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The scope of this paper is to outline the main marks and performances of the MagneDyn beamline, which was designed and built to perform ultrafast magnetodynamic studies in solids. Open to users since 2019, MagneDyn operates with variable circular and linear polarized femtosecond pulses delivered by the externally laser-seeded FERMI free-electron laser (FEL). The very high degree of polarization, the high pulse-to-pulse stability, and the photon energy tunability in the 50-300 eV range allow performing advanced time-resolved magnetic dichroic experiments at the K-edge of light elements, e.g., carbon and at the M- and N-edge of the 3d-transition-metals and rare earth elements, respectively. To this end, two experimental end-stations are available. The first is equipped with an in situ dedicated electromagnet, a cryostat, and an extreme ultraviolet Wollaston-like polarimeter. The second, designed for carry-in user instruments, hosts also a spectrometer for pump-probe resonant x-ray emission and inelastic spectroscopy experiments with a sub-eV energy resolution. A Kirkpatrick-Baez active optics system provides a minimum focus of similar to 20x20 mu m(2) FWHM at the sample. A pump laser setup, synchronized with the FEL-laser seeding system, delivers sub-picosecond pulses with photon energies ranging from the mid-IR to near-UV for optical pump-FEL probe experiments with a minimal pump-probe jitter of few femtoseconds. The overall combination of these features renders MagneDyn a unique state-of-the-art tool for studying ultrafast magnetic and resonant emission phenomena in solids. Published under an exclusive license by AIP Publishing.

We utilize coherent femtosecond extreme ultraviolet (EUV) pulses derived from a free electron laser (FEL) to generate transient periodic magnetization patterns with periods as short as 44 nm. Combining spatially periodic excitation with resonant probing at the dichroic M-edge of cobalt allows us to create and probe transient gratings of electronic and magnetic excitations in a CoGd alloy. In a demagnetized sample, we observe an electronic excitation with 50 fs rise time close to the FEL pulse duration and ~0.5 ps decay time within the range for the electron-phonon relaxation in metals. When the experiment is performed on a sample magnetized to saturation in an external field, we observe a magnetization grating, which appears on a sub-picosecond time scale as the sample is demagnetized at the maxima of the EUV intensity and then decays on the time scale of tens of picoseconds via thermal diffusion. The described approach opens prospects for studying dynamics of ultrafast magnetic phenomena on nanometer length scales.

Understanding how a spin current flows across metal-semiconductor interfaces at pico- and femtosecond time scales is of paramount importance for ultrafast spintronics, data processing, and storage applications. However, the possibility to directly access the propagation of spin currents, within such time scales, has been hampered by the simultaneous lack of both ultrafast element-specific magnetic sensitive probes and tailored well-built and characterized metal-semiconductor interfaces. Here, by means of a novel free-electron laser-based element-sensitive ultrafast time-resolved Kerr spectroscopy, we reveal different magnetodynamics for the Ni M 2 , 3 and Si L 2 , 3 absorption edges. These results are assumed to be the experimental evidence of photoinduced spin currents propagating at a speed of ∼ 0.2 nm/fs across the Ni/Si interface.

Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the impairment of taste and olfaction, the detection of the internal chemical environment may also be incapacitated by COVID-19. If this is the case, different consequences can be expected. (1) In some patients, hypoxia does not trigger distressing dyspnea (“silent” hypoxia): Long-term follow-up may determine whether silent hypoxia is related to malfunctioning of carotid body chemoreceptors. Moreover, taste/olfaction and oxygen chemoreceptors may be hit simultaneously: Testing olfaction, taste, and oxygen chemoreceptor functions in the early stages of COVID-19 allows one to unravel their connections and trace the recovery path. (2) Solitary chemosensory cells are also involved in the regulation of the innate mucosal immune response: If these cells are affected in some COVID-19 patients, the mucosal innate immune response would be dysregulated, opening one up to massive infection, thus explaining why COVID-19 has lethal consequences in some patients. Similar to taste and olfaction, oxygen chemosensory function can be easily tested with a non-invasive procedure in humans, while functional tests for solitary chemosensory or pulmonary neuroendocrine cells are not available, and autoptic investigation is required to ascertain their involvement.

Here, we report on the conceptual design, the hardware realization, and the first experimental results of a novel and compact x-ray polarimeter capable of a single-pulse linear polarization angle detection in the extreme ultraviolet photon energy range. The polarimeter is tested by performing time resolved pump-probe experiments on a Ni80Fe20 Permalloy film at the M-2,M-3 Ni edge at an externally seeded free-electron laser source. Comparison with similar experiments reported in the literature shows the advantages of our approach also in view of future experiments.

Protein kinase A (PKA) are tetramers of two catalytic and two regulatory subunits, docked at precise intracellular sites to provide localized phosphorylating activity, triggered by cAMP binding to regulatory subunits and subsequent dissociation of catalytic subunits. It is unclear whether in the brain PKA dissociated subunits may also be found. PKA catalytic subunit was examined in various mouse brain areas using immunofluorescence, equilibrium binding and western blot, to reveal its location in comparison to regulatory subunits type RI and RII. In the cerebral cortex, catalytic subunits colocalized with clusters of RI, yet not all RI clusters were bound to catalytic subunits. In stria terminalis, catalytic subunits were in proximity to RI but separated from them. Catalytic subunits clusters were also present in the corpus striatum, where RII clusters were detected, whereas RI clusters were absent. Upon cAMP addition, the distribution of regulatory subunits did not change, while catalytic subunits were completely released from regulatory subunits. Unpredictably, catalytic subunits were not solubilized; instead, they re-targeted to other binding sites within the tissue, suggesting local macromolecular reorganization. Hence, the interactions between catalytic and regulatory subunits of protein kinase A consistently vary in different brain areas, supporting the idea of multiple interaction patterns.

Here we demonstrate that the 0-dimensional confinement of Ge2Sb2Te5 results in a drastic reduction of the minimum critical fluence required for optical-induced amorphization when compared to the thin-film cases. We show that by using single-shot laser pulses, the investigated nanoparticles display a crystalline-to-amorphous transition, satisfying a mandatory requirement of a bit-memory element. These unprecedented results open a viable route to boost energy efficient phase-change processes.

Author(s): Malvestuto, M; Caretta, A; Casarin, B; Ciprian, R; Dell'Angela, M; Laterza, S; Chuang, YD; Wurth, W; Revcolevschi, A; Wray, LA; Parmigiani, F | Abstract: Using high resolution resonant inelastic x-ray scattering measurements, we have observed that the orbital excitations of the quasi-1D spin chain compound CuGeO3 has nontrivial and noticeable orbital mixing effects from 3d valence spin-orbit coupling. In particular, the SOC leads to a significant correction of dz2 state, which has a direct interplay with the low energy physics of cuprates. Guided by atomic multiplet based modeling, our results strongly support a 3d spin-orbit mixing scenario and explore in detail the nature of these excitations.

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration, these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

The future Magneto Dynamics (MagneDyn) beamline will be devoted to study the electronic states and the local magnetic properties of excited and transient states of complex systems by means of the time-resolved X-ray absorption spectroscopy technique. The beamline will use FERMI's high-energy source covering the wavelength range from 60 nm down to 1.3 nm. An on-line photon energy spectrometer will allow spectra to be measured with high resolution while delivering most of the beam to the end-stations. Downstream the beam will be possibly split and delayed, by means of a delay line, and then focused with a set of active Kirkpatrick–Baez mirrors. These mirrors will be able to focus the radiation in one of the two MagneDyn experimental chambers: the electromagnet end-station and the resonant inelastic X-ray scattering end-station. After an introduction of the MagneDyn scientific case, the layout will be discussed showing the expected performances of the beamline.

Phytoremediation represents a solution for treating soils contaminated by heavy metals, provided that appropriate plant species are selected and the proper strategy chosen. When dealing with soil contaminated with arsenic and/or lead, which are non-essential elements for plants but also among the most toxic metals, this task is particularly difficult to achieve. In a previous contribution we showed that metals accumulation by Lupinus albus, Brassica juncea and Helianthus annuus can be improved by dosing suitable chemicals (i.e. phosphate and EDTA), leading to a quicker and cheaper intervention. This study discusses the assisted phytoremediation of a real site contaminated by several metals, presenting an environmental assessment realized by using the GaBi LCA software. The environmental sustainability of the reclamation technology was analyzed in terms of Global Warming Potential (GWP-100 years), considering different destinations for the harvested biomass, and comparing its ecological footprint with the outcomes of a conventional treatment of excavation and landfill disposal. The comparison clearly shows the great advantage of the phytoremediation, in terms of environmental impact, highlighting the importance of correctly handling the disposal of contaminated biomass produced. In fact, its incineration (aimed at reducing the volumes to be disposed of) could be more onerous than a direct landfilling, but re-qualify as a more sustainable choice if combined with energy recovery. The same applies to fast pyrolysis, which seems to be the most sustainable approach to date, at least in terms of technological maturity, although this requires technical-economic considerations on the quality and use of biofuels produced.

Brain tumor glioblastoma has no clear molecular signature and there is no effective therapy. In rodents, the intracellular distribution of the cyclic AMP (cAMP)-dependent protein kinase (Protein kinase A, PKA) R2Alpha subunit was previously shown to differentiate tumor cells from healthy brain cells. Now, we aim to validate this observation in human tumors. The distribution of regulatory (R1 and R2) and catalytic subunits of PKA was examined via immunohistochemistry and Western blot in primary cell cultures and biopsies from 11 glioblastoma patients. Data were compared with information obtained from 17 other different tumor samples. The R1 subunit was clearly detectable only in some samples. The catalytic subunit was variably distributed in the different tumors. Similar to rodent tumors, all human glioblastoma specimens showed perinuclear R2 distribution in the Golgi area, while it was undetectable outside the tumor. To test the effect of targeting PKA as a therapeutic strategy, the intracellular cyclic AMP concentration was modulated with different agents in four human glioblastoma cell lines. A significant increase in cell death was detected after increasing cAMP levels or modulating PKA activity. These data raise the possibility of targeting the PKA intracellular pathway for the development of diagnostic and/or therapeutic tools for human glioblastoma.

Physical review / B 96(18), 184420 (2017). doi:10.1103/PhysRevB.96.184420, We report a high-resolution resonant inelastic extreme ultraviolet (EUV) scattering study of the quantum Heisenberg antiferromagnet KCoF$_3$. By tuning the EUV photon energy to the cobalt M$_{23}$ edge, a complete set of low-energy 3d spin-orbital excitations is revealed. These low-lying electronic excitations are modeled using an extended multiplet-based mean-field calculation to identify the roles of lattice and magnetic degrees of freedom in modifying the resonant inelastic x-ray scattering (RIXS) spectral line shape. We have demonstrated that the temperature dependence of RIXS features upon the antiferromagnetic ordering transition enables us to probe the energetics of short-range spin correlations in this material., Published by APS, Woodbury, NY

Scientific reports 6, 38796 (2016). doi:10.1038/srep38796, In the past few years, we have been witnessing an increased interest for studying materials properties under non-equilibrium conditions. Several well established spectroscopies for experiments in the energy domain have been successfully adapted to the time domain with sub-picosecond time resolution. Here we show the realization of high resolution resonant inelastic X-ray scattering (RIXS) with a stable ultrashort X-ray source such as an externally seeded free electron laser (FEL). We have designed and constructed a RIXS experimental endstation that allowed us to successfully measure the d-d excitations in KCoF3 single crystals at the cobalt M$_{2,3}$-edge at FERMI FEL (Elettra-Sincrotrone Trieste, Italy). The FEL-RIXS spectra show an excellent agreement with the ones obtained from the same samples at the MERIXS endstation of the MERLIN beamline at the Advanced Light Source storage ring (Berkeley, USA). We established experimental protocols for performing time resolved RIXS experiments at a FEL source to avoid X ray-induced sample damage, while retaining comparable acquisition time to the synchrotron based measurements. Finally, we measured and modelled the influence of the FEL mixed electromagnetic modes, also present in externally seeded FELs, and the beam transport with ~120 meV experimental resolution achieved in the presented RIXS setup., Published by Nature Publishing Group, London

A long-standing question for avant-garde data storage technology concerns the nature of the ultrafast photoinduced phase transformations in the wide class of chalcogenide phase-change materials (PCMs). Overall, a comprehensive understanding of the microstructural evolution and the relevant kinetics mechanisms accompanying the out-of-equilibrium phases is still missing. Here, after overheating a phase-change chalcogenide superlattice by an ultrafast laser pulse, we indirectly track the lattice relaxation by time resolved x-ray absorption spectroscopy (tr-XAS) with a sub-ns time resolution. The approach to the tr-XAS experimental results reported in this work provides an atomistic insight of the mechanism that takes place during the cooling process; meanwhile a first-principles model mimicking the microscopic distortions accounts for a straightforward representation of the observed dynamics. Finally, we envisage that our approach can be applied in future studies addressing the role of dynamical structural strain in PCMs.

The extraordinary electronic and optical properties of the crystal-to-amorphous transition in phase-change materials have led to important developments in memory applications. A promising outlook is offered by nanoscaling such phase-change structures. Following this research line, we study the interband optical transmission spectra of nanoscaled $\text{GeTe}/{\mathrm{Sb}}_{2}{\mathrm{Te}}_{3}$ chalcogenide superlattice films. We determine, for films with varying stacking sequence and growth methods, the density and scattering time of the free carriers, and the characteristics of the valence-to-conduction transition. It is found that the free carrier density decreases with increasing GeTe content, for sublayer thicknesses below $\ensuremath{\sim}3$ nm. A simple band model analysis suggests that GeTe and ${\mathrm{Sb}}_{2}{\mathrm{Te}}_{3}$ layers mix, forming a standard GeSbTe alloy buffer layer. We show that it is possible to control the electronic transport properties of the films by properly choosing the deposition layer thickness, and we derive a model for arbitrary film stacks.

A new-concept approach to room temperature magnetic gas sensing has been developed, based on newly designed Co/ZnO hybrid nanostructures. The sensor prototype has been demonstrated to be sensitive, reversible, fast and scalable. In this work, the role of the Co/ZnO surface and interface in the gas-sensing mechanism has been clarified. In order to attain a comprehensive understanding of the physics governing the remarkable properties of the Co/ZnO stack, an extensive electronic and structural investigation has been carried out. The reaction at room temperature with target gases involves the surface and the lateral faces of the ZnO nanorods, with the formation of structural defects and vacancies. In particular, it has been discovered that the stress enhancement as well as the change in the polarizability of the ZnO nanorods are transduced by Co in a change of its magnetization. The interplay between these phenomena may provide versatile approaches to tune the intrinsic electronic, magnetic and optical properties of the hybrid nanostructure.

In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

Here we report on the magneto-optical Kerr effect employing a nematic liquid crystal (LC) device as an optical modulator. This device allows performing intensity, phase, and polarization modulated measurements with a huge signal-to-noise ratio when compared to those obtained by means of an opto-mechanical chopper and a photo-elastic modulator. The results demonstrate that the optimal performance is achieved modulating the polarization state of the incident light by means of the LCs. © 2018 Author(s).

By comparing the photo-induced magnetization dynamics in simple layered systems we show how light-induced modifications of the magnetic anisotropy directly enhance the magnetization. It is observed that the spin precession in (CH3NH3)2CuCl4, initiated by a light pulse, increases in amplitude at the critical temperature TC. The phenomenon is related to the dependence of the critical temperature on the axial magnetic anisotropy. The present results underline the possibility and the importance of the optical modifications of the anisotropy, opening new paths toward the control of the magnetization state for ultrafast memories., Comment: 5 pages, 3 figures, supplementary info as SIr.pdf

We have synthesized members of an isostructural solid solution series KxBa1-xO2-delta (x

The binding of thioperamide, a known H3-receptor antagonist, to rat plasma proteins and its affinity for rat cerebral phospholipids are investigated. Thioperamide is strongly bound to plasma proteins (95−80% at plasma concentrations of 3.5−400 μg mL−1), and its binding can be resolved into two components: a high-affinity, saturable component and a non-specific component. The drug has a high affinity for cerebral phospholipids, with a partition coefficient of approximately 100 (log K = 2.06 ± 0.14), which should promote brain penetration and accumulation. Protein binding and cerebral phospholipid affinity can suggest the explanation of some differences reported in the literature on thioperamide distribution data: at low plasma concentrations of the drug, its protein binding (95% at 3.5 μg mL−1) can prevent brain accumulation, while at higher concentrations the free plasma fraction suddenly increases (> 10% at 18 μg mL−1) and it allows passive distribution to lipophilic tissues such as brain tissue.

We demonstrate, using a combination of experiment and density functional theory, that orbital ordering drives the formation of a one-dimensional (1D) $S=1/2$ antiferromagnetic spin chain in the 3D rocksalt structure of cesium superoxide (${\mathrm{CsO}}_{2}$). The magnetic superoxide anion (${\mathrm{O}}_{2}^{\ensuremath{-}}$) exhibits degeneracy of its $2p$-derived molecular orbitals, which is lifted by a structural distortion on cooling. A spin chain is then formed by zigzag ordering of the half-filled superoxide orbitals, promoting a superexchange pathway mediated by the ${p}_{z}$ orbitals of ${\mathrm{Cs}}^{+}$ along only one crystal direction. This scenario is analogous to the $3d$-orbital-driven spin chain found in the perovskite ${\mathrm{KCuF}}_{3}$ and is the first example of an inorganic quantum spin system with unpaired $p$ electrons.

The accessory olfactory system is present in most tetrapods. It is involved in the perception of chemical stimuli, being implicated also in the detection of pheromone. However, it is sensitive also to some common odorant molecules, which have no clear implication in intraspecific chemical communication. The accessory olfactory system may complement the main olfactory system, and may contribute different perceptual features to the construction of a unitary representation, which merges the different chemosensory qualities. Crosstalk between the main and accessory olfactory systems occurs at different levels of central processing, in brain areas where the inputs from the two systems converge. Interestingly, centrifugal projections from more caudal brain areas are deeply involved in modulating both main and accessory sensory processing. A high degree of interaction between the two systems may be conceived, and partial overlapping appears to occur in many functions. Therefore, the central chemosensory projections merge inputs from different organs to obtain a complex chemosensory picture.

We investigate the structural, magnetic, and dielectric properties of the organic-inorganic hybrid material CuCl4(C6H5CH2CH2NH3)(2) and demonstrate that spontaneous ferroelectric order sets in below 340 K, which coexists with ferromagnetic ordering below 13 K. We use X-ray diffraction to show that the electric polarization results from the spatial ordering of hydrogen bonds that link the organic block comprised of phenylethylammonium cations to the inorganic copper chloride block. The hydrogen bond ordering is driven by buckling of the corner-linked copper chloride octahedra. Because the magnetic exchange pathways are also determined by this octahedral buckling, a potentially large coupling is induced. Our results imply that such hybrids form a new family of multiferroic materials. KEYWORDS: multiferroic, ferroelectric, ferromagnetic, organic inorganic hybrid, metal-oxide framework

We report the hydrogenation of single and bilayer graphene by an argon-hydrogen plasma produced in a reactive ion etching (RIE) system. Electronic transport measurements in combination with Raman spectroscopy are used to link the electric mean free path to the optically extracted defect concentration. We emphasize the role of the self-bias of the graphene in suppressing the erosion of the akes during plasma processing. We show that under the chosen plasma conditions the process does not introduce considerable damage to the graphene sheet and that hydrogenation occurs primarily due to the hydrogen ions from the plasma and not due to fragmentation of water adsorbates on the graphene surface by highly accelerated plasma electrons. For this reason the hydrogenation level can be precisely controlled. The hydrogenation process presented here can be easily implemented in any RIE plasma system., 7 pages

Em virtude de a canção popular brasileira ser uma importante representação de nossa cultura, muitas pesquisas vêm sendo realizadas com o intuito de investigar, analisar e até avaliar nosso cancioneiro. Nesse contexto, esta tese apresenta um estudo dialógico-discursivo do gênero canção popular brasileira e de seu papel na formação do imaginário da cidade de São Paulo na primeira metade do século XX. A partir das teorias do Círculo de Bakhtin para o estudo dos gêneros discursivos, realizamos uma descrição do gênero canção popular, dando atenção ao seu caráter dialógico e ao sincretismo linguístico-melódico. Juntamente com as teorias do Círculo de Bakhtin, trabalhamos com as propostas de Dominique Maingueneau para o estudo da enunciação e propomos um modelo de análise discursiva da canção popular fundamentado nos conceitos de ethos, cenas de enunciação e interdiscurso. Na primeira metade do século XX, o imaginário da cidade de São Paulo constituiu-se a partir da polêmica entre os discursos progressista e nostálgico, que orientou a produção de enunciados em diversas esferas discursivas, dentre as quais a da música popular. A partir da análise de canções que abordam essa polêmica, estudamos as relações dialógicas interdiscursivas entre os discursos ufanista, nostálgico e paródico, responsáveis pela configuração do imaginário da cidade de São Paulo no seu processo de metropolização. As Brazilian popular music is an important representation of our culture, many researches have been focusing on investigating, analyzing and evaluating our songs. In this context, this thesis presents a dialogical discourse study of genre of Brazilian popular music and its role in creating the imaginary of the city of São Paulo during the first half of the twentieth century. From the theories developed by Bakhtin Circle on the study of discourse genres, we describe the popular music genre, highlighting its dialogical characteristics, and the syncretism between lyric and melodic lines. Besides Bakhtin´s theories, we worked on Dominique Maingueneau´s proposals for the enunciation study in order to propose a discourse analysis pattern for Brazilian popular music based on the concepts of ethos, enunciation scenes and discourse. In the earlier decades of the twentieth century, the imaginary of the city of São Paulo was formed by the controversy between the progressive and nostalgic discourses, which guided the production of many discourses, including popular music. From the song analysis, we study the dialogic and interdiscursive relations among the nationalistic, nostalgic and parodic discourses, responsible for the construction of the imaginary of the city of São Paulo in the process of becoming a metropolis.

Magnetic dioxygen molecules can be used as building blocks of model systems to investigate spin-polarization that arises from unpaired p-electrons, the scientific potential of which is evidenced by phenomena such as spin-polarized transport in graphene. In solid elemental oxygen and all of the known ionic salts comprised of magnetic dioxygen anions and alkali metal cations, the dominant magnetic interactions are antiferromagnetic. We have induced novel ferromagnetic interactions by introducing oxygen deficiency in rubidium superoxide (RbO(2)). The anion vacancies in the resulting phase with composition RbO(1.72) provide greater structural flexibility compared to RbO(2) and facilitate a Jahn-Teller-driven order-disorder transition involving the anion orientations at similar to 230 K, below which their axes become confined to a plane. This reorganization gives rise to short-range ferromagnetic ordering below similar to 50 K. A ferromagnetic cluster-glass state then forms below similar to 20 K, embedded in an antiferromagnetic matrix that orders at similar to 5 K. We attribute this inhomogeneous magnetic order to either subtly different anion geometries within different structural nanodomains or to the presence of clusters in which double exchange takes place between the anions, which are mixed-valence in nature. We thus demonstrate that nonstoichiometry can be employed as a new route to induce ferromagnetism in alkali metal oxides.

The high-order harmonic generation (HHG) of coherent light pulses in gases is strictly dependent on the ionization dynamics that delocalizes the electron wave function in the laser field continuum. Here we report on the investigation of such dynamics by varying the energy of a 400 nm, 60 fs driving laser pulse. The experimental data provide the unambiguous evidence of a hybrid dynamical region, not described by the full-tunneling approximation models, where the HHG photon number exponentially decays when the Keldysh parameter is varied from 1 to 3. Finally, a phenomenological model, suitable to account for this hybrid regime, is reported.

Differential diagnosis of brain tumor types is mainly based on cell morphology and could benefit from additional markers. The cAMP second-messenger system is involved in regulating cell proliferation and differentiation and is conceivably modulated during cancer transformation. The cAMP second-messenger system mainly activates protein kinases, which are in part docked to cytoskeleton, membranes, or organelles by anchoring proteins, forming protein aggregates that are detergent insoluble and not freely diffusible and that are characteristic for each cell type. The intracellular distribution of the detergent-insoluble regulatory subunits (R) of the cAMP-dependent protein kinase has been examined in mouse and rat glioma cells both in vitro and in vivo by immunohistochemistry. In normal rodent brains, the RIIalpha regulatory subunit is detergent insoluble only in ependymal cells, while in the rest of the brain it is present in soluble form. Immunohistochemistry shows that in both mouse and rat glioma cell lines, RIIalpha is mainly detergent insoluble. RIIalpha is localized close to the nucleus, associated with smooth vesicles in the trans-Golgi network area. Both paclitaxel and vinblastine cause a redistribution of RIIalpha within the cell. Under conditions that increased intracellular cAMP, apoptosis of glioma cells was observed, and it was accompanied by RIIalpha redistribution. Also in vivo, detergent-insoluble RIIalpha can be observed in mouse and rat gliomas, where it delineates the border between normal brain tissue and glioma. Therefore, intracellular distribution of detergent-insoluble RIIalpha can assist in detecting tumor cells within the brain, thus making the histologic diagnosis of brain tumors more accurate, and may represent an additional target for therapy.

Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg), to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

Psychiatric or depressed patients show alterations in both olfactory projection areas and mucosa. In rodents, ablation of olfactory bulbs causes a depression-like syndrome, useful to test antidepressant agents. We studied in mice the behavioral symptoms and neuroanatomical correlates after mucosal damage or ablation of the olfactory bulb. Our results are based on a battery of tests exploiting anxious, aggressive, and depressive behavior, on morphological and immunohistochemical analysis. We found similar results in both sensory-damaged and bulbectomized animals, with a behavioral dissociation concerning different forms of aggression. These findings do not support a simple downregulation of social interactions in damaged mice. The most prominent modifications in the brains of sensory damaged and bulbectomized mice are detected in the subventricular zone (SVZ), the source area of neural stem cells, and in the content of cAMP-dependent protein kinase within the amygdala, suggesting a central role of this structure in the functional modulation of behavior.

The attractive properties of male urinary pheromones were tested on adult or prepubertal male and female mice. An androgen-dependent protein is present in adult male urine (major urinary protein, MUP) which has been suggested to be a pheromone-binding protein. We tested the pheromonal properties of the protein-bound volatiles in a test of attractiveness. These molecules, that co-purify with MUP, attract females and repel adult males. In prepubertal animals, females are repelled and males are attracted by the same stimuli. These results are similar to those obtained by others with adult male whole urine. Therefore MUP binds molecules with a pheromonal activity, and these molecules are sufficient to act as male signals.

Background Previous studies showed a differential distribution of the four regulatory subunits of cAMP-dependent protein kinases inside the brain, that changed in rodent gliomas: therefore, the distribution of these proteins inside the brain can give information on the functional state of the cells. Our goal was to examine human brain tumors to provide evidence for a differential distribution of protein kinase A in different tumors. Methods The distribution of detergent insoluble regulatory (R1 and R2) and catalytic subunits of cAMP dependent kinases was examined in pediatric brain tumors by immunohistochemistry and fluorescent cAMP analogues binding. Results R2 is organized in large single dots in medulloblastomas, while it has a different appearance in other tumors. Fluorescent cAMP labelling was observed only in medulloblastoma. Conclusions A different distribution of cAMP dependent protein kinases has been observed in medulloblastoma.

Guanosine 3/,5′-monophosphate (3′,5'GMP) activates an influx of calcium ions into vesicles of rod outer segments washed free of water-soluble proteins and filled with a hihg-affinity ligand for calcium (EDTA, Arsenazo III, aequorin). Addition of 3′,5′GMP activates calcium inflix without any appreciable delay, studied with methods that resolve 40 ms. A direct interaction between the cyclic nucleotide and an intrinsic membrane component is considered.

The apparently cooperative binding of 8-(5-thioacetamidofluorescein)-cGMP (SAF-cGMP) to cGMP-binding sites of the rod outer segments is regulated by Ca2+ in the 0.1-1 microM activity range. High Ca2+ reduces, and low Ca2+ increases the affinity of SAF-cGMP binding. This regulation involves only intrinsic membrane components. It is proposed that an allosteric regulation of cGMP binding by Ca2+ can contribute to photoreceptor potential adaptation.

Light triggers the cyclic nucleotide cascade in photoreceptor disk membranes. We report here that light-induced changes in the apparent viscosity of disk membrane suspensions can also be observed using either native disk membranes or washed membranes reconstituted with G protein and PDE. The viscosity changes are light- and GTP-dependent and require the presence of G protein and PDE. The magnitude of the viscosity change increases with increasing membrane concentration. Under the same conditions in which light elicits a change in viscosity, we observe a large increase in light scattering by the disk membrane suspension.

Binding of two long wavelength fluorescent cAMP analogues, 8-thioacetamido-fluorescein-cAMP (SAF-cAMP) and 8-thioacetamido-rhodamine-cAMP (SAR-cAMP), to the RI (from bovine muscle) and RII (from bovine heart) regulatory subunits of cAMP dependent kinases has been studied. Displacement of [3H]cAMP from RI and RII and equilibrium dialysis measurements show that the fluorescent nucleotides are high affinity ligands for the cAMP binding sites. The binding is characterized by complex fluorescence spectral and fluorescence anisotropy changes, more evident for the fluorescein than for the rhodamine derivative. The fluorescence excitation spectrum of the bound SAF-cAMP is characterized by the appearance of a red shifted shoulder at 500–510 nm excitation wavelength region. Any change of the bound/free ratio in a solution equilibrium is accompanied by changes in fluorescence and anisotropy signals which are best detected at suitable wavelengths. It is proposed that fluorescence and anisotropy changes can distinguish between binding to type B (slow dissociating) and A (fast dissociating) cAMP binding sites of regulatory subunits. Applications of the fluorescent nucleotides to kinase localization and cAMP determination in living cells are discussed.

1. The diffusion of sodium, potassium and rubidium (not chloride) ions across the disk membrane is increased by cyclic guanosine monophosphate (cyclic GMP). 2. The increase is greater for sodium than for rubidium in the 0.01-0.1 mM concentration range. 3. Cyclic adenosine monophosphate (cyclic AMP) is less efficient than cyclic GMP; GMP and guanosine triphosphate are without effect. 4. The effect is present with either 1.8 mM calcium ions or 4 mM-EGTA in the perfusion fluid. 5. The presence of the cyclic GMP phosphodiesterase on the disk membranes is not needed for this effect. 6. The effect is present in both unbleached and fully bleached membranes.

Electrical photoresponses of rods in the isolated toad retina were recorded during ionic manipulations of the Na+-free extracellular medium. In the presence of a concentration of external Ca2+ above 10(-5) M, voltage photoresponses were observed only in the presence of external Na+ or Li+. When external Ca2+ was reduced below 10(-6) M, voltage photoresponses of normal polarity could be detected even in the absence of Na+ or Li+, but in the presence of external Mg2+. In the presence of normal extracellular Ca2+ hyperpolarizing photoresponses were observed even in the absence of Na+ or Li+, provided small amounts of phosphodiesterase inhibitors (IBMX, RO 20-1724, papaverine, caffeine, theophylline) were added to the perfusate. Responses obtained in low-Na+ IBMX solutions required the presence of millimolar amounts of a variety of divalent cations, among which Mn2+ and Ba2+ were the most effective. When the concentration of both external Ca2+ and Mg2+ was reduced to micromolar amounts, depolarizing photoresponses were observed. In these conditions measurements with radioactive tracers showed a light-modulated efflux of 42K+ or 86Rb+. The light-modulated 42K+ or 86Rb+ efflux was halved by 2 X 6 mM-external K+ and was completely blocked when K+ was raised above 10 mM. These results show that ionic movements through light-sensitive channels are controlled by Ca2+ and Mg2+ and possibly also be the intracellular level of cyclic nucleotides. Moreover, the movement of ions through the light-sensitive channel, does not obey the independence principle.

Background Olfaction is often affected in parkinsonian patients, but dopaminergic cells in the olfactory bulb are not affected by some Parkinson-inducing drugs. We investigated whether the drug MPTP produces the olfactory deficits typical of Parkinson and affects the olfactory bulb in mice. Findings Lesioned and control mice were tested for olfactory search, for motor and exploratory behavior. Brains and olfactory mucosa were investigated via immunohistochemistry for thyrosine hydroxylase, Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic neurotransmission. MPTP induced motor impairment, but no deficit in olfactory search. Thyrosine hydroxylase did not differ in olfactory bulb, while a strong decrease was detected in substantia nigra and tegmentum of MPTP mice. Olfactory Marker Protein decreased in the olfactory bulb of MPTP mice, while a cyclic AMP-dependent protein kinase increased in the inner granular layer of MPTP mice. Conclusions MPTP mice do not present behavioural deficits in olfactory search, yet immunoreactivity reveals modifications in the olfactory bulb, and suggests changes in intracellular signal processing, possibly linked to neuron survival after MPTP.

The high-affinity binding of the cGMP analogue 8-(5-thioacetamidofluorescein)-cGMP to rod outer segment membranes depleted of peripherally bound proteins has been defined by equilibrium dialysis (mean ± SD): (a) membranes contain about one cGMP binding site per 130 rhodopsin molecules; (b) the concentration of free ligand for half saturation is 2.0 ± 0.6 μM; (c) the apparent Hill coefficient of the bound versus free ligand relationship is 1.7 ± 0.5; (d) half saturation of the binding sites is sufficient for 85% activation of calcium permeability. A gating mechanism is proposed.