Comparative analysis of different preparation methods of chalcogenide glasses: Molecular dynamics structure simulations

Two different preparation methods (liquid-quenching and evaporation) of chalcogenide glasses have been investigated by molecular dynamics simulations. Our particular aim was to determine how the structural changes occur due to the different preparation methods. We applied a classical empirical three-body potential of selenium to describe the interactions between atoms. Our simulation shows that a significant difference can be observed in the homogeneities

Dopaminergic Inhomogeneity of Human Putamen

Among the basal ganglia-thalamocortical circuits, the putamen plays a critical role in the “motor” circuits that control voluntary movements and motor learning. The human neostriatum comprises two functional subdivisions known as the striosome (patch) and matrix compartments. Accumulating evidence suggests that compartment-specific dysregulations of dopamine activity might be involved in the disease-specific pathology and symptoms of human striatal diseases including movement disorders. This study was undertaken to examine whether or how striatal dopaminergic innervations are organized into the compartmentalized architecture found in the putamen of adult human brains. For this purpose, we used a highly sensitive immunohistochemistry (IHC) technique to identify tyrosine hydroxylase (TH; EC 1.14.16.2), a marker for striatal dopaminergic axons and terminals, in formalin-fixed paraffin-embedded (FFPE) tissues obtained from autopsied human brains. Herein, we report that discrete compartmentalization of TH-labeled innervations occurs in the putamen, as in the caudate nucleus (CN), with a higher density of TH labeling in the matrix compared to the striosomes. Our results provide anatomical evidence to support the hypothesis that compartment-specific dysfunction of the striosome-matrix dopaminergic systems might contribute to the genesis of movement disorders

PSD-95 in the Striosome-matrix Systems of the Human Striatum

The human neostriatum consists of two functional subdivisions referred to as the striosome (patch) and matrix compartments. The striosome-matrix dopamine systems play a central role in cortico-thalamo-basal ganglia circuits, and their involvement is thought to underlie the genesis of multiple movement and behavioral disorders, and of drug addiction. Human neuropathology also has shown that striosomes and matrix have differential vulnerability patterns in several striatal neurodegenerative diseases. Postsynaptic density protein 95 (PSD-95), also known as disks large homolog 4, is a major scaffolding protein in the postsynaptic densities of dendritic spines. PSD-95 is now known to negatively regulate not only N-methyl-D-aspartate glutamate signaling, but also dopamine D1 signals at sites of postsynaptic transmission. Accordingly, a neuroprotective role for PSD-95 against dopamine D1 receptor (D1R)-mediated neurotoxicity in striatal neurodegeneration also has been suggested. Here, we used a highly sensitive immunohistochemistry technique to show that in the human neostriatum, PSD-95 is differentially concentrated in the striosome and matrix compartments, with a higher density of PSD-95 labeling in the matrix compartment than in the striosomes. This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R. In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment. This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration

Dystonia : Still a Mysterious Syndrome

The diagnosis of dystonia is sometimes complicated due to its many clinical manifestations, causes, and the lack of specific diagnostic examinations or simple algorithms [...

Postsynaptic Density Protein 95 in the Striosome and Matrix Compartments of the Human Neostriatum

The human neostriatum consists of two functional subdivisions referred to as the striosome (patch) and matrix compartments. The striosome-matrix dopamine systems play a central role in cortico-thalamo-basal ganglia circuits, and their involvement is thought to underlie the genesis of multiple movement and behavioral disorders, and of drug addiction. Human neuropathology also has shown that striosomes and matrix have differential vulnerability patterns in several striatal neurodegenerative diseases. Postsynaptic density protein 95 (PSD-95), also known as DLG4, is a major scaffolding protein in the postsynaptic densities of dendritic spines. PSD-95 is now known to negatively regulate not only N-methyl-D-aspartate glutamate signaling, but also dopamine D1 signals at sites of postsynaptic transmission. Accordingly, a neuroprotective role for PSD-95 against dopamine D1 receptor (D1R)-mediated neurotoxicity in striatal neurodegeneration also has been suggested. Here, we used a highly sensitive immunohistochemistry technique to show that in the human neostriatum, PSD-95 is differentially concentrated in the striosome and matrix compartments, with a higher density of PSD-95 labeling in the matrix compartment than in the striosomes. This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R. In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment. This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration

Striatal Vulnerability in Huntington’s Disease : Neuroprotection Versus Neurotoxicity

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection

A Short Commentary on Globus Pallidus Internus Deep Brain Stimulation in Primary Meige Syndrome

Meige syndrome is a type of segmental dystonia that manifests a combination of blepharospasm and oromandibular dystonia and is often associated with other types of craniocervical dystonia. Although the precise pathogenesis of primary Meige syndrome remains to be elucidated, it has been suggested that this movement disorder might be a basal ganglia disorder. Multiple single case reports and open-labeled small case series have shown that globus pallidus internus deep brain stimulation (GPi-DBS) could result in therapeutic benefits in patients with severe Meige syndrome. However, randomized and controlled trials are necessary to accurately assess the safety and therapeutic efficacy of GPi-DBS in treating patients with Meige syndrome. This short commentary introduces the current use of GPi-DBS in the treatment of medically refractory Meige syndrome

Polymerization of diacetylene phospolipid bilayers on solid substrate: Influence of the film deposition temperature

Micropatterned phospholipid bilayers on solid substrates offer an attractive platform for various applications, such as high throughput drug screening. We have previously developed a photopolymerization-based methodology for generating micropatterned bilayers composed of polymerized and fluid lipid bilayers. Lithographic photopolymerization of a diacetylene-containing phospholipid (DiynePC) allowed facile fabrication of compartmentalized arrays of fluid lipid membranes. Herein, we report on a key experimental parameter that significantly influences the homogeneity and quality of the fabricated polymeric bilayers, namely the temperature at which monolayers of monomeric DiynePC were formed on the water surface and transferred onto solid substrates by the Langmuir-Blodgett/Langmuir-Schaefer (LB/LS) technique. Using fluorescence microscopy and atomic force microscopy, it was found that polymerized bilayers were homogeneous, if bilayers of DiynePC were prepared below the triple point temperature (ca. 20 C) of the monolayer, where a direct transition from the gaseous state to the liquid condensed state occurred. Bilayers prepared above this temperature had a markedly increased number of crack-like line defects. The differences were attributed to the domain structures in the monolayer that were transferred from the water surface to the substrate. Domain size, rather than the molecular packing in each domain, was concluded to play a critical role in the formation of defects. The spontaneous curvature and area changes of bilayers were postulated to cause destabilization and detachment of the films from the substrate upon polymerization. Our present results highlight the importance of controlling the domain structures for the homogeneity of polymerized bilayers required in technological applications

Clinicopathological Phenotype and Genetics of X-Linked Dystonia–Parkinsonism (XDP; DYT3; Lubag)

X-linked dystonia–parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or “Lubag” disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in the later years of life. Among the primary monogenic dystonias, XDP has been identified as a transcriptional dysregulation syndrome with impaired expression of the TAF1 (TATA box-binding protein associated factor 1) gene, which is a critical component of the cellular transcription machinery. The major neuropathology of XDP is progressive neuronal loss in the neostriatum (i.e., the caudate nucleus and putamen). XDP may be used as a human disease model to elucidate the pathomechanisms by which striatal neurodegeneration leads to dystonia symptoms. In this article, we introduce recent advances in the understanding of the interplay between pathophysiology and genetics in XDP

Photo-induced volume changes in selenium. Tight-binding molecular dynamics study

Tight-binding molecular dynamics simulations of photo-excitations in small Se clusters (isolated Se$_8$ ring and helical Se chain) and glassy Se networks (containing 162 atoms) were carried out in order to analyse the photo induced instability inside the amorphous selenium. In the cluster systems after taking an electron from the highest occupied molecular orbital to the lowest unoccupied molecular orbital a bond breaking occurs. In the glassy networks photoinduced volume expansion was observed and at the same time the number of coordination defects changed significantly due to illumination