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Articles by John A. Stanford
In JoVE (1)
Other Publications (38)
- Neurobiology of Aging
- Pharmacology, Biochemistry, and Behavior
- Neurobiology of Aging
- Neuroscience Letters
- Experimental and Clinical Psychopharmacology
- Neurobiology of Aging
- The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
- Brain Research
- Neuroscience Letters
- Neurobiology of Aging
- Journal of Neurochemistry
- Neuroscience Letters
- Behavioural Pharmacology
- Neurobiology of Aging
- Physiology & Behavior
- Behavioural Pharmacology
- Behavioural Brain Research
- Experimental Neurology
- Neuroscience Letters
- Behavioural Brain Research
- Pharmacology, Biochemistry, and Behavior
- American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
- Behavioural Brain Research
- PloS One
- Behavioural Brain Research
- Journal of Neuroscience Methods
- Neuroscience Letters
- Neuro-degenerative Diseases
- Muscle & Nerve
- Physiology & Behavior
- Psychopharmacology
- Brain Research
- Pediatric Research
- Brain Research
- Neurochemistry International
- Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology
- Neurorehabilitation and Neural Repair
- Cell Transplantation
Articles by John A. Stanford in JoVE
שיטות וטיפים על עירוי לוריד של Adeno-הקשורים וירוס חולדות והערכה של מערכת העצבים המרכזית התמרה חושית Mychal S. Grames1, Kasey L. Jackson1, Robert D. Dayton1, John A. Stanford2, Ronald L. Klein1 1Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, 2Department of Molecular & Integrative Physiology, University of Kansas Medical Center שיטות משלוח הגן רחב היקף מערכת העצבים המרכזית בחולדה מכוסים. בדוגמה זו, המטרה היא לחקות מחלה המשפיעה על חוט השדרה כולו. התמרה חושית רחבה יכול לשמש כדי לספק חלבון טיפולית מערכת העצבים מהמינהל, היקפי חד פעמי.
Other articles by John A. Stanford on PubMed
Aged F344 Rats Exhibit an Increased Proportion of Dopamine Agonist-excited Striatal Neurons Neurobiology of Aging. Mar-Apr, 2002 | Pubmed ID: 11804712 In order to study age-related differences in striatal electrophysiological activity in freely-moving animals, multi-wire electrode arrays were chronically implanted in the striatum of young (6-8 months) and aged (24-26 months) Fischer 344 rats. After recording baseline activity, d-amphetamine (D-AMPH; 1.0 mg/kg) and apomorphine (APO; 0.5 mg/kg) were administered to the two age groups. For both the D-AMPH and APO series, the percentage of striatal neurons that increased firing rates as a result of the DA agonists was 19% higher in the old animals than in the young animals. In addition, D-AMPH increased the firing rates of D-AMPH-excited neurons to a greater extent in the old animals than in the young animals. While the rate-increasing effects of APO did not differ significantly as a function of age, its effects were slightly greater in the old animals as well. These results suggest that age-related decreases in nigrostriatal DA function may result in alterations in the way in which the striatum integrates corticostriatal and nigrostriatal inputs to influence motor function.
Acute Locomotor Effects of Fluoxetine, Sertraline, and Nomifensine in Young Versus Aged Fischer 344 Rats Pharmacology, Biochemistry, and Behavior. Jan-Feb, 2002 | Pubmed ID: 11812540 Spontaneous locomotor activity was measured in young (6-8 months) and aged (24-26 months) Fischer 344 (F344) rats. Following habituation to the activity monitors, aged rats demonstrated significantly diminished motor activity as quantified by total distance traveled and vertical activity. Movement speed did not differ significantly between the two groups. Following habituation, rats were administered acute doses of fluoxetine, sertraline, or nomifensine (1.0, 3.0, and 10.0 mg/kg). Fluoxetine diminished all three behavioral measures in the young rats, while in the old rats, fluoxetine's effects were limited to a robust attenuation of vertical activity. Sertraline decreased movement speed and vertical activity, but not total distance traveled, in the young rats. Unlike fluoxetine, sertraline produced no significant effects on any of the three behavioral variables in the old rats. Nomifensine increased behavioral scores for both age groups. The results are discussed in relation to acute motor side effects of selective serotonin reuptake inhibitors (SSRIs) in motor-impaired aged individuals, as these effects may influence their eventual use in the clinic.
Effects of Chronic Intraputamenal Infusion of Glial Cell Line-derived Neurotrophic Factor (GDNF) in Aged Rhesus Monkeys Neurobiology of Aging. Sep-Oct, 2002 | Pubmed ID: 12392792 In this study, 17-23 year old Rhesus monkeys were used as an early model of Parkinson's disease (PD). Four animals received chronic infusions of GDNF and four received vehicle infusions into the right putamen via programmable pumps for 8 weeks. Weekly videotaping was performed to record general motor performance and a monkey movement analysis panel (mMAP) was used to quantify fine and coarse upper limb motor performance. The GDNF-treated animals showed significant improvements in their overall motor performance in the last 3 weeks of the study compared to controls. Fine motor time of the upper limbs improved significantly in both the GDNF-treated and control animals. After 8 weeks of drug administration, the animals were euthanized and tissue punches were taken from the basal ganglia for measures of dopamine (DA) and DA metabolite levels. In the right putamen, GDNF infusion produced a 217% increase in homovanillic acid (HVA) levels. In addition, DA levels increased by 50% in the right caudate nucleus and there were 122 and 76% increases in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the right and left caudate nucleus, respectively. HVA levels were also seen to be increased by 212% in the right caudate nucleus. Finally, changes were seen in the right globus pallidus, with 390 and 171% increases in DA and HVA levels, respectively. These data support the hypothesis that GDNF may be beneficial for the treatment of damaged or degenerating DA neurons in aged monkeys and possibly in aged humans.
Aged Fischer 344 Rats Exhibit Altered Locomotion in the Absence of Decreased Locomotor Activity: Exacerbation by Nomifensine Neuroscience Letters. Nov, 2002 | Pubmed ID: 12429381 A novel force plate actometer was used to measure locomotor activity and gait in young (6 months) versus aged (24 months) Fischer 344 rats. The actometer revealed altered gait in the aged rats in the absence of decreased locomotor activity. The catecholamine uptake inhibitor, nomifensine increased locomotor activity in both groups and exacerbated the gait alteration in the aged group. Analyses of whole brain tissue levels of dopamine (DA), 3,-4 dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the substantia nigra and dorsal striatum revealed no significant differences between the two age groups. In the young (but not aged) rats, distance traveled was negatively correlated with striatal DOPAC + HVA/DA tissue ratios (a measure of DA turnover). In the aged (but not the young) rats, positive correlations were observed between distance traveled and DOPAC + HVA/DA ratios in the substantia nigra. Neither striatal nor nigral DA content was significantly correlated with distance traveled in either age group. These findings demonstrate that aged rats may exhibit functional changes in locomotor activity in the absence of quantitative changes in nigrostriatal DA content.
Dantrolene Diminishes Forelimb Force-related Tremor at Doses That Do Not Decrease Operant Behavior in the Rat Experimental and Clinical Psychopharmacology. Nov, 2002 | Pubmed ID: 12498335 A behavioral preparation that affords concurrent measurement of forelimb force and tremor in rats was used to assess the effects of dantrolene sodium, a muscle relaxant and potential neuroprotective drug. Rats that were trained to press downward on an isometric force transducer while simultaneously licking water reinforcement were administered dantrolene (5.0 mg/kg, 7.5 mg/kg, and 10.0 mg/kg). Dantrolene diminished force output at the 7.5 mg/kg and 10.0 mg/kg doses and decreased tremor at all three doses. Dantrolene decreased the ratio of forelimb tremor to force output at all three doses. Dantrolene did not suppress operant behavioral output at these doses. These results suggest that dantrolene may affect fine motor control and decrease tremor at doses that do not produce behavioral suppression.
Aged Fischer 344 Rats Exhibit Altered Orolingual Motor Function: Relationships with Nigrostriatal Neurochemical Measures Neurobiology of Aging. Mar-Apr, 2003 | Pubmed ID: 12498959 The present study utilized a novel behavioral preparation to measure differences in orolingual motor function between young (6 months) and aged (24 months) Fischer 344 (F344) rats. Rats were trained to lick an isometric force-sensing operandum for water reinforcement so that the number of licks per session, licking rhythm and lick force could be compared between the two groups. The aged rats exhibited a greater number of licks per session, but a slowed licking rhythm, compared to the young rats. Lick force did not differ significantly between the groups. The dopamine (DA) uptake inhibitor nomifensine decreased all three measures in both groups. Analyses of whole brain tissue content of DA, 3,4 dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the substantia nigra and dorsal striatum revealed no significant differences between the two age groups. Differences were observed between the two groups with respect to relationships between behavioral and neurochemical tissue measures. Striatal DA content and the number of licks per session were positively correlated for the young rats but not for the aged rats. In the aged rats, but not the young rats, positive correlations were also observed between licking rhythm and the DOPAC+HVA/DA ratio in the substantia nigra. These findings suggest that age-related alterations in orolingual motor function may relate in part to functional changes in DA neuronal circuits.
Glial Cell Line-derived Neurotrophic Factor Increases Stimulus-evoked Dopamine Release and Motor Speed in Aged Rhesus Monkeys The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Mar, 2003 | Pubmed ID: 12629203 Changes in the functional dynamics of dopamine release and regulation in the basal ganglia have been posited to contribute to age-related slowing of motor functions. Here, we report the effects of glial cell line-derived neurotrophic factor (GDNF) on the stimulus-evoked release of dopamine and motor speed in aged monkeys (21-27 years of age; n = 10). Although no changes were observed in the vehicle controls (n = 5), chronic infusions of 7.5 microg of GDNF per day for 2 months into the right lateral ventricle initially increased hand movement speed up to 40% on an automated hand-reach task. These effects were maintained for at least 2 months after replacing GDNF with vehicle, and increased up to another 10% after the reinstatement of GDNF treatment for 1 month. In addition, upper-limb motor performance times of the aged GDNF-treated animals (n = 5) recorded at the end of the study were similar to those of five young adult monkeys (8-12 years of age). The stimulus-evoked release of dopamine was significantly increased, up to 130% in the right caudate nucleus and putamen and up to 116% in both the right and left substantia nigra of the aged GDNF recipients compared with vehicle controls. Also, basal extracellular levels of dopamine were bilaterally increased, up to 163% in the substantia nigra of the aged GDNF-treated animals. The data suggest that the effects of GDNF on the release of dopamine in the basal ganglia may be responsible for the improvements in motor functions and support the hypothesis that functional changes in dopamine release may contribute to motor dysfunctions characterizing senescence.
Microdialysis Studies of D-amphetamine-evoked Striatal Dopamine Overflow in Young Versus Aged F344 Rats: Effects of Concentration and Order of Administration Brain Research. Jul, 2003 | Pubmed ID: 12850587 In order to measure the effects of different concentrations of D-amphetamine (D-AMPH) infusions on striatal dopamine (DA) overflow in young versus aged rats, and to determine the influence of preceding infusions on subsequent stimuli, two microdialysis studies were conducted. In the first study, D-AMPH (100, 200, and 2000 microM) was infused in ascending order of concentration, while in the second study the order of administration was reversed. The order of administration significantly affected DA overflow and extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC). Generally, DA overflow was greater for a given concentration when it was administered first in a sequence than when it was administered later in a sequence. The two age groups did not differ on measures of DA overflow. The order of administration also significantly influenced the effect of D-AMPH on extracellular DOPAC, as the D-AMPH-related decreases in DOPAC were greater for a concentration when it was administered earlier versus later in the sequence. This effect was greater in the young rats than in the aged rats. D-AMPH also resulted in diminished levels of DOPAC in the aged rats compared to the young rats. These results suggest that between-groups studies may be more appropriate for determining the effects of different concentrations of D-AMPH on striatal DA overflow. They also demonstrate that while some measures of stimulus-evoked DA overflow may not differ between young and aged F344 rats, extracellular regulation of striatal DA (as measured by changes in DOPAC) may be altered. These alterations may contribute to age-related decreases in motor function.
Differential Effects of Post-implantation Time on Potassium- Versus D-amphetamine-evoked Dopamine Overflow in the Striatum of F344 Rats Neuroscience Letters. Sep, 2003 | Pubmed ID: 12902027 Effects of post-implantation time on potassium (K+)- versus D-amphetamine (D-AMPH)-evoked striatal dopamine (DA) overflow were measured using microdialysis in freely moving young and aged Fischer 344 rats. In one group, samples were collected on the day of probe insertion (Day 1 group). In a second group, samples were collected 24 h after probe insertion (Day 2 group). While analyses revealed no significant differences between the two age groups, the 100 mM K+ stimulus evoked a significantly greater amount of DA overflow in the Day 1 group compared to the Day 2 group. The decrease in 3,4-dihydroxyphenylacetic acid (DOPAC) produced by K+ stimulation was not influenced by post-implantation time. The effect of the 250 microM D-AMPH stimulus on DA overflow did not differ between the Day 1 and Day 2 groups, nor did the decrease in DOPAC that accompanied D-AMPH stimulation. These results support the hypothesis that under some stimulus conditions, post-implantation time is an important variable in microdialysis studies.
Aged F344 Rats Exhibit Altered Electrophysiological Activity in Locomotor-unrelated but Not Locomotor-related Striatal Neurons Neurobiology of Aging. Apr, 2004 | Pubmed ID: 15013572 Multi-wire electrode arrays were chronically implanted and striatal electrophysiological activity was recorded in young (4-9 months) versus aged (24-29 months) Fischer 344 (F344) rats in order to determine whether locomotor-related striatal neurons exhibit age-related changes in electrophysiological activity during freely-moving conditions. Individual neurons were classified as locomotor-related if they exhibited significant differences in their firing rates between periods of locomotion versus periods of non-movement. While the activity of locomotor-related striatal neurons did not differ between young and aged rats, neurons that were not related to locomotion exhibited significantly greater activity in the aged rats during both periods of non-movement and bouts of locomotion. These results suggest that in the aged striatum, increased activity of nonlocomotor-related neurons may contribute to hypokinesia through their influence on basal ganglia output nuclei. Such studies may aid in the understanding of movement disorders seen in aging and Parkinson's disease.
Striatal GDNF Administration Increases Tyrosine Hydroxylase Phosphorylation in the Rat Striatum and Substantia Nigra Journal of Neurochemistry. Jul, 2004 | Pubmed ID: 15198683 Glial cell line-derived neurotrophic factor (GDNF) improves motor dysfunction associated with aging in rats and non-human primates, in animal models of Parkinson's disease, and may improve motoric function in patients with advanced Parkinson's disease. These improvements are associated with increased dopamine function in the nigrostriatal system, but the molecular events associated with this increase are unknown. In these studies, 100 micro g of GDNF was injected into the striatum of normal aged (24-month-old) male Fischer 344 rats. The protein levels and phosphorylation of TH, ERK1/2, and related proteins were determined by blot-immunolabeling of striatum and substantia nigra harvested 30 days after injection. In GDNF-treated rats, TH phosphorylation at Ser31 increased approximately 40% in striatum and approximately 250% in the substantia nigra. In the substantia nigra, there was a significant increase in ERK1 phosphorylation. In striatum, there was a significant increase in ERK2 phosphorylation. Microdialysis studies in striatum showed that both amphetamine- and potassium-evoked dopamine release in GDNF recipients were significantly increased. These data show that GDNF-induced increases in dopamine function are associated with a sustained increase in TH phosphorylation at Ser31, which is greatest in the substantia nigra and maintained for at least one month following a single striatal administration of GDNF. These findings, taken from the nigrostriatal system of normal aged rats, may help explain the long lasting effects of GDNF on dopamine function and prior studies supporting that a major effect of GDNF involves its effects on dopamine storage and somatodendritic release of dopamine in the substantia nigra.
CGP 56999A, a GABA(B) Receptor Antagonist, Enhances Expression of Brain-derived Neurotrophic Factor and Attenuates Dopamine Depletion in the Rat Corpus Striatum Following a 6-hydroxydopamine Lesion of the Nigrostriatal Pathway Neuroscience Letters. Oct, 2006 | Pubmed ID: 16890350 Rats were injected (i.p.) once daily with either 1 mg/kg CGP 56999A, a gamma-aminobutyric acid(B) (GABA(B)) receptor antagonist, or an equivalent volume of saline beginning 7 days prior to, and continuing for 7 days following, a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine (DA) pathway. At the end of the CGP 56999A treatment period the concentrations of DA and dihydroxyphenylacetic acid (DOPAC), as well as the expression of brain-derived neurotrophic factor (BDNF), were analyzed in corpus striatum ipsilateral and contralateral to the lesioning. No significant differences in these parameters were noted in the contralateral striatum between saline- and CGP 56999A-treated subjects. In contrast, as compared to animals receiving saline only, daily treatment with the GABA(B) receptor antagonist significantly attenuated the 6-hydroxydopamine-induced decline in DA and increased the expression of BDNF in the ipsilateral striatum. The results indicate that CGP 56999A enhances BDNF gene expression in the rat corpus striatum and prevents the decline in DA content that is a characteristic sequela of 6-hydroxydopapmine lesions of the nigrostraital dopamine pathway. These findings suggest that GABA(B) receptor antagonists may be of value in the treatment of Parkinson's disease and other conditions that would benefit from an enhanced production of neurotrophic factors in brain.
Measuring Forelimb Force Control and Movement in Fischer 344/Brown Norway Rats: Effects of Age and Lorazepam Behavioural Pharmacology. Dec, 2006 | Pubmed ID: 17110798 The purpose of this study was to measure forelimb force control and movement kinetics in rats, as they are affected by normal aging and the benzodiazepine lorazepam. Young (6 months), middle-aged (18 months), and aged (24 months) rats were trained to emit discrete forelimb responses on an isometric force disk within a 20-25 g force band for water reinforcement. Dependent variables included number of responses, percentage of reinforced responses, peak response forces, and inter-response times. Inter-response times were divided into two categories: inter-response times
Bilateral Effects of Unilateral Intrastriatal GDNF on Locomotor-excited and Nonlocomotor-related Striatal Neurons in Aged F344 Rats Neurobiology of Aging. Jan, 2007 | Pubmed ID: 16314001 In order to determine its effects on locomotor-related striatal electrophysiology in aged rats, glial cell line-derived neurotrophic factor (GDNF) was infused (vehicle or 30mug) into the right striatum of 24-25-month-old Fischer 344 (F344) rats. Multi-wire electrode arrays were then chronically implanted in striatum bilaterally. Thirty days later, striatal electrophysiological activity was recorded during freely moving conditions. Individual neurons were classified as locomotor-excited if they exhibited significant increases in firing rates during locomotor bouts versus periods of nonmovement. GDNF produced a significant increase in overall firing rates in locomotor-excited striatal neurons. This effect was observed in both the infused and the contralateral striatum. GDNF also attenuated the bursting activity of nonlocomotor-related striatal neurons, an effect that was also present bilaterally. These results suggest that GDNF's antiparkinsonism effects are associated with increased excitability of motor-related striatal neurons and diminished activity of neurons that do not exhibit explicit motor-related changes in activity. Such studies may aid in understanding the mechanism of potential therapies for movement disorders seen in aging and Parkinson's disease.
Age-related Changes in Orolingual Motor Function in F344 Vs F344/BN Rats Physiology & Behavior. Feb, 2008 | Pubmed ID: 17980393 Normal aging is associated with both locomotor and orolingual motor deficits. Preclinical studies of motor function in normal aging, however, have focused primarily on locomotor activity. The purpose of this study was to measure age-related changes in orolingual motor function and compare these changes between two rat strains commonly used in aging studies: Fischer 344 (F344) and Fischer 344/Brown Norway hybrid (F344/BN) rats. Rats (6-, 12-, 18- and 24-months of age) were trained to lick water from an isometric force-sensing operandum so that the number of licks per session, licking rhythm (licks/second) and lick force could be measured. In both strains, the number of licks per session was greatest in the oldest group, while this measure was greater for F344/BN rats at all ages. Peak tongue force increased with age in F344/BN rats, did not change with age in the F344 rats, and was greater for the F344/BN rats at all ages. Both strains exhibited an age-related slowing of licking rhythm beginning with the 18-month-old group. These findings suggest that despite lifespan differences between these two rat strains, diminished tongue motility emerges at the same age.
Acute and Rebound Effects of Lorazepam on Orolingual Motor Function in Young Versus Aged Fischer 344/Brown Norway Rats Behavioural Pharmacology. Mar, 2008 | Pubmed ID: 18332681 The purpose of this study was to measure the acute effects of lorazepam [a short-acting benzodiazepine (BZ) with no active metabolites] on orolingual motor function in young (6 months) versus aged (24 months) Fischer 344/Brown Norway hybrid (F344/BN) rats. Rats licked water from an isometric force-sensing operandum so that the number of licks per session, licking rhythm (licks/second), and lick force could be measured during daily sessions. Acute doses (1.0 and 2.0 mg/kg) of lorazepam were administered 30 min before the testing sessions, 4 days apart. Whereas aged rats produced more licks per session, lorazepam increased this measure primarily in the young group. On the days after each lorazepam dose, rats licked less than they did before receiving the drug. This effect was shown by both groups. Aged rats showed significantly slower licking rhythm than young rats. Lorazepam slowed this measure in both groups. Peak tongue forces were significantly increased by lorazepam. These findings suggest that BZs such as lorazepam can affect tongue force output and exacerbate age-related tongue motility deficits. They also suggest that although BZs can directly influence motivation to engage in water-reinforced tasks, opposite 'rebound' effects may occur, even after acute dosing.
Effects of Tongue Force Training on Orolingual Motor Cortical Representation Behavioural Brain Research. Jul, 2009 | Pubmed ID: 19428638 Previous research has demonstrated that training rats in a skilled reaching condition will induce task-related changes in the caudal forelimb area (CFA) of motor cortex. The purpose of the present study was to determine whether task-specific changes can be induced within the orofacial area of the motor cortex in rats. Specifically, we compared changes of the orofacial motor cortical representation in lick-trained rats to age-matched controls. For 1 month, six water-restricted Sprague-Dawley rats were trained to lick an isometric force-sensing disc at increasing forces for water reinforcement. The rats were trained daily for 6 min starting with forces of 1g, and increasing over the course of the month to 10, 15, 20, 25 and finally 30 g. One to three days following the last training session, the animals were subjected to a neurophysiological motor mapping procedure in which motor representations corresponding to the orofacial and adjacent areas were defined using intracortical microstimulation (ICMS) techniques. We found no statistical difference in the topographical representation of the control (mean=2.03 mm(2)) vs. trained (1.87 mm(2)) rats. This result indicates that force training alone is insufficient to drive changes in the size of the cortical representation. We also recorded the minimum current threshold required to elicit a motor response at each site of microstimulation. We found that the lick-trained rats had a significantly lower average minimum threshold (29.1+/-1.0 microA) for evoking movements related to the task compared to control rats (34.6+/-1.1 microA). These results indicate that while tongue force training alone does not produce lasting changes in the size of the orofacial cortical motor representation, tongue force training decreases the current thresholds necessary for eliciting an ICMS-evoked motor response.
Bilateral Effects of Unilateral GDNF Administration on Dopamine- and GABA-regulating Proteins in the Rat Nigrostriatal System Experimental Neurology. Sep, 2009 | Pubmed ID: 19460370 Dopamine (DA) affects GABA neuronal function in the striatum and together these neurotransmitters play a large role in locomotor function. We recently reported that unilateral striatal administration of GDNF, a growth factor that has neurotrophic effects on DA neurons and enhances DA release, bilaterally increased striatal neuron activity related to locomotion in aged rats. We hypothesized that the GDNF enhancement of DA function and resulting bilateral enhancement of striatal neuronal activity was due to prolonged bilateral changes in DA- and GABA-regulating proteins. Therefore in these studies we assessed dopamine- and GABA-regulating proteins in the striatum and substantia nigra (SN) of 24 month old Fischer 344 rats, 30 days after a single unilateral striatal delivery of GDNF. The nigrostriatal proteins investigated were the DA transporter (DAT), tyrosine hydroxylase (TH), and TH phosphorylation and were examined by blot-immunolabeling. The striatal GABA neuron-related proteins were examined by assay of the DA D1 receptor, DARPP-32, DARPP-32 Thr34 phosphorylation, and glutamic acid decarboxylase (GAD). Bilateral effects of GDNF on TH and DAT occurred only in the SN, as 30 microg GDNF increased ser19 phosphorylation, and 100 microg GDNF decreased DAT and TH protein levels. GDNF also produced bilateral changes in GAD protein in the striatum. A decrease in DARPP-32 occurred in the ipsilateral striatum, while increased D1 receptor and DARPP-32 phosphorylation occurred in the contralateral striatum. The 30 microg GDNF infusion into the lateral striatum was confined to the ipsilateral striatum and substantia nigra. Thus, long-lasting bilateral effects of GDNF on proteins regulating DA and GABA neuronal function likely alter physiological properties in neurons, some with bilateral projections, associated with locomotion. Enhanced nigrostriatal excitability and DA release by GDNF may trigger these bilateral effects.
Age-related Changes in HSP25 Expression in Basal Ganglia and Cortex of F344/BN Rats Neuroscience Letters. Mar, 2010 | Pubmed ID: 20144690 Normal aging is associated with chronic oxidative stress. In the basal ganglia, oxidative stress may contribute to the increased risk of Parkinson's disease in the elderly. Neurons are thought to actively utilize compensatory defense mechanisms, such as heat shock proteins (HSPs), to protect from persisting stress. Despite their protective role, little is known about HSP expression in the aging basal ganglia. The purpose of this study was to examine HSP expression in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month-old Fischer 344/Brown Norway rats. We found robust age-related increases in phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72 (the inducible form of HSP70) was reduced with age, but only in the striatum. p38 MAPK, a protein implicated in activating HSP25, did not change with age, nor did HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that HSP25 is especially responsive to age-related stress in the basal ganglia.
Measures of Bulbar and Spinal Motor Function, Muscle Innervation, and Mitochondrial Function in ALS Rats Behavioural Brain Research. Jul, 2010 | Pubmed ID: 20211206 Symptom onset in amyotrophic lateral sclerosis (ALS) may occur in the muscles of the limbs (spinal onset) or those of the head and neck (bulbar onset). Most preclinical studies have focused on spinal symptoms, despite the prevalence of and increased morbidity and mortality associated with bulbar disease. We measured lick rhythm and tongue force to evaluate bulbar disease in the SOD1-G93A rat model of familial ALS. Body weight and grip strength were measured concomitantly. Testing spanned the early (maturation), middle (pre-symptomatic), and late (symptomatic and end-stage) phases of the disease. We measured a persistent tongue motility deficit that became apparent in the early phase of the disease, providing behavioral evidence of bulbar pathology. At end-stage, however, cytochrome oxidase (CO) activity was normal in the hypoglossal nucleus, and in the tongue, neuromuscular innervation, citrate synthase (CS) protein levels and activity, and uncoupling protein 3 (UCP3) protein levels remained unchanged. Interestingly, significant denervation and atrophy were evident in the end-stage sternomastoid muscle, providing peripheral anatomical evidence of bulbar pathology. Changes in body weight and grip strength occurred in the late phase of the disease. Extensive atrophy and denervation were observed in the end-stage gastrocnemius muscle. In contrast to our findings in the tongue, CS protein levels were decreased in the extensor digitorum longus (EDL) and soleus, although CS activity was maintained or increased. UCP3 protein was decreased also in the EDL. These data provide evidence of differential effects in muscles that were more or less affected by disease.
Within-session Analysis of Amphetamine-elicited Rotation Behavior Reveals Differences Between Young Adult and Middle-aged F344/BN Rats with Partial Unilateral Striatal Dopamine Depletion Pharmacology, Biochemistry, and Behavior. Oct, 2010 | Pubmed ID: 20600242 Preclinical modeling of Parkinson's disease using 6-hydroxydopamine (6-OHDA) has been valuable in developing and testing therapeutic strategies. Recent efforts have focused on modeling early stages of disease by infusing 6-OHDA into the striatum. The partial DA depletion that follows intrastriatal 6-OHDA is more variable than the near-complete depletion following medial forebrain bundle infusion, and behavioral screening assays are not as well characterized in the partial lesion model. We compared relationships between amphetamine-elicited rotation behavior and DA depletion following intrastriatal 6-OHDA (12.5 microg) in 6 month vs. 18 month F344/BN rats, at 2-weeks and 6-weeks post-lesion. We compared the total number of rotations with within-session (bin-by-bin) parameters of rotation behavior as indicators of DA depletion. Striatal DA depletion was greater in the young adult than in the middle-aged rats at 2 weeks but not at 6 weeks post-lesion. The total number of rotations for the whole session and striatal DA depletion did not differ between the two age groups. Regression analysis revealed a greater relationship between within-session parameters of rotation behavior and DA depletion in the middle-aged group than in the young adult group. These results have implications for estimating DA depletion in preclinical studies using rats of different ages.
Neurodegeneration in an Animal Model of Parkinson's Disease is Exacerbated by a High-fat Diet American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Oct, 2010 | Pubmed ID: 20702796 Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.
Young and Middle-aged Rats Exhibit Isometric Forelimb Force Control Deficits in a Model of Early-stage Parkinson's Disease Behavioural Brain Research. Nov, 2011 | Pubmed ID: 21767573 Deficits in manual motor control often accompany the early stages of Parkinson's disease (PD), and are often revealed through isometric force tasks. In order to determine whether similar deficits occur in a rat model of early-stage PD, young (8 months) and middle-aged (18 months) rats were trained to produce sustained press-hold-release isometric forelimb responses that allowed for analyses of force output and spectral analysis of forelimb stability and tremor. Rats then received a 6-hydroxydopamine (6-OHDA) infusion into the striatum contralateral to the trained forelimb and were tested for 4 weeks post-lesion. The resulting partial striatal dopamine depletions (which at 41±12% and 43±6% in young and middle-aged rats, respectively, did not differ between the two groups) resulted in isometric forelimb deficits. Specifically, rats exhibited significantly diminished force stability and increased high frequency (10-25Hz) tremor, indicating potential postural disturbances and increased postural tremor, respectively. Durations of press-hold-release bouts were also increased post-lesion, suggesting difficulty in task disengagement. Despite pre-lesion differences in some of the force measures, the effects of partial nigrostriatal DA depletion did not differ between the two age groups. These results support the use of the press-while-licking task in preclinical studies modeling isometric force control deficits in PD.
Active Zone Protein Bassoon Co-localizes with Presynaptic Calcium Channel, Modifies Channel Function, and Recovers from Aging Related Loss by Exercise PloS One. 2012 | Pubmed ID: 22701595 The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca(2+) influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise.
Tongue Force and Tongue Motility Are Differently Affected by Unilateral Vs Bilateral Nigrostriatal Dopamine Depletion in Rats Behavioural Brain Research. Oct, 2012 | Pubmed ID: 22796604 In addition to its cardinal symptoms of bradykinesia, muscle rigidity, resting tremor and postural disturbances, Parkinson's disease (PD) also affects orolingual motor function. Orolingual motor deficits can contribute to dysphagia, which increases morbidity and mortality in this population. Previous preclinical studies describing orolingual motor deficits in animal models of PD have focused on unilateral nigrostriatal dopamine (DA) depletion. In this study we compared the effects of unilateral vs bilateral 6-hydroxydopamine (6-OHDA)-induced DA depletion in rats trained to lick water from an isometric force-sensing disc. Rats received either unilateral or bilateral 6-OHDA into the medial forebrain bundle and were tested for four weeks post-lesion. Dependent variables included task engagement (the number of licks per session), tongue force (mean and maximum), and tongue motility (the number of licks per second). While both lesion groups exhibited decreased tongue force output, tongue motility deficits were present in only the group that received unilateral nigrostriatal DA depletion. Task engagement was not significantly diminished by 6-OHDA. Analysis of striatal DA tissue content revealed that DA depletion was ∼97% in the unilateral group and ∼90% in the bilateral group. These results suggest that while nigrostriatal DA depletion affects tongue force output, deficits in tongue motility may instead result from a functional imbalance in neural pathways affecting this midline structure.
A Novel Use of Combined Tyrosine Hydroxylase and Silver Nucleolar Staining to Determine the Effects of a Unilateral Intrastriatal 6-hydroxydopamine Lesion in the Substantia Nigra: a Stereological Study Journal of Neuroscience Methods. Sep, 2012 | Pubmed ID: 22850559 Neurotoxic lesions of the nigrostriatal pathway model the deficits found in Parkinson's disease. This study used stereology and a novel staining method to examine the effects of a partial unilateral striatal 6-hydroxydopamine (6-OHDA) lesion on substantia nigra pars compacta (SNpc) dopamine neuron number and morphology in rats. Adult male Long-Evans rats were subjected to unilateral lesion of the SNpc by intrastriatal microinjection of 6-OHDA (12.5 μg). Lesions were verified by d-amphetamine-stimulated rotation (2.5 mg/kg, sc) by force-plate rotometry 7 days post-surgery. Seven days after rotation testing, rats were euthanized, and brains were prepared for either histology (n=12) or determination of striatal dopamine content by HPLC-EC (n=20). Brains prepared for histology were stained for tyrosine hydroxylase (TH) combined with a silver nucleolar (AgNOR) stain using a modified protocol developed for stereological assessment. The AgNOR counterstain allowed for precise definition of the nucleolus of the cells, facilitating both counting and qualitative morphometry of TH-positive neurons. Stereological quantitation determined a 54% decrease in TH-positive neuron number (P
Altered Nucleolar Morphology in Substantia Nigra Dopamine Neurons Following 6-hydroxydopamine Lesion in Rats Neuroscience Letters. Jun, 2013 | Pubmed ID: 23643997 The nucleolus, the site of ribosomal ribonucleic acid (rRNA) transcription and assembly, is an important player in the cellular response to stress. Altered nucleolar function and morphology, including decreased nucleolar volume, has been observed in Parkinson's disease; thus the nucleolus represents a potential indicator of neurodegeneration in the disease. This study determined the effects of a partial unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion, which models the dopaminergic loss found in Parkinson's disease, on the nucleoli of dopaminergic cells in the substantia nigra pars compacta (SNpc). Adult male Long-Evans rats underwent unilateral intrastriatal infusion of 6-OHDA (12.5μg). Lesions were verified by amphetamine-stimulated rotation 7 days later, and rats were euthanized 14 days after infusion. Coronal sections (50μm) were stained for tyrosine hydroxylase-silver nucleolar (TH-AgNOR) stain using MultiBrain Technology (NeuroScience Associates), which resulted in clearly defined nucleoli and neuronal outlines. Stereological methods were used to compare dopaminergic morphology between lesioned and intact hemispheres in each rat. In cells exhibiting a definable nucleolus, nucleolar volume was decreased by 16% on the ipsilateral side. The ipsilateral SNpc also exhibited an 18% decrease in SNpc planimetric volume, a 46% decrease in total TH-positive neuron number, and an 11% decrease in neuronal body volume (all P
SOD1-G93A Mice Exhibit Muscle-fiber-type-specific Decreases in Glucose Uptake in the Absence of Whole-body Changes in Metabolism Neuro-degenerative Diseases. 2014 | Pubmed ID: 24021858 Skeletal muscles play an important role in systemic glucose homeostasis and are purported to be the origin of the altered metabolic state observed in amyotrophic lateral sclerosis (ALS).
Role of Exercise in Maintaining the Integrity of the Neuromuscular Junction Muscle & Nerve. Mar, 2014 | Pubmed ID: 24122772 Physical activity plays an important role in preventing chronic disease in adults and the elderly. Exercise has beneficial effects on the nervous system, including at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and improves recovery from peripheral nerve injuries, whereas decreased physical activity causes degenerative changes in NMJs. Recent studies have begun to elucidate molecular mechanisms underlying the beneficial effects of exercise. These mechanisms involve Bassoon, neuregulin-1, peroxisome proliferator-activated receptor gamma coactivator 1α, insulin-like growth factor-1, glial cell line-derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of activated T cells c1. For example, NMJ denervation and active zone decreases have been observed in aged NMJs, but these age-dependent degenerative changes can be ameliorated by exercise. In this review we assess the effects of exercise on the maintenance and regeneration of NMJs and highlight recent insights into the molecular mechanisms underlying these exercise effects.
Relationships Between Tongue Motility, Grip Force, and Survival in SOD1-G93A Rats Physiology & Behavior. Feb, 2014 | Pubmed ID: 24291387 Most preclinical studies of amyotrophic lateral sclerosis (ALS) have focused on spinal symptoms, despite the importance of bulbar deficits in progression of the disease. We sought to determine how bulbar deficits are related to spinal deficits and survival in the SOD1-G93A rat model of ALS. We examined forelimb and hindlimb grip force and tongue motility in SOD1-G93A rats using statistical cluster analysis. Decrements in forelimb grip force, hindlimb grip force, and tongue motility were used to cluster affected rats into groups. The analysis clustered one group that exhibited primarily forelimb deficits (forelimb group) and a second group that exhibited forelimb and tongue motility deficits (forelimb+bulbar group). The analysis did not identify a distinct hindlimb phenotype group because all SOD1-G93A rats exhibited deficits in hindlimb grip force. Rats in the forelimb+bulbar group exhibited earlier and greater forelimb deficits, and earlier mortality than rats without bulbar deficits. Hindlimb deficits were similar in both groups. There was a significant correlation between forelimb grip force and tongue motility deficits, but not between forelimb and hindlimb deficits. These data extend clinical findings of a more rapid disease progression in individuals with bulbar symptoms to the SOD1-G93A rat model of ALS.
Differential Effects of Amphetamine and GBR-12909 on Orolingual Motor Function in Young Vs Aged F344/BN Rats Psychopharmacology. Dec, 2014 | Pubmed ID: 24923981 Orolingual motor deficits, such as dysarthria and dysphagia, contribute to increased morbidity and mortality in the elderly. In preclinical studies, we and others have reported age-related decreases in tongue motility in both F344 and F344/BN rats. The fact that these deficits are associated with nigrostriatal dopamine (DA), tissue measures suggest that increasing dopamine function might normalize tongue motility.
Differential Effects of Intrastriatal 6-hydroxydopamine on Cell Number and Morphology in Midbrain Dopaminergic Subregions of the Rat Brain Research. Jul, 2014 | Pubmed ID: 24924804 The midbrain dopaminergic perikarya are differentially affected in Parkinson׳s disease (PD). This study compared the effects of a partial unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion model of PD on the number, morphology, and nucleolar volume of dopaminergic cells in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and retrorubral field (RRF). Adult, male rats (n=10) underwent unilateral intrastriatal infusion of 6-OHDA (12.5μg). Lesions were verified by amphetamine-stimulated rotation 7 days post-infusion. Rats were euthanized 14 days after treatment with 6-OHDA and brains were stained with a tyrosine hydroxylase-silver nucleolar (TH-AgNOR) stain. Dopaminergic cell number and morphology in the lesioned and intact hemispheres were quantified using stereological methods. The magnitude of decrease in planimetric volume, neuronal number, cell density, and neuronal volume resulting from 6-OHDA lesion differed between regions, with the SNpc exhibiting the greatest loss of neurons (46%), but the smallest decrease in neuronal volume (13%). The lesion also resulted in a decrease in nucleolar volume that was similar in all three regions (22-26%). These findings indicate that intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the SNpc, VTA, and RRF; however, the resulting changes in nucleolar morphology suggest a similar cellular response to the toxin in all three cell populations.
Hyperactivity in the Gunn Rat Model of Neonatal Jaundice: Age-related Attenuation and Emergence of Gait Deficits Pediatric Research. Mar, 2015 | Pubmed ID: 25518009 Neonatal jaundice resulting from elevated unconjugated bilirubin occurs in 60-80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention-deficit hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND.
Effects of Discontinuing a High-fat Diet on Mitochondrial Proteins and 6-hydroxydopamine-induced Dopamine Depletion in Rats Brain Research. Jul, 2015 | Pubmed ID: 25862572 Diet-induced obesity can increase the risk for developing age-related neurodegenerative diseases including Parkinson's disease (PD). Increasing evidence suggests that mitochondrial and proteasomal mechanisms are involved in both insulin resistance and PD. The goal of this study was to determine whether diet intervention could influence mitochondrial or proteasomal protein expression and vulnerability to 6-Hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine (DA) depletion in rats' nigrostriatal system. After a 3 month high-fat diet regimen, we switched one group of rats to a low-fat diet for 3 months (HF-LF group), while the other half continued with the high-fat diet (HF group). A chow group was included as a control. Three weeks after unilateral 6-OHDA lesions, HF rats had higher fasting insulin levels and higher Homeostasis model assessment of insulin resistance (HOMA-IR), indicating insulin resistance. HOMA-IR was significantly lower in HF-LF rats than HF rats, indicating that insulin resistance was reversed by switching to a low-fat diet. Compared to the Chow group, the HF group exhibited significantly greater DA depletion in the substantia nigra but not in the striatum. DA depletion did not differ between the HF-LF and HF group. Proteins related to mitochondrial function (such as AMPK, PGC-1α), and to proteasomal function (such as TCF11/Nrf1) were influenced by diet intervention, or by 6-OHDA lesion. Our findings suggest that switching to a low-fat diet reverses the effects of a high-fat diet on systemic insulin resistance, and mitochondrial and proteasomal function in the striatum. Conversely, they suggest that the effects of the high-fat diet on nigrostriatal vulnerability to 6-OHDA-induced DA depletion persist.
A High Fat Diet alters Metabolic and Bioenergetic Function in the Brain: A Magnetic Resonance Spectroscopy Study Neurochemistry International. Jul, 2016 | Pubmed ID: 27125544 Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet.
Extracellular Mitochondria and Mitochondrial Components Act As Damage-Associated Molecular Pattern Molecules in the Mouse Brain Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology. Dec, 2016 | Pubmed ID: 27562848 Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfα and decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation. Some of these effects were also observed in brains injected with mtDNA (decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation), and mtDNA injection also caused several unique changes including increased CSF1R protein and AKT phosphorylation. To further establish the potential relevance of this response to Alzheimer's disease (AD), a brain disorder characterized by neurodegeneration, mitochondrial dysfunction, and neuroinflammation we also measured App mRNA, APP protein, and Aβ1-42 levels. We found mitochondria (but not mtDNA) injections increased these parameters. Our data show that in the mouse brain extracellular mitochondria and its components can induce neuroinflammation, extracellular mtDNA or mtDNA-associated proteins can contribute to this effect, and mitochondria derived-DAMP molecules can influence AD-associated biomarkers.
Effects of Tongue Force Training on Bulbar Motor Function in the Female SOD1-G93A Rat Model of Amyotrophic Lateral Sclerosis Neurorehabilitation and Neural Repair. Feb, 2017 | Pubmed ID: 27573800 The use of exercise in amyotrophic lateral sclerosis (ALS) is controversial. Although moderate exercise appears to be beneficial for limb muscles in ALS, the effects of exercise on bulbar muscles such as the tongue have not been studied.
Fate of Neural Progenitor Cells Transplanted Into Jaundiced and Nonjaundiced Rat Brains Cell Transplantation. Apr, 2017 | Pubmed ID: 28155818 High levels of bilirubin in infants can cause kernicterus, which includes basal ganglia damage and dystonia. Stem cell transplantation may be an effective treatment for this disease. In this study, we transplanted human neural progenitor cells differentiated toward propriospinal interneurons into the striatum of 20-day-old spontaneously jaundiced (jj) Gunn rats and nonjaundiced (Nj) littermates. Using immunohistochemical methods, we found that grafted cells survived and grew fibers in jj and Nj brains 3 weeks after transplantation. Grafted cells had a higher survival rate in jj than in Nj brains, suggesting that slightly elevated bilirubin may protect graft survival due to its antioxidative and immunosuppressive effects. Despite their survival, only a small portion of grafted neurons expressed GAD-6 or ChAT, which mark GABAergic and cholinergic neurons, respectively, and are the cells that we are attempting to replace in kernicterus. Thus, NPCs containing large populations of GABAergic and cholinergic neurons should be used for further study in this field.


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Originally posted by Skyfloating
Jeeez...the Judgments were almost as long as the Debate. Needed two posts for the Judgments in the Animation Debate.
And the winner is....
Originally posted by PatrickGarrow17
reply to post by Skyfloating
Thanks, I have some regrets about the way I presented it and suggested the topic because I genuinely believe that the statement it true.
Also, I'm pretty insulted by your comment above.
Hopefully someday I'll debate a worthy opponent...
Originally posted by PatrickGarrow17
Thanks for the encouragement. I have an open debate with Sublimecraft, who has let me know he is busy and is working on posting ASAP.
In the meantime, there are two topics I was thinking about that I'd like to debate because they are ones that I want to learn more about...
1. Atlantis existed. - I would be arguing the pro, and Atlantis would serve as a blanket term for a lost civilization that rivals or exceeds our current advancement.
Originally posted by Skyfloating
Some day I want to debate unbeatables like Hefficide or top-ranks like adjensen...
Originally posted by Skyfloating
Some day I want to debate unbeatables like Hefficide or top-ranks like adjensen...
Yoko Ono and others have praised the inscribed messages as "a stirring call to rational thinking", while opponents have labeled them as the "Ten Commandments of the Antichrist". (Source: Wikipedia)
The Internet: Greatest creation since writing or downfall of the human race?

subset: commoncrawl


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Jun 30 2016
Versioning, Branching and Testing Infrastructure as Code
Derek DeJonghe
Infrastructure management is evolving. Instead of provisioning hardware and tracking infrastructure in Excel spreadsheets, we can now interact with virtualized infrastructure resources in programmatic ways. Enter Infrastructure as Code (IaC). IaC allows us greater reliability and flexibility than traditional hardware. We can now treat the infrastru …Read more
Jun 28 2016
5 Ways to Ensure an Amazon RDS Migration Failure
Patrick Delaney
In my last blog post I provided eight tips to surviving a live database migration to Amazon Relational Database Service (RDS). Today, I'm going to give you five ways (plus a bonus) to ensure your database migration is a failure. In other words, these are five common mistakes you should avoid if you don't want […] …Read more
Jun 23 2016
Up and Running with the Internet of Things Using Raspberry Pi and AWS IoT
Ian DesJardins
Amazon Web Services (AWS) previously released its Internet of Things (IoT) platform, AWS IoT. This managed cloud platform brings IoT development, small device programming and automation to a totally different level. Not only does it provide everything you need to communicate to the devices around you, but it does so in a way that gives […] …Read more
Jun 21 2016
Anatomy of a Self-Healing App on AWS
Jamie Begin
One of the great things about the cloud is that it enables you to scale workloads so that you pay only for what you use. But another important benefit that doesn't get quite the same attention is the cloud's ability to self-heal. To get the most out of your applications running on AWS, you want […] …Read more
Jun 16 2016
8 Tips for Surviving a Live Database Migration to Amazon RDS
Patrick Delaney
There are a lot of benefits to migrating an on-premises database to Amazon Relational Database Service (RDS). I've found that RDS is much easier to operate than MySQL or PostgreSQL. RDS makes it easier to manage multiple databases, the interface is easy to use, it has a good API, and it maintains good uptime. But […] …Read more


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Calls for Papers
The Calls for Papers listed below are for meeting which are sponsored or co-sponsored by PES. For CFPs of technically co-sponsored meetings, and to check the web pages of individual meetings, visit the Meetings Page.
Current and Future Calls for Papers
- IEEE PES 2015 General Meeting
26-30 July 2015, Denver, Colorado, USA
- IEEE PES Innovative Smart Grid Technologies Europe 2014 (ISGT Europe 2014)
12-15 October 2014, Istanbul, Turkey


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Wednesday and Thursday 9 to 12 and Friday 12.30 to 3.30
(Answerphone at other times)
St Peter's is about one kilometre from the A34 (Stratford Road) which runs from Birmingham City Centre to Junction 4 of the M42. The church is a short walk from the Yardley Wood railway station, which is on the line between Birmingham Moor Street and Shirley. For local buses, consult Travel West Midlands. It is set down a short drive.


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Hearing the term "comprehensive car insurance" probably makes your eyelids droop or your wallet cringe, but it's a term you don't want to write off. Knowing what's covered by comprehensive coverage (versus collision coverage) will help you determine what car insurance policy is right for you.
Fast, Free Auto Insurance Quotes
Comprehensive vs. Collision Coverage
Comprehensive car coverage does not, as the name might suggest, cover you in any circumstance. Comprehensive insurance is also known as other than collision coverage, since it covers—you guessed it—vehicle damage not caused by a collision. This includes damage from:
- Fire
- Theft
- Vandalism
- Flooding
- Earthquakes
- Falling objects
- Animals
- Riots
In a nutshell, comprehensive coverage applies to perils that are outside your control as a driver, like a falling tree branch, a deer jumping in front of your vehicle, a hail storm, or an instance of vandalism.
Collision coverage, on the other hand, covers damages caused in an accident with another vehicle or with a stationary object. It's important to know the distinction between what's considered a collision and what's considered a comprehensive event on your policy because your carrier treats these instances differently.
Comprehensive coverage claims are usually non-surchargeable events, and should not impact your future insurance premiums. Collision events, on the other hand, could be surchargeable, depending on the percentage of fault you have in the accident.
Do I Need Comprehensive Coverage?
Some insurance companies require drivers to have both comprehensive and collision coverage, while other carriers allow drivers to opt for only comprehensive coverage. In order to have collision coverage on your vehicle, you will normally be required to have comprehensive coverage as well.
If there is a loan or lease contract on your vehicle, comprehensive coverage is typically required. This requirement protects the lender or leasing company when a vehicle needs expensive repairs that the insured might not otherwise be able to afford.
If you own your vehicle, you can decide whether or not to purchase comprehensive insurance. To weigh the costs and benefits, determine the value of your car and see whether or not you would be able to pay for damages or replacement if something happened. These expenses can be especially high if you own a newer model vehicle, so be sure that you can afford to go without coverage before deciding against it.
Opting out might save you on your car insurance premium, but if you don't have the financial means to pay out of pocket, comprehensive (and perhaps collision) coverage is a good investment.
As always, consult with your insurance company representative or trusted insurance agent to get guidance on which coverage makes the most sense for you.
Other Comprehensive Insurance Considerations
Some insurance companies offer a separate glass deductible option since broken windshields can be a recurring problem for people who frequently travel on highways. If this issue applies to you and your insurance carrier offers a separate glass deductible, opt for a lower glass deductible to avoid paying out-of-pocket for windshield repair or replacement.
Another common choice for car or motorcycle owners who use their vehicles seasonally is opting for comprehensive-only coverage while their vehicle is parked or garaged during the off-season. This is normally only available for clients who do not have a loan or lease agreement on their vehicle. When a vehicle is parked and/or garaged for long periods of time (like during the winter or when college students head back to school), clients can reduce their insurance premiums considerably by leaving only comprehensive coverage, since any damage that occurs while the vehicle is garaged would most likely be considered a comprehensive event.


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SOURCE: Discovery Minerals Ltd.
February 13, 2014 09:15 ET
RENO, NV--(Marketwired - Feb 13, 2014) - Discovery Minerals Ltd. (OTC Pink: DSCR) is pleased to inform its shareholders that the company has currently short listed two candidates to fulfill the strategic technology and marketing partnership needed to complete the M.I.N.E.™ app. This will provide the necessary technology, marketing and social media expertise with a proven track record of launching Apps with a wide range of capabilities. Mr. Smith commented, "We feel that by engaging one of these experts, we can reduce the developmental and technological costs, along with providing an earlier roll out date for the fully functional M.I.N.E.™ app. We have identified the 2 candidates that will be the most compatible fit, and anticipate our decision to be made by the start of next week."
Furthermore, Mr. Smith added, "The Board of Directors is currently reviewing and cautiously considering the benefits of reducing the number of common shares issued by an exchange of certain common shares for Preferred shares and will keep the shareholders apprised of these discussions."
About Discovery Minerals Ltd.
Discovery Minerals Ltd. (Frankfurt WKN: A0LB3X) (Kurzel: D7Z) (OTC Pink: DSCR) is a production stage company formed to acquire and develop natural resource properties. Activities include gold, precious metals and petroleum minerals, including rare earth minerals production and sales. The Company initiated a new program to evaluate undervalued assets, including clean tech and alternative energy investments, for potential addition to its portfolio.
Safe Harbor: This release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 27E of the Securities Act of 1934. Statements contained in this release that are not historical facts may be deemed to be forward-looking statements. Investors are cautioned that forward-looking statements are inherently uncertain. Actual performance and results may differ materially from that projected or suggested herein due to certain risks and uncertainties including, without limitation, ability to obtain financing and regulatory and shareholder approval for anticipated actions.
Contact Person:
Henry Manayan
At: email@example.com
Contact Person:
Henry Manayan
At: email@example.com
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Smolensk State Medical University (SSMU) was founded in 1920. It is located on the Dnieper River, 360 kilometers (220 mi) west-southwest of Moscow. Smolensk State Medical University is one of the leaders in medical training, medical research, curative and preventive activities. It trains medical and pharmaceutical specialists for various areas of Russia as well as for a number of overseas countries.
SSMU is a government medical university recognized by WHO and all countries of the world including USA, UK and India.
The Smolensk State Medical University is placed on the 22nd position in the international rating. Because of high results, the Russian Government in March 2015 has raised the level to highest i.e. from Academy to University. That is why the name has been changed from Smolensk State Medical Academy to Smolensk State Medical University.
From 50 countries Students are coming for study in Smolensk State Medical University.
There are 31 hospitals working under the Smolensk State Medical University out of them 8 hospitals with about 6000 beds is used for education of students. Today this University is a big scientific establishment where fundamental, applied and methodical scientific researchers are carried out.
• Faculty of General Medicine
• Faculty of Dentistry
• Faculty of Pediatrics
• Faculty for Foreign Students
• Faculty of Pharmaceutics
• Faculty of Clinical Psychology and Social Work
• Faculty of Postgraduate Studies
• Faculty of Higher Nursing
There are 4 hostels, which can accommodate more than 2000 students. All the hostels are flat type i.e. with attached bathroom, toilet and kitchen. The hostels are fully furnished. The basic system is two students in one room. Separate arrangements for boys and girls. Separate arrangements are being made for boys and girls. Every hostel has internet facilities provided by University. All the hostels are well guarded with police security.
|Tuition Fee
|1st Year
|2nd-6th Year
|Total Fee
|Per Year
|6000 USD (390000 INR approx)
|6000 $ x 5= 30000 USD (1950000 INR approx)
|36500 USD(234000 INR approx)
|Subsidized Fee Package
|8 Lac INR
|1.2 Lac INR x 5= 6 Lac INR
|14 Lac INR
1 USD=65 INR(approx for calculation)
Fees includes Tuition Fee, Basic Hostel Fee and Medical Insurance.
Over the phone or online


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The Preliminary SAT/ National Merit Scholarship Qualifying Test, or PSAT/ NMSQT, is a standardized test that predicts success on the SAT and ranks students according to ability to qualify for scholarships. High school students can take the PSAT/ NMSQT in either 10th or 11th grade, but only 11th grade students are eligible for scholarships. Nevertheless, taking the test in 10th grade gives students a picture of where they are in their knowledge of the tested areas -- critical reading, math problem-solving and writing.
Know the Test
The entire test takes two hours and 10 minutes and is divided into five sections. There are 48 critical reading questions, which are tested in two 25-minute sessions and include sentence completions and comprehension. Math also includes two 25-minute sections, for a total of 38 questions, including arithmetic, algebra, geometry, statistics and probability. Test-takers have 30 minutes for the 39 writing questions, focusing on improving sentences or paragraphs. Most questions are multiple-choice, except for 10 "grid-in" math questions that require students to write in an answer.
Know Your Strengths and Weaknesses
Many test prep companies, including the College Board, Peterson's and the Princeton Review, offer practice PSAT/ NMSQT tests. Taking several practice tests will help identify areas of weakness, giving a test-taker an idea of how to focus study sessions. The official PSAT/ NMSQT practice test must be accessed from a school official, but the College Board does have the answer key available online, as well as some practice questions. The Peterson's test is available online for free, but the Princeton Review test prep must be purchased.
Complete Practice Questions
The College Board website offers at least five practice questions for each type of question on the PSAT/ NMSQT, as well as a detailed explanation for each answer. Some question types, including the math multiple choice, have as many as 13 available practice questions online. Additionally, the College Board offers tips for doing well on each question type. For example, some of the hints for the passage-based reading comprehension questions include reading all of the introductory information, marking the passages while reading them, reading the questions first and selecting the best answer for the question.
General Tips
The College Board recommends taking a wide variety of advanced academic courses to develop your abilities in English, mathematics, science, social studies, foreign language and fine arts. Additionally, any club or extracurricular activity that requires problem-solving is a good way to prepare for the exam. Understand the directions for each section before test day to avoid spending valuable testing time rereading them. Practice budgeting time by answering questions under timed conditions to simulate the actual test. Expect the test to be challenging, but a good opportunity for practice before taking it again in 11th grade.
Photo Credits
- Ableimages/Digital Vision/Getty Images


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copy and paste much P:
This member has provided no bio about themself...
copy and paste much P:
I played for 10 mins and got the blue screen of death xD
but it was at the end of the tut mission so I just didn't do it again P:
i had that error...BUT I HAVE FIXED IT ^.^
simply go to tools on steam, right-click "Source SDK 2007" and click on properties, then go to "BETA" and change it to "steampipe", then delete local content in properties and re-install it! then you should just verify the cache afterwards to be sure, then it should work! ^.^ (P.S converting it instead of reinstalling it doesn't work!) :P
so is this the surprise?
me and my friends have recently been playing it, so feel free to join us, just that we're currently trying to figure out how to setup a dedicated server instead of a listen one cause it keeps crashing on a certain part of the campaign then we have to start again :I
looks like it could be a tear between to universes perhaps
awesome mod, can't wait till its done, I'm a big stargate fan and if I remember, its gmod which I originally got me in to it cause of CAP. I had a similar idea to make an RP stargate server for gmod a few months back, but I would have no idea where to start really, so I've just been waiting to find someone else to come up with the idea that actually knows how to do it, also the idea that when you go through the stargate to another world will take you to another server is a great idea, then you could get the maximum out a map for a stargate world, anyways can't wait till it comes out, hope it doesn't die before it comes out and that its gmod 13 compatible, tracking mod ;)
This is a good idea, but it is definatly nowhere near a full release, i don't why you released it as a finished version, you should of released it as an Alpha or Early beta. It is still very buggy and you can't go outside or inside cause it says something like too few players to transfer map or something and you should of done your research for the mod, if you had of gone to the official mod page, you would know it is a Half Life 2: Ep 2 mod!
its a four player coop you know, not 8
im excited for mp and coop so i can scare the s*** out of my friends when i ditch them (sacrifice them :3) with slenderman xD
is the original release date still going to happen (Q1 2013) or has it been delayed to summer time or something because of the AI development stuff?


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A lot: windows, doors, roof trim, porch and gable deco, edge hiders, siding trim, window boxes, shutters, stairs, roof recolors, mailbox recolors and floors and walls.
by Honeywell 15th Jul 2018 at 4:10am in Build Mode » Build Mode Sets88 7,278 99
Mod that allows to take toddlers, cats, dogs, kittens and puppies to vacation destinations.
by Lamare 10th Feb 2018 at 12:10pm in Game Mods » Global Mods » Gameplay Changes37 13,694 90
Make having kids possible and comfortable for young adults and sims living on campus.
by Lamare 20th Sep 2017 at 12:17am in Game Mods » Global Mods » Gameplay Changes89 36,386 101
by Nopke 13th Apr 2017 at 9:27pm in Game Mods » Global Mods » Added Gameplay138 63,838 667
Collection - Simple houses #02 -...
by iSandor Yesterday at 11:39pm
by simler90 Yesterday at 1:51pm
by kestrellyn Yesterday at 1:02am
SUD Housing Project ~ low rent...
by CatherineTCJD 20th Aug 2018 at 7:01pm
by billielith 20th Aug 2018 at 1:28am
by simler90 19th Aug 2018 at 4:29pm
Multi-Storey Parking Lot/Garage -...
by dragomander 19th Aug 2018 at 4:22pm
Default replacement - BG underwear...
by dharden 18th Aug 2018 at 10:33pm
by razin 18th Aug 2018 at 3:44pm
by Meduza 17th Aug 2018 at 12:40am
Dorsal Stripe marking for Dogs
by Shickamru 17th Aug 2018 at 12:34am


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-----BEGIN PGP SIGNED MESSAGE----- Hash: SHA1 Hello, Am Freitag, 7. November 2003 08:37 schrieb Anne van Kesteren: > [suggests a @titlelang attribute, which is especially useful when using @title in combination with @xml:lang and @hreflang] I 100% agree. I didn't consider a title language attribute yet because I don't use the title attribute within the <body/> element so often, I mainly use it on <link/> elements in the <head/> element, and <link/> elements could not have a content, so the problem did not arise for me. I like your idea of adding a titlelang attribute. Bye - -- ITCQIS GmbH Christian Wolfgang Hujer Geschäftsführender Gesellschafter (Shareholding CEO) Telefon: +49 (0)89 27 37 04 37 Telefax: +49 (0)89 27 37 04 39 E-Mail: firstname.lastname@example.com WWW: http://www.itcqis.com/ -----BEGIN PGP SIGNATURE----- Version: GnuPG v1.2.2-rc1-SuSE (GNU/Linux) iD8DBQE/q1Rxzu6h7O/MKZkRAjYdAJwL05N64dzobzdKlHcQ0bgT3Zp78ACgz/Sr 7OInARu6hJiFVqbwdaJyZT4= =xYeg -----END PGP SIGNATURE-----Received on Friday, 7 November 2003 03:17:50 UTC
This archive was generated by hypermail 2.3.1 : Wednesday, 7 January 2015 15:06:06 UTC


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chimneypieces is a valid word in this word list. For a definition, see the external dictionary links below.
The word "chimneypieces" uses 13 letters: C C E E E H I I M N P S Y.
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Friday, 25 March 2011
The Return
Image Above: Reliance retuning to Erraid in the mist.
Location: Isle Of Erraid, Mull, Scotland
24th March
The Return
The cable is humming or buzzing or possibly vibrating on the edge audibility like the whining noise of an old television set. I wonder if it's the breeze or the billions of electrons charged and crackling their way down the line. If it wasn't for the high voltage I would be tempted to climb the post and place my ear against the wire to listen in on the world. If my hearing was better I could separate out the strands of noise into the conversations of power plant workers at the furthest reach of this piece of string.
Maybe the grid spans the country like a wed or metal brace on wayward teeth, soaking up waves as sounds cycle; snatched conversations, barking dogs, a school yard at break time, car alarm, ring tone, a gate on rusted hinges, a child muttering beneath his breath, or sheep pushing through tall moor land grasses. Every bird that lands or springs into flight from a line no matter how remote plucks a chord. Everything that vibrates adds something be it wave or particle even the last bolt of light from a dying star. Here, as the line crosses high over the sand onto the island the fog is condensing into droplets that tap like tiny glass hammers, the rattle of a cough escapes my chest but not the high wire.
I am stopped weighted to the spot with feet sunk into the soft sand listening to the cacophony. I have come home and in the silence of a drawn breath the wire and world are one.
Posted by Paul Adams at 10:23
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Popular Now
Popular Now
Popular Now
Popular Now
01803 865913
+44 1803 865913
Series: QRA Field Guides
By: AG Dawson(Editor), S Dawson(Editor)
123 pages, b/w photos, b/w illustrations, b/w maps
Quaternary Research Association
During recent years a considerable body of information has been obtained on Quaternary environmental changes in Scotland. The studies conducted have been concerned primarily with mainland areas and, to date, relatively few have considered the Quaternary morphology of the Inner Hebridean islands of Islay and Jura. The papers in this volume represent a compilation of results of recent research.
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Customer rank: +1
Vol. 4, No. 6, January 2009; 68 pages.
Cover: Chris Cox
Table of Contents
If you find anything wrong with this product listing, perhaps the description is wrong, the author is incorrect, or it is listed in the wrong category, then please contact us. We will promptly address your feedback.


text:
Buffett Design employs a multidisciplinary approach to sustainable design and regenerative architecture. We specialize in unique and efficient custom homes that define a sense of place and celebrate habitation.
Services include BIM facilitated consultation, design, drafting and permitting. Buffett Design is guided by simple concepts and principles yet utilizes complex 3D software and tools to produce creative, efficient, and engaging projects.
Tyler Buffett holds a Bachelor of Architecture degree from Woodbury University, a minor degree in Regenerative Studies from California Polytechnic University Pomona and received his general education from California State University San Marcos.
Buffett Design prides itself on generating site specific architecture that defines time and place. We like to feel that we are contributing to a contemporary vernacular based on local conditions. Although we specialize in architecture that lends itself to the Southern California biome, we have projects spanning North America.


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Newborn Baby Photography
Newborn Baby Photography: Capture Your Baby's Inner Radiance
The magic of a newborn baby is tangible, effervescent and fleeting. The days go by so quickly; before you know it, your perfect little miracle will be a magic toddler, a magic child and eventually, a (perhaps) not-quite-so-magic teenager! You can immortalize the inherent purity and delicacy of your newborn with a series of artfully composed photographs by a highly experienced and respected baby photo studio. The team at The Pod Photography studio is dedicated to creating gorgeous memories of your little one, and we pride ourselves in bringing you individually crafted photographs you and your family will cherish for generations.
Newborn baby photography is a specific skill, and the crew at The Pod Photography has cultivated that skill during years of newborn, child and maternity photography. In order to achieve exceptional results, a baby photographer not only needs a substantial amount of experience, she also must have a keen compositional eye. The newborn photographs from The Pod Photography are all personalized and tailored to the particular style of the parents; the results are always vibrant, hip and beautiful.
The Pod Photography studio promises a safe, professional and comfortable environment for you and your little one. We offer dozens of themed sets, costumes and props, all of which give the subject a uniquely beautiful effect. We will provide a thorough style and design consultation prior to the shoot, and we ask that newborn bookings are made approximately 3 months before the delivery in order to guarantee availability. Once the baby is delivered, you can proceed with scheduling – our newborn photography sessions take place when the baby is 5-10 days old.
We at The Pod Photography are a small but devoted group of baby photographers, and we are convinced that we can provide you with a glorious portrait of your precious little bundle. Give us a call today to schedule an appointment!


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Foursquare © 2018 Lovingly made in NYC & SF
People tend to check in during these times:
The Grove
University (Frat row)
"Stroll through the lush grass, read a book or have a picnic and you will know why The Grove is the heart of the Ole Miss campus. On gameday, The Grove is the only place to be prior to kick-off."
Student Union
Student Center
Student Union Drive (at University of Mississippi)
"Want a light and healthy meal? Go for white steamed rice + chicken w mushroom of Panda Express. H"
J.D. Williams Library
1 Library Loop
"You can see first editions and letters by authors such as Katherine Anne Porter, Kurt Vonnegut and Tim O'Brien. Faulkner first editions and some of his prizes are also on display."
Make sure your information is up to date. Plus use our free tools to find new customers.
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Public Health Ethics
Given the array of stakeholders and issues dealt with by local health departments (LHDs), health officials and their staff must be ready to handle ethical dilemmas that arise in day-to-day practice. Ethical considerations underlie numerous aspects of public health practice, ranging from staffing decisions at LHDs to distribution of vaccines during pandemics to media strategies related to sensitive subjects such as obesity. Tension often emerges as LHD staff try to find balance between individual rights or preferences and a community's claims to health and safety. Since 2010, NACCHO has partnered with the CDC Public Health Ethics Unit to provide public health ethics education and training for local health departments. The following resources include products and information resulting from the NACCHO-CDC ethics partnership, as well as related tools and content.
In the Spotlight
Upcoming Ethics Training Opportunity
The APHA Annual Meeting includes a full-day ethics course on October 31 in Chicago, IL. Click on the "More" button to view full details about the opportunity. More »
Build an Ethics Infrastructure at Your Health Department
As an increasing number of LHDs seek accreditation, LHDs need resources and advocates to handle public health ethics issues effectively. The Public Health Accreditation Board requires LHDs to document processes for dealing with ethical concerns. This fact sheet will help accreditation coordinators and LHD practitioners understand and promote the importance of public health ethics. More »
Fact Sheet: NACCHO & CDC Ethics Partnership
This fact sheet summarizes the key activities and products resulting from the NACCHO and CDC public health ethics partnership thus far. Key achievements include collaboration (along with other subject matter experts and partners) on the "Good Decision Making in Real Time" ethics training and the subsequent eLearning version of the course recently launched on NACCHO University. More »


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Podcast: Play in new window | Download
Subscribe: iTunes | Android | RSS
René from German Montana was truly awesome to have a conversation with. I learned so much from him and was extremely impressed with their view point and direction they want to go with the Montana company. There's a bunch of cool flicks you can check out those on the LT website.
Thanks again Tucker and René this was awesome. Here's some IG links to check out the paint and products @montanacans @montanacans_usa
The website has been updated and the next episode this Thursday is with Pen from Freightophiles


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Although Ginnie Mae saw its profits fall by almost 50% for the fiscal year ending in September, agency president Ted Tozer said the government guarantor has enough cash reserves to handle any potential losses.
"Our reserves are fine," Ginnie Mae president Tozer told ASR sister publication National Mortgage News in an interview.
Those reserves total roughly $357 million.
GNMA earned $610 million for the year ending Sept. 30, compared to $1.18 billion in FY 2011. The reason for the decline was an addition to loan loss reserves.
Tozer noted that in 2010 the agency set up a reserve fund but was told by its accountants that its set-asides were "too aggressive" but then changed their mind and asked for increases. "We have to do what our accountants say," he told NMN.
The GNMA chief anticipates that the guarantor will post earnings of $800 million to $900 million in the immediate years ahead.
The agency's guarantee covers roughly $1.3 trillion of home mortgages, or 14% of the entire mortgage market, according to figures compiled by the Quarterly Data Report.


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Mike Check: A Few More Words on L'Affaire Daisey | The Nation:
I didn't learn much in that straight sense from Agony—I'd read NGO and news reports about Foxconn before—and never thought that was the show's main point, anyway. Not having seen the note in the program labeling the show nonfiction (though if I had, it might not have mattered), I also didn't take it to be unvarnished. Daisey's honed prose and his fine-tuned performance—the well-placed sudden shouts, the comic slow takes, the repeated, careful small gestures—all pointed to admirable artifice, which at the very least always frames the factual. Nonetheless, Daisey was trying to strike a bargain with the audience that he could not keep, as if he could deliver the veracity of Lawrence Wright's The Human Scale and My Trip to Al Qaeda—elegantly wrought, staged lectures by a seasoned journalist with a personable presence, but little acting skill and not a sliver of Daisey's kinesthetic command onstage. Daisey belongs more to the varied tradition of Wally Shawn's The Fever, Spalding Gray's Swimming to Cambodia and Holly Hughes's Preaching to the Perverted, works that twine personal narratives around journeys of political discovery or entanglement.
There's a longstanding joke about performance artists doing psychotherapy onstage, and it's true of myriad bad cases. But the best performers—like Daisey—put the audience in the shrink's chair in a different manner: they prime us to listen for emotional honesty above all. And that is the truth I responded to and admired in his show: Daisey's own ecstasy and agony, his abiding romance with his gorgeous iStuff and his disgust with the injustice of its production, his—and our—urgent and frustrated desire to reconcile those feelings with action. Like many of his shows I've seen, Agony traces an experience of seduction and betrayal. This time, in more ways than one.


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Ultimate Pond Cleaner
Clarity-Blast Plus multi-purpose cleaning action cleans ponds with barley, bacteria, enzymes and a powerful secret ingredient. These substances clean, polish and break down attached organic debris that create problems for pond hobbyists on and around waterfalls, streams, plant pots and filtration systems. Clarity-Blast Plus contains Activated Barley. It is the only product that utilizes this patented process to combine bacteria cultures on barley. In tandem these ingredients help to remove and control pond hobbyist's worst pond problem for the long term
|Atlantic Biocuda Clarity-Blast Application Rates
|Pond Size (gallons)
|1,000 gallons
|2 oz.
|2,000 gallons
|4 oz.
|3,000 gallons
|6 oz.
|4,000 gallons
|8 oz.
|Apply Clarity-Blast+ once per week directly to the pond or filtration system.
|Persistent Problem Application Rate
|Apply Clarity-Blast+ up to every 3 days at the prescribed rate per gallon until the problem is corrected, then return to normal weekly application rate
|For Best Results
|Pond water pH should be maintained between 7.0 & 8.5. Water temperature should be at least 50°F and dissolved oxygen levels should be above 3ppm.
|Pond may become cloudy after application. Cloudiness should clear within 24-48 hours after application
|Treats (up to)
08119 - Atlantic Biocuda Clarity Blast + 3/4 lb (MPN 5CB3/4)
$16.92 $9.99 | 25 Points
3/4 lb
6,000 gallons
3/4 lb
6,000 gallons
Out of Stock