Switching of Dirac-Fermion Mass at the Interface of Ultrathin Ferromagnet and Rashba Metal.

We have performed spin- and angle-resolved photoemission spectroscopy on tungsten (110) interfaced with an ultrathin iron (Fe) layer to study an influence of ferromagnetism on the Dirac-cone-like surface-interface states. We found an unexpectedly large energy gap of 340 meV at the Dirac point, and have succeeded in switching the Dirac-fermion mass by controlling the direction of Fe spins (in plane or out of plane) through tuning the thickness of the Fe overlayer or adsorbing oxygen on it. Such a manipulation of Dirac-fermion mass via the magnetic proximity effect opens a promising platform for realizing new spintronic devices utilizing a combination of exchange and Rashba-spin-orbit interactions.

Chronic granulomatous disease: two decades of experience from a tertiary care centre in North West India.

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57%) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.

Dynamics of oxygen Rydberg atom generation following O 1s inner-shell excitation of H2O.

The emission of low-energy electrons from H2O has been investigated at photon excitation energies in the vicinity of the O 1s ionization threshold. Neutral oxygen Rydberg atoms (O*) were found to form, and the correlation between the initial inner-shell excited state of H2O and the Rydberg state of O* was determined. The initially excited electron in a Rydberg orbital is shown to remain associated with O* even after the cleavage of two O-H bonds. We also show that the energy discrepancy between two Rydberg states of H2O and O* can be explained by the influence of the post-collision interaction, which becomes stronger as the excitation energy approaches the 1s ionization threshold.

Genetic characteristics and pathogenic mechanisms of periodontal pathogens.

Periodontal disease is caused by a group of bacteria that utilize a variety of strategies and molecular mechanisms to evade or overcome host defenses. Recent research has uncovered new evidence illuminating interesting aspects of the virulence of these bacteria and their genomic variability. This paper summarizes some of the strategies utilized by the major species - Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis - implicated in the pathogenesis of periodontal disease. Whole-genome sequencing of 14 diverse A. actinomycetemcomitans strains has revealed variations in their genetic content (ranging between 0.4% and 19.5%) and organization. Strikingly, isolates from human periodontal sites showed no genomic changes during persistent colonization. T. forsythia manipulates the cytokine responses of macrophages and monocytes through its surface glycosylation. Studies have revealed that bacterial surface-expressed O-linked glycans modulate T-cell responses during periodontal inflammation. Periodontal pathogens belonging to the "red complex" consortium express neuraminidases, which enables them to scavenge sialic acid from host glycoconjugates. Analysis of recent data has demonstrated that the cleaved sialic acid acts as an important nutrient for bacterial growth and a molecule for the decoration of bacteria surfaces to help evade the host immune attack. In addition, bacterial entry into host cells is also an important prerequisite for the lifestyle of periodontal pathogens such as P. gingivalis. Studies have shown that, after its entry into the cell, this bacterium uses multiple sorting pathways destined for autophagy, lysosomes, or recycling pathways. In addition, P. gingivalis releases outer membrane vesicles which enter cells via endocytosis and cause cellular functional impairment.

Photodissociation investigation of doubly charged ethanol clusters induced by inner-shell electron ionization.

Fragmentation of doubly charged ethanol clusters [(C(2)H(5)OH)(n)] following the O 1s ionization has been investigated by means of the photoelectron-photoion-photoion coincidence (PEPIPICO) method. The dominant fission channel of (C(2)H(5)OH)(n)(2+) was the formation of protonated cluster ion pairs [H(C(2)H(5)OH)(l)(+)/H(C(2)H(5)OH)(m)(+)]. The fragmentation mechanisms of these ion pairs were discussed based on the analysis of the PEPIPICO contour shape. It was clarified that the prominent fragmentation channel was a secondary decay mechanism, where neutral evaporation occurs after charge separation. On the other hand, the formation of small fragment ions was suppressed, excluding the formation of certain specific fragments (H(3)O(+), C(2)H(5)(+)/COH(+), and C(2)H(4)OH(+)). The formation of small fragment ions was suppressed due to the cooling effect caused by the neutral evaporation and the decrease in the electrostatic repulsive force caused by charge separation.

Hydrogen bonding in acetone clusters probed by near-edge x-ray absorption fine structure spectroscopy in the carbon and oxygen K-edge regions.

Hydrogen bonding in acetone clusters was investigated using near-edge x-ray absorption fine structure (NEXAFS) spectroscopy and density functional theory calculations in the carbon and oxygen K-edge regions. The partial-ion-yield (PIY) curves of the cluster ions were measured as the NEXAFS spectra of acetone clusters. In the carbon K-edge region, the first resonance peak, which was assigned to the C(CO) 1s-->pi( *)(C=O) resonance transition, showed no substantial change in the PIY curves of the acetone clusters, while the C(CH3) 1s-->3ppi(CH(3)) excitation feature was found to be strongly suppressed. The selective suppression of the C(CH3) 1s-->3ppi(CH(3)) resonance transition can be explained by the change in the character of the 3ppi(CH(3)) orbital due to the C=O...H-C type of hydrogen-bonding interaction. On the other hand, the NEXAFS spectra of the acetone molecule and clusters were almost identical in the oxygen K-edge region, except for a small shift in the pi( *)(C=O) resonance of 0.13 eV, because the character of the pi( *)(C=O) orbital remained, regardless of the C=O...H-C hydrogen bonding interaction.

The ipsilateral cortico-spinal tract is activated after hemiparetic stroke.

BACKGROUND AND PURPOSE: The presence of a projection from the primary motor cortex to the ipsilateral muscles has been established in human, but whether this pathway contributes to functional recovery after stroke is unclear. We investigated whether the ipsilateral tract is activated in hemiparetic stroke. METHODS: Motor-evoked potentials (MEPs) were simultaneously recorded from the bilateral trapezius or abductor digiti minimi (ADM) muscles after magnetic stimulation to the motor cortex in 40 acute stroke patients. RESULTS: At rest, ipsilateral trapezius MEPs were recordable in none of the 24 normal controls, and in 38% of the patients after stimulation to the non-affected hemisphere (P < 0.001). With voluntary contraction, ipsilateral trapezius MEPs were elicited in 21% of the normal controls and 73% of the patients (P < 0.001). Ipsilateral ADM MEPs were rarely recordable in both controls (0%) and patients (3%). The presence of ipsilateral trapezius MEPs was associated with less severe paresis in the trapezius (P = 0.04) and deltoid (P = 0.07), but not in the more distal muscles. CONCLUSIONS: The ipsilateral cortico-spinal tract is acutely facilitated after stroke in the trunk or proximal muscles, but not in the hand muscles. Activation of such pathway appears to partly compensate motor dysfunction of the trunk/proximal muscles.

Tannerella forsythia-produced methylglyoxal causes accumulation of advanced glycation endproducts to trigger cytokine secretion in human monocytes.

The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival-crevicular fluid are increased and are correlated with the T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. forsythia. While wild-type T.forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. forsythia parental strain, the spent medium of the T. forsythia mgsA-deletion strain induced significantly lower nuclear factor-kappa B activity as well as proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The ability of T. forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis-based collagen chain mobility shift assay. Together these data demonstrated that T. forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.

[Large malignant mesenchymoma of the left posterior mediastinum; report of a case].

Malignant mesenchymoma is a soft tissue tumor arising preferentially in the extremities and retroperitoneum. We report a case of primary malignant mesenchymoma of the left posterior mediastinum. A 24-year-old woman was admitted to our hospital for complaining of cough. Chest X-ray showed a giant mass occupying the 2/3 of the left hemithorax. Chest computed tomography (CT) revealed a lobulated large mass with fat density area and calcified spot in the mediastinum and left pleural space. Chest magnetic resonance imaging (MRI) demonstrated a large solid mass consisting mainly of areas with the same intensity as fatty tissue and partly of areas with heterogenous moderate intensity. The tumor was resected completely under left posterolateral thoracotomy. The pathologic diagnosis was malignant mesenchymoma; well differentiated liposarcoma with osteocartilagenous differentiation. The patient has been well for 3 years and 3 months after surgery.

Partial amino acid sequence of glycophorin from porcine erythrocyte membranes.

Glycophorin from porcine erythrocyte membranes was digested with trypsin and chymotrypsin. Some of the peptides were isolated by conventional techniques. The amino acid sequence was determined for two isolated peptides: a chymotryptic glycopeptide of 19 residues and a tryptic peptide of 36 residues which represented the carboxy terminal of the glycophorin.

Alkali-labile oligosaccharide units of a sialoglycoprotein from rabbit erythrocyte membranes.

Two glycoproteins (apparent molecular weights 120,000 and 70,000) were extracted from rabbit erythrocyte membranes, and only one (Mr 120,000), which is a sialoglycoprotein, contained O-glycosidically linked sugar chains. Alkali-labile oligosaccharide units of the sialoglycoprotein were released as reduced oligosaccharides by NaOH-NaB3H4 treatment, and then purified by gel filtration on a Bio-Gel P-4 column followed by ion-exchange chromatography. From the results of methylation analysis, mass spectrometry and chromium trioxide oxidation, the main oligosaccharide unit was determined to be a linear trisaccharide (85% by weight), NeuNGc alpha(2----3)Gal beta(1----3)GalNAcol. In addition, small amounts of a tetrasaccharide (11% by weight) and a disaccharide (4% by weight) were found, which were determined to have the following structures, NeuNGc alpha(2----3)Gal beta(1----3)[NeuNGc alpha(2----6)] GalNAcol and Gal-GalNAcol, respectively.

Tannerella forsythia-induced alveolar bone loss in mice involves leucine-rich-repeat BspA protein.

Tannerella forsythia (formerly Bacteroides forsythus) is one of the periodontal pathogens recently implicated in the development of periodontal disease. The cell-surface-associated, as well as the secreted, leucine-rich-repeat protein (BspA) of this bacterium have been suggested to play roles in bacterial adherence, and also in inflammation, by triggering release of pro-inflammatory cytokines from monocytes and chemokines from osteoblasts, leading to inflammation and bone resorption. In this study, we sought to determine the pathogenic potential of T. forsythia and the in vivo role of the BspA protein in pathogenesis in the mouse model of infection-induced alveolar bone loss. The results showed alveolar bone loss in mice infected with the T. forsythia wild-type strain, whereas the BspA mutant was impaired. In conclusion, evidence is presented in support of T. forsythia as an important organism involved in inducing alveolar bone loss, and the BspA protein is an important virulence factor of this bacterium.

Clock gene expression in the submandibular glands.

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes-including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbalpha-showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1-/- background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.

Acetylsalicylate-human serum albumin interaction as studied by NMR spectroscopy--antigenicity-producing mechanism of acetylsalicylic acid.

To discover the antigenicity-producing mechanism of acetylsalicylic acid, the interaction of this drug and relevant salicylic acid with human serum albumin (HSA) has been studied by means of nuclear magnetic resonance (NMR) spectroscopy. The determination of spin-lattice relaxation rates (1/T1) of some protons have revealed that one HSA molecule can bind acetylsalicylate and salicylate up to 80 and 290 molecules, respectively. The hydrolysis rates of acetylsalicylate were greatly enhanced in the presence of HSA, especially when the drug/HSA mole ratio was small. Thus, the esterase-like activity of HSA was verified. This activity of HSA was effectively inhibited by salicylate; the effect was ascribed to the stronger binding affinity of salicylate toward HSA as compared with that of acetylsalicylate. Based on these results, the antigenicity-producing mechanism of acetylsalicylate and salicylate has been discussed.

[Successful removal of T4 lung cancer with left atrial invasion after induction chemotherapy].

A 53-year-old man presented with cough, sputa and chest pain. The chest X-ray revealed a large mass shadow in the right lower lobe. Massive tumor extending into the left atrium was diagnosed by computed tomography (CT). The brushing cytology by broncoscopy was squamous cell carcinoma and its stage was IIIB. Chemothrapy using cisplatin, paclitaxel and gemcitabine hydrochloride was performed 8 courses during 6 months. The effect of the chemotherapy was complete response, enabling the surgical treatment. The right pneumonectomy with partial resection of the left atrium was performed by using vascular clamp. The defect of the left atrium could be sutured directly. Wide-spread necrotic change with very small amount of cancer cells in the atrial wall was confirmed by pathology. The patient has been well for 3 years and 6 months after surgery.

Maternal phase setting of fetal circadian oscillation underlying the plasma corticosterone rhythm in rats.

We examined the entraining effect of the maternal circadian system on the fetal circadian oscillation during pregnancy. The circadian rhythm of locomotor activity and plasma corticosterone of pregnant rats was abolished by bilateral ablation of the suprachiasmatic nuclei at day 10 of gestation. At term, pups were removed by Cesarean section and were blinded immediately. To avoid possible rhythmic influences of a nursing mother on the pups' circadian rhythms, alternating nursing was imposed on blinded infants. Thus, pups were exchanged every 12 h between two foster mothers, one entrained to a light-dark cycle and the other to dark-light, so that one group of pups were always nursed in the light period and the other in the dark. Both groups of pups showed free-running circadian hormone rhythms with similar phase angles. However, the circadian rhythm of these pups was always phase delayed by about 8 h to that of blinded control pups which were born to unoperated mothers. Furthermore, blinded pups born to and nursed by a suprachiasmatic nuclei lesioned mother developed a circadian hormone rhythm which was phase delayed by 4 h to that of the control. It is concluded that the circadian oscillation underlying the rhythm of corticosterone release in rats has entrained to the maternal circadian system during fetal life. It is further suggested that the entrainment starts before day 10 of gestation.

Effects of elimination of maternal circadian rhythms during pregnancy on the postnatal development of circadian corticosterone rhythm in blinded infantile rats.

The influence of maternal circadian rhythms on fetal circadian oscillations during pregnancy was examined. Circadian rhythms of spontaneous locomotor activity and plasma corticosterone level in pregnant rats were eliminated by bilateral lesions of the suprachiasmatic nuclei (SCN) at different stages of gestation and the postnatal manifestation of the circadian corticosterone rhythm was examined in individual pups. Effective lesions of SCN at day 3 of gestation resulted in an abortion in all rats examined. Rats whose SCN were lesioned at day 10 or 17 of gestation maintained their pregnancies. At term, pups were removed by Cesarean operation and immediately blinded by bilateral ocular enucleation; they were reared by unoperated foster mother afterwards. All pups from SCN lesioned mothers showed a clear free running circadian rhythm of plasma corticosterone levels after the 4th week of postnatal life. Furthermore, the circadian rhythm that developed in pups from SCN-lesioned mother at day 10 of gestation (G10 pups) was always phase-delayed about 4 h as compared with that in pups from mothers whose SCN were lesioned at day 17 of gestation (G17 pups) and in pups from sham-operated mothers (S pups). It is concluded that the circadian hormone rhythmicity develops in normal fashion postnatally when the maternal SCN are effectively lesioned after day 10 of gestation. The phase-angle difference in the circadian rhythm between G10 pups and G17 or S pups suggests that fetal circadian oscillation is entrainable at least after day 10 of gestation.

Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells.

In the present study, we show that melatonin induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme of glutathione (GSH) synthesis, in ECV304 human vascular endothelial cells. One micromolar melatonin induced the expression of gamma-GCS mRNA followed by an increase in the concentration of GSH with a peak at 24 h. An electrophoretic mobility shift assay showed that melatonin stimulates the DNA-binding activity of activator protein-1 (AP-1) as well as retinoid Z receptor/retinoid receptor-related orphan receptor alpha (RZR/RORalpha). ECV304 cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with melatonin. The melatonin-dependent luciferase activity was found in the gamma-GCS promoter containing AP-1 site. The luciferase activity mediated by AP-1 was repressed in the promoter containing RZR/RORalpha site. In addition, cell cycle analysis showed that melatonin increases the number of cells in the G0/G1 phase; however, treatment of the cells with buthionine sulfoximine, a specific inhibitor of gamma-GCS, abolished the effect of melatonin on the cell cycle, suggesting induction of cell arrest by melatonin requires GSH. As conclusion, induction of GSH synthesis by melatonin protects cells against oxidative stress and regulates cell proliferation.

Identification of an epitope derived from human proteolipid protein that can induce autoreactive CD8+ cytotoxic T lymphocytes restricted by HLA-A3: evidence for cross-reactivity with an environmental microorganism.

The demyelination process that occurs in the central nervous system (CNS) of patients with multiple sclerosis (MS) is in part due to an inflammatory response in which CD4+ and CD8+ T cells and macrophages infiltrate white matter. In this study, we have identified a peptide sequence derived from the CNS-specific myelin protein proteolipid protein (PLP) which could bind to HLA-A3 and induce a HLA-A3-restricted CD8+ CTL response from HLA-A3+ donors. These PLP peptide-specific CTL could lyse HLA-A3+ target cells pulsed with a homologous peptide derived from the CRM1 protein of Saccharomyces cerevisae. These findings demonstrate the immunogenic potential of a PLP-derived peptide for generation of autoreactive HLA-A3-restricted CD8+ CTL, and further show that these CTL can be activated by a peptide derived from a common environmental microorganism.

Circadian rhythms of arginine vasopressin and vasoactive intestinal polypeptide do not depend on cytoarchitecture of dispersed cell culture of rat suprachiasmatic nucleus.

Dispersed cells of rat suprachiasmatic nucleus were cultured for more than a month with chemically defined medium. Arginine vasopressin and vasoactive intestinal polypeptide in the culture medium showed robust circadian rhythms starting 24 h after the cell dissociation. The two rhythms had similar periods, with a phase-lead of the vasoactive intestinal polypeptide peaks to the arginine vasopressin peak of about 1 h. The two rhythms remained two weeks later, with both peaks appearing at almost the same time, suggesting the synchronization of the two rhythms. Significant differences in cell architecture were detected depending on precoating matrices of culture dishes, which did not affect the circadian rhythms of arginine vasopressin and vasoactive intestinal polypeptide. Antimitotic treatment at the beginning of the culture not only reduced the number, but also changed the type of glial cells developed. The treatment did not interrupt the synchronized arginine vasopressin and vasoactive intestinal polypeptide rhythms until day 31. Early appearance of circadian rhythms indicates that neural networks in the suprachiasmatic nucleus are not necessary for the synchronous release of arginine vasopressin and vasoactive intestinal polypeptide. Glial proliferation is not essential for the generation, expression and synchronization of arginine vasopressin and vasoactive intestinal polypeptide rhythms in the dispersed suprachiasmatic nucleus cell culture.