Migraine and cluster headache show impaired neurosteroids patterns

Background: Perturbation of neuronal excitability contributes to migraine. Neurosteroids modulate the activity of γ-aminobutyric acid A and N-methyl-d-aspartate receptors, and might be involved in the pathogenesis of migraine. Here, we measured plasma levels of four neurosteroids, i.e., allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate, in patients affected by episodic migraine, chronic migraine, or cluster headache. Methods: Nineteen female patients affected by episodic migraine, 51 female patients affected by chronic migraine, and 18 male patients affected by cluster headache were recruited to the study. Sex- and age-matched healthy control subjects (31 females and 16 males) were also recruited. Patients were clinically characterized by using validated questionnaires. Plasma neurosteroid levels were measured by liquid chromatography-tandem mass spectrometry. Results: We found disease-specific changes in neurosteroid levels in our study groups. For example, allopregnanolone levels were significantly increased in episodic migraine and chronic migraine patients than in control subjects, whereas they were reduced in patients affected by cluster headache. Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were reduced in patients affected by chronic migraine, but did not change in patients affected by cluster headache. Conclusion: We have shown for the first time that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders, raising the interesting possibility that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache. Whether the observed changes in neurosteroids are genetically determined or rather result from exposure to environmental or intrinsic stressors is unknown. This might also be matter for further investigation because stress is a known triggering factor for headache attacks in both migraineurs and cluster headache patients

Order in the Chaos: Spin-up and Spin-down during the 2002 Outburst of SAX J1808.4-3658

We present a timing analysis of the 2002 outburst of the accreting millisecond pulsar SAX J1808.4-3658. A study of the phase delays of the entire pulse profile shows a behavior that is surprising and difficult to interpret: superposed to a general trend, a big jump by about 0.2 in phase is visible, starting at day 14 after the beginning of the outburst. An analysis of the pulse profile indicates the presence of a significant first harmonic. Studying the fundamental and the first harmonic separately, we find that the phase delays of the first harmonic are more regular, with no sign of the jump observed in the fundamental. The fitting of the phase delays of the first harmonic with a model which takes into account the observed exponential decay of the X-ray flux (and therefore of the mass accretion rate onto the neutron star) gives important information on the torque acting on the neutron star during the outburst. We find that the source shows spin-up in the first part of the outburst, while a spin-down dominates at the end. From these results we derive an estimate of the neutron star magnetic field strength.Comment: 6 pages, including 3 figures. ApJ Letters, in pres

Response of the Pacific Sector of the Southern Ocean to wind stress variability from 1995 to 2017

AbstractDrifter, satellite, expendable bathythermograph (XBT), and Argo float data are used to study the response of the Pacific Sector of the Southern Ocean (PSSO) to the wind stress field in the period 1995–2017, in terms of eddy field, water mass transport, and heat fluxes at large and regional scales. Increasing wind stress over the PSSO in those two decades led to a growth of the Eddy Kinetic Energy (EKE) in the region of the Antarctic Circumpolar Current (ACC). Increases of the EKE occur with delays of 1–4 years with respect to peaks in the zonal component of the wind stress. The persistent ACC meander located south of New Zealand (between 150°E and 180°W and 50°S to 66°S) responds to the interannual wind variations earlier than the entire ACC branch in the PSSO. In the same area, an estimate of the ACC transport based on in situ data shows interannual variability but no significant decadal trend over the study period. The effects of the EKE variability on the meridional eddy heat fluxes are significant on interannual scales. The strengthening of the EKE field leads to a local increase in the poleward meridional eddy heat fluxes in the PSSO, especially in the ACC band. The weakening of the EKE field defines an area of equatorward meridional eddy heat fluxes in the middle of the PSSO (south of 40°S, between 130°W and 160°W) and prevalent poleward fluxes in the further western and eastern regions

The X-ray spectrum of the newly discovered accreting millisecond pulsar IGR J17511−3057

We report on a 70 ks XMM-Newton Target of Opportunity (ToO) observation of the newly discovered accreting millisecond pulsar, IGR J17511−3057. Pulsations at 244.833 9512(1) Hz are observed throughout the outburst with an rms-pulsed fraction of 14.4(3) per cent. Pulsations have been used to derive a precise solution for the Porb= 12 487.51(2) s binary system. The measured mass function indicates a main-sequence companion star with a mass between 0.15 and 0.44 M⊙. The XMM-Newton 0.5-11 keV spectrum of IGR J17511−3057 can be modelled by at least three components, which we interpret, from the softest to the hardest, as multi-coloured disc emission, thermal emission from the neutron star surface and thermal Comptonization emission. Spectral fit of the XMM-Newton data and of the Rossi X-ray Timing Explorer (RXTE) data, taken in a simultaneous temporal window, well constrain the Comptonization parameters: the electron temperature, kTe= 51+6−4 keV, is rather high, while the optical depth (τ= 1.34+0.03−0.06) is moderate. The energy dependence of the pulsed fraction supports the interpretation of the cooler thermal component as coming from the accretion disc, and indicates that the Comptonizing plasma surrounds the hot spots on the neutron star surface, which in turn provides the seed photons. Signatures of reflection, such as a broadened iron Kα emission line and a Compton hump at ∼30 keV, are also detected. We derive from the smearing of the reflection component an inner disc radius of ≳40 km for a 1.4 M⊙ neutron star, and an inclination between 38° and 68°. XMM-Newton also observed two type I X-ray bursts, whose fluence and recurrence time suggest that the bursts are ignited in a nearly pure helium environment. No photospheric radius expansion is observed, thus leading to an upper limit on the distance to the source of 10 kpc. A lower limit of 6.5 kpc can be also set if it is assumed that emission during the decaying part of the burst involves the whole neutron star surface. Pulsations are observed during the burst decay with an amplitude similar to the persistent emission. They are also compatible with being phase locked to pre-burst pulsations, suggesting that the location on the neutron star surface where they are formed does not change much during burst

Heterogeneity matters: Different regions of glioblastoma are characterized by distinctive tumor-supporting pathways

The glioblastoma microenvironment plays a substantial role in glioma biology. However, few studies have investigated its spatial heterogeneity. Exploiting 5-ALA Fluorescence Guided Surgery (FGS), we were able to distinguish between the tumor core (ALA+), infiltrating area (ALAPALE) and healthy tissue (ALA-) of the glioblastoma, based on the level of accumulated fluorescence. The aim of this study was to investigate the properties of the microenvironments associated with these regions. For this purpose, we isolated glioma-associated stem cells (GASC), resident in the glioma microenvironment, from ALA+, ALA-PALE and ALA-samples and compared them in terms of growth kinetic, phenotype and for the expression of 84 genes associated with cancer inflammation and immunity. Differentially expressed genes were correlated with transcriptomic datasets from TCGA/GTEX. Our results show that GASC derived from the three distinct regions, despite a similar phenotype, were characterized by different transcriptomic profiles. Moreover, we identified a GASC-based genetic signature predictive of overall survival and disease-free survival. This signature, highly expressed in ALA+ GASC, was also well represented in ALA PALE GASC. 5-ALA FGS allowed to underline the heterogeneity of the glioma microenvironments. Deepening knowledge of these differences can contribute to develop new adjuvant therapies targeting the crosstalk between tumor and its supporting microenvironment

The X-ray spectrum of the newly discovered accreting millisecond pulsar IGR J17511-3057

We report on an XMM-Newton observation of the accreting millisecond pulsar, IGR J17511-3057. Pulsations at 244.8339512(1) Hz are observed with an RMS pulsed fraction of 14.4(3)%. A precise solution for the P_orb=12487.51(2)s binary system is derived. The measured mass function indicates a main sequence companion with a mass between 0.15 and 0.44 Msun. The XMM-Newton spectrum of the source can be modelled by at least three components, multicoloured disc emission, thermal emission from the NS surface and thermal Comptonization emission. Spectral fit of the XMM-Newton data and of the RXTE data, taken in a simultaneous temporal window, constrain the Comptonization parameters: the electron temperature, kT_e=51(+6,-4) keV, is rather high, while the optical depth (tau=1.34(+0.03,-0.06)) is moderate. The energy dependence of the pulsed fraction supports the interpretation of the cooler thermal component as coming from the accretion disc, and indicates that the Comptonizing plasma surrounds the hot spots on the NS surface, which provide the seed photons. Signatures of reflection, such as a broadened iron K-alpha emission line and a Compton hump at 30 keV ca., are also detected. We derive from the smearing of the reflection component an inner disc radius of ~> 40 km for a 1.4 Msun neutron star, and an inclination between 38{\deg} and 68{\deg}. XMM-Newton also observed two type-I X-ray bursts, probably ignited in a nearly pure helium environment. No photospheric radius expansion is observed, thus leading to an upper limit on the distance to the source of 10 kpc. A lower limit of 6.5 kpc can be also set if it is assumed that emission during the decaying part of the burst involves the whole neutron star surface. Pulsations observed during the burst decay are compatible with being phase locked, and have a similar amplitude, than pre-burst pulsations.Comment: 16 pages, 10 figures, 4 tables, accepted for publication in MNRA

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

The Eps8/IRSp53/VASP Network Differentially Controls Actin Capping and Bundling in Filopodia Formation

There is a body of literature that describes the geometry and the physics of filopodia using either stochastic models or partial differential equations and elasticity and coarse-grained theory. Comparatively, there is a paucity of models focusing on the regulation of the network of proteins that control the formation of different actin structures. Using a combination of in-vivo and in-vitro experiments together with a system of ordinary differential equations, we focused on a small number of well-characterized, interacting molecules involved in actin-dependent filopodia formation: the actin remodeler Eps8, whose capping and bundling activities are a function of its ligands, Abi-1 and IRSp53, respectively; VASP and Capping Protein (CP), which exert antagonistic functions in controlling filament elongation. The model emphasizes the essential role of complexes that contain the membrane deforming protein IRSp53, in the process of filopodia initiation. This model accurately accounted for all observations, including a seemingly paradoxical result whereby genetic removal of Eps8 reduced filopodia in HeLa, but increased them in hippocampal neurons, and generated quantitative predictions, which were experimentally verified. The model further permitted us to explain how filopodia are generated in different cellular contexts, depending on the dynamic interaction established by Eps8, IRSp53 and VASP with actin filaments, thus revealing an unexpected plasticity of the signaling network that governs the multifunctional activities of its components in the formation of filopodia

Species Accumulation Curves and Incidence-Based Species Richness Estimators to Appraise the Diversity of Cultivable Yeasts from Beech Forest Soils

Background: Yeast-like fungi inhabit soils throughout all climatic zones in a great abundance. While recent estimations predicted a plethora of prokaryotic taxa in one gram of soil, similar data are lacking for fungi, especially yeasts. Methodology/Principal Findings: We assessed the diversity of soil yeasts in different forests of central Germany using cultivation-based techniques with subsequent identification based on rDNA sequence data. Based on experiments using various pre-cultivation sample treatment and different cultivation media we obtained the highest number of yeasts by analysing mixed soil samples with a single nutrient-rich medium. Additionally, several species richness estimators were applied to incidence-based data of 165 samples. All of them predicted a similar range of yeast diversity, namely 14 to 16 species. Randomized species richness curves reached saturation in all applied estimators, thus indicating that the majority of species is detected after approximately 30 to 50 samples analysed. Conclusions/Significance: In this study we demonstrate that robust species identification as well as mathematical approaches are essential to reliably estimate the sampling effort needed to describe soil yeast communities. This approach has great potential for optimisation of cultivation techniques and allows high throughput analysis in the future