Differential Cross Section and Photon-Beam Asymmetry for the γ[over →]p → π

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7

Interference Effect between ϕ and Λ(1520) Production Channels in the γp→K

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

Molecular dynamics analysis on wetting and interfacial properties of water-alcohol mixture droplets on a solid surface.

Molecular dynamics simulations of single water, water-methanol, or water-IPA (isopropyl-alcohol) mixture droplets on a solid surface were performed with various mixture ratios. An increase in alcohol fraction generally gave an increase in droplet wettability. Both methanol and IPA molecules showed a strong preference to gather at various interfaces, with methanol molecules also showing a tendency to diffuse into the droplet bulk. Specific interfacial tensions were investigated using quasi-one-dimensional simulation systems, and liquid-vapor and solid-liquid interfacial tensions were found to decrease greatly due to the presence of interfacial alcohol, while solid-vapor interfacial tensions were proved to have little influence on wettability. Young's relation was found to hold quantitatively well for both water-methanol and water-IPA droplets. The validity of using Bakker's equation on solid-liquid interfaces was also investigated, and it was shown that for tightly spaced crystal surfaces, the introduced uncertainly is small.

Molecular dynamics analysis of multiphase interfaces based on in situ extraction of the pressure distribution of a liquid droplet on a solid surface.

Molecular dynamics simulations of a nanoscale liquid droplet on a solid surface are carried out in order to examine the pressure tensor field around the multiphase interfaces, and to explore the validity of Young's equation. By applying the virial theorem to a hemicylindrical droplet consisting of argon molecules on a solid surface, two-dimensional distribution of the pressure tensor is obtained. Tensile principal pressure tangential to the interface is observed around the liquid-vapor transition layer, while both tensile and compressive principal pressure tangential to the interface exists around the solid-liquid transition layer due to the inhomogeneous density distribution. The two features intermix inside the overlap region between the transition layers at the contact line. The contact angle is evaluated by using a contour line of the maximum principal pressure difference. The interfacial tensions are calculated by using Bakker's equation and Young-Laplace equation to the pressure tensor distribution. The relation between measured contact angle and calculated interfacial tensions turns out to be consistent with Young's equation, which is known as the description of the force balance at the three-phase interface.

Spin-density matrix elements for γp→K*0Σ+ at Eγ=1.85-3.0 GeV with evidence for the κ(800) meson exchange.

The exclusive reaction γp→K(+)π(-)Σ(+) was measured for the first time using linearly polarized photons at beam energies from 1.85 to 2.96 GeV. Angular distributions in the rest frame of the K(+)π(-) system were fitted to extract spin-density matrix elements of the K(*0) decay. The measured parity spin asymmetry shows that natural-parity exchange is dominant in this reaction. This result clearly indicates the need for t-channel exchange of the κ(800) scalar meson.

Analysis on wetting and local dynamic properties of single water droplet on a polarized solid surface: a molecular dynamics study.

Molecular dynamics simulations of single water droplets on a solid surface were carried out in order to investigate the effects that the Coulomb interaction between liquid and solid molecules has on wetting behavior by appending vertical electric polarization on a solid surface. The water droplet became more wettable both on upward and downward polarized surfaces, although structures of the adsorption layer appearing near the solid surface were clearly different, and the relation between droplet contact angle and surface polarization was also different for upward and downward polarization directions. The probability density distribution of molecular orientation around the adsorption layer indicated that preferable water molecule orientations varied largely by the surface polarization, and the rotational mobility around the preferable orientations was also affected. The dynamic property due to this rotational mobility was clearly captured by means of distribution of rotational diffusion coefficient, which potentially corresponded to local viscosity distribution.

HtrA2/Omi-immunoreactive intraneuronal inclusions in the anterior horn of patients with sporadic and Cu/Zn superoxide dismutase (SOD1) mutant amyotrophic lateral sclerosis.

AIMS: HtrA2/Omi is a mitochondrial serine protease that promotes the apoptotic processes, but the relationship between HtrA2/Omi and amyotrophic lateral sclerosis (ALS) is still unknown. The purpose of the present study was to determine whether abnormal expression of HtrA2/Omi occurs in patients with ALS. METHODS: We prepared autopsied spinal cord tissues from 7 control subjects, 11 patients with sporadic ALS (SALS) and 4 patients with Cu/Zn superoxide dismutase (SOD1)-related familial ALS (FALS). We then performed immunohistochemical studies on HtrA2/Omi using formalin-fixed, paraffin-embedded sections from all of the cases. RESULTS: In the control subjects, the anterior horn cells were mildly to moderately immunostained with HtrA2/Omi. In the patients with SALS, strong HtrA2/Omi immunoreactivity was found in some skein-like inclusions and round hyaline inclusions as well as many spheroids, but Bunina bodies were immunonegative for HtrA2/Omi. In the patients with SOD1-related FALS, Lewy body-like hyaline inclusions were observed in three cases and conglomerate inclusions were observed in the remaining case, and both types of inclusions were intensely immunopositive for HtrA2/Omi. CONCLUSIONS: These results suggest that abnormal accumulations of HtrA2/Omi may occur in several types of motor neuronal inclusions in the anterior horn from SALS and SOD1-linked FALS cases, and that HtrA2/Omi may be associated with the pathogenesis of both types of ALS.

Near-threshold Lambda(1520) production by the gamma(p)-->K{+}Lambda(1520) reaction at forward K+ angles.

Differential cross sections and photon-beam asymmetries for the gamma(p)-->K{+}Lambda(1520) reaction have been measured with linearly polarized photon beams at energies from the threshold to 2.4 GeV at 0.6or=5/2 or by a new reaction process, for example, an interference effect with the phi photoproduction having a similar bump structure in the cross sections.

Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice.

Several lines of evidence show the importance of angiotensin II (AII) in renal injuries, especially when hemodynamic abnormalities are involved. To elucidate the role of AII in immune-mediated renal injury, we studied anti-glomerular basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation of the renin-angiotensin system (RAS) was observed in both groups of mice at around day 1. A renal expression of monocyte chemoattractant protein-1 (MCP-1) was transiently induced at six hours in both groups, which was then downregulated at day 1. In the AT1a+/+ mice, after RAS activation, the glomerular expression of MCP-1 was exacerbated at days 7 and 14. Thereafter, severe proteinuria developed, and the renal expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I increased, resulting in severe glomerulosclerosis and interstitial fibrosis. In contrast, glomerular expression of MCP-1, proteinuria, and tissue damage were markedly ameliorated in the AT1a-/- mice. Because this amelioration is likely due to the lack of AT1a, we can conclude that AII action, mediated by AT1a, plays a pathogenic role in anti-GBM nephritis, in which AII may contribute to the exacerbation of glomerular MCP-1 expression. These results suggest the involvement of AII in immune-mediated renal injuries.

The yeast G-protein homolog is involved in the mating pheromone signal transduction system.

I have isolated a new type of sterile mutant of Saccharomyces cerevisiae, carrying a single mutant allele, designated dac1, which was mapped near the centromere on chromosome VIII. The dac1 mutation caused specific defects in the pheromone responsiveness of both a and alpha cells and did not seem to be associated with any pleiotropic phenotypes. Thus, in contrast to the ste4, ste5, ste7, ste11, and ste12 mutations, the dac1 mutation had no significant effect on such constitutive functions of haploid cells as pheromone production and alpha-factor destruction. The characteristics of this phenotype suggest that the DAC1 gene encodes a component of the pheromone response pathway common to both a and alpha cells. Introduction of the GPA1 gene encoding an S. cerevisiae homolog of the alpha subunit of mammalian guanine nucleotide-binding regulatory proteins (G proteins) into sterile dac1 mutants resulted in restoration of pheromone responsiveness and mating competence to both a and alpha cells. These results suggest that the dac1 mutation is an allele of the GPA1 gene and thus provide genetic evidence that the yeast G protein homolog is directly involved in the mating pheromone signal transduction pathway.

Neuronal intranuclear hyaline inclusion disease with rapidly progressive neurological symptoms.

This report describes a male patient who presented with symptoms suggestive of spinocerebellar degeneration and who died of respiratory failure at the age of 7 years but was diagnosed, at autopsy, as having neuronal intranuclear hyaline inclusion disease. Neuronal intranuclear hyaline inclusion disease is a progressive and degenerative disease; diagnosis is possible only by neuropathological analysis. This is a rare disorder; few cases with early childhood onset and rapidly progressive neurologic symptoms have been documented. According to previous reports, most neurons in the central nervous system exhibited intranuclear eosinophilic inclusion bodies; neuronal depletion appeared to be restricted to the cerebellar cortex and the medullary inferior olivary nuclei, consistent with the fact that clinical deficit appears to correspond to the site of neuronal depletion and not to where eosinophilic bodies are detected. Immunohistochemical analysis revealed that these inclusions were positive for ubiquitin. The case presented herein clearly indicates that neuronal intranuclear hyaline inclusion disease should be considered as a differential diagnosis of cases involving spinocerebellar degeneration with childhood onset.

Saccharomyces cerevisiae MLF3/YNL074C gene, encoding a serine-rich protein of unknown function, determines the level of resistance to the novel immunosuppressive drug leflunomide.

The immunosuppressant leflunomide inhibits the growth of cytokine-stimulated proliferation of lymphoid cells in vitro and also inhibits the growth of the eukaryotic microorganism, Saccharomyces cerevisiae. To elucidate the molecular mechanism of action of the drug, a yeast gene which suppresses the anti-proliferative effect when in increased copy number was cloned and designated MLF3 for multicopy suppressor of leflunomide sensitivity. DNA sequencing analysis revealed that the MLF3 gene is identical to the YNL074C gene which encodes a serine-rich protein of 452 amino acids. Disruption of the MLF3 gene caused increased sensitivity to the immunosuppressant leflunomide.

Identification and characterization of a mutation affecting the division arrest signaling of the pheromone response pathway in Saccharomyces cerevisiae.

Mating pheromones, a- and alpha-factors, arrest the division of cells of opposite mating types, alpha and a cells, respectively. I have isolated a sterile mutant of Saccharomyces cerevisiae that is defective in division arrest in response to alpha-factor but not defective in morphological changes and agglutinin induction. The mutation was designated dac2 for division arrest control by mating pheromones. The dac2 mutation was closely linked to gal1 and was different from the previously identified cell type nonspecific sterile mutations (ste4, ste5, ste7, ste11, ste12, ste18 and dac1). Although dac2 cells had no phenotype in the absence of pheromones, they showed morphological alterations and divided continuously in the presence of pheromones. As a result, dac2 cells had a mating defect. The dac2 mutation could suppress the lethality caused by the disruption of the GPA1 gene (previously shown to encode a protein with similarity to the alpha subunit of mammalian G proteins). In addition, dac2 cells formed prezygotes with wild-type cells of opposite mating types, although they could not undergo cell fusion. These results suggest that the DAC2 product may control the signal for G-protein-mediated cell-cycle arrest and indicate that the synchronization of haploid yeast cell cycles by mating pheromones is essential for cell fusion during conjugation.

Fas has a crucial role in the progression of experimental autoimmune encephalomyelitis.

To investigate the role of Fas in experimental autoimmune encephalomyelitis (EAE) in mice, we examined the susceptibility of EAE in C57BL/6 (B6).lpr mice lacking Fas. The frequency of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in B6.lpr mice was significantly lower than that in B6 mice (19% vs 94%). However, no significant difference was observed between them in either the lymphocyte proliferation response or antibody reactivity to MOG. In addition, the histological examination and semiquantitative reverse transcriptase polymerase chain reaction analysis revealed that the infiltration of inflammatory cells and the up-regulation of gene expression for inflammatory cytokines occurred in the central nervous system (CNS) of B6.lpr mice immunized with MOG, even if they showed no clinical sign. These results indicate that Fas may contribute to the pathogenesis of EAE and may play a crucial role in the expansion of inflammation and/or myelin destruction in the CNS rather than in the activation of encephalitogenic T cells in the periphery and/or the breakdown of blood brain barrier.

Follistatin and activin in bone: expression and localization during endochondral bone development.

The involvement of activin and follistatin, an activin-binding protein, in endochondral bone development was examined by sc implantation of demineralized bone matrix in rats. Immunoreactive follistatin was localized in proliferating chondrocytes and round osteoblasts, whereas it was not detected in hypertrophic chondrocytes and osteoblasts surrounding bone marrow. Western blot analysis also revealed that immunoreactive follistatin was higher during the initial stages of chondrogenesis (day 5) and osteogenesis (days 11 and 14) and lower during the conversion from cartilage to bone (day 9). These results suggest that follistatin is produced by proliferating cells, and the expression decreases with differentiation of the cells. Implants injected with follistatin on days 9 and 10 contained lower calcium levels on day 14 than those injected with rat albumin. Furthermore, the follistatin-injected implants were still mainly composed of cartilage, suggesting that the disappearance of follistatin is necessary for the conversion of cartilage to bone. In contrast, immunoreactive activin beta A (55-60 kDa) was continuously detected in implants on days 7-14. The content of C propeptide of type II procollagen was increased and cartilageous area was enlarged on day 7 by activin A injections on days 5 and 6, suggesting a chondrogenic effect of activin in the initial stage of cartilage formation. These results indicate that proliferating chondrocytes and round osteoblasts produce follistatin, and that the activity of activin is regulated by changes in the expression of follistatin at the stages of chondrogenesis and transition from cartilage to bone.

Molecular cloning of a novel putative G protein-coupled receptor (GPCR21) which is expressed predominantly in mouse central nervous system.

A novel cDNA clone encoding a putative G protein-coupled receptor (named GPCR21) was isolated from a mouse brain cDNA library along with its homologue, GPCR01 (the mouse counterpart of previously reported rat receptor R334 [(1991) FEBS Lett. 292, 243-248]) by the polymerase chain reaction using degenerate oligonucleotide primers. Northern blotting and reverse transcription-polymerase chain reaction analyses showed predominant expression of these two receptors in the central nervous system. In situ hybridization analysis revealed their prominent expression in the limbic system and further demonstrated the differential distribution of their mRNAs in mouse brain. Although the ligands for these receptors are yet to be identified, the significant sequence homology between these receptors suggests that they constitute a new receptor subfamily and they possibly represent different receptor subtypes for an unknown neurotransmitter.

Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is an abundant neurotrophin in brain and peripheral nerves, where it affects neural development, survival and repair after injury. BDNF has been detected in rat and human blood, but the source of circulating BDNF is not established. BDNF messenger and peptide were detected in cultured cells and in the culture medium of human umbilical vein endothelial cells. The expression of BDNF was up-regulated by elevation of intracellular cAMP and down-regulated by Ca(2+) ionophore, bovine brain extract and laminar fluid shear stress. These results suggest that vascular endothelial cells may contribute to circulating BDNF.

Single-photon emission computed tomographic investigation of patients with motor neuron disease.

To investigate the correlation between involvement of the CNS in motor neuron disease (MND) and neuroimaging abnormalities, we studied 18 patients with MND by single-photon emission computed tomography (SPECT) and MRI. Patients were divided into four groups according to the results of SPECT. Group 1 consisted of four patients with reduced isotope uptake in the frontal lobe, including the motor area, and in the anterior part of the temporal lobe; group 2 consisted of two patients with reduced isotope uptake in the motor area spreading to the adjacent frontal lobe; group 3 consisted of eight patients with reduced isotope uptake confined to the motor area; and group 4 consisted of four patients without reduced isotope uptake. We found dementia in group 1, borderline dementia in group 2, and no cognitive deficit in group 3 or four. MRI demonstrated enhanced T2-weighted signals along the pyramidal tract in eight patients, but this finding also existed in some control subjects. SPECT appears useful in identifying the location of cortical neuronal degeneration in patients with MND.

Undetectable dystrophin can still result in a relatively benign phenotype of dystrophinopathy.

We present here a 28-year-old male patient with Becker muscular dystrophy whose skeletal muscle showed an absence of dystrophin. He has had progressive and predominantly proximal muscular wasting since 5 years of age, but was able to walk until 26 years of age. He showed hypertrophic calves, cardiomyopathy, and an elevated serum creatine kinase level (934 U/1). A skeletal muscle biopsy revealed advanced chronic myopathic changes. Immunohistochemical examination using anti-dystrophin antibodies against C-terminus showed deficiency of the protein. Rod domain and N-terminus were also absent in almost all muscle fibers, but only in a small part of the sample, they were faintly stained. beta-Dystroglycan and utrophin were present only in a small number of muscle fibers. DNA and RT-PCR analysis showed a frame-shift deletion of exons 3-7 in the dystrophin gene. In such an exceptional case as this one, it is important to investigate the factors which determine the severity of dystrophinopathy.

Novel nonnarcotic analgesics with an improved therapeutic ratio. Structure-activity relationships of 8-(methylthio)- and 8-(acylthio)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines.

Conversion of the 8-phenolic 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines to the corresponding 8-thiophenolic analogues was achieved by three different routes. Diazotization of 8-amino-2,6-methano-3-benzazocine (2) followed by the reaction with CH3SNa afforded 8-(methylthio)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine (3). Another route using Grewe cyclization was also examined for the synthesis of 3. As the most effective route, Newman-Kwart rearrangement of benzazocines was selected and closely investigated. 8-(N,N-Dimethylthiocarbamoyl)oxy derivatives (6a-e) rearranged to 8-(N,N-dimethylcarbamoyl)thio derivatives (7a-e) in good yields. Reductive cleavage of 7a-e and subsequent methylation or acylations gave the title compounds (3, 8-24). Although analgesic activities of sulfur-containing benzazocines decreased compared to the corresponding hydroxy compounds, the N-methyl derivative (S-metazocine, 8) showed potent analgesic activity.