370 research outputs found
"Agglomeration Economies within IT-Producing and IT-Consuming Industries in U.S. Regions"
No full textThis paper deals with the effects of the geographic concentration of economic activity on productivity through agglomeration economies in the U.S. economy. Our empirical study extends the literature on agglomeration economies in two directions. First we measure and compare the effects on productivity of geographic concentration in either information technology related activity (the IT sector) or in all other economic activities (the non-IT sector). Second we follow Jorgenson’s (2002) reasoning regarding the significance of the differences between IT-producing sectors and IT-using sectors and assess the differential effects of concentration in IT-producing sectors and concentration in IT-using sectors on productivity. We utilize four measures of agglomeration and analyze effects at two levels of geographic disaggregation: U.S. states and U.S. counties. We perform the analysis using a model drawn from the growth accounting literature in which total labor productivity in a region is the dependent variable. It is modeled as a function of the region’s capital-output ratio, the quality of the region’s labor supply as measured by the level of education, and an agglomeration variable measured by concentration in the IT or non-IT sectors or in the IT-producing or IT-using sectors. The cross section estimates for a single year yield mixed results. We find weak evidence in favor of an effect of concentration of IT activity on productivity at the state level. We find stronger effects on productivity at the county level from concentration in IT-producing sectors.Agglomeration Economies, Information Technology, Productivity
Inactivation kinetics of voltage-gated calcium channels in glutamatergic neurons are influenced by SNAP-25
No full textSNAP-25 forms part of the SNARE core complex that mediates membrane fusion. Biochemical and electrophysiological evidence supports an accessory role for SNAP-25 in interacting with voltage-gated calcium channels (VGCCs) to modulate channel activity. We recently reported that endogenous SNAP-25 negatively regulates VGCC activity in glutamatergic neurons from rat hippocampal cultures by shifting the voltage-dependence of inactivation of the predominant P/Q-type channel current in these cells. In the present study, we extend these findings by investigating the effect that manipulating endogenous SNAP-25 expression has on the inactivation kinetics of VGCC current in both glutamatergic and GABAergic cells recorded from 9-13 DIV cultures. Silencing SNAP-25 in glutamatergic neurons significantly slowed the inactivation rate of P/Q-type VGCC current whereas alterations in SNAP-25 expression did not alter inactivation rates in GABAergic neurons. These results indicate that endogenous SNAP-25 plays an important role in P/Q-type channel regulation in glutamatergic neurons
THE SEQUENCE OF 967 AMINO-ACIDS AT THE CARBOXYL END OF RAT THYROGLOBULIN - LOCATION AND SURROUNDINGS OF 2 THYROXINE-FORMING SITES
No full textLagemann, Ellen Condliffe, Contested Terrain: A History of Education Research in the United States, 1890-1990, Educational Researcher, 26(December, 1997), 5-17.
No full textTraces the history of educational research in the U. S. and identifies major researchers and studies in curriculum and other specialties
Reduction of SNAP-25 expression impacts on neuronal calcium currents and network activity
No full textSNAP25 is a member of the SNARE protein complex that participates in synaptic vesicle exocytosis. We previously demonstrated that differential SNAP25 expression in hippocampal neurons regulates intracellular calcium dynamics (Verderio et al., Neuron 2004) and that negative modulation of neuronal voltage-gated calcium channels requires SNAP25 activity-dependent phosphorylation on Ser187 (Pozzi et al., PNAS 2008). A dysregulation of calcium dynamics due to alterations of SNAP25 expression may thus lead to unbalances of neuronal network activity. In line with this possibility, alterations of SNAP25 expression have been associated to several neurological diseases, such as schizophrenia, ADHD and epilepsy (reviewed in Corradini et al., 2009).
In this study we used SNAP25+/- mice to investigate whether reduction of SNAP25 expression induce altered network activity in vitro and in vivo, possibly leading to neurological phenotypes. A significant increase in calcium responsiveness to depolarization was observed in SNAP25+/- neurons as well as in synaptosomes from heterozygous mice relative to wild-type. No structural changes or alterations in protein expression were observed either in developing (P2) or adult (P40) brains, analyzed by immunohistochemistry and western blotting. Behavioural analysis of mice revealed lack of schizophrenic phenotype, as indicated by the absence of differences in prepulse inhibition of the acoustic startle response (PPI) test. Similarly, the elevated plus-maze and 0-maze tests revealed the absence of anxious behaviour. However, the occurrence of partial defects in learning were revealed in heterozygous mice by passive avoidance, object recognition and T maze tests . Heterozygous mice also presented an increased spontaneous motor activity by activity cage in comparison with wild-type mice; furthermore, in vivo electroencephalographic recordings from both cortex and hippocampus showed a significant increase in the number of spikes in SNAP25 +/- mice. Treatment of SNAP25+/- mice with antiepileptic drugs, such as ethosuximide and valproic acid, caused a significant reduction in the number of cortical spikes recorded by EEG. Finally, heterozygous mice showed a high susceptibility to kainate-induced seizures and a strong sprouting of mossy fibers, which is a marker of spontaneous epileptogenesis in mice after kainate injection. These data suggest that alterations of SNAP25 expression may contribute to epilepsy, possibly by dysregulating the normal calcium dynamics and thus altering network activity
Mutant prion protein expression causes impairment of cerebellar synaptic functions in a transgenic mouse model
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Regulation of voltage-gated calcium channels in PC12 cells by Leucine Rich Repeat Kinase 2
No full textLeucine rich repeat kinase two (LRRK2) is a widely expressed protein belonging to the Roco family of proteins, mutations in which have recently been discovered as a cause of familial Parkinson’s disease (PD). Despite an array of interacting proteins having been identified across multiple cellular systems, LRRK2’s functional role remains to be determined. Manipulation of LRRK2 expression disrupts many Ca2+ dependent cellular processes. It, therefore, may act as an upstream regulator of initial Ca2+ signalling events, which could explain LRRK2’s widespread effects. The central aim of this study was to determine whether LRRK2 alters endogenous voltage-gated Ca2+ (CaV) channel function in PC12 cells using whole cell patch clamp electrophysiology. Additionally, transiently transfected PC12 cells underwent epifluorescence imaging to identify morphological changes and identify any effects of L-type Ca2+ blockers on morphology.
Peak CaV channel currents in LRRK2 transfected cells showed a significantly (p=0.0025, n≥7, one way ANOVA with Tukeys post-hoc test) higher current density across a number of holding voltages relative to untransfected and EGFP transfected controls. These results indicate that LRRK2 up regulates endogenous CaV channel function. Morphological assessment, however showed no significant effect of LRRK2 transfection on morphological parameters relative to EGFP transfected and non-transfected controls (N≥63, Kruskal-Wallis test). Furthermore, addition of the L-type Ca2+ channel blocker nifedipine had no significant effect relative to untransfected and ethanol vehicle controls (N≥43,Kruskal-Wallis test). These results suggest that LRRK2 dependent modulation of CaV channel function does not affect neurite differentiation.
Overall, this study has identified a novel effect of LRRK2 on CaV channels, which may explain how LRRK2 has such widespread cellular effects and advances our understanding of LRRK2s functional role. If the effect of LRRK2 on CaV channels is responsible for pathology, CaV channel blockers currently being investigated for Parkinson’s therapy may be particularly effective in Parkinson’s patients harbouring LRRK2 mutations
Regulation of voltage-gated calcium channels in PC12 cells by Leucine Rich Repeat Kinase 2
No full textLeucine rich repeat kinase two (LRRK2) is a widely expressed protein belonging to the Roco family of proteins, mutations in which have recently been discovered as a cause of familial Parkinson’s disease (PD). Despite an array of interacting proteins having been identified across multiple cellular systems, LRRK2’s functional role remains to be determined. Manipulation of LRRK2 expression disrupts many Ca2+ dependent cellular processes. It, therefore, may act as an upstream regulator of initial Ca2+ signalling events, which could explain LRRK2’s widespread effects. The central aim of this study was to determine whether LRRK2 alters endogenous voltage-gated Ca2+ (CaV) channel function in PC12 cells using whole cell patch clamp electrophysiology. Additionally, transiently transfected PC12 cells underwent epifluorescence imaging to identify morphological changes and identify any effects of L-type Ca2+ blockers on morphology.
Peak CaV channel currents in LRRK2 transfected cells showed a significantly (p=0.0025, n≥7, one way ANOVA with Tukeys post-hoc test) higher current density across a number of holding voltages relative to untransfected and EGFP transfected controls. These results indicate that LRRK2 up regulates endogenous CaV channel function. Morphological assessment, however showed no significant effect of LRRK2 transfection on morphological parameters relative to EGFP transfected and non-transfected controls (N≥63, Kruskal-Wallis test). Furthermore, addition of the L-type Ca2+ channel blocker nifedipine had no significant effect relative to untransfected and ethanol vehicle controls (N≥43,Kruskal-Wallis test). These results suggest that LRRK2 dependent modulation of CaV channel function does not affect neurite differentiation.
Overall, this study has identified a novel effect of LRRK2 on CaV channels, which may explain how LRRK2 has such widespread cellular effects and advances our understanding of LRRK2s functional role. If the effect of LRRK2 on CaV channels is responsible for pathology, CaV channel blockers currently being investigated for Parkinson’s therapy may be particularly effective in Parkinson’s patients harbouring LRRK2 mutations
Adapted Sport and Recreation Camps: Examining Physical Activity, Self-Perceptions, and Motivations for Participation in Youth with Physical Disabilities
No full textPurpose: The purpose of this study is to examine whether time spent in moderate-to-vigorous physical activity (MVPA), self-perceptions, and motivation for participation in physical activity (PA) change following participation in a 5-day adapted sport and recreation (S&R) camp in youth aged 7-18 years with physical disabilities. Objectives: The first objective is to examine changes in weekly levels of MVPA in minutes in youth (ages 7-18 years) with a physical disability during, and at 6- and 12-months following participation in a 5-day adapted S&R camp compared to pre-camp MVPA. The second objective is to examine changes in self-perception and motivation for participation in PA in youth with a physical disability following a 5-day adapted S&R camp compared to pre-camp. Methods: This is a one-year longitudinal pre-experimental study that used Actigraphy to measure time spent in MVPA and used The Children’s Attraction to PA and the Self-Perception Profiles in Children measures to examine changes in self-perceptions and motivations for participating in PA. Data was collected pre-camp, during camp, and at 6- and 12-months post-camp. Results: Time spent in MVPA was higher during camp compared to pre-camp for children (z=-2.10; p=0.04) and adolescents (z=-2.31; p=0.03). This increase was not sustained at 6 months post-camp for both groups or at 12-months post-camp for the adolescent group (p>0.05). The children’s camp-group saw an increase in time spent in MVPA at 12-months post-camp relative to pre-camp (z=-2.02; p=0.04). Self-perceptions and attraction to physical activity did not meaningfully change on day 3, and 6-months and 12-months following participation in an adapted S&R camp. No apparent trends or patterns were seen based on individual level data. Conclusion: Time spent in MVPA, self-perceptions and attraction to PA in children did not change following participation in the adapted S&R camp. Future studies should consider a larger sample, a study design including a control group for comparison, and ways to improve psychosocial aspects when planning adapted S&R camps for youth with physical disabilities
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