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Chronic early life lead (Pb2+) exposure alters presynaptic vesicle pools in hippocampal synapses
- Sara Rose Guariglia1,
- Kirstie H. Stansfield1,
- Jennifer McGlothan1 and
- Tomas R. Guilarte1Email author
DOI: 10.1186/s40360-016-0098-1
© The Author(s). 2016
Received: 1 June 2016
Accepted: 14 October 2016
Published: 2 November 2016
Lead (Pb2+) exposure has been shown to impair presynaptic neurotransmitter release in both in vivo and in vitro model systems. The mechanism by which Pb2+ impairs neurotransmitter release has not been fully elucidated. In previous work, we have shown that Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites in cultured hippocampal neurons. We have also shown that Pb2+ exposure inhibits vesicular release and alters the distribution of presynaptic vesicles in Shaffer Collateral – CA1 synapses of rodents chronically exposed to Pb2+ during development.
In the present study, we used transmission electron microscopy to examine presynaptic vesicle pools in Mossy Fiber-CA3 synapses and in Perforant Path-Dentate Gyrus synapses of rats to determine if in vivo Pb2+ exposure altered presynaptic vesicle distribution in these hippocampal regions. Data were analyzed using T-test for each experimental endpoint.
We found that Pb2+ exposure significantly reduced the number of vesicles in the readily releasable pool and recycling pool in Mossy Fiber-CA3 terminals. In both Mossy Fiber-CA3 terminals and in Perforant Path-Dentate Gyrus terminals, Pb2+ exposure significantly increased vesicle nearest neighbor distance in all vesicular pools (Rapidly Releasable, Recycling and Resting). We also found a reduction in the size of the postsynaptic densities of CA3 dendrites in the Pb2+ exposed group.
In our previous work, we have demonstrated that Pb2+ exposure impairs vesicular release in Shaffer Collateral - CA1 terminals of the hippocampus and that the number of docked vesicles in the presynaptic active zone was reduced. Our current data shows that Pb2+ exposure reduces the number of vesicles that are in proximity to release sites in Mossy Fiber- CA3 terminals. Furthermore, Pb2+ exposure causes presynaptic vesicles to be further from one another, in both Mossy Fiber- CA3 terminals and in Perforant Pathway – Dentate Gyrus terminals, which may interfere with vesicle movement and release. Our findings provide a novel in vivo mechanism by which Pb2+ exposure impairs vesicle dynamics and release in the hippocampus.
KeywordsLead (Pb2+) Synapses Presynaptic Vesicles Postsynaptic Density (PSD) Mitochondria
Effective neurotransmission requires appropriate expression, packaging, release, reception and degradation or reuptake of neurotransmitters [1]. Mechanisms underlying the release of neurotransmitters are highly complex and require precise interactions between pre-synaptic membrane proteins, vesicular proteins, ions and energy [2]. Exposure to lead (Pb2+) has been shown to inhibit the release of neurotransmitters, including glutamate and γ-aminobutyric acid (GABA), in various in vivo, in vitro and ex vivo models [3–6].
It is well known that the brain is a primary target of Pb2+ toxicity [7, 8]. Pb2+ can readily cross the blood brain barrier (BBB), and is found in brain homogenate following Pb2+ exposure [9], which is likely due to the ability of Pb2+ to substitute for Ca2+ ions [10, 11]. On the cellular level, Pb2+ exposure results in a myriad of direct effects in brain, which include apoptosis, excitotoxicity and alterations in neurotransmitter storage and release [12–20].
The mechanism by which Pb2+ exposure impairs vesicular release appears to involve presynaptic releasing sites [18–20]. In hippocampal neuron cultures, we have shown that Pb2+ exposure increased the number of nascent presynaptic contact sites. These release sites may be immature and lack the necessary vesicular release machinery proteins, thus contributing to reduced vesicular docking and release [18]. The mechanism by which Pb2+ exposure decreases the number of vesicular docking sites may involve retrograde Brain Derived Neurotrophic Factor (BDNF) – Receptor Tyrosine Kinase B (TrkB) receptor signaling [19]. Pb2+ is a potent inhibitor of the N-Methyl-d-Aspartate (NMDA) receptor, [21–23] whose activation is essential for cAMP Response Element (CREB) phosphorylation and subsequent BDNF expression [19]. Inhibition of the NMDA receptor by Pb2+ exposure reduces the expression of BDNF and impairs presynaptic BDNF-TrkB receptor signaling [5, 18, 19]. Reduced BDNF-TrkB interaction on presynaptic sites decreases the phosphorylation of synapsin-1, a vesicular protein which is important in vesicle-synaptic membrane interactions and is imperative to vesicular release [23–25]. Previously, we have shown that synapsin I phosphorylation at sites 4 (serine 62) and 5 (serine 67) were significantly decreased by Pb2+ exposure with no effect on total synapsin I protein levels [18]. The effect of Pb2+ on these particular signaling mechanisms is not reversed when Pb2+ is removed from the system which suggests that Pb2+ exposure results in persistent, deleterious effects on neurotransmission. On the other hand, the inhibitory effect of Pb2+ on L-type calcium channels can be reversed with removal of Pb2+ [26]. Therefore, the permanent effect of Pb2+ exposure on vesicular exocytotic mechanisms appears to be exceedingly important in Pb2+ exposure induced deficits in neurotransmission.
Mechanistic studies demonstrate that Pb2+ can have an effect on multiple cellular constituents that are involved in neurotransmission, thus leading to differential effects of Pb2+ exposure on neurotransmission in different brain regions, even within the same structure. For example, chronic, low-level exposure to lead has been shown to reduce long term potentiation (LTP) in NMDA receptor-dependent CA1 synapses, while having no effect on LTP in NMDA receptor - independent synapses of the CA3 region of the hippocampus [27]. Recently, we have shown that Pb2+ markedly inhibits presynaptic vesicular release in the hippocampal Shaffer Collateral – CA1 synapses in young adult rats. In support of previous data, impairments in vesicular release were found in CA1 but not in CA3 immediately following stimulation. This decrease in vesicular release in CA1 was found along with a decrease in both the rapidly releasable pool/docked (RRP/docked) vesicle pools as well as the recycling pool of vesicles, with no overall reduction in the total number of presynaptic vesicles. Furthermore, vesicles in the Pb2+ exposure group were further apart from one another, irrespective of the distance of the vesicle to the presynaptic active zone (PAZ). Interestingly, at later time points, impairments in vesicular release became apparent in the CA3, demonstrating the differential effects of Pb2+ on neurotransmission in the CA1 and CA3 brain regions [20].
Mitochondria are organelles that are intricately involved in neurotransmission, as they provide energy for vesicular biogenesis, packaging, movement and release [28]. Mitochondria are typically synthesized in the cell body, are sent to the axonal terminal for energy and then sent back to the cell body for degradation [29]. Exposure to Pb2+ has been shown to have numerous detrimental effects on mitochondria [30–32]. Our previous work has shown that chronic Pb2+ exposure reduces the number of mitochondria found in Shaffer Collateral- CA1 synapses [20]. Mechanistically, Pb2+ exposure can impair ATP synthesis, which would in turn limit energy-expending activities. Therefore, the effect of Pb2+ on presynaptic mitochondria may contribute to impaired vesicular release.
In light of our previous work, which demonstrated that there was a latent but significantly impaired neurotransmission in the CA3 following Pb2+ exposure, we sought to determine if Pb2+ exposure could affect the distribution of vesicular pools in the presynaptic terminals of asymmetric Mossy Fiber-CA3 synapses, using electron microscopy. We also examined the effect of Pb2+ exposure on asymmetric Perforant Pathway-Dentate Gyrus synapses, another region of the hippocampus in which Pb2+ exposure has been shown to impair long term potentiation [33]. Asymmetric synapses can be identified using electron microscopy by identification of the postsynaptic density (PSD). We have selected to examine the synapses of rats exposed to 1500 ppm lead. Feeding rats this concentration of lead yields a blood lead level of approximately 21 ug/dL. Previous studies have shown that a BLL of approximately 27 ug/dL yields a significant change in NMDA receptor expression as compared to low level Pb2+ exposure and highly concentrated Pb2+ exposure [9]. Since we examined asymmetric synapses via identification of the PSD, which typically contain NMDA receptors, we thought that a creating a model with a BLL comparable to that which produces Pb2+ mediated effects on NMDA receptor would allow us to characterize the maximal effect of Pb2+ on vesicular pools. Furthermore, we have found that this particular exposure produced profound spatial learning deficits [6, 34], which likely reflect the effect of this particular concentration of Pb2+ on hippocampal function. Additionally, we studied the number and size of mitochondria in the presynaptic terminals to determine if there were changes in mitochondrial size, number and distribution that could affect energy availability in the presynaptic terminals and examined the size of the postsynaptic density in asymmetrical synapses.
All chemicals used for electron microscopy (Glutaraldehyde, Paraformaldehyde, Osmium Tetroxide, Uranyl Acetate, Ethanol, Propylene Oxide and Spurr's Low Viscosity Resin Embedding Kit) were purchased from Electron Microscopy Sciences (Hatfield, PA, USA).
Adult female Long-Evans rats were purchased from Charles River, Inc. (Wilmington, MA) and fed 0 (control) or 1500 ppm lead acetate (PbAc) in the diet (Dyets, Bethlehem, PA) 10 days prior to breeding with normal Long-Evans males. Litters were culled to 10 on postnatal day 1 (PN1). Dams were maintained on their respective diet until weaning of pups. After weaning, offspring remained on respective maternal diet until PN 50. Rats were housed in pairs in rectangular plastic cages at 22 ± 2 °C on a 12/12 light:dark cycle. Food and water were allowed ad libitum. Rats were provided with corn cob bedding which was changed on a weekly basis. 10 litters of rats were bred for these studies. We used a litter based design in which one male rat per litter was randomly selected for inclusion into either the control group or the control group (n = 10, n = 5 Pb2+; n = 5 control). The number of animals to be used was calculated with a Power Analysis using G*Power 3.1 statistical software. This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by Columbia University Institutional Animal Care and Use Committees (AC-AAAF4810). All non-survival procedures were performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering.
Specimen preparation
All perfusion procedures were carried out during the light cycle (1300–1600 h). At PN 50, Long-Evans male rats were anesthetized with 20 mg/kg pentobarbital via intraperitoneal injection in their home cage. Pentobarbital was selected because it acts upon the GABAA receptor to induce anesthesia. Blood was transcardially perfused with 2.5 % Glutaraldehyde + 2 % Paraformaldehyde in 0.1 M Phosphate Buffered Saline (PBS). The brain was removed and post-fixed in the same solution overnight at room temperature (RT). Brains were sectioned into 500 um slices with a vibratome. Sections were laid flat and two regions of interest (Perforant Pathway – Dentate Gyrus synapses and Mossy Fiber – CA3 synapses) were dissected from the right hippocampus using a hole-punch method (Fig. 2). The right side of the brain is typically associated with visuospatial processing and spatial memory [35]. Since Pb2+ exposure results in decreased spatial learning ability, we chose to investigate the right hippocampus because it isassociated with spatial learning [6, 34]. Male rats, in particular, exhibit prominent laterality [36]. Dissected tissue was placed in the 2.5 % Glutaraldehyde + 2 % Paraformaldehyde in PBS mixture for 3 additional h at RT and rinsed with PBS. Secondary fixation in 1 % osmium tetraoxide in PBS was then done for 60 m at RT. Following osmium fixation, tissue was rinsed in PBS then rinsed in water to remove all traces of phosphate from samples. Tissue was subsequently dehydrated in 50 % ethanol, a mixture of 70 % ethanol + 1 % uranyl acetate, 85 % ethanol and 2 changes of 100 % ethanol (15 m per step). Tissue was then placed in the transition solvent propylene oxide twice (15 m per step) and was left to infiltrate in a 1:1 mixture of propylene oxide-Spurr's Resin overnight at RT. Steps involving osmium tetraoxide and uranyl acetate were done in containers covered with foil to block light. Tissue was transferred to pure Spurr's Resin for infiltration for 24 h at RT. Tissue was then placed into Beem Capsules with fresh Spurr's Resin, allowed to sit for 30 m and then placed in a 70 C oven for 24 h for polymerization. After polymerization, ultrathin sections (70 nm) were obtained using a Leica Ultracut ultramicrotome and placed onto 200 mesh copper grids. 2 um of tissue was cut in between each collected section to prevent repeat analysis of any synapses. Sections on grids were then stained with uranyl acetate for 45 m, rinsed with water, stained with lead citrate for 90 s, rinsed with water and left to dry on clean filter paper.
Image analysis
To obtain the appropriate number of images for these analyses, we calculated the number of images needed using G*Power statistical software. 40 images of the Mossy Fiber - CA3 synapses were needed for each rat. We then made 17 measurements per image. Each measurement reflected a single experimental endpoint under investigation (ex. Docked vesicle number, PSD length, number of mitochondria in terminals, etc). We then used the 40 images to obtain the mean measurement for each of the experimental endpoints per rat. This led to the generation of 10 mean values for each experimental endpoint under investigation (ex. 5 Control means vs. 5 Pb2+ means for the Mossy Fiber - CA3 synapses per endpoint). We used a T-test to compare the mean values of the Control vs. Pb2+ exposed groups to determine if there were differences in the particular endpoint being investigated (GraphPad Prism). Data is reported as SEM, as we were examining differences between the means of each experimental group [40]. We also analyzed the same endpoints in the Perforant Pathway - DG synapses, a functionally distinct part of the hippocampus, using the same strategy. Differences were considered significant if p < 0.05.
Blood Lead Level (BLL) and weight
The Pb2+ exposure paradigm used in the present study does not produce any overt toxicity based on body weight gain. Body weight at postnatal day 50 (PN50) were: 294.4 ± 4.8 grams (n = 24) for control animals and 281.6 ± 6.9 grams for Pb2+ -exposed animals. Blood Pb2+ levels of littermates to animals used in this study at PN50 were: 0.8 ± 0.3 μg/dL (n = 11) for control animals and 21.1 ± 1.6 μg/dL (n = 15) for Pb2+-exposed animals.
Analysis of vesicle number
Vesicle, clustering, and mitochondrial measurements in Dentate Gyrus –Perforant Pathway (DG-PP) synapses and CA3-Mossy Fiber Pathway (CA3-MF) Synapses
CA3 – Mossy Fiber Terminals
Dentate Gyrus – Perforant Pathway Terminals
Control (Mean ± SEM)
Pb2+ (Mean ± SEM)
P value
Control (Mean ± SEM)
Pb2+ (Mean ± SEM)
P value
I. Raw Vesicle Counts
A) Rapidly Releasable/Docked Vesicle Pool
8.527 ± 0.8456
6.018 ± 0.001
7.013 ± 1.003
5.232 ± 0.9928
B) Recycling Vesicle Pool
35.19 ± 7.804
29.26 ± 7.381
31.48 ± 9.315
26.09 ± 5.835
C) Resting Vesicle Pool
43.64 ± 5.570
51.80 ± 7.427
51.66 ± 8.374
59.80 ± 11.44
D) Total Number of Vesicles
87.36 ± 10.61
87.17 ± 1.761
90.07 ± 9.363
91.12 ± 10.46
II. Vesicular Diameters
A) Rapidly Releasable/Docked Diameter
20.67 ± 1.644
21.20 ± 1.137
20.82 ± 1.521
23.27 ± 2.12
B) Recycling Vesicle Diameter
22.09 ± 0.8383
22.77 ± 0.6942
22.10 ± 0.8234
24.41 ± 2.072
C) Resting Vesicle Diameter
24.83 ± 1.746
24.70 ± 1.322
24.69 ± 2.481
26.28 ± 2.506
D) Average Diameter of all vesicles
23.77 ± 1.406
23.84 ± 0.8775
23.72 ± 1.565
25.64 ± 2.094
III. Length Measurements
A) PSD length
309.1 ± 13.48
259.7 ± 18.74
269.3 ± 9.680
266.6 ± 15.31
B) PAZ length
311.6 ± 11.15
281.2 ± 19.53
265.6 ± 14.45
308.2 ± 26.90
IV. Nearest Neighbor Distance (Clustering)
A) Rapidly Releasable/Docked + Recycling (0–200 nm)
40.19 ± 1.398
45.56 ± 1.498
41.75 ± 0.7873
48.57 ± 1.115
B) Resting (201–500 nm)
42.04 ± 1.834
48.47 ± 1.157
45.35 ± 0.7979
51.19 ± 0.7168
V. Mitochondrial Measurements
A) Terminals with mitochondria
15.40 ± 2.227
17.60 ± 1.806
27.00 ± 3.050
22.60 ± 3.280
B) Terminals with multiple mitochondria
2.00 ± 0.5477
1.250 ± 0.2500
4.200 ± 0.9695
2.600 ± 0.5099
C) Total number of mitochondria
48.60 ± 6.577
54.20 ± 7.690
69.60 ± 0.4964
62.80 ± 0.2518
D) Diameter of mitochondria
231.6 ± 16.18
224.4 ± 15.53
221.8 ± 0.8072
226.5 ± 8.529
E) Large mitochondria (300 nm or greater)
4.800 ± 1.594
6.800 ± 0.9695
8.00 ± 2.345
7.200 ± 1.530
We also measured postsynaptic density (PSD) and presynaptic active zone (PAZ) length in Mossy Fiber-CA3 and Perforant Path-Dentate Gyrus synapses. We found that PSD length in CA3 dendrites was significantly reduced in rats chronically exposed to Pb2+ (p = 0.0382; Table 1 , IIIA). There was no change in Dentate Gyrus dendrites (p = 0.4432; Table 1 , IIIA). PAZ length was similar in the dendridic fields of the control and Pb2+ exposed rats (p = 0.0899 and p = 0.1553, respectively; Table 1 , IIIB). The reduction in the RRP/docked vesicle pool may contribute to the reduced size of the PSD that was found in the striatum radiatum of CA3 dendrites.
Vesicle clustering (nearest neighbor distance)
A reduction in vesicle clustering was the most ubiquitous effect of chronic Pb2+ exposure. Vesicles were more dispersed in Pb2+ exposed animals relative to controls in both Mossy Fiber and Perforant Pathway terminals. For example, the nearest neighbor distance in vesicles that are within 200 nm of the PAZ in both the Mossy Fiber and the Perforant Path were significantly greater in Pb2+ exposed animals as compared to controls (p = 0.0062 and 0.0001, respectively; Table 1 , IVA). Similarly, nearest neighbor distance of vesicles in the resting pool (greater than 200 nm from the PAZ) are also less clustered in Mossy Fiber and Perforant Pathway axon terminals from Pb2+ exposed animals as compared to controls (p = 0.0020 and 0.0001, respectively; Table 1 , IVB).
Chronic Pb2+ exposure did not result in any remarkable changes in mitochondria number or size. In the Pb2+ exposure group, there are no differences in the total number of terminals with mitochondria (p = 0.2340 and p = 0.1793, respectively, Table 1 , VA). In Pb2+ exposed rats, there is a modest reduction in Perforant Pathway terminals that contained multiple mitochondria, but the difference did not reach statistical significance (p = 0.0970, respectively; Table 1 , VB). The mean number of total mitochondria in both Mossy Fiber and Perforant Pathway terminals were not significantly different from controls (p = 0.5972 and p = 0.1375, respectively; Table 1 , VC). The mean diameter of Mossy Fiber and Perforant Pathway terminal mitochondria was similar between control and Pb2+ exposed groups (p = 0.7566 and p = 0.3500, respectively, Table 1 , VD). The number of mitochondria with a cross sectional diameter greater than 300 nm were not significantly between Pb2+ exposed groups and control groups in Mossy Fiber terminals or in Perforant Pathway Terminals (p = 0.1624 and p = 0.3924, respectively; Table 1 , VE).
The purpose of our work was to determine if Pb2+ effected the distribution of presynaptic vesicular pools, distribution of vesicles, and mitochondrial size in the Mossy Fiber – CA3 and Perforant Pathway – Dentate Gyrus terminals of the hippocampus of rats. Our work shows that Pb2+ exposure results in a decreased number of RRP/docked vesicles and recycling pool vesicles in Mossy Fiber – CA3 terminals. Pb2+ exposure did not alter vesicle number in the different pools of the Perforant Pathway – Dentate Gyrus terminals. Pb2+ treatment did not appear to affect the size of the vesicles or affect the biogenesis of the vesicles, as there were no differences in the total number of vesicles present in the terminals. Nearest neighbor distance of vesicles in both the Mossy Fiber – CA3 terminals and in Perforant Pathway – Dentate Gyrus terminals of Pb2+ exposed animals were significantly greater than controls, indicating that the vesicles were more dispersed in the Pb2+ exposed animals.
With respect to the RRP/docked vesicles, Pb2+ exposure consistently induced a significant reduction in the number of vesicles that were contacting the PAZ in Mossy Fiber terminals. In primary hippocampal culture, we found that Pb2+ exposure increased the number of nascent presynaptic docking sites, but many of these docking sites were lacking NSF attachment protein receptor complex, which is involved in vesicular exocytosis [5, 7]. It seems plausible that Pb2+ exposure may have a similar effect in vivo, which may contribute to the reduced number of RRP/docked vesicles that were found in the Pb2+-exposed animals. In our previous work, we found that Pb2+ exposure reduced the expression of synaptophysin and synaptobrevin, two vesicular proteins that are imperative to vesicular docking and release [5], which may contribute to the Pb2+ -induced changes that we have found in our current study.
We found fewer vesicles in the recycling pool of Pb2+ exposed animals, but no decrease in the total number of vesicles in each terminal. Pb2+ exposure also altered the distribution of the vesicles, as they were significantly further apart from one another in all hippocampal regions that were examined. Our data suggests that Pb2+ does not affect the biogenesis of the vesicles. The spatial arrangement of vesicles relative to the PAZ was highly affected by Pb2+ exposure, which likely reflects Pb2+ induced changes to the expression and activation of vesicular trafficking proteins and scaffolding proteins, such as synapsin. We have previously demonstrated that Pb2+ reduces phosphorylation of synapsin I in primary hippocampal culture. Synapsin I is a vesicular protein that in its unphosphorylated state keeps reserve pool vesicles bound to actin filaments. Once phosphorylated, vesicles are released from actin filaments and allowed to move into the recycling and RRP/docked vesicle pools [23–25]. We have shown that synapsin I phosphorylation at sites 4 (serine 62) and 5 (serine 67) were significantly decreased by Pb2+ exposure with no effect on total synapsin I protein levels [18]. It is possible that Pb2+ reduces synapsin I phosphorylation in vivo as well, which may contribute to the decreased number of vesicles in the recycling and RRP/docked vesicle pools that we observed in the present study.
Mitochondria, which provide energy for vesicular biogenesis, were largely unaffected by Pb2+ exposure in the Mossy Fiber-CA3 and Perforant Path- Dentate Gyrus synapses. This suggests that Pb2+ exposure may not effect energy production in these terminal regions, which is supported by the idea that there does not appear to be any reduction in vesicular biogenesis, evidenced by no observable changes in presynaptic vesicle number or diameter. Interestingly, we did find that Pb2+ exposure did reduce the number of Shaffer-Collateral terminals with multiple mitochondria [20], demonstrating varying aberrant pathological effects in the different hippocampal regions. This study does not rule out the possibility of mitochondrial dysfunction, but from the measures that we investigated, there appear to be no gross ultrastructural differences. Mitochondrial cristae morphology may reveal differences in energy production and may be examined in future investigations.
The PSD length in CA3 dendrites was significantly reduced in Pb2+ exposed animals. Pb2+ exposure may impair the maturation of the PSD. PSD-95 expression enhances pre-synaptic maturation [41] thus a Pb2+ exposure-induced reduction of PSD size may contribute to the presynaptic changes that we observed. In previous work, we found that Pb2+ exposure results in a significant reduction in Timm's-positive staining in Mossy Fibers terminal fields [42]. Perhaps a reduction in the PSD in CA3 results in fewer axonal terminals that innervate this region. The length of the PSD in the dendrites of the Dentate Gyrus were not affected by Pb2+ exposure.
Chronic, early life Pb2+ exposure alters the distribution of vesicles in both Mossy Fiber and Perforant Pathway terminals, which is in concurrence with our previous in vitro data. Such a redistribution of vesicles impairs fast and effective neurotransmission, which likely contributes to learning and memory impairments found in models of Pb2+ intoxication. The mechanisms underlying this redistribution of vesicles likely involve reduced expression in presynaptic proteins, such synaptophysin and synaptobrevin as well as reduced phosphorylation of synapsin I. The mechanisms underlying changes in the Mossy Fiber – CA3 and Perforant Pathway – Dentate Gyrus terminals likely involve different pathways, which reflect the physiological heterogeneity of these various hippocampal regions. Uncovering behavioral and pharmacological interventions that could help to rescue the distribution of vesicles will likely promote fast and efficient neurotransmission.
Presynaptic active zone
Postsynaptic density
Readily releasable pool
We would like to thank Mrs. Katerina Mancevska for her assistance in the care of animals that were used in this project and Dr. E. Charles Jenkins, Jr. for his proofreading of our manuscript. We would also like to thank the New York Institute for Basic Research for generous usage of their Electron Microscope and the City University of New York - College of Staten Island Advanced Imaging Facility.
This work was funded by NIEHS grants ES006189 and ES020465 to TRG.
Availability of supporting data and material
The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.
Authors' contributions
SRG performed perfusions, electron microscopy sample preparation, imaging and analysis, participated in experimental design drafted the manuscript. KHS and JMD bred and maintained experimental animals. TRG conceived the study, and participated in its design and drafted the manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Animals were treated in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85–23, revised 1996). The protocol was approved by Columbia University Institutional Animal Care and Use Committees (AC-AAAF4810).
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text: France Financial Markets Are Closed Updated May 27, 1996 2:25 p.m. ET All financial markets, banks and government offices in France were closed for a... To Read the Full Story Subscribe Sign In Most Popular Videos March for Science: The Signs, Sights and Sounds Two Countries, Same Flag. What Gives? Amateur Sailors Can Now Fly on Water Like America's Cup Skippers What Did Georgia Election Results Tell Us? France's Presidential Election: What You Need to Know Most Popular Articles Brick-and-Mortar Stores Are Shuttering at a Record Pace What Would a Le Pen Victory in France Mean for Markets? Russian Military Planes Crowd the U.S. for a Fourth Day Opinion: Those 'Snowflakes' Have Chilling Effects Even Beyond the Campus Opinion: The Challenge of Our Disruptive Era

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Getting you more information on this room
Another excellent night here. This is always my go to hotel whenever I have travel needs to Olympia area. Fast and efficient check in & out. Friendly, smiling staff. Great, healthy choices for food with the included breakfast. Only concern was the really weak hot tub jets in the pool area which is open 24 hours.
Hello YoungMD_24k, thanks for the compliments! I'm glad you enjoy our breakfast and our staff. We're working with a local company to see if our hot tub jet pressure can be improved. Hopefully it won't involve ripping out the hot tub altogether! Hope to see you again soon.
We enjoyed our stay as usual. The breakfast was great and room great. We appreciated that the hotel found a package with inexpensive jewelry left in the room and left a message that it was found. It was returned to us two days later. We would like to give our upmost thanks to the person who found it in room...
We spent 2 nights here as tourists and were happy we chose he Ramada. It is conveniently located just off the highway and overall a great hotel.
We enjoyed the large room. We were on the second floor and the hotel was very quiet, we never heard anybody else. The room was very clean and the heater worked well.
Are the rooms non-smoking?
I want to walk from the hotel to the Supreme Court bldg. Would it take 20 min.? 30 min.? Please advise.
See all questions
"I was on the 1st floor"
"Unless you like hearing the elevator try to stay in a room away from it"
"we like upper floors, away from elevators, as they are usually quieter"
"Even numbered rooms would be quieter as they are in the rear of the building although the building is set back a bit from the road"
"Second floor, back side of the property, less street and city noise."


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Home > England > Premier League > Arsenal > Squad > Profile: Mohamed Elneny
Mohamed Elneny Arsenal
Profile of the Egyptian footballer Mohamed Elneny, who currently plays as a midfielder at Arsenal. The 24-year old player Elneny joined Arsenal from and wears the number 35 shirt.
Mohamed Elneny Career
Mohamed Elneny Videos
Your Comments on Mohamed Elneny
Mohamed Elneny Photos
Beta! Some pictures may be inaccurate...
Mohamed Elneny : Arsenal News
"A few weeks ago Arsene Wenger quipped, in reply to a question about Alexis Sanchez and speculation linking him with a move to Chelsea, that there was "only one team in London."
ESPN 16 days ago
"Wenger reveals the man who could scupper Chelsea's transfer move for Alexis Injuries suffered by the pair on international duty handed Granit Xhaka and Mohamed Elneny an opportunity their time together at FC Basel."
Metro 16 days ago
"Arsenal's legendary coach Arsene Wenger complimented Egyptian midfielder Mohamed Elneny after he took part in his team's win against West Ham United in the English Premier League."
kingfut.com 17 days ago
"Although he was only 89% successful compared to Mohamed Elneny's 97%, his progressive style of play As you can see from Xhaka's heatmap, he was massive for Arsenal's midfield against the Hammers, taking a grand total of 133 touches."
arsenal.com 17 days ago
"That was the mantra at the Emirates after Arsenal won their first Premier League match in who scored one and created another, and Mohamed Elneny. Others were impressed, as ever, by Alexis Sanchez and, more surprisingly, Granit Xhaka."
The Week 17 days ago
"during the Premier League match between Arsenal and West Ham United at Emirates Stadium on April 5, 2017 in London, England. Arsene Wenger believes Mohamed Elneny can play a vital role in Arsenal's midfield during the remainder of the season."
Metro 17 days ago
"Arsenal edged back up into fifth place and after the nervy Héctor Bellerín had a shot blocked by José Fonte before half-time and Collins threw himself at Mohamed Elneny's rebound while, after the interval, Collins jumped into a wonderful saving"
The Guardian 17 days ago
"Santi Cazorla's absence continues to cast a long shadow over Arsenal but Mohamed Elneny showed signs here that he could help stabilise the team through a difficult period."
London Evening Standard 17 days ago
"Mohamed Elneny 7, Theo Walcott 7, Mesut Ozil 8, Danny Welbeck 6, Alexis Sanchez 7. "I feel for a few weeks now in training he's really focused again, and that comes out in the game"."
fxcnews.com 17 days ago
"Arsene Wenger has praised Mohamed Elneny's 'generous' style of play following Arsenal's 3-0 win over West Ham United on Wednesday."
squawka.com 17 days ago
Mohamed Elneny Career Honours
Source: wikipedia.org
Mohamed Elneny Wiki, Stats & Links
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Chelsea's Antonio Conte the tactical werewolf bares teeth and bites Spurs
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YP - The Real Yellow PagesSM - helps you find the right local businesses to meet your specific needs. Search results are sorted by a combination of factors to give you a set of choices in response to your search criteria. These factors are similar to those you might use to determine which business to select from a local Yellow Pages directory, including proximity to where you are searching, expertise in the specific services or products you need, and comprehensive business information to help evaluate a business's suitability for you. "Preferred" listings, or those with featured website buttons, indicate YP advertisers who directly provide information about their businesses to help consumers make more informed buying decisions. YP advertisers receive higher placement in the default ordering of search results and may appear in sponsored listings on the top, side, or bottom of the search results page.
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Smoking Cannon Brewery dwells in the foothills
"The bigger the cannon, the bigger the beer."
Ian Anderson 5 p.m., April 25
This photo was taken from the second floor of the County Administration building on Pacific Highway on May 2nd.
Photo by donthebeachcomber
Posted May 19, 2010
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What Our Clients Think
Our focus is working by referral. This creates a natural venue for relational versus a transactional-based business.
Pat Rooney
Lee and Paul were terrific! Kept us informed about potential buyers and current market trends over the course of the listing. Outstanding marketing skills to bring potential buyers view the property. Excellent realtors; excellent results.
Brian Meaghan Dunn
Lee and Paul are a fantastic team! They helped us through a very difficult personal and professional time in our lives. We are grateful for their professionalism and knowledge and happily recommend them in any circumstances.
Craig & Jillian
We met Paul & Lee at an open house when we were just starting to look for a home. When we started seriously looking for a house we knew that we had to work with them. As first time home buyers, we had no idea where to begin. Paul & Lee were able to guide us through the process and support us along the way. They were patient when we were overwhelmed and helped us purchase a wonderful home. We would highly recommend working with The Kouri Team if you are looking for a new home. They are professional, caring, and supportive throughout the entire process. - Craig & Jillian
Joe & Diana
Dear Paul and Lee, We want to thank you for making the process of selling our house a great experience. Your advice and your attention to detail cannot be matched. You made us feel special and you were there to guide us through the process. We thank you also for the gifts you gave. That was also special. Definitely we will stay in touch. Our most heart-felt appreciation. -Joe & Diana
Dzmitry & Tatsiana
My wife and I met Paul at an open house. His caring attitude and questions to find out my families needs led us to a wonderful advisory relationship. Paul & Lee have a very systematic approach to working with clients. Not only finding and discovering our needs but made sure we were positioned properly each and every step of the process. Their obvious focus on our needs during the process was clear to us. We had many questions about towns, construction, systems and generally how things work all of which they clearly explained to us. Paul and Lee were very knowledgeable in their areas of expertise and it is clear to see why they are respected in the industry. We are glad to have met them and will gladly refer our friends and family members.


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Eighty-two percent of recently bad teams have some tough news to share with Jazz fans: getting off the lottery hamster wheel is tough work.
It's easy for teams to get stuck on the treadmill of multiple losing seasons. The experience other teams have had trying to get out of the NBA's basement can certainly inform our expectations for a Jazz team that keeps adding young talent but ultimately wants to begin its ascent back to relevance.
The last 15 NBA seasons[ref]'98-99 through '12-13, since '13-14 doesn't have a "next season" to analyze yet.[/ref] have included exactly 100 teams to win 30 or fewer games[ref]Lockout-adjusted where applicable.[/ref], which makes for tidy math. Here's what we can learn from the previous 100 teams to traverse these waters.
The main lesson: winning doesn't happen overnight. Here are some stark data points from those 100 teams and the seasons they had after dipping down to ≤30 levels (or .366 in a lockout year).
The next logical question is: did those 18 successful teams follow a template that is remotely applicable to the Jazz? As we analyze the Jazz's chances in 2014-15, do the moves that rapidly rebuilt those teams seem congruous to what the Jazz are doing, or will Utah's road be a longer one?
To begin to answer those questions, let's look at the teams who went straight from 30-minus to contender. For the sake of argument, we'll call "contender" the 50-win level. There were five teams in the last 15 years to do that just one year removed from the basement.
2007-08 Celtics: From 24 wins to 66. This team also won the championship.
From basement to banner. This story, though, has the least to do with the Jazz's rebuild. The Celtics did the opposite of the Jazz, flipping all of their future assets to compile a just-add-water contender. They didn't build through the draft, actually trading their pick and some nice young players[ref]Eventual Jazz center Al Jefferson among them.[/ref] to land Kevin Garnett and Ray Allen. They surrounded those two and Paul Pierce with filler free agents in support the win-now model, not with youth.
2004-05 Suns: From 29 wins to 62. Went to the Western Conference Finals.
Like the Celtics, the Suns did the opposite of what the Jazz are doing… mostly. They traded their pick and otherwise dumped salary so they could pursue free agent Steve Nash, who would quickly become MVP material. Those cap-clearing moves[ref]Jahidi White, Tom Gugliotta.[/ref] cost them future pieces as well, including the pick that would later become Gordon Hayward. Also, Amar'e Stoudemire blew up that year. Probably largely due to the Nash signing, Stoudemire went from being a 4.4 WS player (role player levels) to an elite breakout year. He his a 26.2 PER and 14.6 WS, both elite levels[ref]That WS would be third this past year, behind only Kevin Durant and LeBron James.[/ref].
2001-02 Nets: 26 wins to 52. Went to the NBA Finals.
This team's boldest move en route to doubling the win total was trading its best player to land Jason Kidd. Kidd was a 9-10 WS player at that point, which is All-star level, and better than what they were getting from Stephon Marbury. They did add a draft pick, but it wasn't exactly a tank-your-way-to-a-star approach. They actually traded backwards to land Richard Jefferson along with role players Brandon Armstrong and Jason Collins. Then they added more veteran role players.
2003-04 Grizzlies: 28 wins to 50. Went to the playoffs but lost in the first round.
Here's another team that quickly retooled without the help of the draft. They actually traded both picks away that summer for bench help[ref]Troy Bell and Dahntay Jones; might have been better off keeping Kendrick Perkins and Marcus Banks[/ref]. Other than that, they really just added decent players via trades (Bo Outlaw, Jake Tsakalidis) and signings (James Posey). They also got Mike Miller back from injury, which helped modestly (3.9 WS). Even Pau Gasol didn't have a breakout year, scoring, rebounding and playing slightly less than the year before. Honestly, Memphis' 22-win turnaround is a bit of a head scratcher on paper. They made minor tweaks and were a well-coached[ref]So well, in fact, that COY voters looked past a masterpiece by Jazz coach Jerry Sloan and awarded the trophy to Hubie Brown.[/ref], but really their biggest addition was Posey.
2009-10 Thunder: 23 wins to 50. Also lost in the first round.
The Thunder's improvement had something to do with the draft, but this was actually the end of a sustained, youth-focused rebuild, so it would be tough to say that drafting James Harden accounted for 27 wins. Russell Westbrook and Jeff Green also stayed at roughly the same level, and they added only supporting pieces. The story of this turn-around is all about a transcendental player cracking the code. Kevin Durant exploded from the fringe All-star level (7.9 WS in 2008-09) to an elite superstar (16.1 WS and ridiculous scoring efficiency).
These five teams' roadmaps don't offer much to the Jazz. Let's assume, then, that 50 is out of the question. Let's see, in shorter form, if the other 13 teams who went from 30-minus to 42-49 wins can proffer some models. In this group, we do see some teams who got instantly better at least in part because of an instant contribution from a high draft pick and/or a well-timed coaching change.
Four of these teams got back to winning records largely because of a marquee trade.
For two, the main ingredient was getting good players back healthy (Curry, Wade).
For one, it chiefly had to do with an impact free agent (and, importantly, a new system).
Those seven probably don't have much to offer the Jazz in the way of applicable rebuilding advice, because the Jazz probably aren't making marquee trades or adding impact free agents[ref]So few are left.[/ref], and we don't have a star-level player to bring off the injured list. The other six, though, might represent templates Utah could follow: they added more young talent to developing rosters, and signed the right veterans.
The teams of Wade, Melo, Yao, Bargs and Gordon/Deng got enough immediate juice from those guys, and added the right supporting pieces around them. There's no telling yet if Exum can have that type of first-year impact, though.
I also like the approach of this past year's Wizards, something of a hybrid. Their best player made another step forward, they drafted a player who was solid-but-not-yet-great as a rookie, Beal continued to progress modestly, and the addition of Gortat gave them an identity inside along with Nene. If Gordon Hayward is ready for his next step, Exum produces something like 4(ish) WS[ref]Which isn't asking too much; that would only make him one of the best 200 rookies or so of the modern era. Not like we're asking him to be LeBron.[/ref], Favors provides the interior scoring and D, and the other youngs continue their forward progress at even a modest pace, the Jazz could start the climb just like the Wizards did.
But if this exercise shows us anything, it's that even if the Jazz take steps forward, there's a strong historical precedent suggesting they might not make it back above .500 next year.
Some games should be recapped. This wasn't one of them. No, we're not going to simply recap everything that happened...Read More
Six minutes of futility cost the Jazz a chance to score a Game 4 win against the Clippers on Friday night. After controlling...Read More
On the one hand, the Utah Jazz are in fine shape overall, returning home for Game 3 of their first-round NBA Playoff series with...Read More
The saying goes, "Gobert or go home." The meaning of those words often eludes even Jazz Nation faithful, but game...Read More
Another Key Factor for any team would be injuries. You mention teams got a healthy player back . I don't remember the last player that the Jazz lost significant time to an injury. I don't count Burke from last year.
I know the jazz are a different team than what they typically are… But, I really like the fact that we are only on this list once.


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Nationally, the collective silence from GOP elected reps at all levels supports the theory that the R's and D's are becoming one party.
The lack of resistance to tyranny displayed recently by Obama and other Democrats by our elected leaders speaks volumes of their allegiance to a blended system of government where "reaching across the aisle and sitting there" is the expected norm and preferred.
The end result is a maturation of a system that rewards turning a red blue situation into a purple one leaving a blended party to represent we the people.
This scenario puts our republic at a great disadvantage and leaves us with no real representative type of government that separates different political ideaologies.
In Chattanooga with the Hamilton County Republican Party choosing to back a true Democrat who has chosen to run as a Republican we are seeing this type of politics personified and accepted.
Candidate for the 27th District state representative seat Patsy Hazlewood is a perfect example of this type of blending that is destroying the fiber of our country.
Mrs Hazlewood has chosen to enter this race as a spoiler propped up by Bill Haslam, Claude Ramsey and the Chamber of Commerce against a true conservative Republican.
Tommy Crangle, the true GOP candidate is happy to brag of his distinction as a one-party candidate representing the values of his constituency. With Tommy Crangle you know you are getting a true Republican GOP candidate, his opponent, the opposite.
Candidate Patsy Hazlewood entering this race as a true Democrat in a Republican race speaks volumes of the direction the establishment GOP has chosen to pursue. In conservative land we call these candidates RINOs a label many choose to avoid in the strongly red state, she appears to run to it!
Bill Haslam has propped candidate Patsy Hazelwood up as a state leader by assigning her as a regional director of the Tennessee Department of Economic and Community Development for three years. She was also organizer and founding director of Capital Mark Banking and Trust and also served for many years with AT&T.
Claude Ramsey has endorsed her for the Tennessee state representative, 27th District. Hazlewood had this to say about Ramsey, in an article found on the Hamilton County GOP website recently. "I am grateful and honored to receive Claude Ramsey's endorsement. He is one of our state's greatest Republican leaders, and I admire his commitment to job creation and education in our region— a commitment I will continue on behalf of District 27."
Ramsey quipped back with his assessment of her on the HCGOP site, " Citizens deserve a proven leader and a representative they can trust to faithfully serve their interests in Nashville. Patsy Hazlewood will do just that. Patsy is competent, qualified, and ready to serve."
Only one problem with this scenario. As we draw the line inside a republic that begs for party indifference and separation necessary to balance the powers of a potentially tyrannical government one thing stands out as a truth. She is not a Republican running for this state GOP seat, She is a Democrat.
Mrs Hazlewood has been called by the GOP as "politically flexible" with "no political obligations." She has recently described herself as a "Conservative and a Republican."
Her voting record paints a much different picture.
In four previous primaries back to 1992, she has voted on a Democratic ticket, three of which were Presidential primaries of which she cast votes for Obama, Biden, Clinton, Edwards, Kerry and Brown. To date, her voting record in local and state races is unknown but if party allegiance directs her as it did in four primaries, I can assume the Democratic ticket was punched.
It has even been reported that she has written a letter to the Hamilton County GOP requesting the status of her political affiliation, seeking confirmation of her GOP status and her true allegiance to the GOP.
This does not make her apolitical with no political political obligations, this makes her a RINO with the assumed long-term intent to swing the state blue under the guises of a Republican.
These actions and acceptance by high-level GOP elected reps such as Governor Bill Haslam and Claude Ramsey supporting her as a GOP candidate is disturbing. "Staunch Republicans" supporting and endorsing a "registered Democrat" for a GOP seat leaves many questions as to their direction of our state and their leadership decisions made that affect its citizenry.
My assessment is this. What is really a Republican or Democrat in the state of Tennessee and what values are represented when we endorse our leaders of tomorrow that are aligned with the opposite party?
Where does the line blur stop? Why do we continue to ignore past party affiliations and associations in the name of politics?
Sure this is America and we can vote for who and when we want. Mrs Hazlewood can vote as she pleases, but when the lines of demarcation no longer exist and GOP party seats are won by Dems we yield to a tyrannical mindset where accountability is extremely difficult to establish.
The Rs and Ds are rendering a political fruit that will die on the vine. This blending is dangerous and will only create deeper division as true independents and conservatives will only levitate towards a truer color that represents our values and interests.
If you want a Democrat in a Republican State House seat then by all means vote for Patsy Hazlewood in the 27th District.
April 25, 2017
April 24, 2017
The proposal to turn Hixson Pike in Riverview into a more pedestrian friendly street is more than absurd. Let's be honest. This is the last semi-unobstructed route into town from ... (click for more)
As of April 11th, according to Gallup polling, Congressional approval stood at twenty percent. Let's think about that. Eighty percent of Americans disapproved of the way the United States ... (click for more)
In Chattanooga last Saturday approximately 1,000 people joined a faith-based group calling itself "March for Science - Chattanooga" who demanded that you and me pay for their special beliefs ... (click for more)
As of April 11th, according to Gallup polling, Congressional approval stood at twenty percent. Let's think about that. Eighty percent of Americans disapproved of the way the United States Congress operates! Then, at the next election, we send the same people back expecting a different outcome. Why? We seem to vote for folks who say they want to work ... (click for more)
In Chattanooga last Saturday approximately 1,000 people joined a faith-based group calling itself "March for Science - Chattanooga" who demanded that you and me pay for their special beliefs in fake science. Their sincere, deeply held beliefs are found on their Facebook page. And, they are not alone. Thousands of other people of similar faith marched in various ... (click for more)
Erlanger Health System reported substantial growth in revenue and effective cost management for the third quarter. Net income from operations of $8.5 million exceeded prior year by $7 million and also exceeded budget by $1.3 million. The health system had an 8.8 percent increase in total net revenue. Officials said the quarter generated strong EBITDA (e arnings ... (click for more)
A former Hamilton County corrections officer pleaded no contest on Monday to charges that he got time off from work and donations from co-workers after he faked having cancer. Dale Daniel was granted diversion through an agreement with the district attorney's office. The charges will go off his record if he does not get into any further trouble for a year. Daniel will have ... (click for more)
Strong defense meant more for Ooltewah than any other aspect of Monday's key District 5-3A prep baseball game against Walker Valley at A.C. "Bud" Ball Field. ** Owls center fielder Jake Sullivan made an ESPN-worthy diving catch in left-center that probably saved two runs in the first inning. ** Pitcher Daniel Willie picked off a Mustangs runner at first base in the ... (click for more)
(click for more)


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Sunday, 3 February 2008
Brewed less than two miles from where I'm sitting, it's arguably the most recognisable beer brand in the world, in part due to the incredibly imaginative ad campaigns mounted by the owners, Diageo.
This is the latest - bizarre but cool:
Guinness, ELO and Donald Sutherland - doesn't get better than that...
2 comments:
- Marina Martin said...
I really love these Guinness ads - I don't watch television, let alone ad spots, but I always watch these.
I've written a blog post on this video and it's scheduled to post in a few days. (I have a blog just about Guinness -- I'd love it if you'd check it out!)
I'm very jealous you get to live so close to where it's brewed -- have you noticed a significant difference in taste between where you are and, say, another European country? I know that the Guinness I had in London was a lot better than the (still great) Guinness I've had elsewhere.
- Monday, 18 February, 2008
- Captain Incredible said...
I've always found Guinness's ad campaigns to be imaginative and entertaining without being as intrusive as other commercials. They don't shout at you, just say what they have to say and move on.
As for the Guinness at home and away - my experiences have been largely positive, especially in Paris and, curiously, San Diego, where I had several decent pints in an Irish-themed bar called The Field, in the Gaslamp Quarter. I don't know if it's still there - hang on, I'll check......
Yep, it is (www.thefield.com)...
But I have to be honest and say the best Guinness I've had has been here in Dublin. It won't be the same if Diageo decide to move the operation away from St James's Gate and sell the land for redevelopment, as has been rumoured.
I think I'd switch to Murphy's if that happened.
- Wednesday, 20 February, 2008


text:
There are certain men and women who, from the minute they step in front of a camera, that's exactly where they belong. Connery's one.
Posttraumatic stress is something that's always existed. I think that the earliest recording was during the Trojan War, but it's only recently that we're beginning to be aware of it.
I don't think there's any question that America is safer as a result of the bin Laden operation.
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Up Now
Christchurch 89-year-old shares the secret of his longevity (2:57)
Added: 7:28PM Wednesday May 18, 2016
Source: Seven Sharp
Seven Sharp's Mike Thorpe met Gordon Proctor, a man hooked on new beginnings.
Up Next
How do you want your news?
Copyright © 2017, Television New Zealand Limited. Breaking and Daily News, Sport & Weather | TV ONE, TV2 | Ondemand


text:
From Bridget Liszewski of The TV Junkies:
Link: Saving Hope preview: Dealing with a 'Midlife Crisis'
"Alex is really struggling with the choice she made last week. And the people around her, Shahir, Maggie, Dana, and especially Charlie, are all struggling to understand what's going on with her too. Problem is, she can't tell them because she doesn't know herself. She just feels it in her gut that something's wrong – and that something's ALWAYS going to be wrong – if she stays with Charlie." Continue reading.
Greg David
Prior to becoming a television critic and owner of TV, Eh?, Greg David was a critic for TV Guide Canada, the country's most trusted source for TV news. He has interviewed television actors, actresses and behind-the-scenes folks from hundreds of television series from Canada, the U.S. and internationally. He is a podcaster, public speaker, weekly radio guest and educator, and past member of the Television Critics Association.
Latest posts by Greg David (see all)
- Link: 90210's Jason Priestley returns to TV to star in drama Private Eyes - April 30, 2017
- Link: And the 2017 AMPIA Rosies film and television winners are … - April 30, 2017
- Odd Squad and Beat Bugs win Creative Arts Daytime Emmys - April 29, 2017


text:
Today's Devotional
Representing JesusIn what practical ways can you effectively represent Christ?
Top Music Videos
Let's Make ItFacebook official!
superchick-stand in the rain
Anthem Lights Performs Worship Medley Of 'Because He Lives' And 'Arise My Love' - @anthem-lights
00:00:00 7484 views
Embed guitargurl52 4194 views 2011-07-12T14:09:48 i luv this band and this is like one of my fave songs


text:
Karmen Baumgartner
Weitere Ideen von Karmen
What I like
30+ Homemade Body Scrubs
What I like
Umbria Residence by Paola Navone #decorateyourspace
Wohnzimmer mit Galerie
Our industrial furniture and industrial lighting and home decor is crafted with city chic style that celebrates utility and function as well as beautiful design. Shop now at kathykuohome.com.
forthefreshkids : Foto
Get Inspired, visit: www.myhouseidea.com
Week_29.2014 - Titpixel


text:
Beard ornaments
Explore related topics
Beard Ornaments Ugly Christmas Party Christmas Ornament Beard Baubles Christmas Decoration Beard Art Beardaments Beard Bling Pack of 12
These Guys Created Beard Ornaments To Decorate Your Face For The Holidays... Oh Christmas Beard Oh Christmas Beard!
Beardaments - St Patrick's Day Beard Ornaments - 12 Pack with Mini-Clips!
Hot future Santas are decking their whiskers with Beard Baubles , Christmas ornaments designed specifically for facial hair.
"It started off as a relatively small project — a bit of fun for a good cause — but it's just (pardon the pun) grown and grown over the past few days," Ollie Dearn, PR Manager of Grey London, told BuzzFeed Life. | These Guys Created Beard Ornaments To Decorate Your Face For The Holidays
Funny Beard Ornament, Christmas Tree Jokes for Him, Beards are the New Six Pack by kitchenniche on Etsy https://www.etsy.com/listing/479762764/funny-beard-ornament-christmas-tree
Get your beard excited for the holidays! The official Beardaments Beard Ornaments (www.beardaments.com) include 12-pack of original Beardaments beard
Buying gifts for men is difficult – especially for the man who has everything. Our unique list of hand picked men's gifts has everything you need to find a ...
These Guys Created Beard Ornaments To Decorate Your Face For The Holidays buzzfeed.com
Hand Carved Santa w long beard ornament 6"


text:
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I was charged with a DUI last year. I was referred to James Greene by a friend. I wasn't sure about attorneys because I never once had to have one. I called James and he answered on the third ring. This was one of the best decisions I made throughout my case. Even though I decided to plead guilty to my charge, James was there every step of the way. He aided me through the entire process. Even after the case James checked on me to make sure that I was doing okay. He even referred me to one of the best probation programs in the city. Also any time I had a run in with police about anything minor James shows up in court to help me out free of charge. To me, James is very talented in his field, and also a good mentor. I would refer James to anyone who needs help in criminal court. Thank you so much James, you are my right hand man!
Jason Matthews, Criminal defense Attorney
Relationship: Fellow lawyer in community
James is a great lawyer! He will work hard to ensure you receive effective legal representation.
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text:
PowerColor Radeon X1950PRO with Arctic Cooling
The Card
The Radeon X1950PRO from PowerColor is quite basic minus the large Accelero X2 from Arctic Cooler placed on it but with positive reviews all over the place, it's clear that it's a serious piece of cooling equipment and it's excellent that PowerColor have chosen to adopt on their latest graphics card.
The cooler does take up majority of the front of the card which doesn't let see a whole lot outside of it.
The back of the card is very standard with the product details along with a number of screws to hold quite the large cooler in place. Speaking of the cooler, it is very quiet using its heat pipe design but do take note that it will take up a total of two slots.
Moving back to the front and the side we can see the PCI Express connector, for some reason ATI have chosen to drop it down to the middle of the card, it doesn't really seem to have any benefit though it's not exactly an issue either.
We can again see just how large the cooler is here height wise along with the new Crossfire connection method used on all the new mid-range ATI cards which should also be seen in the R600 in the next few months. This new connection (much like nVidia's SLI) makes setting up dual graphics Crossfire much easier and it's how ATI should have done things from the very beginning of the Crossfire birth.
The last bit of the card is of course the I/O panel and we have the standard dual DVI layout along with TV out port. The DVI ports support HDCP, so you'll able to playback next-generation HD content from HD-DVD or Blu-ray discs using software like CyberLink PowerDVD HD.
Apart from the cooler the card is very standard with nothing else that is changed from most other models. Keep in mind though that the core is slightly overclocked compared to other standard Radeon X1950 cards by 19MHz on the core.
PRICING: You can find products similar to this one for sale below.
United States: Find other tech and computer products like this over at Amazon's website.
United Kingdom: Find other tech and computer products like this over at Amazon UK's website.
Canada: Find other tech and computer products like this over at Amazon Canada's website.
- Page 1 [Introduction]
- Page 2 [The Package]
- Page 3 [The Card]
- Page 4 [Benchmarks - Test System Setup and 3DMark05]
- Page 5 [Benchmarks - 3DMark06]
- Page 6 [Benchmarks - Half Life 2 (Lost Coast)]
- Page 7 [Benchmarks - PREY]
- Page 8 [Benchmarks - F.E.A.R.]
- Page 9 [Benchmarks - Company of Heroes]
- Page 10 [Benchmarks - High Quality AA and AF]
- Page 11 [Final Thoughts]
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text:
English Brothers Company
20 - 49
Not Available
Construction/Agriculture->Construction Services
SIC Code:
1542 - Nonresidential Construction, Nec
Full company description is available with the free trial.
Only for logged in user.
Additional Info:
Lead411 offers quality contact information on a variety of companies including that of English Brothers Company's CEO . The company profile also contains facebook info, linkedin accounts, phone numbers, cfo contacts, and English Brothers Company email addresses with the domain format of @englishbrothers.com. English Brothers Company, is in the Construction services field. If you sign up for our free trial you will see our email@example.com addresses.
Company Background:
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3 Dimension Construction Management, Inc.
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text:
One of the hotter articles on the Washington Post website on Sunday raised serious questions about a Post legend: Bob Woodward. A new book from journalist Barbara Feinman Todd chronicles her career in aiding three Post "icons" as well as Hillary Rodham Clinton. She says Woodward ruined her book deal with Hillary by breaking a promise to her.
Bob Woodward
It's now been 256 days since Hillary Clinton has done a formal press conference and the Washington Post's Bob Woodward is wondering about the Democrat's potential "transparency" as President. Woodward appeared on CBS This Morning, Tuesday, to offer some critiques of Clinton. But the famous Watergate journalist was sometimes mild in his assessments. He wondered, "I think people say if she became president, are we going to have some kind of transparency?"
The Clinton Foundation is back in the spotlight for their precarious ties to Hillary Clinton's State Department. The conservative watchdog group, Judicial Watch, released e-mails suggesting major Clinton foundation donors bought access to the department. While the Clinton campaign insisted "the e-mails don't relate to the foundation's work," email scandals appear to be a perpetual monkey on the back of the Clinton campaign. Thursday on Morning Joe, the Washington Post's Bob Woodward said what most Americans are thinking: the revelation of Clinton's e-mails is "a ticking time bomb."
Mount Rushmore has become an ongoing reference to historical greatness. GQ editor Jim Nelson recently proclaimed Barack Obama was "Mount Rushmore great." In 1991, as the Soviet Union collapsed, NBC reporter Jim Maceda gushed its last dictator Mikhail Gorbachev deserved a place on Mount Rushmore.
Paul Bedard at the Washington Examiner reports that Washington Post bigwig Bob Woodward envisions Bill, Hillary, and even Chelsea Clinton on Mount Rushmore, at least in their minds.
Appearing on Wednesday's CBS This Morning, Washington Post associate editor Bob Woodward declared that the defeat of Ted Cruz in the Republican primary revealed that "Conservatism in America, in the Republican Party, is in a crisis. It just does not sell." He argued that Cruz lost because "his ideas have not taken hold and they were totally overwhelmed by the Trump campaign."
While discussing President Obama's appointment of D.C. Circuit Court of Appeals Chief Judge Merrick Garland to the Supreme Court on Wednesday, The Washington Post's Bob Woodward emphasized on Fox News Sunday that while Garland would provide a fifth vote for liberals in cases before the Court, but was someone who's "not really partisan in anyway."
During an appearance on Fox News' O'Reilly Factor Monday night, veteran journalist Bob Woodward had a bleak assessment of Hillary Clinton's presidential campaign which he said was clearly in trouble. Woodward explained that "there are lots of unanswered questions, particularly on the e-mail but as I read your book about Reagan, which is a full excavation of his biography and everything in his life, every stage, we need to do that with Hillary Clinton."
During an appearance on MSNBC's Morning Joe on Monday, veteran journalist Bob Woodward expressed his frustration with Hillary Clinton's private e-mail system and her continued refusal to turn over her server "reminds me of the Nixon tapes."
After having stayed silent on the George Stephanopoulos scandal on Thursday, MSNBC finally covered the story with multiple segments on Friday's Morning Joe devoted to Stephanopoulos's previously undisclosed donations to the Clinton Foundation. Surprisingly, the main theme that was derived from segments of banter was how the panelists were struck by the ABC News chief anchor's inability to disclose the $75,000.
Former Newsweek and New York Times Magazine writer Matt Bai has a new book out making the wild claim that the 1987 adultery scandal around Sen. Gary Hart marked "the week politics went tabloid" and ruined everything in national politics by pushing the media into focusing incessantly on the "character issue."
In a review Sunday in The New York Times Book Review, Reuters media columnist Jack Shafer pointed out the press was so cozy with Hart that Nixon-ruining Bob Woodward offered to let Hart quietly bunk at his house during marital troubles:
Appearing on Fox News Sunday, veteran journalist Bob Woodward had some harsh words for the Obama Administration over it's handling of the terrorist group ISIS.
Speaking on Sunday, August 24, Woodward blasted the White House for having a confusing message on how to combat the terrorist group, insisting "there's an inconsistency here. I mean, Hagel and the Chairman of the Joint Chiefs have said -- and Kerry, the Secretary of State, made it very clear, all options are on the table, and the president has said no boots on the ground." [See video below.]
Bob Woodward came close. Oh so close to discerning how much of the mainstream media were blindsided by the stunning defeat of former House Majority Leader Eric Cantor in his congressional primary in Virginia. In fact, Woodward came so close that your humble correspondent thought he was going to say it out loud today while being interviewed by CNN's Candy Crowley on State of the Union.
Instead Woodward skipped the real reason and gave the secondary reason for neglect of this story. Woodward did mention that too many reporters don't like to do the hard footwork to investigate stories in favor of sitting around the air conditioned newsroom and surfing the web for research. Unfortunately, Woodward completely overlooked the fact that much of the mainstream media reside in a liberal cocoon and miss much of what is going on in the conservative world as happened in that Virginia election. First let us look at Woodward's very partial explanation for what went wrong with that election coverage:


text:
Fellow made a name for themselves by making the only good-looking pour over kettle ever, but they're not stopping there.
The Stagg Dripper + Carafe join the Kettle to complete Fellow's coffee system. The Dripper is minimalist, compact, easy to use, and as you can probably guess, makes great coffee.
Stagg Dripper
- Vacuum insulated for better heat retention during brewing
- No-clog drainage system for consistent drip duration every time
- Steep slope increases coffee-to-water contact to boost extraction
- Drip cup to catch wayward drops of black gold
- Measurements on drip cup to measure coffee before starting
The coffee winds up in the Carafe, a beautiful, handblown, double-walled affair that you'll want to pour everything into. They should sell it separately, and I've started pouring the tea from my Breville into it as the latter lacks its own insulation.


text:
Warehouse Worker
Owner Operators Needed. Non-forced Dispatch. More Home Time.
Seeking experienced, certified or licensed caregivers - competitive pay and very flexible schedules
Sieman's - Warehouse Workers
Customer Service Reps. Work At Home!
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Find the career you've been looking for.
The Edmondson, AR Job Market
Shopping around for a job in Edmondson, AR? Edmondson, AR has a population of approximately 500, derived from 2013 BLS data. The median household earning value of the city of Edmondson, AR is approximately $27,000, determined by government data information since somewhere around 2013 Edmondson's cost of living, as of 2013, was in the region of 79 out of 100, which is actually lower in comparison with the national average.
One additional point that's beneficial to be conscious of is the fact that, recently since 2014, the city of Edmondson has a rate of unemployment just about 10.6%. Furthermore,this is significantly higher than the United States average unemployment ratio, from the later part of 2015. This is certainly well worth examining if you might be attempting to find jobs in the city, are located some other place and are looking in nearby areas, or if you are searching for places well worth relocating to, which also have beneficial job opportunities.


text:
A sitcom about a group of students who have a phobia of English. They are enrolled into a "Secret Class" that is known for a high success rate of teaching students English. Each student has their own 'secrets' and problems with studying English.
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text:
FRANKFURT GERMANY!!! NIGHT 2 @festhalle with @ironmaiden and @Shinedown for the 2017 #bookofsoulstour Who's coming with us!!!
Shinedown - Rock on the Range 2016 Music Festival at MAPFRE Stadium in Columbus, OH, USA on May 20, 2016 at MAPFRE Stadium - Columbus, Ohio, United States - Friday 20th May 2016
Shinedown - Louder Than Life Music, Whiskey, Gourmet Man Food Festival 2015 at Champions Park - Day 2 at Champions Park - Louisville, Kentucky, United States - Sunday 4th October 2015
Shinedown Friday 2nd November 2012 concert at Cardiff University Great Hall,
Brent Smith and Shinedown - Brent Smith of Shinedown Saturday 19th May 2012 Rock on the Range 2012 - Day 1
Review of Shinedown's album The Sound Of Madness
Continue reading: Shinedown, The Sound Of Madness Album Review
Shinedown - Brent Smith of Shinedown Florida, California, USA - 'Buzz Bake Sale' concert at the Cruzan Amphitheatere on West Palm Beach, Florida. Sunday 7th December 2008
Band form
FRANKFURT GERMANY!!! NIGHT 2 @festhalle with @ironmaiden and @Shinedown for the 2017 #bookofsoulstour Who's coming with us!!!
RT @IronMaiden: #ViewFromTheStage #IronMaiden #TheBookOfSoulsWorldTour #Frankfurt #Germany #Festhalle https://t.co/YJVb5hfD2X
... @thebrentsmith FRANKFURT GERMANY... LETS DO THIS!!! #ironmaiden #shinedown #bookofsoulstour https://t.co/fIgcL6ekHM
RT @Scullysgirl0208: @Shinedown @ZMyersOfficial @BKerchofficial @ebassprod @TheBrentSmith TC 7/3 and Lansing 7/8...i see @machineshopfnt so…
RT @jennylynnbatch: I'm going to @Shinedown at Common Ground Festival in Lansing, MI -... https://t.co/JMu05X3nUG
... WITNESS!!! 😉 RT @JamesPllu: @Shinedown on the train home. I want to stand up in the quiet coach and shout 'WITNESS' #cutthecord
RT @CarnivalMadness: Carnival alumni @Highly_Suspect, @Halestorm, @ChevelleInc & @Shinedown are on @Loudwire's Best Rock Album list! Read h…
RT @Indegoot: Read @Loudwire's "Best Hard Rock Album of Each Yr" list, ft @Highly_Suspect, @LZZYHALE, @ChevelleInc & @Shinedown: https://t.…
RT @CGMusicFest: JUST ANNOUNCED: @Shinedown @Freaks4Live @hctmummies and @legalimmigrants are playing #cgmf on 7/8. Tickets on sale tomorro…
😉RT @JedmacPhee: @deesidedon Open Spotify and listen to @Shinedown I've been listening to them before the @IronMaiden gig they are superb
RT @thursdayrocker: @thursdayrocker today 20.00(UK) https://t.co/RSyWXfwlWA with @OffiLIFEOFAGONY @Shinedown @LordsOfBlack @firewindmusic @…
... @TheBrentSmith love this... RT @livtheghost: amaryllis bloom thank you for always insipiring me @Shinedown 🖤💉 https://t.co/JsKBmbYptl
"Can I get a Witness" 😉 RT @Leafs_Tk: Love this song by @Shinedown "Cut the Cord" is one hell of a song https://t.co/NHjDa9kjwd
... The one, the only Mr. @bkerchofficial Night 2, in OBERHAUSEN GERMANY!!! Much love, and… https://t.co/nR9oTbaGSw
RT @ShinedownInk: .@Shinedown Tattoo submitted by Chris Moore #HowDidYouLove #ShinedownTattoos https://t.co/tRu9xcdY5L
RT @koepi_arena: That was AWESOME! Many Thanks to @IronMaiden & @Shinedown for two unbelievable shows in #Oberhausen! #ironmaiden #köpiaren…
RT @IronMaiden: Thank you Oberhausen. We are all Blood Brothers! Frankfurt, get ready... #IronMaiden… https://t.co/hJP445DzAI
OBERHAUSEN!!! Let's do it again tonight!!! NIGHT 2... #bookofsoulstour #ironmaiden #shinedown https://t.co/TFKfroP6Ia
RT @AngerAndAgony13: I sang Unity by @Shinedown to unite my campus against hatred today. I wasn't great, but love united us all here at @Ca…
OBERHAUSEN!!! @sparkygrt is gonna be here tonight!!! He's ready to rock, are you? #ironmaiden… https://t.co/3QjX9TfGGG