Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease

Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS

Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species

Engineering the future with America's high school students

The number of students enrolled in engineering is declining while the need for engineers is increasing. One contributing factor is that most high school students have little or no knowledge about what engineering is, or what engineers do. To teach young students about engineering, engineers need good tools. This paper presents a course of study developed and used by the authors in a junior college course for high school students. Students learned about engineering through independent student projects, in-class problem solving, and use of career information resources. Selected activities from the course can be adapted to teach students about engineering in other settings. Among the most successful techniques were the student research paper assignments, working out a solution to an engineering problem as a class exercise, and the use of technical materials to illustrate engineering concepts and demonstrate 'tools of the trade'

EVALUATION OF METHANE GAS PRODUCTION IN A SIMULTANEOUS REGRESSION SYSTEM

Methane gas production is a function of volatile solids activity in anaerobic digesters. Increasing the solids retention time of the swine manure digester system without increasing the hydraulic retention time would theoretically increase the methane gas production efficiency. Coagulation treatments were performed on the effluent of the second digester in a system of two digesters in series . The objective of this paper is to describe mathematically the relationship of the Coagulation treatments in the second digester to biogas production and volatile solids retention. An initial, single equation, ordinary least squares regression produced statistically significant parameter estimates, but failed to accurately describe the treatment activity occurring in the second digester. To assess the treatment activity of the second digester and account for the activity of first digester on the second, data was regressed through a simultaneous equation system. Both two-stage and three-stage least squares regression were examined

A Stratabound Zinc-Lead Deposit in Meguma Group Metasediments at Eastville, Nova Scotia

The Eastville zinc-lead deposit, discovered by soil sampling in 1976, occurs near the contact of the Goldenvllle and Halifax Formations, the two divisions of the Cambro-Ordovician Meguma Group. The stratigraphic succession in the contact zone comprises an assemblage of quartz metawacke, calcareous quartz metawacke and slate. Quartz metawacke is predominant in the Goldenvllle Formation and slate is the dominant lithology in the overlying Halifax Formation. These rocks are interpreted as the middle to outer fan and basin plain deposits of a submarine fan complex. Pyrrhotite and pyrite, the predominant Bulphide minerals in all lithologles in the contact zone, were deposited by reduction of iron in the sediments, independent of the mineralizing process. Sphalerite and galena occur in rocks over a 10 km strike length in elongate blebs, 2 to 5 mm long, distributed parallel to bedding and in cross-cutting fractures. The deposit is stratabound and generally occurs in black slate beds near the Goldenvllle-Halifax contact. Geochemical analyses of the rocks have indicated a concentration of Mn in the calcareous quartzite member, the upper unit of the Goldenville Formation. A relationship between the Mn enrichment and the abundance of sphalerite and galena in the section has not been established. The sulphide mineralogy, laterally continuous stratigraphy and lack of metal zonation and underlying feeder structures indicate the sphalerite and galena were syngenetically deposited from metal-rich brines at a site distant from where the brines entered the basin of deposition- RÉSUMÉ Le dépôt de plomb at de zinc de Eastville, qui a été découvert par des prises d'échantillons de terre en 1976, est situé pré du contact des formations Goldenville et Halifax (les deux unités du groupe Meguma). La succession stratigraphique dans la zone de contact est constitué d'un assemblage de métagrauwacke de quartz, de métagrauvacke calcaire de quartz, et d'ardoise. Le métagrauwacke de quartz est prédominant dans la formation Goldenville et l'ardoise est la lithologie dominate de la formation de Halifax, qui est superposé sur la première. Ces roches sont expllquées comme étant le cône central ou extérieur et des dépôts de la plaine d'un basin d'un compiexe de cône. La pyrrhotite et la pyrite, les minéraux sulfides principalis dans toutes les lithologles de la zone de contact, ont été déposés par une réduction de fer dans les sédiments, indépendement des processus de minéralisation. La sphalérite et la galène se trouvent dans les roches sur une longueur de 10 kilomètres le long de la couche en temps que soufflures de 2 à 5 mm de longueur, réparties paralèllement à la couche et dans les fractures à trafers banc. Le dépôt est limite aux strates et se crouve en général dans de l'ardoise noire près du contact Goldenville-Halifax. Des analyses géochimiques des roches ont indiqué une concentration de Mn dans les quartzites calcaires, l'unité la plus é1evé de la formation Goldenville. Un rapport entre l'enrichiasement en Mn et l'abondance de la sphalerite et de la galène dans la section, n'a pas été établie. La minéralogie des sulfides, la stratigraphie laterale continue, et le manque de zonation de métaux et de structures de conduite d'alimentation, indique que la sphalerite et la galène ont été déposées sygénétiquement à partir de saumures riches en métaux dans un site éloigné de l'endroit où les saumures pénétrent le basin de dépôt. [Traduit par le journal

Reliability of the running vertical jump test in female team sport athletes

Injury rates to the lower limb have increased over the past 40 years, coinciding with increases in female sport participation rates. Sport specific tests such as the running vertical jump (RVJ) are utilised for injury risk profiling, however the test-retest reliability is unknown. Objectives: The aim of this study was to investigate the test-retest reliability of the thorax, pelvis and lower limb joint angular kinematics and kinetics for the RVJ test in female team sport athletes. Design: Three-dimensional motion capture with force plate integration was utilised as participants performed five trials on each limb on three separate days. Setting: Testing occurred in a biomechanics laboratory. Participants: Thirty-four females (Australian Rules Football = 15, Netball = 12, Soccer = 7) participated in this study. Main Outcome Measures: Intraclass correlation coefficients (ICC), effect sizes and typical errors (TE) of segment and joint angular kinematics and kinetics were calculated. Results: Poor to excellent reliability (ICC = −0.12 – 0.92), small to large effect sizes (0.00–0.90) and TE (0.02–289.24) were observed across segment and joint angular kinematics and kinetics. Conclusions: The RVJ test is recommended when analysing ground reaction forces and joint angular kinematics in female team sport athletes

CD90 is not constitutively expressed in functional innate lymphoid cells

Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts in T cell biology. As such, flow cytometry gating strategies and markers, such as CD90, have been applied to indentify ILC. Here, we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly a sub-population of cells exhibit low or even no expression of this marker. CD90-negative and CD90-low CD127+ ILC were present amongst all ILC subsets in the gut. The frequency of CD90-negative and CD90-low CD127+ ILC was dependent on stimulatory cues in vitro and enhanced by dysbiosis in vivo. CD90-negative and CD90-low CD127+ ILC were a potential source of IL-13, IFNγ and IL-17A at steady state and upon dysbiosis- and dextran sulphate sodium-elicited colitis. Hence, this study reveals that, contrary to expectations, CD90 is not constitutively expressed by functional ILC in the gut

Turnip mosaic potyvirus probably first spread to Eurasian brassica crops from wild orchids about 1000 years ago

Turnip mosaic potyvirus (TuMV) is probably the most widespread and damaging virus that infects cultivated brassicas worldwide. Previous work has indicated that the virus originated in western Eurasia, with all of its closest relatives being viruses of monocotyledonous plants. Here we report that we have identified a sister lineage of TuMV-like potyviruses (TuMV-OM) from European orchids. The isolates of TuMV-OM form a monophyletic sister lineage to the brassica-infecting TuMVs (TuMV-BIs), and are nested within a clade of monocotyledon-infecting viruses. Extensive host-range tests showed that all of the TuMV-OMs are biologically similar to, but distinct from, TuMV-BIs and do not readily infect brassicas. We conclude that it is more likely that TuMV evolved from a TuMV-OM-like ancestor than the reverse. We did Bayesian coalescent analyses using a combination of novel and published sequence data from four TuMV genes [helper component-proteinase protein (HC-Pro), protein 3(P3), nuclear inclusion b protein (NIb), and coat protein (CP)]. Three genes (HC-Pro, P3, and NIb), but not the CP gene, gave results indicating that the TuMV-BI viruses diverged from TuMV-OMs around 1000 years ago. Only 150 years later, the four lineages of the present global population of TuMV-BIs diverged from one another. These dates are congruent with historical records of the spread of agriculture in Western Europe. From about 1200 years ago, there was a warming of the climate, and agriculture and the human population of the region greatly increased. Farming replaced woodlands, fostering viruses and aphid vectors that could invade the crops, which included several brassica cultivars and weeds. Later, starting 500 years ago, inter-continental maritime trade probably spread the TuMV-BIs to the remainder of the world

Impact of submarine groundwater discharge on biogeochemistry and microbial communities in pockmarks

The impact of submarine groundwater discharge (SGD) on coastal sea biogeochemistry has been demonstrated in many recent studies. However, only a few studies have integrated biogeochemical and microbiological analyses, especially at sites with pockmarks of different degrees of groundwater influence. This study investigated biogeochemical processes and microbial community structure in sediment cores from three pockmarks in Hanko, Finland, in the northern Baltic Sea. Pockmark data were supplemented by groundwater and seawater measurements. Two active pockmarks showed SGD rates of 0.02 cm d-1 and 0.31 cm d-1, respectively, based on porewater Cl- profiles, while a third pockmark had no SGD influence. Reactive transport modelling (RTM) established that the porewater systems of these active pockmarks are dominated by advection, resulting in the focusing of biogeochemical reactions and the microbial community into a thin zone at the sediment surface. The advection further reduces the accumulation of organic matter in the surface sediments, resulting in the absence of a sulfate-methane transition zone (SMTZ) at these pockmarks. Furthermore, the RTM estimated low rates of consumption of SO42-, and low rates of production of CH4, NH4+, DIC at the active pockmarks. Archaeal communities in the active pockmarks were dominated by ammonia-oxidizing archaea of predominantly groundwater origin. In contrast, at the inactive pockmark, the lack of SGD has permitted rapid deposition of organic-rich mud. The porewater system in the inactive pockmark is dominated by diffusion, leading to orders of magnitude higher metabolite concentrations at depth compared to the active pockmarks. The biogeochemical environment in the inactive pockmark resembles typical organic-rich mud seafloor in the area, with sulphate reduction and methanogenesis dominating organic matter remineralization. Accordingly, methanogens dominate the archaeal community, whereas sulfate reducers dominate the bacterial community. RTM results suggest that sulfate-mediated anaerobic oxidation of methane (S-AOM) also occurs at this site. Although depth-integrated fluxes of SO42-, CH4, NH4, DIC at the inactive pockmark are orders of magnitude higher compared to the active pockmarks, processes at the inactive pockmark represent internal recycling in the coastal sea. Fluxes observed at the active pockmarks, although comparatively small in magnitude, are partly influenced by external inputs to the sea through SGD. Hence, effluxes across the sediment-water interface at these sites partly represent direct external fluxes to the marine environment, in addition to diagenetic recycling at the benthic interface. The study highlights that SGD can result in significant spatial heterogeneity of biogeochemical processes and microbial community structure in the coastal zone, and that the overall effects of SGD and associated solute fluxes at an SGD site are a function of the number of pockmarks, the rate of SGD, and the ratio of active to inactive pockmarks.Peer reviewe