Doping dependent intrinsic magnetization in silicon in Ni/Si heterostructures.

This investigation delves into the complex interaction at metal-semiconductor interfaces, highlighting the magnetic proximity effect in Ni/Si interfaces through systematic X-ray magnetic circular dichroism (XMCD) studies at Ni and Si edges. We analyzed two Ni/Si heterostructures with differing semiconductor doping, uncovering a magnetic proximity effect manifesting as equilibrium magnetization in the semiconductor substrate induced by the adjacent Ni layer. Our results display distinct magnetization signs corresponding to the doping levels: low-doped samples show parallel alignment to the Ni layer, while high-doped samples align antiparallel, indicating a nuanced interplay of underlying magnetization mechanisms. These findings pinpoint the roles of electron tunneling and exchange splitting modification in the magnetization behavior. The study enriches the understanding of ferromagnetic-semiconductor interface behavior, setting a precedent for the design of advanced spintronic devices that leverage the nuanced magnetic properties of these hybrid systems.

Estimation of cAMP binding in hippocampus CA1 field by a fluorescent probe.

The hippocampus is an allocortex structure involved in many complex processes, from memory formation to spatial navigation. It starts developing during prenatal life but acquires its adult functional properties around the peripubertal age, in both humans and mice. Such prolonged maturation is accompanied by structural changes in microcircuitry and functional changes involving biochemical and electrophysiological events. Moreover, hippocampus undergoes plasticity phenomena throughout life. In murine rodents, the most relevant maturation steps in Cornu Ammonis 1 (CA1) hippocampal subfield occur during the third-fourth weeks of life. During this period, also the expression and localization of cAMP-dependent protein kinases (PKA) refines: many regulatory (R1A) PKA clusters appear, bound to the cytoskeleton. Here the binding characteristics of R1A are determined in CA1 by using confocal microscopy. Apparently, two binding sites are present with no evidence of cooperativity. Equilibrium dissociation constant is estimated around 22.9 nM. This value is lower from that estimated for R1A in soluble form, suggesting a different binding site conformation or accessibility in the tissue. The method described here may be useful to track the developmental changes in binding activity, which affects cAMP availability at selected intracellular microzones. Possible relations with functional consequences are discussed.

The MagneDyn beamline at the FERMI free electron laser.

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 ∼20×20µm2 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.

Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases.

Chemosensory systems are deemed marginal in human pathology. In appraising their role, we aim at suggesting a paradigm shift based on the available clinical and experimental data that will be discussed. Taste and olfaction are polymodal sensory systems, providing inputs to many brain structures that regulate crucial visceral functions, including metabolism but also endocrine, cardiovascular, respiratory, and immune systems. Moreover, other visceral chemosensory systems monitor different essential chemical parameters of "milieu intérieur," transmitting their data to the brain areas receiving taste and olfactory inputs; hence, they participate in regulating the same vital functions. These chemosensory cells share many molecular features with olfactory or taste receptor cells, thus they may be affected by the same pathological events. In most COVID-19 patients, taste and olfaction are disturbed. This may represent only a small portion of a broadly diffuse chemosensory incapacitation. Indeed, many COVID-19 peculiar symptoms may be explained by the impairment of visceral chemosensory systems, for example, silent hypoxia, diarrhea, and the "cytokine storm". Dysregulation of chemosensory systems may underlie the much higher mortality rate of COVID-19 Acute Respiratory Distress Syndrome (ARDS) compared to ARDSs of different origins. In chronic non-infectious diseases like hypertension, diabetes, or cancer, the impairment of taste and/or olfaction has been consistently reported. This may signal diffuse chemosensory failure, possibly worsening the prognosis of these patients. Incapacitation of one or few chemosensory systems has negligible effects on survival under ordinary life conditions but, under stress, like metabolic imbalance or COVID-19 pneumonia, the impairment of multiple chemosensory systems may lead to dire consequences during the course of the disease.

Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?

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.

A novel free-electron laser single-pulse Wollaston polarimeter for magneto-dynamical studies.

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 M2,3 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.

Nanoscale Transient Magnetization Gratings Created and Probed by Femtosecond Extreme Ultraviolet Pulses.

We utilize coherent femtosecond extreme ultraviolet (EUV) pulses 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 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 a rise time close to the FEL pulse duration and ∼0.5 ps decay time indicative of electron-phonon relaxation. When the sample is magnetized to saturation in an external field, we observe a magnetization grating, which appears on a subpicosecond 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 multiple avenues for studying dynamics of ultrafast magnetic phenomena on nanometer length scales.

Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain.

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.

A new sensitive and subunit-selective molecular tool for investigating protein kinase A in the brain.

Despite cellular complexity, a limited number of small molecules act as intracellular second messengers. Protein kinase A (PKA) is the main transducer of the information carried by cyclic adenosine monophosphate (cAMP). Recently, cellular imaging has achieved major technical advancements, although the search for more specific and sensitive low-molecular-weight probes to explore subcellular events involving second messengers is still in progress. The convergent synthesis of a novel, fluorescent small molecule comprising the cAMP structure and a rhodamine-based fluorescent residue, connected through a flexible linker, is described here. The interaction motif of this compound with PKA was investigated in silico using a blind docking approach, comparing its theoretical binding energy with the one calculated for cAMP. Moreover, the predicted pharmacokinetic properties were also computed and discussed. The new probe was tested on three areas of the mouse central nervous system (parietal cerebral cortex, hippocampus, and cerebellar cortex) with different fixation methods demonstrating remarkable selectivity towards the PKA RIα subunit. The probe showed overall better performances when compared to other commercially available fluorescent cAMP analogues, acting at lower concentrations, and providing stable labeling.

Protein Kinase A Distribution in Meningioma.

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.

Enhancements in phytoremediation technology: Environmental assessment including different options of biomass disposal and comparison with a consolidated approach.

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.

Ultralow-fluence single-shot optical crystalline-to-amorphous phase transition in Ge-Sb-Te nanoparticles.

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.

Ultrafast magnetodynamics with free-electron lasers.

The study of ultrafast magnetodynamics has entered a new era thanks to the groundbreaking technological advances in free-electron laser (FEL) light sources. The advent of these light sources has made possible unprecedented experimental schemes for time-resolved x-ray magneto-optic spectroscopies, which are now paving the road for exploring the ultimate limits of out-of-equilibrium magnetic phenomena. In particular, these studies will provide insights into elementary mechanisms governing spin and orbital dynamics, therefore contributing to the development of ultrafast devices for relevant magnetic technologies. This topical review focuses on recent advancement in the study of non-equilibrium magnetic phenomena from the perspective of time-resolved extreme ultra violet (EUV) and soft x-ray spectroscopies at FELs with highlights of some important experimental results.

Giant magneto-electric coupling in 100 nm thick Co capped by ZnO nanorods.

Here we report a giant, completely reversible magneto-electric coupling of 100 nm polycrystalline Co layer in contact with ZnO nanorods. When the sample is under an applied bias of ±2 V, the Co magnetic coercivity is reduced by a factor 5 from the un-poled case, with additionally a reduction of total magnetic moment in Co. Taking into account the chemical properties of ZnO nanorods measured by X-rays absorption near edge spectroscopy under bias, we conclude that these macroscopic effects on the magnetic response of the Co layer are due to the microstructure and the strong strain-driven magneto-electric coupling induced by the ZnO nanorods, whose nanostructuration maximizes the piezoelectric response under bias.

Protein Kinase A Distribution Differentiates Human Glioblastoma from Brain Tissue.

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.

Drug-induced Parkinson's disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb.

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.

Revisiting the Local Structure in Ge-Sb-Te based Chalcogenide Superlattices.

The technological success of phase-change materials in the field of data storage and functional systems stems from their distinctive electronic and structural peculiarities on the nanoscale. Recently, superlattice structures have been demonstrated to dramatically improve the optical and electrical performances of these chalcogenide based phase-change materials. In this perspective, unravelling the atomistic structure that originates the improvements in switching time and switching energy is paramount in order to design nanoscale structures with even enhanced functional properties. This study reveals a high- resolution atomistic insight of the [GeTe/Sb2Te3] interfacial structure by means of Extended X-Ray Absorption Fine Structure spectroscopy and Transmission Electron Microscopy. Based on our results we propose a consistent novel structure for this kind of chalcogenide superlattices.

MagneDyn: the beamline for magneto dynamics studies at FERMI.

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.

Molecular targets in glioblastoma.

Glioblastoma is the most lethal brain tumor. The poor prognosis results from lack of defined tumor margins, critical location of the tumor mass and presence of chemo- and radio-resistant tumor stem cells. The current treatment for glioblastoma consists of neurosurgery, followed by radiotherapy and temozolomide chemotherapy. A better understanding of the role of molecular and genetic heterogeneity in glioblastoma pathogenesis allowed the design of novel targeted therapies. New targets include different key-role signaling molecules and specifically altered pathways. The new approaches include interference through small molecules or monoclonal antibodies and RNA-based strategies mediated by siRNA, antisense oligonucleotides and ribozymes. Most of these treatments are still being tested yet they stay as solid promises for a clinically relevant success.

Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

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.