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

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

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

Binge-watching: Video-on-demand, quality TV and mainstreaming fandom

This article explores the concept of the binge as viewing protocol associated with fan practices, industry practice and linked to ‘cult’ and ‘quality’ serialised content. Viewing binge-watching as an intersection of discourses of industry, audience and text, the concept is analysed here as shaped by a range of issues that dominate the contemporary media landscape. In this, factors like technological developments, fan discourses and practices being adopted as ‘mainstream’ media practice, changes in the discursive construction of ‘television’ and an emerging Video-on-Demand industry contribute to the construction of binge-watching as deliberate, self-scheduled alternative to ‘watching TV’

High lability of sexual system over 250 million years of evolution in morphologically conservative tadpole shrimps

Background Sexual system is a key factor affecting the genetic diversity, population structure, genome structure and the evolutionary potential of species. The sexual system androdioecy – where males and hermaphrodites coexist in populations – is extremely rare, yet is found in three crustacean groups, barnacles, a genus of clam shrimps Eulimnadia, and in the order Notostraca, the tadpole shrimps. In the ancient crustacean order Notostraca, high morphological conservatism contrasts with a wide diversity of sexual systems, including androdioecy. An understanding of the evolution of sexual systems in this group has been hampered by poor phylogenetic resolution and confounded by the widespread occurrence of cryptic species. Here we use a multigene supermatrix for 30 taxa to produce a comprehensive phylogenetic reconstruction of Notostraca. Based on this phylogenetic reconstruction we use character mapping techniques to investigate the evolution of sexual systems. We also tested the hypothesis that reproductive assurance has driven the evolution of androdioecy in Notostraca. Results Character mapping analysis showed that sexual system is an extremely flexible trait within Notostraca, with repeated shifts between gonochorism and androdioecy, the latter having evolved a minimum of five times. In agreement with the reproductive assurance hypothesis androdioecious notostracans are found at significantly higher latitudes than gonochoric ones indicating that post glacial re-colonisation may have selected for the higher colonisation ability conferred by androdioecy. Conclusions In contrast to their conserved morphology, sexual system in Notostraca is highly labile and the rare reproductive mode androdioecy has evolved repeatedly within the order. Furthermore, we conclude that this lability of sexual system has been maintained for at least 250 million years and may have contributed to the long term evolutionary persistence of Notostraca. Our results further our understanding of the evolution of androdioecy and indicate that reproductive assurance is a recurrent theme involved in the evolution of this sexual system

Accelerator system for the PRISM based muon to electron conversion experiment

The next generation of lepton flavor violation experiments need high intensity and high quality muon beams. Production of such beams requires sending a short, high intensity proton pulse to the pion production target, capturing pions and collecting the resulting muons in the large acceptance transport system. The substantial increase of beam quality can be obtained by applying the RF phase rotation on the muon beam in the dedicated FFAG ring, which was proposed for the PRISM project.This allows to reduce the momentum spread of the beam and to purify from the unwanted components like pions or secondary protons. A PRISM Task Force is addressing the accelerator and detector issues that need to be solved in order to realize the PRISM experiment. The parameters of the required proton beam, the principles of the PRISM experiment and the baseline FFAG design are introduced. The spectrum of alternative designs for the PRISM FFAG ring are shown. Progress on ring main systems like injection and RF are presented. The current status of the study and its future directions are discussed.Comment: Studies performed within the PRISM Task Force initiativ

Study of 2b-decay of Mo-100 and Se-82 using the NEMO3 detector

After analysis of 5797 h of data from the detector NEMO3, new limits on neutrinoless double beta decay of Mo-100 (T_{1/2} > 3.1 10^{23} y, 90% CL) and Se-82 (T_{1/2} > 1.4 10^{23} y, 90% CL) have been obtained. The corresponding limits on the effective majorana neutrino mass are: m < (0.8-1.2) eV and m < (1.5-3.1) eV, respectively. Also the limits on double-beta decay with Majoron emission are: T_{1/2} > 1.4 10^{22} y (90% CL) for Mo-100 and T_{1/2}> 1.2 10^{22} y (90%CL) for Se-82. Corresponding bounds on the Majoron-neutrino coupling constant are g < (0.5-0.9) 10^{-4} and < (0.7-1.6) 10^{-4}. Two-neutrino 2b-decay half-lives have been measured with a high accuracy, T_{1/2} Mo-100 = [7.68 +- 0.02(stat) +- 0.54(syst) ] 10^{18} y and T_{1/2} Se-82 = [10.3 +- 0.3(stat) +- 0.7(syst) ] 10^{19} y.Comment: 5 pages, 4 figure