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

Brain muscarinic cholinergic receptors in Huntington's disease

Muscarinic cholinergic receptors and choline acetyltransferase (ChAT) activity were studied in postmortem brain tissue from patients with Huntington's disease and matched control subjects. In comparison with controls, reductions in ChAT activity were found in the hippocampus, but not in the temporal cortex in Huntington's disease. Patients with Huntington's disease showed reduced densities of the total number of muscarinic receptors and of M-2 receptors in the hippocampus while the density of M-1 receptors was unaltered. Muscarinic receptor binding was unchanged in the temporal cortex. These results indicate a degeneration in Huntington's disease of the septo-hippocampal cholinergic pathway, but no impairment of the innominato-cortical cholinergic system

Cumulate causes for the low contents of sulfide-loving elements in the continental crust

Despite the economic importance of chalcophile (sulfide-loving) and siderophile (metal-loving) elements (CSEs), it is unclear how they become enriched or depleted in the continental crust, compared with the oceanic crust. This is due in part to our limited understanding of the partitioning behaviour of the CSEs. Here I compile compositional data for mid-ocean ridge basalts and subduction-related volcanic rocks. I show that the mantle-derived melts that contribute to oceanic and continental crust formation rarely avoid sulfide saturation during cooling in the crust and, on average, subduction-zone magmas fractionate sulfide at the base of the continental crust prior to ascent. Differentiation of mantle-derived melts enriches lower crustal sulfide- and silicate-bearing cumulates in some CSEs compared with the upper crust. This storage predisposes the cumulate-hosted compatible CSEs (such as Cu and Au) to be recycled back into the mantle during subduction and delamination, resulting in their low contents in the bulk continental crust and potentially contributing to the scarcity of ore deposits in the upper continental crust. By contrast, differentiation causes the upper oceanic and continental crust to become enriched in incompatible CSEs (such as W) compared with the lower oceanic and continental crust. Consequently, incompatible CSEs are predisposed to become enriched in subduction-zone magmas that contribute to continental crust formation and are less susceptible to removal from the continental crust via delamination compared with the compatible CSEs

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

Efficient inference and identifiability analysis for differential equation models with random parameters

Heterogeneity is a dominant factor in the behaviour of many biological processes. Despite this, it is common for mathematical and statistical analyses to ignore biological heterogeneity as a source of variability in experimental data. Therefore, methods for exploring the identifiability of models that explicitly incorporate heterogeneity through variability in model parameters are relatively underdeveloped. We develop a new likelihood-based framework, based on moment matching, for inference and identifiability analysis of differential equation models that capture biological heterogeneity through parameters that vary according to probability distributions. As our novel method is based on an approximate likelihood function, it is highly flexible; we demonstrate identifiability analysis using both a frequentist approach based on profile likelihood, and a Bayesian approach based on Markov-chain Monte Carlo. Through three case studies, we demonstrate our method by providing a didactic guide to inference and identifiability analysis of hyperparameters that relate to the statistical moments of model parameters from independent observed data. Our approach has a computational cost comparable to analysis of models that neglect heterogeneity, a significant improvement over many existing alternatives. We demonstrate how analysis of random parameter models can aid better understanding of the sources of heterogeneity from biological data.Comment: Minor changes to text. Additional results in supplementary material. Additional statistics regarding results given in main and supplementary materia

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