Scanning transmission electron microscopy of gate stacks with HfO2 dielectrics and TiN electrodes

High-angle annular dark-field (HAADF) imaging and electron energy-loss spectroscopy (EELS) in scanning transmission electron microscopy were used to investigate HfO2 gate dielectrics grown by atomic layer deposition on Si substrates, and their interfaces with TiN electrodes and silicon, as a function of annealing temperature. Annealing at high temperatures (900 °C) caused significant roughening of both bottom (substrate) and top (electrode) interface. At the bottom interface, HAADF images showed clusters of Hf atoms that protruded into the interfacial SiO2 layer. Low-loss EELS established that even crystalline HfO2 films exposed to relative high temperatures (700 °C) exhibited significant differences in their electronic structure relative to bulk HfO2. Further annealing caused the electronic structure to more closely resemble that of bulk HfO2, with the most significant change due to annealing with the TiN electrode

A Paracoccidioides brasiliensis glycan shares serologic and functional properties with cryptococcal glucuronoxylomannan

The cell wall of the yeast form of the dimorphic fungus Paracoccidioides brasiliensis is enriched with alpha 1,3-glucans. in Cryptococcus neoformans, alpha 1,3-glucans interact with glucuronoxylomannan (GXM), a hetero-polysaccharide that is essential for fungal virulence. in this study, we investigated the occurrence of P. brasiliensis glycans sharing properties with cryptococcal GXM. Protein database searches in P. brasiliensis revealed the presence of sequences homologous to those coding for enzymes involved in the synthesis of GXM and capsular architecture in C. neoformans. in addition, monoclonal antibodies (mAbs) raised to cryptococcal GXM bound to P. brasiliensis cells. Using protocols that were previously established for extraction and analysis of C neoformans GXM, we recovered a P. brasiliensis glycan fraction composed of mannose and galactose, in addition to small amounts of glucose, xylose and rhamnose. in comparison with the C. neoformans GXM, the P. brasiliensis glycan fraction components had smaller molecular dimensions. the P. brasiliensis components, nevertheless, reacted with different GXM-binding mAbs. Extracellular vesicle fractions of P. brasiliensis also reacted with a GXM-binding mAb, suggesting that the polysaccharide-like molecule is exported to the extracellular space in secretory vesicles. An acapsular mutant of C. neoformans incorporated molecules from the P. brasiliensis extract onto the cell wall, resulting in the formation of surface networks that resembled the cryptococcal capsule. Coating the C. neoformans acapsular mutant with the P. brasiliensis glycan fraction resulted in protection against phagocytosis by murine macrophages. These results suggest that P. brasiliensis and C. neoformans share metabolic pathways required for the synthesis of similar polysaccharides and that P. brasiliensis yeast cell walls have molecules that mimic certain aspects of C. neoformans GXM. These findings are important because they provide additional evidence for the sharing of antigenically similar components across phylogenetically distant fungal species. Since GXM has been shown to be important for the pathogenesis of C neoformans and to elicit protective antibodies, the finding of similar molecules in P. brasiliensis raises the possibility that these glycans play similar functions in paracoccidiomycosis. (C) 2012 Elsevier Inc. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)NIHCenter for AIDS Research at EinsteinInterhemispheric Research Training Grant in Infectious Diseases, Fogarty International CenterDepartment of EnergyFiocruz MS, CDTS, BR-21040360 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, BR-21941902 Rio de Janeiro, BrazilAlbert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USAUniversidade Federal de São Paulo, Disciplina Biol Celular, BR-04023062 São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941903 Rio de Janeiro, BrazilAlbert Einstein Coll Med, Div Infect Dis, Dept Med, Bronx, NY 10461 USAUniversidade Federal de São Paulo, Disciplina Biol Celular, BR-04023062 São Paulo, BrazilNIH: AI033142NIH: AI033774NIH: AI052733NIH: HL059842Interhemispheric Research Training Grant in Infectious Diseases, Fogarty International Center: NIH D43-TW007129Department of Energy: DE-FG-9-93ER-20097Web of Scienc

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Observation of Pulsed Gamma-rays Above 25 GeV from the Crab Pulsar with MAGIC

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.Comment: Slight modification of the analysis: Fitting a more general function to the combined data set of COMPTEL, EGRET and MAGIC. Final result and conclusion is unchange

First bounds on the high-energy emission from isolated Wolf-Rayet binary systems

High-energy gamma-ray emission is theoretically expected to arise in tight binary star systems (with high mass loss and high velocity winds), although the evidence of this relationship has proven to be elusive so far. Here we present the first bounds on this putative emission from isolated Wolf-Rayet (WR) star binaries, WR 147 and WR 146, obtained from observations with the MAGIC telescope.Comment: (Authors are the MAGIC Collaboration.) Manuscript in press at The Astrophysical Journal Letter

Capsules from Pathogenic and Non-Pathogenic Cryptococcus spp. Manifest Significant Differences in Structure and Ability to Protect against Phagocytic Cells

Capsule production is common among bacterial species, but relatively rare in eukaryotic microorganisms. Members of the fungal Cryptococcus genus are known to produce capsules, which are major determinants of virulence in the highly pathogenic species Cryptococcus neoformans and Cryptococcus gattii. Although the lack of virulence of many species of the Cryptococcus genus can be explained solely by the lack of mammalian thermotolerance, it is uncertain whether the capsules from these organisms are comparable to those of the pathogenic cryptococci. In this study, we compared the characteristic of the capsule from the non-pathogenic environmental yeast Cryptococcus liquefaciens with that of C. neoformans. Microscopic observations revealed that C. liquefaciens has a capsule visible in India ink preparations that was also efficiently labeled by three antibodies generated to specific C. neoformans capsular antigens. Capsular polysaccharides of C. liquefaciens were incorporated onto the cell surface of acapsular C. neoformans mutant cells. Polysaccharide composition determinations in combination with confocal microscopy revealed that C. liquefaciens capsule consisted of mannose, xylose, glucose, glucuronic acid, galactose and N-acetylglucosamine. Physical chemical analysis of the C. liquefaciens polysaccharides in comparison with C. neoformans samples revealed significant differences in viscosity, elastic properties and macromolecular structure parameters of polysaccharide solutions such as rigidity, effective diameter, zeta potential and molecular mass, which nevertheless appeared to be characteristics of linear polysaccharides that also comprise capsular polysaccharide of C. neoformans. The environmental yeast, however, showed enhanced susceptibility to the antimicrobial activity of the environmental phagocytes, suggesting that the C. liquefaciens capsular components are insufficient in protecting yeast cells against killing by amoeba. These results suggest that capsular structures in pathogenic Cryptococcus species and environmental species share similar features, but also manifest significant difference that could influence their potential to virulence