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Journal of Neurochemistry Lippincott Williams & Wilkins, Inc., Philadelphia © 2000 International Society for Neurochemistry Effect of Exogenous and Endogenous Antioxidants on 3-Nitropropionic Acid-Induced In Vivo Oxidative Stress and Striatal Lesions: Insights into Huntington's Disease *†Michael A. La Fontaine, ‡§James W. Geddes, *Andrea Banks, and *†§D. Allan Butterfield Departments of *Chemistry and ‡Anatomy and Neurobiology, †Center of Membrane Sciences, and §Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, U.S.A. Abstract: 3-Nitropropionic acid (3-NP) is an irreversible tingtin has been reported to associate with inhibitor of complex II in the mitochondria. 3-NP toxicity glyceraldehyde 3-phosphate dehydrogenase and possibly has gained acceptance as an animal model of Hunting- to impair activity of aconitase (Burke et al., 1996; ton's disease (HD). In the present study, we confirmed Tabrizi et al., 1999, 2000), the underlying mechanisms of that rats injected with 3-NP (20 mg/kg, i.p., daily for 4 days) exhibit increased oxidative stress in both striatum selective striatal damage are unknown. Recently, the and cortical synaptosomes as well as lesions in the stri- activation of excitatory amino acid receptors has been atum. Synaptosomal membrane proteins from rats in- implicated in HD (Albin and Greenamyre, 1992; Beal, jected with 3-NP exhibited a decrease in W/S ratio, the 1992). In addition, several mitochondrial toxins, when relevant electron paramagnetic resonance (EPR) param- injected in rats, have been found to cause behavioral eter used to determine levels of protein oxidation, and alterations and striatal lesions similar to the neurochem- western blot analysis for protein carbonyls revealed di- ical and anatomical changes associated with HD (Beal rect evidence of increased synaptosomal protein oxida- et al., 1991, 1993a; Brouillet et al., 1993; Koutouzis tion. Treatment of rats with the brain-accessible free rad- et al., 1994; Schulz et al., 1995). One such toxin that is ical spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO; 30 mg/kg, i.p., daily 2 h before 3-NP gaining prominence for use in animal models of HD is injection) or with N-acetylcysteine (NAC; 100 mg/kg, i.p., the mitochondrial toxin 3-nitropropionic acid (3-NP) daily 2 h before 3-NP injection), a known glutathione (Beal et al., 1993b; Brouillet et al., 1993; Guyot et al., precursor, before 3-NP treatments protects against oxi- 1997). 3-NP is an irreversible inhibitor of the electron dative damage induced by 3-NP as measured by EPR transport enzyme succinate dehydrogenase (Beal, 1992; and western blot analysis for protein carbonyls. Further- Ludolph et al., 1992; Brouillet et al., 1993; Palfi et al., more, both DEPMPO and NAC treatments before 3-NP 1996). administration significantly reduce striatal lesion vol- Oxidative stress has been suggested to play a role in umes. These data suggest oxidative damage is a prereq- 3-NP toxicity; however, the processes behind oxidative uisite for striatal lesion formation and that antioxidant treatment may be a useful therapeutic strategy against damage are not fully understood (Schulz et al., 1996). 3-NP neurotoxicity and perhaps against HD as well. Key NMDA receptors can be activated by 3-NP, leading to Words: 3-Nitropropionic acid—Huntington's disease — generation of superoxide radicals (Lafon-Cazal et al., Glutathione —5-Diethoxyphosphoryl-5-methyl-1-pyrro- 1993) and allowing calcium influx into the cell, both of line-N-oxide —N-Acetylcysteine —Electron paramagnetic which can further exacerbate oxidative damage (Wullner resonance — Oxidative stress. et al., 1994). Other evidence has also supported the J. Neurochem. 75, 1709 –1715 (2000). theory of free radical involvement with excitotoxicity (Coyle and Puttfarcken, 1993), and our laboratory has directly measured increased protein oxidation on admin- Huntington's disease (HD) is an inherited neurodegen- Received April 17, 2000; revised manuscript received June 19, 2000; erative disorder characterized by progressive choreiform accepted June 20, 2000. movements, cognitive impairment, and loss of neurons in Address correspondence and reprint requests to Prof. D. A. the striata (Albin et al., 1990; Kremer et al., 1992; Guyot Butterfield at Department of Chemistry and Center of Membrane et al., 1997; Nakao and Brundin, 1997). HD is known to Sciences, University of Kentucky, Lexington, KY 40506-0055, U.S.A. be caused by an abnormality in the IT15 gene (Hunting- E-mail: firstname.lastname@example.com Abbreviations used: DEPMPO, 5-diethoxyphosphoryl-5-methyl-1- ton's Disease Collaborative Research Group, 1993), giv- pyrroline N-oxide; EPR, electron paramagnetic resonance; HD, Hun- ing rise to a mutant "huntingtin" protein with an ex- tington's disease; MAL-6, 4-maleimido-2,2,6,6-tetramethylpiperidine- panded polyglutamine domain. Although mutant hun- N-oxyl; NAC, N-acetylcysteine; 3-NP, 3-nitropropionic acid. 1709 1710 M. A. LA FONTAINE ET AL. istration of 3-NP to rats and showed that oxidative stress preceded the formation of striatal lesions (La Fontaine et al., 2000). In the present study, we examined whether the brain- accessible spin trap 5-diethoxyphosphoryl-5-methyl-1- pyrroline N-oxide (DEPMPO) can attenuate oxidative stress caused by 3-NP toxicity as measured by electron paramagnetic resonance (EPR) and protein carbonyl analyses. The ability of DEPMPO to protect against 3-NP-induced striatal lesions also was examined. In ad- dition, the importance of endogenous antioxidants in protection against 3-NP-induced oxidative stress was studied. We reasoned that elevation of levels of the endogenous antioxidant glutathione should be protective. Accordingly, the effect of increasing glutathione levels using the glutathione precursor N-acetylcysteine (NAC) on 3-NP toxicity was investigated. NAC, when injected in rodents, has been found to increase brain glutathione FIG. 1. A typical EPR spectrum of MAL-6-labeled synaptosomal levels significantly (Testa et al., 1998; Pocernich et al., membrane proteins depicts the W and S components of the low-field resonance line. 2000). Taken together, these studies may offer insight into the role of oxidative stress in 3-NP-induced in vivo toxicity and lesion formation and possibly the neuro- chemistry and neuropathology of HD. mM HEPES]. The samples were then spun at 82,500 g for 2 h at 4°C in a Beckman swinging-bucket rotor. Synaptosomes were collected from the 1.18/1.0 M sucrose interface and re- MATERIALS AND METHODS suspended in 20 ml of lysing buffer (10 mM HEPES, 2 mM Chemicals EDTA, and 2 mM EGTA, pH 7.4). The samples were then spun 3-NP was obtained from Aldrich Chemical. Ultrapure sucrose, at 32,000 g at 4°C for 10 min. The pellet was resuspended in 4-maleimido-2,2,6,6-tetramethylpiperidine-N-oxyl (MAL-6), lysing buffer and spun twice more. After the third spin, the NAC, and anti-rabbit IgG antibody were obtained from Sigma protein concentration was determined by the method of Lowry Chemical Co. DEPMPO was obtained from Oxis International. et al. (1951). The protease inhibitors aprotinin, leupeptin, and pepstatin A Spin labeling were obtained from Calbiochem. The OxyBlot oxidized protein Each sample was separated into 4-mg aliquots. Spin labeling detection kit was obtained from Oncor. All remaining chemi- of synaptosomal membrane proteins was done as previously cals were obtained from Sigma in the highest possible purity. described (Umhauer et al., 1992; Hensley et al., 1994). Lysed Animals synaptosomal membranes were labeled with 20 g of MAL- All animal protocols have been approved by the University 6/mg of protein. After an 18-h incubation at 4°C, samples were of Kentucky Animal Care and Use Committee. Male rats were washed six times with lysing buffer to remove excess spin purchased from Harlan and housed in the Sanders-Brown Cen- label. Each 4-mg pellet was resuspended in a 1 ml of lysing ter on Aging Animal Care Facility. The Sprague–Dawley rats buffer. EPR spectra were acquired on a Bruker model EMX were exposed to 12-h light/12-h dark conditions and were fed EPR spectrometer operating at an incident microwave power of Purina Rodent Laboratory Chow with no restrictions to feed or 16 mW, a modulation amplitude of 0.4 G, a time constant of water. At 4 months of age, rats treated with 3-NP were injected 1.28 ms, and a conversion time of 10 ms. intraperitoneally daily for 4 days with 3-NP dissolved in phys- The W/S ratio (Fig. 1) of EPR spectra from MAL-6-labeled iologic saline at a dose of 20 mg/kg, pH 7.4. Control animals membrane proteins has been extensively studied in both brain received corresponding injections of physiologic saline. synaptosomal membranes and erythrocyte membranes (Hall DEPMPO-treated animals were injected intraperitoneally daily et al., 1995a; Hensley et al., 1995; Howard et al., 1996; But- with 30 mg/kg DEPMPO dissolved in physiologic saline 2 h terfield et al., 1997). Increased steric hindrance of the protein- before 3-NP treatment. NAC-treated animals were injected bound spin label will cause a decrease in the W/S ratio. This intraperitoneally daily with 100 mg/kg NAC dissolved in phys- can be caused by various changes in the environment of the iologic saline 2 h before 3-NP treatment. Animals were anes- spin label, including altered protein conformation, a decrease in thetized with sodium pentobarbital and decapitated 24 h after segmental motion in spin labeled proteins, and/or changes in the final injection. the interactions between proteins. Several oxidative conditions used in our laboratory, including Fenton chemistry to produce Synaptosome preparation hydroxyl radicals (Hensley et al., 1994), hyperoxia (Howard Synaptosomes were purified as previously described (But- et al., 1996), ischemia–reperfusion (Hall et al., 1995a–c), ac- terfield et al., 1994; Hensley et al., 1994). The homogenate was celerated aging (Butterfield et al., 1997), -amyloid-derived respun at 20,000 g at 4°C for 10 min. The resulting pellet was free radicals (Hensley et al., 1995; Butterfield, 1997; Butterfield suspended in 1 ml of isolation buffer and layered on a et al., 1997; Subramaniam et al., 1998), lipid peroxidation discontinuous sucrose gradient [10 ml of 1.18 M sucrose (pH products (Subramaniam et al., 1997), and menadione (Trad and 8.5)/10 ml of 1.0 M sucrose (pH 7.4)/10 ml of 0.85 M sucrose Butterfield, 1994), have shown that an increase in protein (pH 7.4), each containing 2 mM EDTA, 2 mM EGTA, and 10 oxidation is associated with a decrease in the W/S ratio. J. Neurochem., Vol. 75, No. 4, 2000 ANTIOXIDANTS AND 3-NP NEUROTOXICITY 1711 Protein carbonyl measurements Protein carbonyls are an index of protein oxidation (Butter- field and Stadtman, 1997). To determine the level of protein oxidation, an oxidized protein detection kit based on immuno- chemical detection of protein carbonyl groups derivatized with 2,4-dinitrophenylhydrazine was used. Synaptosomal membrane proteins were isolated as above and treated with 20 mM 2,4- dinitrophenylhydrazine in 10% trifluoroacetic acid and Deri- vatization-Control solution and incubated for 20 min. Deriva- tization was neutralized with OxyBlot neutralization solution (2 M Tris/30% glycerol) and 19% 2-mercaptoethanol. Polyacrylamide gel electrophoresis was performed in mini- slabs (0.75 60 70 mm, 12% acrylamide) according to the method of Laemmli (1970). Following electrophoresis, proteins were transferred to nitrocellulose paper (pore size, 0.45 m) FIG. 2. Effect of DEPMPO and increased glutathione levels (via according to the procedure adapted from Glenney (1986). Tris- NAC) on the physical state of synaptosomal membrane proteins glycine and 20% methanol at a pH of 8.5 was used as the assessed by EPR in conjunction with the protein-specific spin transfer buffer. Following transfer, nitrocellulose paper was label MAL-6. Synaptosomal membrane proteins were isolated blocked in 3% bovine serum albumin (in phosphate-buffered from the striatum and cortex of rats treated with 3-NP, 3-NP and saline with 0.01% sodium azide and 0.2% Tween-20) for 1 h at DEPMPO, 3-NP and NAC, and saline (control). Synaptosomes room temperature. Membranes were washed three times with were labeled with MAL-6, and EPR spectra were analyzed. Sig- washing buffer (1% NaCl, 2% phosphate-buffered saline, nificant decreases in W/S ratios, consistent with protein oxida- 0.01% sodium azide, and 0.1% Tween-20). To the membranes, tion (see text), were observed in both brain regions in animals treated with 3-NP compared with control (striatum, control n rabbit anti-2,4-dinitrophenol antibody (1:150 dilution in 90% 10, 3-NP n 9, p 0.01; cortex, control n 11, 3-NP n 10, washing buffer/10% blocking buffer) was added and incubated p 0.01). W/S ratios of MAL-6-labeled synaptosomes isolated at room temperature for 1 h under mild shaking. Following from animals coinjected with DEPMPO were significantly higher incubation, membranes were washed three times with washing in both brain regions than W/S ratios of MAL-6-labeled synap- buffer. Anti-rabbit IgG (1:15,000 dilution in blocking buffer) tosomes isolated from animals treated with 3-NP only (striatum, was added to the membranes and incubated at room tempera- 3-NP DEPMPO n 6, p 0.01; cortex, 3-NP DEPMPO n ture for 1 h with mild shaking. Following incubation, mem- 6, p 0.01). W/S ratios of MAL-6-labeled synaptosomes branes were washed three times and then developed using isolated from animals coinjected with NAC were also signifi- 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium cantly higher compared with animals treated with 3-NP only (striatum, 3-NP NAC n 7, p 0.01; cortex, 3-NP NAC n solution (1 SigmaFast tablet per 10 ml of deionized water). 6, p 0.01). **p 0.01. Western blots were analyzed using computer-assisted imag- ing software (MCID/M4; Imaging Research, St. Catharine's, Ontario, Canada). significant decrease in oxidative stress. The W/S ratios of Lesion volume analysis MAL-6-labeled synaptosomal membranes isolated from Lesion volumes in the striatum were analyzed by freezing DEPMPO-treated animals were significantly higher than the intact brain on dry ice on removal from decapitated rats. those of animals treated with 3-NP only (Fig. 2). Protein Twenty-micrometer slices with an intersectional distance of carbonyl levels were also significantly decreased in syn- 180 m were mounted on microscope slides and stained using aptosomes isolated from animals treated with DEPMPO purple cresol tissue stain. The lesion volume of individual compared with animals treated with 3-NP only (Fig. 3). slices was analyzed using NIH Image version 6.1 for the Macintosh on images collected using a 2 ocular. Lesion Animals treated with NAC exhibited a similar decrease volume was obtained by multiplying the total lesion areas times in oxidative stress, by both EPR analysis (Fig. 2) and the intersectional distances. protein carbonyl analysis (Fig. 3). Treatment with either DEPMPO or NAC reduced striatal lesion volumes com- Statistical analysis pared with animals treated with 3-NP only (Fig. 4). One-way ANOVA was used for comparison of the means. Figure 5 shows a cross-section from striatum of 3-NP- Student's t test was used where applicable. Results are ex- and 3-NP plus DEPMPO-treated animals. pressed as mean SD data. Throughout the course of this study, three animals treated with 3-NP only died before the time of harvest- RESULTS ing. Therefore, brain tissue analyses from these animals were not conducted. All other test groups exhibited a The W/S ratios of MAL-6-labeled synaptosomal zero mortality. membrane proteins isolated from rats treated with 3-NP were significantly decreased in both striatum and cortex DISCUSSION when compared with control animals injected with saline vehicle (Fig. 2). Confirming the EPR results, protein The effect of 3-NP administration on rodent behavior, carbonyl levels in synaptosomes isolated from rats physical dexterity, and neuropathology has been studied treated with 3-NP were significantly higher than control by several groups; 3-NP is unique among toxin models levels (Fig. 3). Animals treated with the free radical spin of HD in that it can be used to mimic the two-stage trap DEPMPO before 3-NP administration exhibited a progression of HD by leading to both hyperactivity and J. Neurochem., Vol. 75, No. 4, 2000 1712 M. A. LA FONTAINE ET AL. striatal synaptosomal membrane proteins of rats exposed to 3-NP (La Fontaine et al., 2000). Despite the evidence of oxidative stress in 3-NP tox- icity, the role of reactive oxygen species is not clear. Given the oxidative nature of 3-NP toxicity, we reasoned that the brain-accessible spin trap DEPMPO would mod- ulate protein oxidation in this model of HD. DEPMPO is a phosphorylated analogue of 5,5-dimethyl-1-pyrroline N-oxide that exhibits greater stability and can be used in spin-trapping studies to discriminate specific radical spe- cies (Clement et al., 1998). We found a significant de- crease in levels of protein carbonyls due to 3-NP toxicity in rats cotreated with DEPMPO. Furthermore, we found FIG. 3. Effect of DEPMPO and increased glutathione levels (via a significant increase in W/S ratios of the DEPMPO- NAC) on protein oxidation of synaptosomal proteins assessed treated rats compared with those that were not cotreated by levels of protein carbonyls after 3-NP treatment. Synapto- with DEPMPO. In both EPR experiments and protein somes were isolated from animals treated with 3-NP, 3-NP and carbonyl level measurements, DEPMPO protection gave DEPMPO, 3-NP and NAC, and saline (control) and analyzed for protein carbonyl content. A significant increase in levels of pro- mean values of the respective parameters that were close tein carbonyls was observed in both brain regions in animals to values for control animals. The commonly used spin treated with 3-NP compared with control (striatum, control n trap -phenyl-N-tert-butyl nitrone and analogues were 9, 3-NP n 9, p 0.01; cortex, control n 10, 3-NP n 10, not considered for this study owing to their apparent p 0.01). Protein carbonyl levels of synaptosomes isolated from exacerbation of 3-NP toxicity (Schulz et al., 1996; Nakao animals coinjected with DEPMPO were significantly lower in both brain regions than protein carbonyls in synaptosomes iso- and Brundin, 1997). lated from animals treated with 3-NP only (striatum, 3-NP Evidence of decreased glutathione levels in 3-NP- DEPMPO n 6, p 0.01; cortex, 3-NP DEPMPO n 6, p treated animals and attenuation of 3-NP toxicity in cop- 0.01). Protein carbonyl levels of synaptosomes isolated from per/zinc superoxide dismutase transgenic mice (Beal animals coinjected with NAC were also significantly lower com- pared with animals treated with 3-NP only (striatum, 3-NP et al., 1995) suggest endogenous antioxidants may play a NAC n 6, p 0.01; cortex, 3-NP NAC n 6, p 0.01). role in protecting against 3-NP-induced oxidation. Our **p 0.01. laboratory reported that increased glutathione levels re- sulting from NAC injections protect rat synaptosomes from oxidation caused by hydroxyl radicals (Pocernich hypoactivity (Borlongan et al., 1997). A correlation be- et al., 2000). In support of the hypothesis that glutathione performs an antioxidant role in 3-NP toxicity, we report tween severity of 3-NP-induced striatal lesions and mo- a significant decrease in synaptosomal protein oxidation tor deficits, including bradykinesia, gait length, and gait velocity, was shown by Guyot et al. (1997) along with regional selectivity similar to that seen in HD. Tsai et al. (1997) demonstrated a dose-dependent decrease in glu- tamine synthetase activity with 3-NP injections. These researchers also showed an age-dependent increase in susceptibility toward 3-NP toxicity. The decrease of glu- tamine synthetase activity coupled with the age-depen- dent susceptibility suggests an oxidative mechanism un- derlying 3-NP toxicity (Hensley et al., 1995; Aksenov et al., 1997; Butterfield et al., 1997). In addition, the deficiencies in behavior and motor control are reminis- cent of the loss of motor skills associated with increased brain protein oxidation (Forster et al., 1996). Considerable evidence exists to support an oxidative process underlying 3-NP toxicity. Beal et al. (1995) showed an attenuation of 3-NP toxicity in copper/zinc superoxide dismutase-overexpressing transgenic mice. FIG. 4. Whole brains were isolated from animals treated with 3-NP, 3-NP plus DEPMPO, and 3-NP plus NAC and were sliced The hydroxyl radical products 2,3-dihydroxybenzoic into 20- m-thick cross-sections. Every 10th cross-section was acid and 2,5-dihydroxybenzoic acid were detected also stained with purple cresol (cresyl violet) tissue stain, and lesion by these researchers as indirect evidence of hydroxyl area was measured. Lesion volume was calculated by adding radical formation. Pang and Geddes (1997) showed that the individual lesion areas and multiplying by intersectional dis- tance. Lesion volumes in striata of animals coinjected with one mechanism of cell death in 3-NP toxicity was exci- DEPMPO (n 4, p 0.01) and NAC (n 4, p 0.01) were totoxic necrosis. Consistent with these researchers, our significantly less than lesion volumes in striata of animals in- laboratory has shown an increase in protein oxidation in jected with 3-NP only (n 8). **p 0.01. J. Neurochem., Vol. 75, No. 4, 2000 ANTIOXIDANTS AND 3-NP NEUROTOXICITY 1713 FIG. 5. Cross-section slide 400 m into striatum of brains isolated from animals treated with 3-NP (left) and 3-NP DEPMPO (right). on NAC injections similar to, but not as extensive as, that mechanism of 3-NP toxicity (Beal et al., 1993a). 3-NP seen with DEPMPO protection. irreversibly binds succinate dehydrogenase, an enzyme Furthermore, both DEPMPO treatment and elevated that functions to oxidize succinate to fumarate by trans- glutathione levels significantly decrease striatal lesion ferring two electrons to flavin adenine dinucleotide and volume, again with DEPMPO being more effective than is the entry point of the citric acid cycle into the mito- the NAC-induced glutathione level elevation. Because chondrial electron transport chain. DEPMPO and glutathione both protect against oxidative 3-NP and other metabolic inhibitors also leads to re- damage by scavenging reactive free radicals (Fig. 6), the moval of the Mg2 block on the ion channel of NMDA greater protection afforded by DEPMPO may be due to receptors through depolarization of the neuronal mem- dosage. Presumably, NAC protection could be improved brane (Albin and Greenamyre, 1992; Beal, 1992). The with greater dosage; however, because NAC itself may resulting influx of Ca2 may lead to increased superox- be toxic, higher dosage was not tested. In previous stud- ide production and activation of calcium-dependent ni- ies in this laboratory, rats were injected intraperitoneally tric oxide synthase, causing an increase in oxidative with 300 mg of NAC/kg of body mass NAC (Pocernich stress (Lafon-Cazal et al., 1993; Reynolds and Hastings, et al., 2000). This dosage, however, often led to death of 1995). There is also evidence of an inflammatory re- the animal after 2 days of injections (authors' unpub- sponse to 3-NP toxicity, most notably increased levels of lished data), so a lesser dose was chosen for this study. tumor necrosis factor- (Geddes et al., 2000) and in- The mechanisms of oxidative stress in 3-NP toxicity creased expression of inducible NOS (Nishino et al., are as yet unknown. Possible sources of oxidation are 1996). mitochondrial impairment, NMDA receptor activation The ability of both brain-accessible spin traps and leading to an increase in superoxide production, and elevated levels of glutathione to attenuate 3-NP toxicity, inflammatory response due to neuronal degeneration. a good model of HD, suggests antioxidants may be of Mitochondrial impairment is believed to be the major therapeutic value in HD. Studies are ongoing to investi- FIG. 6. Mechanism of radical scavenging of DEPMPO (top) and glutathione (bottom) with hy- droxyl radical. J. 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Biol. Chem. 200, 710 –715. 193, 265–275. Butterfield D. A., Howard B. J., Yatin S., Allen K. L., and Carney J. M. Ludolph A. C., Seelig M., Ludolph A., Novitt P., Allen C. N., Spencer (1997) Free radical oxidation of brain proteins in accelerated P. S., and Sabri M. I. (1992) 3-Nitropropionic acid decreases senescence and its modulation by N-tert-butyl- -phenylnitrone. cellular energy levels and causes neuronal degeneration in cortical Proc. Natl. Acad. Sci. USA 94, 674 – 678. explants. Neurodegeneration 1, 155–161. Clement J., Gilbert B., Ho W., Jackson N., Newton M., Silvester S., Nakao N. and Brundin P. (1997) Effects of -phenyl-tert-butyl nitrone Timmons G., Tordo P., and Whitwood A. (1998) Use of a phos- on neuronal survival and motor function following intrastriatal phorylated spin trap to discriminate between the hydroxyl radical injections of quinolinate or 3-nitropropionic acid. Neuroscience and other oxidizing species. J. Chem. Soc. Perkin Trans. 28, 1215. 76, 749 –761. Coyle J. T. and Puttfarcken P. (1993) Oxidative stress, glutamate and Nishino H., Fujimoto I., Shimano Y., Hida H., Kumazaki M., and neurodegenerative disorders. Science 262, 689 – 695. Fukuda A. (1996) 3-Nitropropionic acid produces striatum selec- J. Neurochem., Vol. 75, No. 4, 2000 ANTIOXIDANTS AND 3-NP NEUROTOXICITY 1715 tive lesions accompanied by iNOS expression. J. Chem. Neuro- protects cortical synaptosomal membrane proteins from amyloid anat. 10, 209 –212. -peptide (25–35) toxicity but not from hydroxynonenal toxicity: Palfi S., Ferrante R. J., Brouillet E., Beal M. F., Dolan R., Guyot M. C., relevance to the free radical hypothesis of Alzheimer's disease. Peschanski M., and Hantraye P. (1996) Chronic 3-nitropropionic Neurochem. Res. 23, 1403–1410. acid treatment in baboons replicates the cognitive and motor Tabrizi S. J., Cleeter M. W., Xuereb J., Taanman J. W., Cooper J. M., deficits of Huntington's disease. J. Neurosci. 16, 3019 –3025. and Schapira A. H. (1999) Biochemical abnormalities and exci- Pang Z. and Geddes J. (1997) Mechanisms of cell death induced by the totoxicity in Huntington's disease brain. Ann. Neurol. 45, 25–32. mitochondrial toxin 3-nitropropionic acid: acute excitotoxic ne- Tabrizi S. J., Workman J., Hart P. E., Mangiarini L., Mahal A., Bates crosis and delayed apoptosis. J. Neurosci. 17, 3064 –3073. G., Cooper J. M., and Schapira A. H. (2000) Mitochondrial Pocernich C., La Fontaine M., and Butterfield D. A. (2000) In-vivo dysfunction and free radical damage in the Huntington r6/2 trans- glutathione elevation protects against hydroxyl free radical-in- genic mouse. Ann. Neurol. 47, 80 – 86. duced protein oxidation in rat brain. Neurochem. Int. 36, 185–191. Testa R., Ghia M., Mattioli F., Borzone S., Caglieris S., Mereto E., Reynolds I. J. and Hastings T. G. (1995) Glutamate induces the Giannini E., and Risso D. (1998) Effects of reduced glutathione production of reactive oxygen species in cultured forebrain neu- and N-acetyl cysteine on lidocaine metabolism in cimetidine rons following NMDA receptor activation. J. Neurosci. 15, 3318 – treated rats. Fund. Clin. Pharmacol. 12, 220 –224. 3327. Trad C. and Butterfield D. A. (1994) Membrane induced cytotoxicity Schulz J. B., Henshaw D. R., Siwek D., Jenkins B. G., Ferrante R. J., Cipollini P. B., Kowall N. W., Rosen B. R., and Beal M. F. (1995) effects on human erythrocyte membranes studied by electron Involvement of free radicals in excitotoxicity in vivo. J. Neuro- paramagnetic resonance. Toxicol. Lett. 73, 145–155. chem. 64, 2239 –2247. Tsai M. J., Goh C. C., Wan Y. L., and Chang C. (1997) Metabolic Schulz J. B., Henshaw D. R., MacGarvey U., and Beal M. F. (1996) alterations produced by 3-nitropropionic acid in rat striata and Involvement of oxidative stress in 3-nitropropionic acid neurotox- cultured astrocytes: quantitative in vitro 1H nuclear magnetic icity. Neurochem. Int. 29, 167–171. resonance spectroscopy and biochemical characterization. Neuro- Subramaniam R., Roediger F., Jordan B., Mattson M. P., Keller J. N., science 79, 819 – 826. Waeg G., and Butterfield D. A. (1997) The lipid peroxidation Umhauer S., Isbell D., and Butterfield D. A. (1992) Spin-labeling of product, 4-hydroxy-2-trans-nonenal, alters the conformation of membrane proteins in mammalian brain synaptic plasma mem- cortical synaptosomal membrane proteins. J. Neurochem. 70, branes; partial characterization. Anal. Lett. 25, 1201–1215. 1161–1169. Wullner U., Young A. B., Penney J. B., and Beal M. F. (1994) Subramaniam R., Koppal T., Green M., Yatin S., Jordan B., and 3-Nitropropionic acid toxicity in the striatum. J. Neurochem. 63, Butterfield D. A. (1998) The free radical antioxidant vitamin E 1772–1781. J. Neurochem., Vol. 75, No. 4, 2000
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Jimmy Fallon
Jimmy Fallon Singing 'Barbara Ann' with Wax Statues of Himself Is a Little Creepy
It's cool and fun for Jimmy Fallon…until it's not.
Ice-T Thinks 'Fifty Shades of Grey' Was So Boring It Should Have Been on Nickelodeon
Don't worry, it wasn't in the same sentence.
Watch Jimmy Fallon Perform 'It Takes Two' with Will Smith
The Loopy iPad app sure comes in handy when you want to rock out with the big stars.
Watch Will Ferrell & Kevin Hart Take on Beyoncé, Katy Perry in Epic Super Bowl Lip Sync Battle
The biggest battle on Super Bowl Sunday wasn't really between the New England Patriot and Seattle Seahawks, it was between Will Ferrell and Kevin Hart.
Watch Jimmy Fallon Lead a Drunken Singalong of 'Piano Man'
Because why not?
Watch Blake Shelton Do a Lot of Whispering & Find Out Benedict Cumberbatch is a Real Person
Shelton was not that into the game Jimmy Fallon wanted him to play, like really not into it, which made it a whole lot funnier.
Watch Gwyneth Paltrow Sing Broadway Versions of Drake, Nicki Minaj & Big Sean
Gwyneth Paltrow's been on a good will tour in the media this week.
Soft Rock Beef Alert: Little River Band Vs. Jimmy Fallon
He had a few choice words and one of them has four letters and starts with an "f."
One Direction Sit on the Floor with Jimmy Fallon: 'This Is How We Always Hang Out'
One Direction return to the Tonight Show for a chat with Fallon while sitting…on the floor.
Watch Steve Carell Do a Barbershop Rendition of 'Sexual Healing' on 'Tonight Show'
For one night and one night only, Steve Carell joined Jimmy Fallon's The Ragtime Gals or, more precisely, to steal all the thunder.
Rae Sremmurd Bring 'No Flex Zone' to 'Fallon': Watch
For anyone who loves choreographed dance moves, you're in for a treat.
Lorde Was Taylor Swift's Manager For One Night, And One Night Only
Lorde also performed her latest hit "Yellow Flicker Beat" off the Mockingjay – Part 1 soundtrack.
Dej Loaf Debuts 'Try Me' With Help From The Roots on 'Tonight Show': Watch
Dressed in a wrap-around sweater and a pair of glitter slip-on sneakers, the Detroit rapper showed us exactly why Drake is such a fan.
Jimmy Fallon & the Roots Fill In for U2, Cover 'Desire': Watch
Meanwhile, U2 is planning U2-less videos of every track on their "Songs of Innocence" album.
Sting Creates Ringtones — aka 'Stingtones' — For Jimmy Fallon: Watch
On last night's episode of The Tonight Show, Sting showed off his pipes, dusting off a few of his hits to turn them into seconds long ringtones for those fans who want to hear his voice every time they receive a call or text.
Jimmy Fallon, will.i.am Celebrate 'Ew!' Success with Fan Supercut: Watch
Just like the original, the supercut has gone viral in its own right.

subset: commoncrawl


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Watch Floyd Mayweather vs. Manny Pacquiao videos and clips from training camp. Floyd Mayweather vs. Manny Pacquiao is approaching, and it's just a hair over a month before their highly anticipated me read news >>
Luke Thomas is back to rant about his dog, March Madness brackets, the NFL Veteran Combine, and more. read news >>
Manny Pacquiao was a key factor in helping unite all the major networks in the Philippines. Instead of fighting over broadcast rights, the bout will now air on all the top platforms and outlets in th read news >>
Ultimate Fighting Championship (UFC ) women's bantamweight champion, Ronda Rousey, stopped by ESPN's First Take earlier this week to offer her breakdown of the upcoming mega fight between Floyd Maywe read news >>
Mind officially blown. In 2013, Justin Verlander signed a contract worth $180 million to remain pitcher for the Detroit Tigers for five more years. Floyd Mayweather Jr. will earn that in one night. T read news >>
With five weeks to go until fight time, check in here on the latest odds for the biggest event of the year: Floyd Mayweather vs. Manny Pacquiao. We are just over five weeks away from what is sure to read news >>
In case you needed another reminder that Mayweather vs. Pacquiao is reality, check out this official poster. Floyd Mayweather vs. Manny Pacquiao is just about 1 month and 1 week away from finally hap read news >>
Like Consuela says on Family Guy: Noooo, N-Nooooo... Outspoken Ultimate Fighting Championship (UFC) 145-pound No. 1 contender, Conor McGregor, originally predicted his upcoming featherweight pay-per- read news >>
Conor McGregor is on a tour hyping his UFC 189 fight with Jose Aldo, and it seems that he let the hype slip into the ridiculous with a comparison to Floyd Mayweather vs. Manny Pacquiao. Floyd Mayweat read news >>
From Yahoo Sports: The challenger predictably went after Jose Aldo, saying the UFC featherweight champ is 'reeking of' fear. read news >>
Trouble in paradise? Floyd Mayweather Jr. and Manny Pacquiao recently held their first press conference (video replay) to promote their upcoming boxing "mega fight," which goes down on May 2, 2015 fr read news >>
Watch full fight video preview for arguably the biggest fight in the history of Boxing as pound-for-pound boxing great Floyd Mayweather will finally take on longtime rival Manny Pacquiao on Showtime read news >>
Watch the first official trailer of Manny Pacquiao vs. Floyd Mayweather from Showtime Sports While there lots of fan-made promos that have been made throughout the years, here is the first official o read news >>


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TCU is committed to enrolling talented, motivated students from diverse backgrounds. The University offers a full range of scholarships, financial aid, and financing options to families of all income levels.
All incoming students (freshmen and transfers) are encouraged to file both the Free Application for Federal Student Aid (FAFSA) and the CSS Profile to be considered for all financial aid options:
· FAFSA- Required for all Federal and State aid programs.
· CSS Profile- Required for TCU funded aid programs. Not required if you are applying for Federal and/or State aid only.
Texas Christian University financial aid policies do not discriminate on the basis of personal status, individual characteristics or group affiliation, including, but not limited to, classes protected under federal and state law.


text:
Wayland cruises past Godwin Heights to claim district title
GRAND RAPIDS—Sometimes you can practice until you drop and still not match your opponent's strength.
GRAND RAPIDS—Sometimes you can practice until you drop and still not match your opponent's strength.
A fire at a business in Hopkins Township totally destroyed a building, several tractors and a semi truck.
The 31st Cabaret Band Show opens March 13 and will bring with it familiar faces and another packed evening of performances.
Someday, maybe somebody will come along who matches A.J. Atwater's accomplishment as a member of the Otsego boys' basketball team. Maybe.
The third annual No One Fights Alone Zumbathon and Silent Auction will expand its reach and split the proceeds among three causes.
Wayland 76 Grand River Prep 46
AmeriCorps veteran resource navigator Darrek Laderman will present a veteran benefits awareness program on Wednesday, March 18, at 7 p.m. in the Carnegie Room at Allegan District Library.
Once again, Wayland's city council room was filled with residents concerned about the city imposing a single citywide trash hauler on its residents.
New parking spaces will replace the former county jail when it is demolished later this year.
The first part of Sam Jacobs' Eagle Scout project has commenced.
Kaechele Publications, Inc.
231 Trowbridge St.
P.O. Box 189
Allegan, MI 49010
Phone: 269-673-5534
Fax: 269-673-5535
The Union Enterprise
P.O. Box 417
Plainwell, MI 49080
The Commercial Record
3217 Blue Star Hwy.
P.O. Box 246
Saugatuck, MI 49453
269-857-8187 or 269-857-4637


text:
News, Events, & Announcements
Russia Kenya connect Sept 2014
God has a unique way of weaving a picture. Often times we do not see it in the making but
What is a Zavalinki??…. by Dale
Upon our arrival in Khabarovsk we met with our host. She had a list ready for us of suggested projects
Return to Russia 2012
Take a quick walk through the ministry in Khabarovsk, Russia. Join us via internet as we prepare to spend the
Meet Tonya
Tonya is a former orphan brought up in orphanage #8 in Khabarovsk. She completed her high school education and attended


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Newcastle Scouts presents:
7th April 2015 to 11th April 2015
Booking now open
A cast of Cubs, Scouts, Guides and Leaders accompanied by a professional band, lighting and sound perform 3 hours of songs, dance and sketches.
21st April 2015 to 25th April 2015
Antony Jay and Jonathan Lynn
Updated to reflect the (comic) realities of modern Government, Jay and Lynn's adaptation of their much-loved 1980s TV series has lost none of the biting wit and wry satire that made it such a memorable hit.
Jim Hacker, governing with a threadbare majority, faces yet another crisis.
5th May 2015 to 9th May 2015
Yasmina Reza
Two successful middle class couples meet to discuss an incident involving their young sons in the local park, but this superficially civilised evening get-together soon degenerates into a grotesque ballet of shifting loyalties and fractious emotions.
19th May 2015 to 23rd May 2015
They Shoot Horses, Don't They?
Ray Herman, ad. from the novel by Horace McCoy
A dance marathon in 1930s Los Angeles serves as a haunting symbol for the struggle for survival in Depression-era. In a shabby ballroom couples are provided food and shelter for as long as they can keep moving, encouraged by a relentlessly cheerful MC.
Newcastle Dance Centre presents:
30th May 2015 to 31st May 2015
Newcastle Dance Centre and Performing Arts Academy proudly presents 'ANight at the Oscars' - a glamorous production packed full of dance and musical theatre numbers from award-winning shows and film scores.<
16th June 2015 to 20th June 2015
Noël Coward
The eccentric, egocentric Bliss family are everything a respectable family are not supposed to be. When each member of this arty and bohemian clan invites a guest to their country house, the unassuming visitors are thrown into a hilarious living melodrama.
Gilholm Campbell School of Dancing presents:
24th June 2015 to 25th June 2015
Gilholm Campbell School of Dancing
The Gilholm Campbell School of Dancing presents OUT OF CONTROL.
Sage Academy for Performing Arts presents:
28th June 2015 to 28th June 2015
Sage Academy Summer Showcase (1) 2015
Part-time, advanced and full-time students of the Sage Academy join together to perform in their annual summer showcase.
Sage Academy for Performing Arts presents:
4th July 2015 to 5th July 2015
Sage Academy Summer Showcase (2) 2015
Part-time, advanced and full-time students of the Sage Academy join together to perform in their annual summer showcase.
14th July 2015 to 18th July 2015
Catherine Cookson, ad. by Rob Bettinson
In early 20th century Jarrow, life for the O'Brien family is one of a bitter struggle for survival in a world of unemployment and grinding poverty. Eldest son and dockworker John O'Brien strives for a better life: one that almost seems within his grasp when he meets a beautiful young teacher.


text: > View Product Details Please select the size of the product. Please enter valid quantity. Pour la Victoire camel suede 'Daina' point toe platform pumps overview details Retail: $250.00 Reduced: $86.97 $86.97 size size chart select size 6 - Wait list 6.5 - Wait list 7 - Wait list 7.5 - Wait list 8 - Wait list 8.5 - Only 1 left! 9 - Wait list 9.5 - Wait list 10 - Only 1 left! in stock add to my bag Add to Wish list Successfully added to the Selected Wish List. color : Camel Pour la Victoire go the spoils, but these sassy pumps couldn't be more fresh! Color: Camel Soft suede upper Pointed toe Lightly padded leather lining Leather sole 4'' covered heel �'' front platform All measurements are approximate Leather; Brazil; style#320534802


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Research supports what common sense has always told us – parents play a critical role in their children's education. Studies show, that parent involvement benefits students and schools in a variety of ways. Student attendance increases; student attitudes and achievements improve; and the number of discipline problems goes down. This is true regardless of a family's socio-economic status, education level, or cultural background. By forming a partnership, parents and schools can work together to identify the challenges in parental involvement - or the lack of it - and find ways to overcome these problems. Find out about innovative approaches Nebraska educators are using to support and engage today's parents in their child's education.
live streaming schedule & on demand videos
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|Living with Cancer: Jon McAlpin - Beating Cancer
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|Cheryl Stevens founded the Flamingos for Hope after being diagnosed with breast cancer. She found...
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|Get an up-close look at Nebraska Baseball Outfielder, Austin Darby. Find out why he picked his walk...
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|Sen. Mike Groene of North Platte discusses his opposition to mandatory vaccinations against...
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|The Omaha News: March 12, 512
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"Completing The Series"
The depth of detail correlates to the wonders of the world in such a manor as to enhance the story and make us believe it actually could be true facts and all the more make the series relavant. I am impressed.
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Office Chairs
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Sodura Aero Bookcase
Large Size
Small Size
Sodura Aero Bookcase
Weights & Dimensions
Large Size
Small Size
|Product Type: Bookcase
|Collection: Aero
|Style: Modern
|Primary Material: Wood
|Solid Wood Construction: No
|Number of Items Included: 1
|Non Toxic: Yes
|Scratch Resistant: Yes
|UV Resistant: Yes
|Chip Resistant: Yes
|Tarnish Resistant: Yes
|Stain Resistant: Yes
|Impact Resistant: Yes
|Cabinets Included: No
|Doors Included: No
|Shelves Included: Yes
|Pockets Included: No
|Wheels Included: No
|Bins Included: No
|Drawers Included: No
|Installation Type: Free standing
|Orientation: Vertical
|Personalized: Yes
|Hand Made: Yes
|Revolving: No
|Double-Sided: No
|Back Panel: Closed back
|Commercial Use: Yes
|Eco-Friendly: Yes
|Product Care: Wipe clean with a damp cloth
|Country of Manufacture: United States
|Weight Capacity: 200 Pounds
|Assembly Required: Yes
|Installation Required: Yes
|Additional Parts Required: No
|Product Warranty: Limited lifetime
|CARB Compliant: Yes
|CPSIA or CPSC Compliant: Yes
About the ManufacturerSodura was established in January of 2011 with one goal: To provide functional, well-made modern furniture. Sodura is made up of parents just like you who want furniture for their child's room that has style, and is still comfortable. In other words, to be modern and have style doesn't mean that it looks like it was made for the Jetson's. You'll see that this furniture is practical, functional, and of the highest quality on the market, and that's backed up by a great guarantee.
Sodura Aero Bookcase
Still have questions about this product? We're here to help
Customer Reviews
|5 star
|4 star
|3 star
|2 star
|1 star
Love this bookcase and this company!
Karla Bynum from Austin, TX
My search for the perfect bookcase for our toddler ended when I found this product, and we couldn't be happier! It was so easy to put together (there's an online instruction video, but I didn't even need to refer to that, as the written instructions that came with the bookcase were sufficient), and it truly is a well-made, beautiful piece. It was important to me to find a U.S.-made product that was eco-friendly and didn't off-gas harmful chemicals, and I was really pleased that the bookcase had no initial or subsequent odors. It's deceptively small (i.e., unobtrusive, with a relatively small footprint), but I was pleasantly surprised at how many books it holds. My toddler adores it and will stand at it for a long period of time just arranging and re-arranging her books, and I like that it gives her a special place in our living room for her "treasures."
Just what we were looking for. Strong smell out of the box.
Trinsley from Boston, MA– Verified Buyer
I searched and searched for a unique, friendly, accessible, natural affordable, modern bookshelf for our just-turned-one daughter. This shelf is all of those things! She unloads and reloads her books all day long. I also love the eco-friendly qualities and that the shelf is produced by a small company (I think?). As advertised, it was easy to assemble (no screws or small tools!). The shelf did initially have a strong varnish-like smell out of the packaging that I found worrying (the only reason for my 4-star review here) and which sent me scurrying back to the online product details to double-check about low VOCs, etc. But the smell went away in a few hours and we were left with a beautiful shelf that makes us happy every day. Definitely recommend and I now have my eye on the table and chairs and large bookshelf!
So easy to assemble!
Cassie from Louisville, KY
After searching online for an eco-friendly bookcase for all of our kids' books, I came across Sodura and they happened to be local for me, which was awesome. I got the small bookcase and it was really easy to assemble, and they just have these small keys that go in the back to lock the shelves in place. If I expand, I'll definitely go with the large bookcase.
Valued Customer from Texas– Verified Buyer


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7,000 Crocodiles Escape Farm in South Africa
(NEW YORK) -- Thousands of crocodiles are on the loose in South Africa.
Some 7,000 of them escaped from a crocodile farm after the gates of a dam were opened to alleviate rising floodwaters.
Only about 2,000 have been recaptured.
Copyright 2013 ABC News Radio
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Quality of Service5.0
Joe did the photography for our Vermont wedding a few weeks ago and he was great to work with. He was flexible and easy going and did all that we asked of him! He was very low profile during the reception as a great photographer should be!
Joe's photography is amazing! He took over 1000 shots and every single one is beautiful! We were able to create our own package that suited our needs - with 2 photographers for the entire day, one main album, and 2 parents' albums. He came to meet me where and when it was conveniant for me. And he was extremely open and responsive to our needs. We looked at several photographers before choosing Joe, and his prices are fantastic for the quality that he is able to produce. He is extremely friendly and easy to work with.
When we were planning our wedding, everyone told us the one thing we would have left after the day was over would be the pictures. We kept that in mind and spent more than we originally planned on a photographer. We were so happy with Joe (of Symphony Photography). He was very flexible and responsive from the beginning and our pictures turned out amazing. We have gotten so many compliments on our photos and our album.


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Book your room at Hampton Inn Fayetteville-Cross Creek Mall
One double bed non smokingMax Occupancy: 3 guests (up to 2 children, 2 infants)
Two double beds non smokingMax Occupancy: 5 guests (up to 4 children, 4 infants)
One king bed non smokingMax Occupancy: 3 guests (up to 2 children, 2 infants)
Family-friendly Fayetteville hotel with a seasonal outdoor pool
This family-friendly hotel is located in the city center, close to Cross Creek Mall. Area attractions also include Cape Fear Valley Medical Center and Fort Bragg.
Hotel Features
In addition to complimentary wireless Internet access, Hampton Inn Fayetteville-Cross Creek Mall provides dry cleaning/laundry services, laundry facilities, and a business center.
Room Amenities
LCD televisions come with cable channels. Guestrooms also feature complimentary wireless Internet access, refrigerators, and microwaves.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
High-speed wireless Internet access is complimentary. This hotel offers access to a business center and a meeting room. Guests can enjoy a complimentary breakfast. Event facilities measure 960 square feet (86 square meters). This family-friendly hotel also offers a seasonal outdoor pool, laundry facilities, and dry cleaning/laundry services. Complimentary self parking is available on site.
- Number of buildings/towers - 1
- Conference space size (meters) - 86
- Conference space size (feet) - 960
- Total number of rooms - 131
- Number of floors - 4
- Elevator/lift
- Free breakfast
- Business center
- Express check-out
- Free WiFi
- 24-hour front desk
- Dry cleaning/laundry service
- Outdoor seasonal pool
- One meeting room
- Laundry facilities
- Safe-deposit box at front desk
- Free self parking
Available in all rooms: Free WiFi
Available in some public areas: Free WiFi
Free self parking
Room Amenities
- Free cribs/infant beds
- Air conditioning
- Premium bedding
- Private bathroom
- Phone
- Free local calls
- Refrigerator
- Coffee/tea maker
- Microwave
- Daily housekeeping
- Free toiletries
- Hair dryer
- Shower/tub combination
- Desk
- Iron/ironing board
- Rollaway/extra beds available
- Cable TV service
- Free WiFi
- Climate control
- Free newspaper
- Connecting/adjoining rooms available
Where to Eat
Guests are offered a complimentary hot/cold buffet breakfast.
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Roll-in shower
Hotel Policies
Minimum check-in age is 18
Check-in time starts at 3 PM
Check-out time is noon
Payment types
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
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On February 28, 2013, the Black Law Students Association presented a panel discussion on blacks and minority images in the media. BLSA President LaToia Williams-Dyson, 2L, moderated a panel featuring OCPD Director Vanita Snow and Professor Wilhelmina Reuben-Cooke. Ms. Williams-Dyson opened the discussion by asking the panelists about stereotypes in reality shows like the Real Housewives of Atlanta. Ms. Snow said reality television is shaped by the dominant cultural perspective of the producers of the show. She also added that blacks are rarely the producers of television shows and lack financial resources to produce images that they might like to see. Prof. Reuben-Cooke spoke about stereotypes in the Amos 'n' Andy show while adding that black professionals are also portrayed negatively in tv shows like Ally McBeal. Clips from Love & Hip Hop and A Different World were shown, and the audience discussed positive vs. negative stereotypes of minorities in the media.
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European Tour "drama on the world stage" by Saatchi & Saatchi London
Rating: 5.0
Outgoing executive creative director
+44 (0)20 7494 9120.
67-69 Beak Street, , London, , W1F
14th March 1966
Stone Roses.
One People by Guy Kennaway.
My children provide the audio entertainment at breakfast time.
Four years at Butterfield Day Devito Hockney, three years at Duckworth Finn Grubb Waters; two and a half years at BMP DDB; eight years at Fallon.
The Guardian.
Wife Rachel; sons Jonah and Sidney.
Look like a model, don't act like one' for Lee jeans written some time during the 80s by, I think, Mike Lescarbeau, the great Fallon McElligott copywriter.
iChat, if I could figure it out.
I've said it before but my boys at home, my boys at work.
World of Interiors, Condé Nast Traveller, Arena, GQ.
You're just fishing for compliments.
Sitting in on a Guardian editorial meeting.
The guy who's opened the Flat White coffee shop in Berwick Street.
The Observer, The Sunday Times.
Match of the Day.
Saab Convertible.
Rating: 5.0
Rating: 5.0


text:
zecheng dou
Quick Facts
- Age at Festival
- 15
China is a sporting superpower having won the medal tally at the 2008 Beijing Olympic Games and only just being beaten by the USA in 2012. It is fantastic they will have the second largest Team at the Festival, behind host nation Australia, with 189 athletes. They will be extremely competitive in all sports they are contesting.
Location: Eastern Asia
AYOF History: 2001, 2003, 2005, 2007, 2009
2013 Sports: Athletics, Badminton, Basketball 3x3 (men & women), Canoe/Kayak Slalom, Diving, Gymnastics (Artistic, Rhythmic, Trampoline), Golf, Hockey (women), Judo, Rugby Sevens (men & women), Shooting, Swimming, Triathlon, Weightlifting, Wrestling
Athletes: 189
Related News
Yuan family puts Australia within reach of golf gold
GOLF: Brother-sister combination Kevin and Celina Yuan have put Australia within reach of its first Australian Youth Olympic Festival medals at Twin Creeks Golf and Country Club on Saturday. Read more...
Did You Know?
Rugby sevens and golf will make their debut in an Olympic competition at the 2013 AYOF. The competing nations will have the chance to test out their wares as they begin the road to the senior Olympic debut at the Rio Games in 2016.


text:
1758 English cricket season
|Cricket formats
|major, including single wicket
Only one major match has been found among reports of the 1758 English cricket season. The reduction in matches was due to the Seven Years' War.
Fresh Light on 18th Century Cricket records a number of parish games: e.g., Saffron Walden v Cambridge; Faversham v Tenterden; Faversham v Dover; New Romney v Ashford. The presence of these and the absence of "great matches" indicates the lack of investment and resource in the game during wartime with the sport falling back onto its parish roots.[1]
Cricket Scores 1730 - 1773 records a "fives" game on Kennington Common in August. Tom Faulkner, one of the Harrises and three more of the London Cricket Club defeated five players from various Surrey clubs by three wickets.[2]
|Match Title
|16 & 17 August (W-Th)
|London & Surrey v Kent [1]
|Artillery Ground?
|London & Surrey won
The venue is uncertain and it is possible a return game took place at any of about five venues but the report in the General Evening Post (three weeks later) is very ambiguous.
- ^ a b G B Buckley, Fresh Light on 18th Century Cricket, Cotterell, 1935
- ^ H T Waghorn, Cricket Scores, Notes, etc. (1730-1773), Blackwood, 1899
- Buckley, G. B. (1935). Fresh Light on 18th Century Cricket. Cotterell.
- McCann, Tim (2004). Sussex Cricket in the Eighteenth Century. Sussex Record Society.
- Waghorn, H. T. (1899). Cricket Scores, Notes, etc. (1730–1773). Blackwood.
- Waghorn, H. T. (1906). The Dawn of Cricket. Electric Press.
- Wilson, Martin (2005). An Index to Waghorn. Bodyline.
Additional reading[edit]
- ACS (1981). A Guide to Important Cricket Matches Played in the British Isles 1709 – 1863. Nottingham: ACS.
- Altham, H. S. (1962). A History of Cricket, Volume 1 (to 1914). George Allen & Unwin.
- Birley, Derek (1999). A Social History of English Cricket. Aurum.
- Bowen, Rowland (1970). Cricket: A History of its Growth and Development. Eyre & Spottiswoode.
- Buckley, G. B. (1937). Fresh Light on pre-Victorian Cricket. Cotterell.
- Major, John (2007). More Than A Game. HarperCollins.
- Maun, Ian (2011). From Commons to Lord's, Volume Two: 1751 to 1770. Martin Wilson. ISBN 978-0-9569066-0-1.
- Mote, Ashley (1997). The Glory Days of Cricket. Robson.
- Underdown, David (2000). Start of Play. Allen Lane.
External links[edit]
- Classification of cricket matches from 1697 to 1825
- CricketArchive – 1758 match list
- From Lads to Lord's; The History of Cricket: 1300 – 1787


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Creekside Home SpacesSeries Website »
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See how the new home spaces are defined as the walls and ceilings get a Level 5 finish.
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text: %%%%%% Our articles are about tropes used in the work. If you want to write a review, feel free to click%% the "reviews:" link at the top of the page. Don't embed your review here.%%%%[[quoteright:350:http://static.tvtropes.org/pmwiki/pub/images/tvtropes-originallifekids_1614.png]][[caption-width-right:350:Thomas, Abigail, and Janie]]''[[http://www.jaynaylor.com/originallife/ Original Life]]'' is a comedy webcomic written by Jay Naylor. The strip began on June 1, 2009, right after Naylor finished up its predecessor, ''BetterDays''. It details the life and times of Fisk and Elizabeth and their children - Abigail, Thomas and Janie - as well as the lives of other ''Better Days'' cast members and their children.Unlike ''Better Days'', ''Original Life'' features a lighter and more humorous plot, with minor segments of dramatic moments interspersed throughout. Also, rather than following Fisk and Lucy as they progress through life as in ''Better Days'', the characters of ''Original Life'' do not age; the comic is also set in modern times, as opposed to the gradual timescale of ''Better Days''. These changes are mainly due to Naylor opting to "just keep it fun," stating that he enjoyed the lighter chapters of ''Better Days'' far more than the somber ones.----!!This webcomic provides examples of:* AbortedArc: The love letter. Maybe. Just when you least expect it, it pops up again.* AscendedMeme: [[http://www.jaynaylor.com/originallife/comic/OL125.10-08-09.jpg Maybe.]] Could be nothing more than a coincidence, though. * BareYourMidriff: Janie, making Elizabeth's refusal to buy her a two-piece bathing suit pretty ridiculous.* DeepImmersionGaming: ** Thomas plays ''VideoGame/GearsOfWar'' in one of the first comics... with the badass protagonist coincidentally drawn like his father.** Semi-justified with ''Franchise/MassEffect'', as Shepard's appearance is customizable.* DisappearedDad: Fisk, since his job keeps him on the road. It's been argued that he just drops by occasionally to enjoy the parts of fatherhood he likes, while skipping out on most of that messy parenting stuff.* GirlsHaveCooties: [[http://www.jaynaylor.com/originallife/archives/2009/11/052.html This storyline]].* HollywoodAtheist: Played straight by Janie when she starts looking into religion, she decides they're all full of it.* LighterAndSofter: Naylor himself said that he wants to "keep it fun".* LittleKnownFacts-->'''Janie:''' Daddy, where does the baby in Mummy's tummy come from?-->'''Fisk:''' Wal-Mart* MostWritersAreAdults: None of the kids in this strip talk or act like kids.* MrImagination - Or ''Ms'' in Abigail's case.* RealLifeWritesThePlot: Bonk redesigned his character, so we get a couple comics dealing with Bonk's redesign in-universe.* ShoutOut:** Abby reenacts scenes from ''Film/TheFly'' and ''Film/{{Darkman}}''. She also quotes random bits of [[AerithAndBob Yoda and Patton]].** Thomas wanted Abigail to train him, like ''[[Franchise/ThePinkPanther Cato did for Inspector Clouseau]]** Abby's stuffed animal is a representation of Naylor's fellow artist friend Bonk.** Abby builds some autoturrets from ''VideoGame.{{Portal}}'' in a rather gratuitous (and past-its-date) reference.** [[Film/{{Patton}} Blalock, you magnificent bastard...]][[http://www.jaynaylor.com/originallife/archives/2009/07/013.html I read your book!]]** [[http://www.jaynaylor.com/originallife/archives/2010/10/145.html This strip]] features an appearance by singer Grace Jones. This was an InJoke that also occurs in ''BetterDays''.* SliceOfLife: The comic shows the daily life of Fisk and Elizabeth and their children.* StrawmanPolitical: Angelica, the bunny girl mentioned above and one of Janie's friends, seems to have this as her entire character purpose. She stands for and likes many things that Naylor dislikes, like belief in anthropogenic global warming, philosophical skepticism, new age spiritualism, and JustinBieber.* WellIntentionedExtremist: Fisk and the group of unsanctioned assassins that employs him seem to fall under this, judging by the explanation in ''Better Days''.----


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I haven't really been taking the baby out around people. I don't trust people. We have been to 1 restaurant. . So this morning I decided to go eat with my ex boss lady. We've been friends a while. She was holding my son and took her biscuit and dipped it in her egg yolk and stuck it in my baby's mouth!!! I was livid. I fussed and told her he only gets breast milk, he isn't old enough for anything other than breast milk and when he is I will give him his first food and that she should have asked first, which I would have told her no. She tells me her kids had teeth by 3 months and were both eating pizza. Okay well we had just had the discussion that my son has no teeth and no little bud like they are coming in. So I let her keep holding him thinking it wouldn't happen again. Then she done it again, I was completely speechless. I took the baby from her and she didn't get him back. I am so upset. I don't trust people and every time I think I can, this happens. What if he would have been allergic to eggs or something. Omg I'm so mad about this. Dh said let it go that it's fine. To me it's not fine, you don't just go around giving other people's 10 week old baby food without permission. The she actually whispered to him that when she babysits him she will give him stuff he isn't supposed to have. Are you kidding me? Maybe I'm over reacting but I'm pretty damn pissed. My mom is just as mad as I am.
She gave my 10 week old son egg yolk :( (twice)
Posted 10/16/2013
Posted 10/16/2013
Uhh don't ever let her babysit him...
Posted 10/16/2013
Her 3 month old was eating pizza? There are so many things wrong with that statement, I don't even know where to start.
Posted 10/16/2013
no, I totally agree with you! I think its just common sense to ask the parent first if the child could have this or that.
Posted 10/16/2013
Wow! I probably would have went off and left. You don't do stuff like that to other peoples baby. I'm very grudgeful so who knows how long I would go without speaking to her. The first time she did it was bad enough but the second time. HELL NO
Posted 10/16/2013
You are not overreacting! I would have been pissed. Yeah, she should definitely not babysit. Teeth or no teeth 3 month olds eating pizza is just wrong.
Posted 10/16/2013
1) her three month old was eating pizza?? Uh, no. She's full of shit.
2) had this been me, she'd have gotten the verbal lashing of a lifetime...I woulda embarrassed the hell out of her. And the second time? Huh-uh. If she hadn't have been holding the baby, she'd be missing some teeth.
2) had this been me, she'd have gotten the verbal lashing of a lifetime...I woulda embarrassed the hell out of her. And the second time? Huh-uh. If she hadn't have been holding the baby, she'd be missing some teeth.
just_lovely22 · Original Poster
Posted 10/16/2013
I'm glad ya'll agree. My mom is mad too. I was so stunned i didnt even know what to say. I fussed at her and couldnt believe she did it again. I Am sitting here now thinking of all these things I should have said. My prepregnancy self would have scratched her eyes out and screamed ar her till she cried. I'm not like that anymore but maybe i should have been right then.
I dont really know that I believe the pizza thing unless she is actually stupid.
I dont really know that I believe the pizza thing unless she is actually stupid.
Posted 10/16/2013
She would never babysit my kids or be alone with them. She has no respect for you for doing that after you told her no and then saying what she said.
Robin (37) married to JP (44)
Proud mommy to Jayin Nov'09 and Rohan Aug'13
Posted 10/16/2013
Never leave LO alone with her. Ever.
You had more restraint than I would have...giving a 10 week old egg yolk is not ok.
You had more restraint than I would have...giving a 10 week old egg yolk is not ok.
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About Us
The Buccaneer is the Caribbean's Longest Running Family- Owned Resort
It is with pleasure that I welcome you to The Buccaneer's website, and I hope that our site will entice you to visit in the near future. The Armstrong family has owned and operated the resort since my grandparents opened the doors in 1947, and we will be looking forward to celebrating 70 years of hospitality in 2017. I hope that you will take time to read The Buccaneer's fascinating history in the pages of this website.
Over the years we have taken great pleasure in the high honors that we have received from the travel industry, as well as a multitude of "World's Best" accolades. Our deepest satisfaction comes from the glowing reports of satisfied guests, many of whom we have been proud to serve for generations. You have our enduring promise that we will strive to meet and exceed the highest standards of taste, elegance and our guests' discerning preferences. When you stay at The Buccaneer, our pledge is best expressed in our mission statement:
Our mission is for every guest to return to The Buccaneer and become part of The Buccaneer family. We pledge to provide world-class service and to share our heritage, warmth and friendliness, ensuring that every visitor becomes an ambassador for St. Croix.
I look forward to greeting you personally during your stay, perhaps at the Tuesday cocktail party at our historic sugar mill or on my weekly nature walk. All of us at The Buccaneer hope to welcome you in the future.
Warm regards,
Elizabeth A. Armstrong
Travel Documents
No passports are required for U.S. citizens. Proof of citizenship is required. Birth certificate with a raised seal plus government issued photo ID or valid US passport will suffice. See www.travel.state.gov for further information.
Customs and Immigration
There is no inbound U.S. Customs nor immigration checks. Outbound immigration and U.S. Customs clearance is processed in St. Croix, which allows you to avoid long lines on your trip home.
Check-in/Check-out times
Check-in is at 3 pm. Check-out is at 11 am. Hospitality rooms will be made available if possible for early arrivals or late departures.
No Smoking
The Buccaneer is a no-smoking facility. Smoking is not allowed in guest rooms, restaurants nor any other public space.
Main entrance, restaurants and lounges, meeting space, entrance to on-site swimming pool, route to registration desk, and guest rooms are accessible. All accommodation categories offer rooms suitable for handicapped guests.
Small, pre-approved dogs are welcome at The Buccaneer, as well as service dogs.
St. Croix Basics
TIME ZONE: Atlantic Standard Time. Daylight savings time is not used. In winter, St Croix is one hour ahead of the eastern US coast. In the summer, the time is the same.
CURRENCY: US dollar. Credit cards and traveler's checks are widely honored.
TEMPERATURE: Winter 72-85F; Summer 77-89F
ELECTRICITY: 110 volt current, the same as the continental US.


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HOme @ GoTell
Greetings and Our Mission
Welcome to our site. We hope to help you develop your biblical storytelling vocation and witness to Jesus' way of peace. The mission of GoTell is to equip people to discover and tell biblical stories as a spiritual discipline for embodying Jesus' way of peace in the world. Please give us feedback or let us know how we can be of service by emailing email@example.com.
Telling the Good News in 21st Century Ministry
Doctor of Ministry Focus Group
This is the focus group for "Telling the Good News in 21st Century Ministry" left to right: Amelia Boomershine, Brice Thomas, Kathy Culmer, Meghan Howard, Elizabeth Green, Tom Boomershine (mentor), Ron Poisel, Joyce Johnson. Faculty mentor Lisa Hess was in Israel at the time. Our action research projects include biblical storytelling/digital media for youth, millennials, incarcerated people, worship, and evangelism. Four of us are on track to graduate this May with our Doctor of Ministry degrees from United Theological Seminary. Three have one more semester to go. In late January we celebrated our last week-long Intensive together in Dayton.
Call Stories for MDiv Students
CinDay Guild Tells at United Theological Seminary
In mid-February the CinDay (Cincinnati-Dayton, Ohio) Guild of the Network of Biblical Storytellers told call stories from both Testaments during a Master of Divinity Intensive Week worship service at United Theological Seminary in Dayton, Ohio. We told the call of Ezekiel (to prophesy to dry bones), the boy Samuel, Jonah, Mary, the fishermen, the rich man (a refused call), and Nathanael. The video below includes all these stories following an introduction by Tom Boomershine.
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Does anyone have an adenium by the name of kulabdam its black and red
There actually is a site if you google it that shows a photo. You may be aware of this, but this site (GW) will not allow that particular site to be used here.
The picture ive seen are so tiny and the tag on my plant is very tiny also i bought it as a bare root plant so i have a long wait for blooms :-( but im very much in love with the two i have bought especially the one with verigated leaves


text:
In the Fall of 2014, Southern Arizona Guide became more than just a website with all of its Dining Reviews and recommended Things To See and Do. We started offering tours to some of the most interesting and historical places in the American Southwest. This slideshow is about our first … Continue reading
Category Archives: Local History – Tombstone
Saturday, December 6, 2014 was the first Tombstone Historic Home Tour. The event was sponsored by The Cameo Ladies of Tombstone, A.T. and Tombstone Forward. The tour was an especially rich experience because these were mostly homes from the historic era and beautifully furnished in period from 1879 to the … Continue reading
Few people have ever seen the Old West from this unique perspective. Please join us Monday, January 19, 2015 for a tour of two historic Southern Arizona ghost towns and a behind the scenes tour of one town that was "too tough to die". Your guide will be Jim Gressinger, … Continue reading
Fairbank ghost town (aka Fairbank Historic Townsite) is about a 20 minute drive from Tombstone. It is located along the San Pedro River within the San Pedro Riparian National Conservation Area. Fairbank was established in 1881 as a depot for the railroad. The town was named for N.K. Fairbank, one … Continue reading
On the 4th Saturday of the month, Tombstone shopkeepers have started keeping their doors open and light on after sunset. They call this event: Tombstone At Twilight.Continue reading
Conspicuous by its absence, the Gunfight At The O.K. Corral, Tombstone's most popular attraction, has not graced the pages of Southern Arizona Guide … until now. Why? At Southern Arizona Guide we have a guiding philosophy. If we cannot wholeheartedly recommend your establishment or event to our friends & family, … Continue reading
Wyatt Earp, now with federal authority, assembled a posse of gunmen to hunt for his brother's would-be assassins.Continue reading
Boothill is authentic. It was Tombstone's first City Cemetery, established in 1879. It wasn't called Boothill until the 1920's, probably as a result of Hollywood westerns or dime novels.Continue reading
TOMBSTONE'S RAILROAD CENTENNIAL reprinted with permission from Tombstone Times. by Larry Jensen & Ray Madzia Picture the day. Feel the event. The Railroad was coming to Tombstone!!!! It had been nearly 25 years that folks had been arriving in Tombstone, but not by rail. The railroad had not laid tracks … Continue reading
In 1880, old age began about 40, the average life expectancy of a U.S. citizen. Life was hard, good nutrition & effective medical treatment were scarce. By age 40, most people, particularly women, were simply worn out. Between 1879 and 1884, about 300 people were buried in the Tombstone Boothill … Continue reading


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Advertising Effectiveness
Mobile marketing: the 7% solutionOctober 01, 2012
A panel of mobile marketing experts at Advertising Week discuss the MMA's contention that brands should be spending 7% of their budgets on mobile.
These are the ads of our timesDecember 29, 2011
As the last sands of 2011 dribble through that great hourglass of life, it's important to take stock and look back.
Ad effectiveness on content sites outranks ad networks and portals, according to studyAugust 13, 2009
Advertising placed through ad networks and portals generated the smallest change for branding metrics, and in some cases made no difference for advertisers, according to findings of a study released August 13 by the Online Publishers Association, a trade organization for publishers such as ABCNews.com, CNN, CondeNet, Time Inc. and The Wall Street Journal.
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As the leading source for direct marketing youth data, ASL Marketing connects your brand to consumers with extensive and unparalleled industry expertise in data content, aggregation and analytics of the youth, young adult and student demographics. We provide access to the most comprehensive, response driven youth database available - over 175 million active high school, college and young adult consumers and their parents. We offer custom solutions devised to meet your specific target and goal. Our data customization allows you to pinpoint your audience by selecting by age, ethnicity, grad year, etc... Our clients range across all industries including Financial Services, Technology, Health & Beauty, Retail, Educational Services, Recruitment, and more.
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While We're Young
While We're Young searches for the blurry line we all cross once we've entered middle age, finds it and tramples all over it, but it…
While We're Young searches for the blurry line we all cross once we've entered middle age, finds it and tramples all over it, but it…
Imagine an "R" rated "Lassie" by way of "Spartacus." That's Kornél Mundruczó's "White God," a brutal but stirring fantasy about street dogs rising up against…
"The Ballad of Narayama" is a Japanese film of great beauty and elegant artifice, telling a story of startling cruelty. What a space it opens…
Patrice Leconte's "Monsieur Hire" is a tragedy about loneliness and erotomania, told about two solitary people who have nothing else in common. It involves a…
A preview of Ebertfest 2015.
An encounter with the legendary documentarian Albert Maysles, who recently passed away.
A film teacher looks back on "The Breakfast Club," partly through the eyes of her students.
A preview of Ebertfest 2015.
Our Far-Flung Correspondent Brings Explosive Polish 1980s Sci-Fi to NYC
"Dear White People" director Justin Simien, editor Phillip J. Bartell, composer Kathryn Bostic and cinematographer Topher Osborn at the Film Independent Directors Close-Up series.
The strange unraveling of Cinderella; Kimmy Schmidt skewers empowerment culture; Charles Grodin's fine art of reaction; Putting "use" back in fair use; Yoga pants are…
A look at recent releases on Netflix and Blu-ray, including "Life Itself," "Annie," "Into the Woods," "The Lady From Shanghai," and more.
More moviegoers see films on video in some form than ever before -- whether streaming on demand, cable or satellite, instant download services, DVD or Blu-ray. Even high-profile pictures become available to home viewers before or at the same time as their theatrical release. Reviewing them is a job for... The Demanders!
I had my doubts. I can still vividly remember watching "Fargo" on its initial theatrical release and being as blown away as the rest of the world. It's one of those rare films that merits the word masterpiece. And while classic films like "Psycho" and "Manhunter" have been reworked into great TV shows like "Bates Motel" and "Hannibal", I wasn't quite ready for "Marge Gunderson: The College Years" or "Lundegaard." Knowing that Joel & Ethan Coen were involved as Executive Producers allayed my fears a bit and the cast was increasingly impressive as it was announced but the fact is that "Fargo" simply didn't feel like something that lent itself to network television. I was wrong.
FX's "Fargo," debuting April 15, 2014, is clever, fun, twisted, and wildly entertaining in the way that fans of not just "Fargo" but all of the Coens' work hoped it would be. With an amazing ensemble driven by great performances from top to bottom, an incredibly smart writers' room, brilliant callbacks to the original that feel more inspired than forced, and a filmmaking style that feels as cinematic as this grand Minnesotan tragedy deserves, "Fargo" is one of the most addictive new shows of the year.
If it's unclear from the clever promotional material for the show, 2014's "Fargo" is not a remake of the 1996 film; using the Coen film as a tonal template more than anything else. Again, there's the "This is a True Story" introduction, building a true crime aesthetic that will reportedly feature new characters every season a la "True Detective". And some of the character archetypes are intentionally familiar. Lester Nygaard (Martin Freeman) may not know what Tru Coat is but he has a similarly soul-crushing job selling life insurance. He is in a loveless marriage with a woman who constantly berates him and compares him to his more successful brother. In the premiere, "The Crocodile's Dilemma", Lester is bullied publicly by the same brute who tortured him in school. Life has beaten Lester down and he's about to strike back.
Enter Lorne Malvo (Billy Bob Thornton), an amalgam of both Carl Showalter (Steve Buscemi) and Gaear Grimsrud (Peter Stormare) from the film in that he's the outsider who stirs up trouble but a character who also bears a striking and I don't believe coincidental tonal resemblance to Anton Chigurh (Javier Bardem) from "No Country For Old Men". Lorne is a psychopath. He's introduced driving through Bemidji, hitting a deer, and watching a mostly-naked man bound from his trunk through the Minnesotan snow. How did the man get in his trunk? Where was he headed with him? The accident creates a detour for Malvo, who crosses paths in the hospital waiting room with the just-bullied Lester.
The day the homicidal lunatic met the man in need of some violent inspiration is only one of many plot plates that are set spinning in the first four episodes of "Fargo" sent for press. We haven't even gotten to the "Marge" of the piece, a sweet, young officer named Molly Solverson (Allison Tolman), who finds herself deep in a criminal investigation when her town is beset upon by extreme violence. The cast of colorful characters includes a grocery store owner (Oliver Platt) being blackmailed, a not-so-grieving widow (Kate Walsh), Molly's supportive father (Keith Carradine, echoing the "times they are a-changing" world-weariness of Tommy Lee Jones' character from "No Country" at times), the hysterically moronic Don Chumph (Glenn Howerton of "It's Always Sunny in Philadelphia"), the misguided Deputy Bill Oswalt (Bob Odenkirk), and a pair of riveting killers known as Mr. Wrench (Russell Harvard) and Mr. Numbers (Adam Goldberg). And then there's the immensely likable Gus Grimly (Colin Hanks) and his daughter Greta (Joey King), who get involved in the drama in a way that it might be considered a spoiler to even mention.
Also like the Coens, Hawley and his writers are fascinated by the stupidity of people who should know better. Many of the adults in the world of "Fargo" are total morons, although there's also a fascinating motif in that their kids are even stupider. Idiotic children who play with bows and arrows in the backyard will become idiotic adults who play with guns. And yet, again like the film, one never feels like "Fargo" is mocking its characters or those who live in the great white North of the U.S. The accents are funny, the suburbia can be soul-draining, and the snow seems to never stop but there are wonderful moments of heartfelt characterization within "Fargo", particularly in the relationships between Molly and her father and Gus and his daughter.
Performances are uniformly fantastic. As much as I'd love to highlight Freeman, who really is fantastic here, Hanks steals later episodes with the best use of his everyman relatability in years and supporting roles like those played by Platt, Goldberg, Odenkirk, and especially Thornton resonate. Everyone works, as one would expect with a cast this talented, and the newcomer, Tolman, more than holds her own with the more recognizable faces. By the fourth episode, I smiled a bit every time she came on-screen.
There's also a visual confidence to "Fargo" that's playful and smart. Director Adam Bernstein (who helmed the first two) and those who follow in his footsteps lovingly callback to the film, whether it's in a shot that echoes Marge's final drive (complete with a nearly identical score) or an overhead shot that won't be spoiled but directly mimics the film. Like the children carrying on the legacy of their parents, for better or worse, in the show, the 2014 "Fargo" resembles the 1996 version but has a personality, drive, and life of its own. Don't doubt it.
Next Article: AMC's "Mad Men" Begins Final Descent Previous Article: Streaming Consumer Guide: April 8, 2014
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