a per piece, versus hourly, basis. And Dale Rogers buses employees to and from work, and provides their supervisor, as well as workers' compensation and liability insurance.
Continue reading this story on the...
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in The Bible
Shalom and welocme as we conitnue through the Tehellim verse by verse to bring out practical applications that can be applied to a daily walk of understanding with our Father Yahuwah, The Yah of Avraham, Yitzack and Yaacob, The Yah of the Living and not the Dead. Join in the study live or via archive to enrich your life and your understanding in Tehellim's prinicpals many of these Tehellims also point to our Messiah Yahushuah who shed his blood on the tree for you and my redempti
The Fallen Angles And Giants in Genesis 6.. With Apostle Rudy Goldstein Jr.
in The Bible
The End-Time Prophetic Zone, Brings (Part 8) of this End-Time insight into the plot of the kingdom of darkness.. In this episode Apostle Rudy Goldstein Jr. Will reveal the UNCUT TRUTH", of the Fallen angles and Giants in genesis 6...These truths had been hidden from mankind for centuries, but the hour has come for the eyes of the church to be open. That's why Elohim has sent one like John the Baptist A WATCHMAN to WARN THE PEOPLE .. You won't likely t
Women Of God don't lose your Inheritance
in The Bible
In him we have obtained an inheritance, having been predestined according to the purpose of him who works all things according to the counsel of his will, so that we who were the first to hope in Christ might be to the praise of his glory. In him you also, when you heard the word of truth, the gospel of your salvation, and believed in him, were sealed with the promised Holy Spirit, who is the guarantee of our inheritance until we acquire possession of it, to the praise of his glory.
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More Articles for MAP-21 and Transportation's Fiscal Cliff. Jack
MAP-21 and Transportation's Fiscal Cliff: What does it all mean?
The nation's economy is on a "fiscal cliff." But how does this affect the U.S. infrastructure system, namely the new highway bill, Moving Ahead for Progress in the 21st Century, or MAP-21 for short?
Jack Schenendorf, a transportation policy veteran who ... Read More...
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Dog coat from knit 1 magazine
Amigurumi Elephant
Entrelac Beret Pattern #: L10502
ladybug pillow pal
Aran Cardigan
Lamb eggs
Ribbon Top
District 12 cowl
Rosie Tea Cozy
Magic Stripes Socks
Double Crochet Amish Afghan
Crocheted Skinny Scarf
Ripple Tan and Blue Afghan
Pumpkin Hat and Booties
These patterns are so much fun. I am...
Francesca dog sweater
Display Order: Newest First
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Price $25
Age Suitability 21 and up
Singles Speed Dating Happy Hour Event (Ages 23-35)
Tuesday, Apr 9, 2013 7:00p to 9:30p
View Wine Bar & Kitchen Las Vegas, NV
Join us Tuesday, April 9th for a night of wine, beer, appetizers and speed dating at View Kitchen and Wine Bar located inside The Market at Tivoli Village. Guests will enjoy happy hour specials, live music and 12 mini dates.
For a successful event, we are RSVP-ing 12 men and 12 women between the ages of 25-35. Payment is required in advance to secure your seat. Dress to impress! You just might meet your Plus One.
Created by KimistryBrands
Location & Nearby Info
View Wine Bar & Kitchen
420 S. Rampart
Las Vegas, NV 89145
420 S. Rampart
Las Vegas, NV 89145
Show nearby:
0.7 mi 3 Via Brasil Steakhouse
0.8 mi 4 The Martini
1.5 mi 6 Outside Inn
1.8 mi 8 Sushi Mon
2.4 mi 9 Shari's Diner
2.6 mi 10 Osaka Japanese Cuisine
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Rock a killer look: Try this sugar skull makeup tutorial
Is it weird for girls to ask out guys?
I love my BFF, but she never wants to do anything!
Were obsessing over Jacquie Lee's Broken Ones EP
Your weekly horoscope!
Brighten up your room with adorbs plants
Spooky Halloween-inspired manis
Is your cereal causing you to have a bad day? Breakfast myth=busted!
Are you the go-to girl?
Ever feel a little jealous? Spill for an upcoming issue of the mag!
Kirby Buckets Clip
More Friends = More Fun
GL Tweets !
AN HOUR AGO Haute 'n' haunted #HalloweenNails: http://t.co/wibxKc4jOc
2 HOURS AGO #Unraveled by @GenniferAlbin is finally in stores! Still need to catch up? Read the first book in the series, #Crewel, on @wattpad for free!
2 HOURS AGO What does your horoscope say this week (dun dun dunnn!): http://t.co/0fOq0gESZ6
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Craft a special workout plan
Each sport uses different muscles in our bod, so be sure your summer workout is targeting the muscles that are specific to your sport. If you're a soccer player, you might want to do more leg workouts to get better at kicking. If you love to play softball, try doing some workouts for your arms. But in any case, don't forget to do some extra cardio. Almost every sport requires excellent stamina.
Practice, practice, practice
You can't improve without practice. Have a girls' day and gather some of your gals to head up to the local rec center. Ask them for advice on how to improve your weaknesses. Chances are, they'll need your help in some aspects too. Whenever ya get free time, head out in the backyard and practice there, too. The more you practice, the better you'll get!
Make goals for yourself
You have to want to get better in order to actually get better. Set goals that you want to achieve by the end of the summer, and vow to reach them. You'll have to be dedicated to getting enough sleep, eating healthy and staying on top of your workout routine.
Don't be afraid of criticism
If you ask a friend or coach for help, don't get upset when they correct you. Although it's sometimes tough to hear what you are doing wrong, they are only trying to help. Remember that you're not the only player the needs improvement. Everyone on the team could develop their skills in some way.
Study other athletes
Use athletes that are great at your sport for inspiration. Look up their workouts and techniques to include some new elements into your training. Using them as a role model will help you when you're trying to achieve your goals.
Work on other aspects besides your sport
POSTED IN sports, fitness, workout dos and don'ts
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Fab Fall Finds giveaway! CLICK HERE to check
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Going on an indefinite hiatus
hijackfb I need to prove to a mate that 2manydjs are worth getting tickets for, your like the main man for em so send me linksss!!!!
(Source: happyhourprofessional)
2manydjs tickets in the bag!!!
Watching the leftovers and from what I can gather the theme seems to be: everything is terrible and we are all assholes
Fire drive make a a pop up ad about how pop up ads are annoying….
Social anxiety activate!!!!!
i've got like 2 friends maybe 2.5
if you ever think about sending me an ask and decide not to cause "oh she doesn't care" or "oh I don't want to bother her" literally I'm the loneliest piece of shit you can find and would still love you if you sent me the word nuzzle over and over again


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