Search

Daily moderate rainfall events, which constitute a major portion of seasonal summer monsoon rainfall over central India, have decreased significantly during the period 1951 through 2005. On the other hand, mean and extreme near-surface daily temperature during the monsoon season have increased by a maximum of 1–1.5 °C. Using simulations made with a high-resolution regional climate model (RegCM4) and prescribed land cover of years 1950 and 2005, it is demonstrated that part of the changes in moderate rainfall events and temperature have been caused by land-use/land-cover change (LULCC), which is mostly anthropogenic. Model simulations show that the increase in seasonal mean and extreme temperature over central India coincides with the region of decrease in forest and increase in crop cover. Our results also show that LULCC alone causes warming in the extremes of daily mean and maximum temperatures by a maximum of 1–1.2 °C, which is comparable with the observed increasing trend in the extremes. Decrease in forest cover and simultaneous increase in crops not only reduces the evapotranspiration over land and large-scale convective instability, but also contributes toward decrease in moisture convergence through reduced surface roughness. These factors act together in reducing significantly the moderate rainfall events and the amount of rainfall in that category over central India. Additionally, the model simulations are repeated by removing the warming trend in sea surface temperatures over the Indian Ocean. As a result, enhanced warming at the surface and greater decrease in moderate rainfall events over central India compared to the earlier set of simulations are noticed. Results from these additional experiments corroborate our initial findings and confirm the contribution of LULCC in the decrease in moderate rainfall events and increase in daily mean and extreme temperature over India. Therefore, this study demonstrates the important implications of LULCC over India during the monsoon season. Although, the regional climate model helps in better resolving land–atmosphere feedbacks over the Indian region, the inferences do depend on the fidelity of the model in capturing the features of Indian monsoon realistically. It is proposed that similar studies using a suite of climate models will further enrich our understanding about the role of LULCC in the Indian monsoon climate.

[1] This study investigates the magnitude and spatial extent of extreme summer temperature and specific humidity events in the extratropical northern hemisphere (NHEXT) using the NCEP Reanalysis (1979–2012) and the 20th century reanalysis (1871–2010). Specifically, we look at the percentage of area exceeding standard deviation thresholds in layer-averaged (500 mb–1000 mb) temperature and surface-level specific humidity to classify extremes. We find that: (1) areas of the NHEXT, including the southwestern tip of Greenland, experienced a summer heat wave during 2012 that was almost as extreme in spatial extent and magnitude as the Russian heat wave of 2010, (2) there is an increasing trend in summer heat waves and positive specific humidity anomalies and a decreasing trend in summer cold waves and negative specific humidity anomalies, and (3) while similar patterns in the global trend (1979–2012) in variability exist for both temperature and specific humidity, areas of increased variability are not necessarily the areas that have experienced extreme heat waves.

Continental temperature inversions significantly influence air quality, yet little is known about their variability in frequency and intensity with time or sensitivity to dynamical changes with climate. Inversion statistics for six upper-air stations in the American Southwest are derived for the period 1994–2008 from radiosonde data reported by the Global Telecommunication System (GTS) and National Climatic Data Center (NCDC), which use different significant level standards. GTS data indicate that low-level elevated inversions have increased in frequency at four of six sites, consistent with enhanced regional stagnation projected by models. NCDC data, in contrast, show remarkable declines in weak, near-surface inversions through 2001, indicating local surface conditions may counteract atmospheric dynamics in regulating inversion activity and air quality. To further test the sensitivity of inversion activity to climate, associations between wintertime inversion frequency and large-scale circulation are quantified using the self-organizing map technique. Twenty-four representative circulation patterns are derived from North American Regional Reanalysis (NARR) 500-hPa geopotential height fields, and these patterns are correlated with inversion frequency at each site. Inversion activity in Salt Lake City, Utah, and Albuquerque and Santa Teresa, New Mexico, is found to correspond well with large-scale anticyclonic ridging; however, sensitivities to large-scale circulation in Denver, Colorado, and Flagstaff and Tucson, Arizona, are weak. Denver stands out in exhibiting a higher percentage of near-surface inversions in winter than the other southwestern sites. These findings indicate that dynamical changes with climate will not uniformly influence inversions and hence urban air quality conditions in the American Southwest.

Updated tropical lower tropospheric temperature datasets covering the period 1979–2009 are presented and assessed for accuracy based upon recent publications and several analyses conducted here. We conclude that the lower tropospheric temperature (TLT) trend over these 31 years is +0.09 ± 0.03 °C decade−1. Given that the surface temperature (Tsfc) trends from three different groups agree extremely closely among themselves (~ +0.12 °C decade−1) this indicates that the “scaling ratio” (SR, or ratio of atmospheric trend to surface trend: TLT/Tsfc) of the observations is ~0.8 ± 0.3. This is significantly different from the average SR calculated from the IPCC AR4 model simulations which is ~1.4. This result indicates the majority of AR4 simulations tend to portray significantly greater warming in the troposphere relative to the surface than is found in observations. The SR, as an internal, normalized metric of model behavior, largely avoids the confounding influence of short-term fluctuations such as El Niños which make direct comparison of trend magnitudes less confident, even over multi-decadal periods.

Several recommendations have been proposed for detecting land use and land cover change (LULCC) on the environment from, observed climatic records and to modeling to improve its understanding and its impacts on climate. Researchers need to detect LULCCs accurately at appropriate scales within a specified time period to better understand their impacts on climate and provide improved estimates of future climate. The US Climate Reference Network (USCRN) can be helpful in monitoring impacts of LULCC on near-surface atmospheric conditions, including temperature. The USCRN measures temperature, precipitation, solar radiation, and ground or skin temperature. It is recommended that the National Climatic Data Center (NCDC) and other climate monitoring agencies develop plans and seek funds to address any monitoring biases that are identified and for which detailed analyses have not been completed.

In recent climate sensitivity experiments with the Community Climate System Model, version 3 (CCSM3), a wide range of studies have found that the Community Land Model, version 3 (CLM3), simulates mean global evapotranspiration with low contributions from transpiration (15%), and high contributions from soil and canopy evaporation (47% and 38%, respectively). This evapotranspiration partitioning is inconsistent with the consensus of other land surface models used in GCMs. To understand the high soil and canopy evaporation and the low transpiration observed in the CLM3, select individual components of the land surface parameterizations that control transpiration, canopy and soil evaporation, and soil hydrology are compared against the equivalent parameterizations used in the Simple Biosphere Model, versions 2 and 3 (SiB2 and SiB3), and against more recent developments with CLM. The findings of these investigations are used to develop new parameterizations for CLM3 that would reproduce the functional dynamics of land surface processes found in SiB and other alternative land surface parameterizations. Global climate sensitivity experiments are performed with the new land surface parameterizations to assess how the new SiB, consistent CLM land surface parameterizations, influence the surface energy balance, hydrology, and atmospheric fluxes in CLM3, and through that the larger-scale climate modeled in CCSM3. It is found that the new parameterizations enable CLM to simulate evapotranspiration partitioning consistently with the multimodel average of other land surface models used in GCMs, as evaluated by Dirmeyer et al. (2005). The changes in surface fluxes also resulted in a number of improvements in the simulation of precipitation and near-surface air temperature in CCSM3. The new model is fully coupled in the CCSM3 framework, allowing a wide range of climate modeling investigations without the surface hydrology issues found in the current CLM3 model. This provides a substantially more robust framework for performing climate modeling experiments investigating the influence of land cover change and surface hydrology in CLM and CCSM than the existing CLM3 parameterizations. The study also shows that changes in land surface hydrology have global scale impacts on model climatology.

A potent 5-hydroxytryptamine (5-HT)2A receptor inverse agonist and antagonist, ACP-103 [N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1, active:salt)], was evaluated for its ability to reduce the primary motor symptom of tremor using tacrine-induced tremulous jaw movements in rats, which is an animal model of parkinsonian tremor. Furthermore, ACP-103 was evaluated for its ability to reduce levodopa-induced dyskinesias in monkeys rendered parkinsonian with MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. ACP-103 reduced tacrine-induced tremulous jaw movements in rats. In addition, ACP-103 administered in combination with levodopa caused a dose-related reduction in dyskinesias in monkeys. These data suggest that ACP-103 may have the potential to reduce tremor and levodopa-induced dyskinesias in Parkinson's disease.

We present the construction of a dynamic area fraction model (DAFM), representing a new class of models for an earth-like planet. The model presented here has no spatial dimensions, but contains coupled parameterizations for all the major components of the hydrological cycle involving liquid, solid and vapor phases. We investigate the nature of feedback processes with this model in regulating Earth's climate as a highly nonlinear coupled system. The model includes solar radiation, evapotranspiration from dynamically competing trees and grasses, an ocean, an ice cap, precipitation, dynamic clouds, and a static carbon greenhouse effect. This model therefore shares some of the characteristics of an Earth System Model of Intermediate complexity. We perform two experiments with this model to determine the potential effects of positive and negative feedbacks due to a dynamic hydrological cycle, and due to the relative distribution of trees and grasses, in regulating global mean temperature. In the first experiment, we vary the intensity of insolation on the model's surface both with and without an active (fully coupled) water cycle. In the second, we test the strength of feedbacks with biota in a fully coupled model by varying the optimal growing temperature for our two plant species (trees and grasses). We find that the negative feedbacks associated with the water cycle are far more powerful than those associated with the biota, but that the biota still play a significant role in shaping the model climate. third experiment, we vary the heat and moisture transport coefficient in an attempt to represent changing atmospheric circulations.

Dopamine reuptake blockers, by enhancing and stabilizing intrasynaptic transmitter levels, could help palliate motor dysfunction in Parkinson's disease. This randomized, double-blind, placebo-controlled study compared the acute effects of the monoamine uptake inhibitor NS 2330 to those of placebo in 9 relatively advanced parkinsonian patients. At the dose administered, no change in parkinsonian scores was found when NS 2330 was given alone or with levodopa. Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa. The drug was well tolerated. Under the conditions of this study, the present results failed to support the usefulness of dopamine reuptake inhibition in the treatment of advanced Parkinson's disease.

Recent model simulations of the effects of increasing greenhouse gases combined with other anthropogenic effects predicted larger rates of warming in the mid and upper troposphere than near the Earth's surface. In multiple model comparisons we find that accelerated upper-level warm- ing is simulated in all models for the greenhouse-gas/direct-aerosol forcing representative of 1979-2000. However, in a test of model predictive skill, a comparison with observations shows no warming of the free troposphere over this period. We assessed the likelihood that such a disparity between model projection and observations could be generated by forcing uncertainties or chance model fluctuations, by comparing all possible 22 yr temperature trends in a series of climate simula- tions. We find that it is extremely unlikely for near-surface air temperatures (surface temperatures) to increase at the magnitude observed since 1979 without a larger warming in the mid-troposphere. Warming of the surface relative to the mid-troposphere was also more likely in control simulations than under anthropogenic forcing. Because errors in the vertical temperature structure would be expected to create errors in water-vapor feedback, cloud cover and moisture content, these results suggest the need for great caution when applying the simulations to future climate predictions and to impact assessments.

The neuronal protein alpha-synuclein has been implicated in the pathogenesis of Parkinson disease and other neurodegenerative diseases. Although many studies report that alpha-synuclein expression is restricted to neuronal presynaptic terminals, this protein aggregates in Lewy bodies in somata that are typically distant from their axon terminals. Few studies have addressed this paradox and there has been no compelling explanation proposed for the apparent discrepancy between the locus of neuronal alpha-synuclein expression and the loci of Lewy bodies in the majority of Parkinson disease cases. We explored this issue by extensively characterizing the monoclonal antibody Synuclein-1 (Syn-1) and using this highly selective antibody to map the distribution of alpha-synuclein throughout rat brain and in human substantia nigra (SN). Additionally, alpha-synuclein expression in rat SN detected by 2 polyclonal antibodies against alpha-synuclein was compared with that detected by the Syn-1 antibody. In contrast with many previous reports, alpha-synuclein was detected by Syn-1 in neuronal somata and dendrites in restricted brain regions, as well as more ubiquitously in axons and terminals. The strongest alpha-synuclein neuronal expression in rat was found in brainstem and cortical regions that are homologous to regions prone to Lewy body formation in humans. The Syn-1 antibody labeled abundant somatodendritic alpha-synuclein in both rat and human SN, a major locus of Lewy body formation and neurodegeneration in Parkinson disease. By contrast, very few immunoreactive somata in the rat SN were labeled by the 2 polyclonal antibodies. We explore possible explanations for the differences in conflicting reports of patterns of alpha-synuclein expression in brain, including differences among antibodies.

In addition to classic motor signs and symptoms, Parkinson's disease (PD) is characterized by neuropsychological and emotional deficits, including a blunted emotional response. In the present study, we explored both the neural basis of abnormal emotional behavior in PD and the physiological effects of dopaminergic therapy on the response of the amygdala, a central structure in emotion processing. PD patients and matched normal controls (NCs) were studied with blood oxygenation level-dependent functional magnetic resonance imaging during a paradigm that involved perceptual processing of fearful stimuli. PD patients were studied twice, once during a relatively hypodopaminergic state (i.e.,or =12 hr after their last dose of dopamimetic treatment) and again during a dopamine-replete state. The imaging data revealed a robust bilateral amygdala response in NCs that was absent in PD patients during the hypodopaminergic state. Dopamine repletion partially restored this response in PD patients. Our results demonstrate an abnormal amygdala response in PD that may underlie the emotional deficits accompanying the disease. Furthermore, consistent with findings in experimental animal paradigms, our results provide in vivo evidence of the role of dopamine in modulating the response of the amygdala to sensory information in human subjects.

The value of the analyses of the 200 mbar zonal winds is proposed as a particularly effective tool to assess variability and trends in atmospheric circulation. Using the thermal wind relation, the 200 mbar zonal wind results from the vertically integrated north-south temperature gradient between the Earth's surface and 200 mbar. We found a tendency for the 200 mbar winds to become somewhat stronger at higher latitudes since 1958.

The close correspondence between the distribution of brain alpha-synuclein and that of muscarinic M1 and M3 receptors suggests a role for this protein in cholinergic transmission. We thus examined the effect of muscarinic stimulation on alpha-synuclein in SH-SY5Y, a human dopaminergic cell line that expresses this protein. Under basal conditions, alpha-synuclein was detected in all subcellular compartments isolated as follows: plasma membrane, cytoplasm, nucleus, and two vesicle fractions. The lipid fractions contained only a 45-kDa alpha-synuclein oligomer, whereas the cytoplasmic and nuclear fractions contained both the oligomer and the monomer. This finding suggests alpha-synuclein exists physiologically as a lipid-bound oligomer and a soluble monomer. Muscarinic stimulation by carbachol reduced the alpha-synuclein oligomer in plasma membrane over a 30-min period, with a concomitant increase of both the oligomer and the monomer in the cytoplasmic fraction. The oligomer was associated with a light vesicle fraction in cytoplasm that contains uncoated endocytotic vesicles. The carbachol-induced alteration of alpha-synuclein was blocked by atropine. Translocation of the alpha-synuclein oligomer in response to carbachol stimulation corresponds closely with the time course of ligand-stimulated muscarinic receptor endocytosis. The data suggest that the muscarine receptor stimulated release of the alpha-synuclein oligomer from plasma membrane, and its subsequent association with the endocytotic vesicle fraction may have a role in muscarine receptor endocytosis. We propose that its function may be a transient release of membrane-bound phospholipase D2 from alpha-synuclein inhibition, thus allowing this lipase to participate in muscarinic receptor endocytosis.

Land cover change (LCC) simulations were performed at 3 different carbon dioxide lev- els (280, 355 and 430 ppmv) using the standard version of the NCAR CCM3 at T42 resolution coupled with the Biosphere-Atmosphere Transfer Scheme (BATS) and a mixed-layer ocean model. We follow the evolution of the initial temperature perturbation within the horizontal and vertical structure of the atmosphere and then examine the 15 yr average of near-surface air temperature and meridional stream function differences between current and natural land cover at the 3 different CO2 levels. Results show that LCC caused temperature perturbations which initially affected only those regions where the land cover was modified. After a short period, however, the effects of LCC propagated to remote regions. While the remote effects of LCC were generally different at each CO2 level, 4 com- mon remote regions of sensitivity were identified in these simulations (North Pacific, North America, northeast Asia and the Indian Ocean). The main factor in explaining the differing remote responses was the change in the zonally averaged background circulation resulting from circulation changes caused by LCC, CO2 level, and the interaction between these 2 forcings. The 15 yr average seasonal results indicate that LCC may have impacts on surface air temperature which vary in sign between seasons, depending on the character of the initial land cover perturbation as well as local meteoro- logical conditions. We find no evidence that the impacts of LCC decrease with increasing CO2, rather we show that LCC does appear to affect regional climate at a statistically significant level.

OBJECTIVE: To evaluate the contribution of amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) glutamate receptors to the pathogenesis of parkinsonian signs and levodopa-induced dyskinesias. BACKGROUND: Motor fluctuations and dyskinesias reflect, in part, altered function of glutamate receptors of the NMDA subtype. The possible role of AMPA receptors, however, has not yet been examined. METHODS: The authors compared the ability of an AMPA agonist (CX516) and a noncompetitive AMPA antagonist (LY300164) to alter parkinsonian symptoms and levodopa-induced dyskinesia in MPTP-lesioned monkeys. Eight levodopa-treated parkinsonian monkeys received rising doses of each drug, first in monotherapy and then in combination with low-, medium-, and high-dose levodopa. RESULTS: CX516 alone, as well as when combined with low-dose levodopa, did not affect motor activity but induced dyskinesia. Moreover, following injection of the higher doses of levodopa, it increased levodopa-induced dyskinesia by up to 52% (p < 0.05). LY300164 potentiated the motor activating effects of low-dose levodopa, increasing motor activity by as much as 86% (p < 0.05), and that of medium-dose levodopa as much as 54% (p < 0.05). At the same time, LY300164 decreased levodopa-induced dyskinesia by up to 40% (p < 0.05). CONCLUSIONS: AMPA receptor upregulation may contribute to the expression of levodopa-induced dyskinesia. Conceivably, noncompetitive AMPA receptor antagonists could be useful, alone or in combination with NMDA antagonists, in the treatment of PD, by enhancing the antiparkinsonian effects of levodopa without increasing and possibly even decreasing levodopa-induced dyskinesia. Neurology

This study examines regional temperature trends during the period 1979–1997 from the Microwave Sounding Unit (MSU) 2r satellite measurements and compares them with the same trends in depth-averaged tropospheric temperatures derived from the National Center for Environmental Prediction (NCEP) reanalysis, in an attempt to determine whether regional trends exist which are larger than known inhomogeneities in the data. Large, statistically significant regional trends were found in both the NCEP and the MSU data that are of both signs and have larger magnitude than documented biases in the data. The datasets have overall agreement on the location and strength of these significant regional trends at mid and high latitudes but agreement decreases in the tropics. A global annual average of the significant regional trends with larger amplitudes than reported data biases and areally weighted over the globe yields −0.02°C over the 19-year period of the record in the MSU 2r Version C dataset, and −0.05°C/19 years in the NCEP data in the 1000–500 mb layer. Increasing the bias threshold by as much as five times still results in an average cooling in both datasets. Subjecting the surface temperature record to the same regional analysis yields a regionally significant trend of 0.17°C/19 years, approximately halving the trend obtained when all regions, regardless of significance, are considered. In addition, many regions with significant warming trends in the surface network occur in areas with limited observations over oceans and are not confirmed by the other datasets. Discrepancies between significant regional trends in the surface record and the upper-air observations are not systematic. In no case are regionally significant, tropical, warming trends at the surface magnified at higher levels in the MSU and NCEP tropospheric data. In the case of the NCEP reanalysis, both warming and cooling trends on average become larger, more significant, and cover larger areas in shallower tropospheric layers. These results suggest that the disparity between global trends in satellite/rawinsonde/reanalysis datasets and those of the surface record are not simply the result of large-scale changes in the vertical structure of the atmosphere or to large-scale biases in the satellite observations, but instead are linked to processes which are regional in nature. Copyright © 2000 Royal Meteorological Society

Mutations in alpha-synuclein are known to be associated with Parkinson's disease (PD). The coexistence of this neuronal protein with ubiquitin and proteasome subunits in Lewy bodies in sporadic disease suggests that alterations of alpha-synuclein catabolism may contribute to the pathogenesis of PD. The degradation pathway of alpha-synuclein has not been identified nor has the kinetics of this process been described. We investigated the degradation kinetics of both wild-type and A53T mutant 6XHis-tagged alpha-synuclein in transiently transfected SH-SY5Y cells. Degradation of both isoforms followed first-order kinetics over 24 h as monitored by the pulse-chase method. However, the t((1)/(2)) of mutant alpha-synuclein was 50% longer than that of the wild-type protein (p0.01). The degradation of both recombinant proteins and endogenous alpha-synuclein in these cells was blocked by the selective proteasome inhibitor beta-lactone (40 microM), indicating that both wild-type and A53T mutant alpha-synuclein are degraded by the ubiquitin-proteasome pathway. The slower degradation of mutant alpha-synuclein provides a kinetic basis for its intracellular accumulation, thus favoring its aggregation.

Using identical observed meteorology for lateral boundary conditions, the Regional Atmospheric Modeling System was integrated for July-August 1973 for south Florida. Three experiments were performed-one using the observed 1973 landscape, another the 1993 landscape, and the third the 1900 landscape, when the region was close to its natural state. Over the 2-month period, there was a 9% decrease in rainfall averaged over south Florida with the 1973 landscape and an 11% decrease with the 1993 landscape, as compared with the model results when the 1900 landscape is used. The limited available observations of trends in summer rainfall over this region are consistent with these trends.

The analysis of thickness derived from the National Center for Environmental Prediction (NCEP) reanalysis indicates that there has been no statistically significant warming trend in layer-averaged global tropospheric temperatures during the period 1979–1996. While this result is at variance with data based on surface information, NCEP trends and interannual variations are closely related to tropospheric mean-layer temperatures obtained from the satellite-based microwave sounding unit (MSU) lower-tropospheric data set. When a longer period, 1973–1996, is used for the NCEP analysis, a warming trend within a 95% confidence interval is derived. However, it is nearly half the magnitude of the surface-derived trends. Strong correlations of the yearly global surface temperature anomalies and those calculated for several layers in the NCEP data indicate coincident interannual temperature variations throughout the depth of the troposphere. The disagreement of both our analysis and satellite-derived estimates with surface data could be due to a land surface measurement bias, a result of land use changes such as deforestation and agricultural expansion whose effects are not yet accounted for in the global temperature records, and/or a decoupling between surface and lower-tropospheric temperature over the last several years.

We examined 50 patients with parkinsonism-dementia complex of Guam (Guam PDC), 10 Guamanian patients with amyotrophic lateral sclerosis (ALS), 5 patients with combined PDC and ALS (PDC-ALS), and 20 non-PDC non-ALS Guamanians, who had been autopsied between 1979 and 1982, paying special attention to glial inclusions. Gallyas-positive and tau-immunopositive intracytoplasmic inclusions were observed in many of the glial cells, in addition to extensive neurofibrillary tangles (NFTs) in the brains of Guam PDC and PDC-ALS patients. Granular hazy inclusions were seen in the astrocytes, and some crescent/coiled inclusions were observed in the oligodendroglia. Many granular hazy inclusions were observed in the amygdaloid nucleus, inferior olivary nucleus, and lateral funiculus of the spinal cord. The crescent/coiled inclusions were observed predominantly in the anterior nucleus of the thalamus, motor cortex, midbrain tegmentum, pyramids of the medulla oblongata, and lateral funiculus of the spinal cord. The granular hazy inclusions have never been reported previously, and the topographic distribution of the crescent/coiled inclusions in Guam PDC and PDC-ALS differs from those reported previously in other NFT-forming diseases. These findings indicate that Guam PDC and PDC-ALS involve not only neurons but also glia, and that their morphological and topographic differences from other NFT-forming diseases may provide further insights into their distinct etiopathogenesis, and thus prove useful for diagnosis.

Land cover plays a key role in various biophysical processes related to global climate and terrestrial biogeochemistry. Although global land cover has dramatically changed over the last few centuries, until now there has been no consistent way of quantifying the changes globally. In this study we used long-term climate and soils data along with coarse resolution satellite observations to quantify the magnitude and spatial extent of large-scale land cover changes attributable to anthropogenic processes. Differences between potential leaf area index (LAI), derived from climate-soil-leaf area equilibrium, and actual leaf area index obtained from satellite data are used to estimate changes in land cover. Further, changes in LAI between potential and actual conditions are linked to climate by expressing them as possible changes in radiometric surface temperatures (Tr) resulting from changes in surface energy partitioning. As expected, areas with high population densities, such as India, China, and western Europe showed large reductions in LAI. Changes in global land cover expressed as summer, midafternoon Tr, ranged from −8° to +16°C. Deforestation resulted in an increase in Tr, while irrigated agriculture reduced the Tr. Many of the current general circulation models (GCMs) use potential vegetation maps to represent global vegetation. Our results indicate that there are widespread changes in global land cover due to deforestation and agriculture below the resolution of many GCMs, and these changes could have a significant impact on climate. Potential and actual LAI data sets are available for climate modelers at 0.5° × 0.5° resolution to study the possible impacts of land cover changes on global temperatures and circulation patterns.

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

[1] This paper is an update from our earlier paper to include data through July 2008. In our earlier paper, which included data through 1998, a mechanism which generally limits Arctic minimum 500 mb temperatures to the −40°C to −45°C range was presented. The current paper is in agreement with those earlier findings and also shows some evidence of later autumn onset dates of the initial appearance of these temperatures, in agreement with the recent reduction of Arctic sea ice cover in the summer and fall. In the southern hemisphere, little change can be seen for the seasonal onset and end of the temperatures reaching −40°C area, while the appearance of temperatures reaching −44°C area seems to show a later onset date beginning about 1998, but this time period is too small to define a clear trend. The limiting of the minimum of these midtropospheric temperatures has important implications for minimum surface temperatures that can occur over land during the Arctic winter.

[1] Changes in both land cover and the atmosphere have impacted the heat fluxes of south Asia in ways that may have altered the timing and magnitude of the monsoon. Century-long budgets of water and energy in the Krishna Basin (258,948 km2) in southern India demonstrate that irrigation impacted the sensible heat flux of the land surface (H) as much as or more than did the atmospheric brown cloud (ABC) over 1960–2005. Annual discharge of the Krishna River fell from 226 mm during pre-irrigation land cover (1901–1960) to 64 mm by 1990–2005, when 14–20% of the basin area was irrigated. Over the same period, annual evaporation increased by 166 ± 32 mm (+28%) causing H to decrease by 12.7 ± 2 W m−2 (−18%) compared to a decrease of 11.2 ± 1.8 W m−2 caused by the atmospheric brown cloud (ABC). The rate of change in H during irrigation expansion (1960–1990) was between −3.4 and −5.0 W m−2 per decade (da−1) due to irrigation expansion and −1.8 to −2.3 W m−2 da−1 due to the ABC. The trend in H caused by irrigation was negligible over 1990–2005 as irrigated area and evaporation stabilized. Previous work using the Parallel Climate Model estimated that the ABC decreased the latent heat flux by 2.4 W m−2; this decrease was more than offset by irrigation, resulting in a net increase in the latent heat flux of 12.9 W m−2. The maximum surface air temperature (Tmax) either decreased or remained the same in areas experiencing irrigation expansion but increased in a majority of unirrigated areas during the post-monsoon season. The results provide observational evidence that irrigation changed both the basin-scale sensible heat flux and surface air temperatures.

[1] Plausibility and reproducibility of the relationship and physical mechanisms proposed between the northern East Asian summer monsoon (NEASM) and El Nino are verified and illuminated using the Community Climate System Model (CCSM) with the Community Atmosphere Model–Community Land Model version 3 (CAM-CLM3). The climate responses over East Asia and western North Pacific to El Nino are simulated in the CCSM3 using dynamic atmosphere and land with prescribed climatological and El Nino sea surface temperature (SST) anomalies. A significantly intensified NEASM is simulated for the El Nino experiments, which validates the positive correlation between NEASM precipitation and El Nino found in recent observational analysis. Analysis of lower level wind vector and vorticity in the model experiments elucidates the physical mechanism behind the positive correlation between NEASM precipitation and El Nino, and shows that the western North Pacific anticyclone plays an important role in the connection between the NEASM and the tropical SST anomalies.

[1] The East Asian summer monsoon greatly influences the lives and property of about a quarter of the people in the world. However, the predictive skill of the monsoon is very low in comparison with that of the Indian summer monsoon because of the complexity of the system which involves both tropical and subtropical climates. Previous monsoon prediction models emphasized ocean factors as the primary monsoon forcing. Here we show that preseason land surface cover is at least as important as ocean indices. New statistical forecast models of the East Asian summer monsoon using land cover conditions in addition to ocean heat sources double and triple, respectively, the predictive skill of the northern and southern East Asian summer monsoon forecasting models relative to models using ocean factors alone. This work highlights the, as yet, undocumented importance of seasonal land cover in monsoon prediction and the role of the biosphere in the climate system as a whole. We also detail the physical mechanisms involved in these land surface forcings.

[1] Southwestern U.S. pinyon tree-ring carbon-isotope indices showed promise two decades ago as an indicator of moisture and drought. However, because those isotopic indices were developed on 5-year ring groups rather than annual rings, the full extent of their effectiveness as environmental proxies was not established. Recent re-sampling of the sites and subsequent availability of annual isotopic indices for 1985 through 1999 has allowed us to more definitively characterize environmental relationships across 14 sites in six southwestern states. Principal component (PC) analysis reveals a significant positive relationship (p ≤ 0.02) between isotope indices and summer-season Normalized Difference Vegetation Index (NDVI), a satellite-derived “greenness index”. Correlation and PC analysis also show a negative relationship of isotope indices with cumulative monthly precipitation (p ≤ 0.05) and confirm a strong positive relationship with Palmer Drought Index (especially spring and summer, p ≤ 0.0002). Although the drought and NDVI relationships are not as simply interconnected as hypothesized, the NDVI link reveals the potential of the existing multi-century record of isotope indices for long-term assessment of southwestern ecology and carbon cycling.

[1] We agree with Connolley [2008] that the 2003 heat wave as measured by the near surface temperature does indeed appear to be much more unusual than the 1000– 500 mb depth-averaged anomaly. We chose, however, the averaged temperature to characterize the heat wave for several reasons. First, a layer average permits a more comprehensive assessment of large scale temperature anomalies than do single point, near-surface temperature anomalies which are more affected by local conditions [e.g., see, Pielke et al., 2007]. Secondly, unlike the depth averaged temperatures which are strongly observationally based, the near-surface, NCAR-NCEP reanalysis temperature is not directly constrained by observations and is therefore, in large part, a model calculation [Kalnay et al., 1996]. Errors in such quantities as soil moisture distribution in the reanalysis (a weakness of most models), for example, would make the calculation of near-surface temperature extremes less precise, especially in a situation where soil moisture seems to have played a strong role. For example, a too dry soil would spuriously amplify a warm anomaly. Finally, the effects of increasing anthropogenic CO2 on atmospheric temperature are expected to extend vertically through the troposphere, at least climatologically [Trenberth et al., 2007; Climate Change Science Program, 2006]. Assuming the near-surface temperature measurements are spatially representative, the conclusion that the heat wave was a shallow phenomenon in terms of its unusualness argues against the point of view that it was a direct manifestation of the effects of increased atmospheric CO2 (note the use of ‘‘SD thresholds exceeded’’ normalizes variability with altitude making all levels directly comparable). [2] Therefore we also conclude that land surface conditions (low soil moisture) are the likely direct cause for such an ‘‘unusual’’ event near the surface. This is supported by Fischer et al. [2007] who reported the lack of rainfall the preceding spring as an important contributing factor in enhancing the 2003 heat wave. Many processes could be responsible for the lack of previous season rainfall including regional processes and natural or anthropogenic changes in circulation patterns. [3] Figure 1 updates Chase et al. [2006] through 2006 for 2.0 and 3.0 SD levels and adds to our original conclusion that 2003 was not very unusual in terms of the spatial coverage of extreme depth-averaged temperatures. For example, the summer of 2004 also exceeded the 2003 warm anomaly extent. This was due to a strong Alaskan heat wave which produced a record breaking wildfire season documented in National Climatic Data Center’s [2004] Annual Climate Report (http://www.ncdc.noaa.gov/oa/climate/ research/2004/ann/events.html), but otherwise received much less public attention than the European heat wave. However, the addition of three additional summers (2004– 2006) to the time series, all of which appear to be relatively warm, now indicates the possible emergence of an upward trend as suggested in previous work [Stott et al., 2004]. For example 2.0 SD warm anomalies now appear to have an upward trend (p = 0.05) though this trend should be viewed with caution because of the small sample size and the dominant effect of data points at the end of the series. The rise in 3.0 SD anomalies comparable to the 2003 heat wave is, however, still insignificant (p = 0.16) and so the increased probability of such extremes with time suggested by Stott et al. [2004] is not yet apparent.

Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms.

[1] Recently a number of studies have found significant differences between Moderate Resolution Imaging Spectroradiometer (MODIS) land surface mapping and the land surface parameters of the Community Land Model (CLM) of the Community Climate System Model (CCSM). To address these differences in land surface description, we have developed new CLM 3.0 land surface parameters that reproduce the physical properties described in the MODIS land surface data while maintaining the multiple Plant Functional Type (PFT) canopy and herbaceous layer representation used in CLM. These new parameters prescribe crop distributions directly from historical crop mapping allowing cropping to be described in CLM for any year from 1700 to current day. The new model parameters are calculated at 0.05 degrees resolution so they can be aggregated and used over a wider range of model grid resolutions globally. Compared to the current CLM 3.0 parameters, the new parameters have an increase in bare soil fraction of 10% which is realized through reduced tree, shrub, and crop cover. The new parameters also have area average increases of 10% for leaf area index (LAI) and stem area index (SAI) values, with the largest increases in tropical forests. The new land surface parameters have strong repeatable impacts on the climate simulated in CCSM 3.0 with large improvements in surface albedo compared to MODIS values. In many cases the improvements in surface albedo directly resulted in improved simulation of precipitation and near-surface air temperature; however, for the most part the existing biases of CCSM 3.0 remained with the new parameters. Further analysis of changes in surface hydrology revealed that the increased LAI of the new parameters resulted in lower overall evapotranspiration with reduced precipitation in CCSM 3.0. This was an unexpected result given that other research into the impacts of vegetation change suggests that the new parameters should have the opposite impact. This suggests that while the new parameters significantly improve the climate simulated in CLM 3.0 and CCSM 3.0, the new surface parameters have limited success in rectifying surface hydrology biases that result from the parameterizations within the CLM 3.0.

[1] We place the European summer heat wave of 2003 in the context of other extreme summer tropospheric temperature events from 22°N to 80°N since 1979, as well as globally using annual averages. The analysis is performed in terms of standard deviations (SD) exceeded and correlations between regional extremes and temperatures at larger spatial scales. As has been pointed out previously the heat wave was statistically unusual and was a deep tropospheric phenomenon. In this analysis we also find the following. (1) Extreme warm anomalies equally, or more, unusual than the 2003 heat wave occur regularly. (2) Extreme cold anomalies also occur regularly and occasionally exceed the magnitude of the 2003 warm anomaly in terms of the value of SD. (3) There is a correlation between global and hemispheric average temperature and the presence of warm or cold regional anomalies of the same sign (i.e., warmer than average years have more regional heat waves and colder than average years have more cold waves). (4) Natural variability in the form of El Nino and volcanic eruptions appear to be of much greater importance in causing extreme regional temperature anomalies than a simple upward trend in time. Extreme temperature anomalies in the wake of the 1997–98 El Nino were larger than the anomalies seen in summer 2003 both in area affected and SD extremes exceeded. (5) Regression analyses do not provide strong support for the idea that regional heat waves are increasing with time.

Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5-HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa-induced dyskinesias and prolonged its antiparkinsonian response (P ≤ 0.05). Under the conditions of this study, our findings suggest that 5-HT1A receptor stimulation in levodopa-treated parkinsonian patients can modulate striatal dopaminergic function and that 5-HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society

The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT+) and parvalbumin positive (PARV+) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i.

[1] Observations indicate a minimum mid-tropospheric Arctic winter temperature of about −45°C at 500 hPa. This minimum temperature coincides with that predicted for moist adiabatic ascent over a sea surface near its salinity-adjusted freezing point. NCAR/NCEP Reanalysis data show that convective heating maxima averaged over the 50–70°N latitude band coincide both in longitude and altitude with total horizontal energy flux maxima entering the Arctic, indicating the significance of convection over open water on the winter Arctic energy budget. NCAR CCM single column model experiments simulating convective warming of a cold airmass moving over open water and radiative cooling as it moves again over cold land/sea ice support the hypothesis that the −45°C threshold can be maintained for 10–14 days after convective warming occurs. We speculate on the implications of this regulatory mechanism on surface temperatures.

Our paper documents that land-use change impacts regional and global climate through the surface-energy budget, as well as through the carbon cycle. The surface-energy budget effects may be more important than the carbon-cycle effects. However, land-use impacts on climate cannot be adequately quantified with the usual metric of 'global warming potential'. A new metric is needed to quantify the human disturbance of the Earth's surface-energy budget. This 'regional climate change potential' could offer a new metric for developing a more inclusive climate protocol. This concept would also implicitly provide a mechanism to monitor potential local-scale environmental changes that could influence biodiversity.

Functional coupling of regional cerebral metabolic rates for glucose measured with [18F]-Fluoro-2-deoxy-D-glucose PET was compared in 18 drug-free patients with Tourette's Syndrome (TS) and 16 age- and sex-matched control subjects. Pearson product-moment correlation matrices containing correlations between metabolic rates in regions sampled throughout the brain were generated independently for TS patients and controls and compared. Significant differences between Z-transformed correlation coefficients were used to identify group differences, and revealed that the connectivity of the ventral striatum was most severely affected in TS. Changes in the coupling of other brain areas—primary motor areas, somatosensory association areas, and insula—also appeared to differentiate TS patients and controls. Evaluation of interrelationships between cortico-striato-thalamo-cortical circuits revealed the existence of functional connections between the motor and lateral orbitofrontal circuits in both groups, however, a reversal in the pattern of these interactions differentiated TS patients and controls. In controls, activity in these circuits appeared to be negatively correlated —i.e. increased activity in one is associated with relative inactivity the other. In TS patients, on the other hand, activity in the motor and lateral orbitofrontal circuits appears to be positively coupled. These results lend further credence to the hypothesis that altered limbic-motor interactions represent a pathophysiological hallmark of this disease.

[1] This paper documents an observed lower extreme of midtropospheric (500 mbar) temperatures in the Arctic of approximately 45C during the winter season in several data sets. Each data set shows that the coldest air masses in the Arctic reach 45C during the fall months but seldom get much colder even into late winter despite a continued net radiative loss. We demonstrate that midtropospheric temperatures are significantly skewed toward warmer temperatures, indicating a regulatory mechanism at work. We further provide evidence that minimum Arctic midtropospheric temperatures are regulated by moist convective processes and that minimum 500 mbar temperatures are controlled to a large extent by high-latitude sea surface temperatures. The temperature 45 Ci s the expected 500 mbar temperature in an atmosphere regulated by moist adiabatic ascent from a surface temperature of 1–2 below 0C, the approximate freezing point of seawater. This implies that Arctic air masses are regularly in contact with unfrozen seawater to the south, an easily verified observation. Climate model simulations of the effects of increased greenhouse gasses hypothesize that high, northern latitude regions should warm at a faster rate than the globe as a whole, a hypothesis which does not appear to have strong observational support. We discuss the implications of this result for the accelerated Arctic warming hypothesis. INDEX TERMS: 3339 Meteorology and Atmospheric Dynamics: Ocean/ atmosphere interactions (0312, 4504); 3314 Meteorology and Atmospheric Dynamics: Convective processes; 1699 Global Change: General or miscellaneous; 3349 Meteorology and Atmospheric Dynamics: Polar meteorology; KEYWORDS: Arctic convection, temperature regulation, atmosphere-ocean interactions

The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning "off"-L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries ("on" without dyskinesia, "on" with dyskinesia, and "off"). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications. Clin Neuropharmacol

BACKGROUND: In a recent acute study, amantadine was found to have antidyskinetic effect against levodopa-induced motor complications in patients with Parkinson disease. The longevity of this effect was not addressed but is of interest in light of the controversy in the literature regarding the duration of amantadine's well-established antiparkinsonian action. OBJECTIVE: To determine the duration of the antidyskinetic effect of amantadine in advanced Parkinson disease. DESIGN: One year after completion of an acute, double-blind, placebo-controlled, crossover study, patients returned for re-evaluation of motor symptoms and dyskinesias using a nonrandomized, double-blind, placebo-controlled follow-up paradigm. SETTING: National Institutes of Health Clinical Center. PATIENTS: Seventeen of the original 18 patients with advanced Parkinson disease complicated by dyskinesias and motor fluctuations participated in this study; 1 was lost to follow-up. Thirteen of the 17 individuals had remained on amantadine therapy for the entire year. INTERVENTIONS: Ten days prior to the follow-up assessment, amantadine was replaced with identical capsules containing either amantadine or placebo. MAIN OUTCOME MEASURES: Parkinsonian symptoms and dyskinesia severity were scored using standard rating scales, while subjects received steady-state intravenous levodopa infusions at the same rate as 1 year earlier. RESULTS: One year after initiation of amantadine cotherapy, its antidyskinetic effect was similar in magnitude (56% reduction in dyskinesia compared with 60% 1 year earlier). Motor complications occurring with the patients' regular oral levodopa regimen also remained improved according to the Unified Parkinson's Disease Rating Scale (UPDRS-IV). CONCLUSION: The beneficial effects of amantadine on motor response complications are maintained for at least 1 year after treatment initiation. Arch Neurol

Nuclear factor kappaB (NF-kappaB) appears to participate in the excitotoxin-induced apoptosis of striatal medium spiny neurons. To elucidate molecular mechanisms by which this transcription factor contributes to NMDA receptor-triggered apoptotic cascades in vivo, rats were given the NMDA receptor agonist quinolinic acid (QA) by intrastriatal infusion, and the role of NF-kappaB in the induction of apoptosis-related genes and gene products was evaluated. QA administration induced time-dependent NF-kappaB nuclear translocation. The nuclear NF-kappaB protein after QA treatment was comprised mainly of p65 and c-Rel subunits as detected by gel supershift assay. Levels of c-Myc and p53 mRNA and protein were markedly increased at the time of QA-induced NF-kappaB nuclear translocation. Immunohistochemical analysis showed that c-Myc and p53 induction occurred in the excitotoxin-sensitive medium-sized striatal neurons. NF-kappaB nuclear translocation was blocked in a dose-dependent manner by the cell-permeable recombinant peptide NF-kappaB SN50, but not by the NF-kappaB SN50 control peptide. NF-kappaB SN50 significantly inhibited the QA-induced elevation in levels of c-Myc and p53 mRNA and protein. Pretreatment or posttreatment with NF-kappaB SN50, but not the control peptide, also substantially reduced the intensity of QA-induced internucleosomal DNA fragmentation. The results suggest that NF-kappaB may promote an apoptotic response in striatal medium-sized neurons to excitotoxic insult through upregulation of c-Myc and p53. This study also provides evidence indicating an unique signaling pathway from the cytoplasm to the nucleus, which regulates p53 and c-Myc levels in these neurons during apoptosis.

The antidyskinetic potential of the glutamate NMDA receptor channel blocker amantadine was evaluated in four levodopa-primed parkinsonian monkeys using two different regimens (1.25 or 2.5 mg/kg administered subcutaneously twice daily for 3-6 days). When administered with a relatively low dose of levodopa, amantadine produced a near-total suppression of choreiform dyskinesias and a substantial reduction in dystonic dyskinesias at the expense of a significant reduction in antiparkinsonian response. With a high dose of levodopa, amantadine had a smaller but still significant effect on dyskinesias without altering the antiparkinsonian response. These results lend support to the view that glutamate receptor-mediated mechanisms contribute to levodopa-induced dyskinesias. They also suggest that amantadine could alleviate such complications in parkinsonian patients, especially with careful dose optimization. Mov Disord

The development of a validated primate model of progressive parkinsonism is a critical step in the evaluation of drugs that might halt or slow progression of Parkinson's disease. In this pilot study, we gradually exposed 14 cynomolgus monkeys to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a weekly dose of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a predetermined endpoint on a disability scale by Kaplan–Meier analysis. Four other MPTP-exposed animals were coadministered the potent free radical scavenger 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6- tetramethylindan (OPC-14117) as a single oral daily dose of 0.6 g/kg, starting 2 weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79% and mean time before reaching endpoint was 6 weeks. Global motor activity, recorded in a subset of animals using a portable activity monitor, declined following the first MPTP dose and never recovered. Several cerebrospinal fluid indices of central monoamine metabolism collected by suboccipital puncture at 0, 5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were found to be “trait” markers for MPTP exposure, whereas CSF DOPAC and tetrahydrobiopterin constituted potential “state” markers for reaching endpoint. The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism. Further attempts to validate this incremental model of neurotoxin-induced parkinsonism as a predictor of patient responses to putative neuroprotective agents appear warranted.

Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain. These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.

Tree-ring widths have long been a useful North American drought proxy [e.g., Cook et al., 1999, 2004]. A potentially rich, new tree-ring proxy associated with the tree's leaf-level moisture status is stable-carbon isotope composition (δ13C = [13C/12Csample ÷ 13C/12Cstandard − 1[ × 1000), which is determined by both the rate of carbon assimilation and the rate of gas conductance through leaf stomata [Farquhar et al., 1982]. In the U.S. Southwest, where evaporation exceeds precipitation, drought may be the dominant influence on plant δ>13C [Warren et al., 2001], so measurements of tree-ring δ13C in a network of southwestern sites has allowed for spatially mapping this ecophysiological indicator back to A.D. 1600. Stomatal portals are the primary avenues of water loss and carbon gain in plants, providing carbon dioxide (CO2) for photosynthesis, which tends to discriminate against fixation of 13CO2 in favor of 12CO2. In principle, under conditions of water stress the stomata close down and the reservoir of CO2 available for continued photosynthesis is reduced, proportionally more 13CO2 is fixed, and the 13C/12C ratio of sugars eventually incorporated into tree rings increases (i.e., δ13C increases), and vice versa during moist conditions.