Comparison of Pharmacological Modulation of APP Metabolism in Primary Chicken Telencephalic Neurons and in a Human Neuroglioma Cell Line

Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases and the formation of Aβ peptides are pivotal for Alzheimer's disease. Therefore, a large number of drugs has been developed targeting APP metabolism. However, many pharmacological compounds have been identified in vitro in immortalized APP overexpressing cell lines rather than in primary neurons. Here, we compared the effect of already characterized secretase inhibitors and modulators on Aβ formation in primary chicken telencephalic neurons and in a human neuroglioma cell line (H4) ectopically expressing human APP with the Swedish double mutation. Primary chicken neurons replicated the effects of a β-secretase inhibitor (β-secretase inhibitor IV), two γ-secretase inhibitors (DAPM, DAPT), two non-steroidal-anti-inflammatory drugs (sulindac sulfide, CW), and of the calpain inhibitor calpeptin. With the exception of the two γ-secretase inhibitors, all tested compounds were more efficacious in primary chicken telencephalic neurons than in the immortalized H4 cell line. Moreover, H4 cells failed to reproduce the effect of calpeptin. Hence, primary chicken telencephalic neurons represent a suitable cell culture model for testing drugs interfering with APP processing and are overall more sensitive to pharmacological interference than immortalized H4 cells ectopically expressing mutant human APP

Caspase-8 dependent apoptosis induction in malignant myeloid cells by TLR stimulation in the presence of IFN-alpha

Pro-apoptotic signalling upon toll-like receptor (TLR) stimulation in myeloid cells is normally antagonized by the simultaneous activation of anti-apoptotic pathways. We have previously reported that IFN-alpha can sensitize human monocytes to apoptosis induction by lipopolysaccharide (LPS). Based on these results we investigated whether similarly apoptosis can be cooperatively induced in myeloid tumor cells. When testing established acute myeloid leukemia (AML) cell lines we found the monocytic cell line THP-1 to be sensitive to IFN-alpha plus LPS induced apoptosis, which was partially dependent on caspase-8 and was associated with an enhanced expression of Fas/CD95. We extended our study to 29 short term blast lines from patients with AML and observed additive effects of IFN-alpha and LPS on cell death only with few samples indicating that sensitivity to IFN-alpha plus LPS inducible apoptosis is present in a fraction of AML samples only with no obvious correlation with certain FAB phenotype

Sub-ionospheric VLF/LF waveguide variations related to natural hazards events over Southern Europe

International audienceThis study outlines a range of sub-ionospheric variations measured along the paths between narrowband VLF/LF transmitters and the mid-latitude receiver knot in Graz, Austria. The facility is part of an extensive receiver network with the ability to sample natural hazards prone areas based on various radio link combinations in the earth-ionosphere waveguide. In particular we investigate ionospheric disturbances related to magnitude M > 5.5 earthquakes over Southern Europe and volcanic eruptions of Mount Etna, Italy, in the year 2021. For both groups we consider a lithosphere-atmosphere-ionosphere coupling (LAIC) mechanism by atmospheric waves and show characteristic VLF/LF signal behavior before and after the events. A third domain is sporadic external waveguide modulations due to x-ray solar flares of the current solar cycle 25. Comparisons between VLF/LF electric field fluctuations and x-ray flux measurements from GOES satellite data are presented. In general, the ground-based VLF/LF receiver network demonstrate the potential for applications in continuous natural hazards monitoring over larger spatial areas. The measurements can be augmented with complementary ground- and space-based observation capabilities to provide a more complete picture of the events

Sub-ionospheric VLF/LF waveguide variations related to natural hazards events over Southern Europe

International audienceThis study outlines a range of sub-ionospheric variations measured along the paths between narrowband VLF/LF transmitters and the mid-latitude receiver knot in Graz, Austria. The facility is part of an extensive receiver network with the ability to sample natural hazards prone areas based on various radio link combinations in the earth-ionosphere waveguide. In particular we investigate ionospheric disturbances related to magnitude M > 5.5 earthquakes over Southern Europe and volcanic eruptions of Mount Etna, Italy, in the year 2021. For both groups we consider a lithosphere-atmosphere-ionosphere coupling (LAIC) mechanism by atmospheric waves and show characteristic VLF/LF signal behavior before and after the events. A third domain is sporadic external waveguide modulations due to x-ray solar flares of the current solar cycle 25. Comparisons between VLF/LF electric field fluctuations and x-ray flux measurements from GOES satellite data are presented. In general, the ground-based VLF/LF receiver network demonstrate the potential for applications in continuous natural hazards monitoring over larger spatial areas. The measurements can be augmented with complementary ground- and space-based observation capabilities to provide a more complete picture of the events

Study of VLF phase and amplitude variations before the Turkey Syria Mw 7.8 EQs

International audienceWe investigate the recent earthquakes (EQs) that occurred on 06 February 2023 principally in the central southern part of Turkey and north western of Syria. The tectonic plate movements between Anatolian, Arabian and African plates are well known to be subject to EQs. The coordinate of the epicenter was 37.08°E and 37.17°N with depth in the order of 10 km and a magnitude Mw7.8. Beside aftershocks, a few hours later a strong Mw7.7 earthquake occurred in the same region . We consider in this analysis the Bafa VLF transmitter (TBB) signal emitting at frequency of 26.7 kHz and localized in the Anatolia region (Turkey) at longitude of 27.31°E and latitude of 37.40°N. TBB transmitter signal is daily monitored by the VLF Graz facility (Biagi et al., 2019; Galopeau et al., 2023) with a sufficient signal to noise ratio principally during night observations. We study the variations of the phase and amplitude of TBB signals, as detected by Graz facility (15.43°E, 47.06°N) few weeks before the earthquakes occurrence. It is essential to note that the geographical latitudes of the epicenter and the TBB transmitter are about 37°N, and the distance, in the order of 850 km, is found smaller than the radius of the earthquake preparation zone, as derived from Dobrovolsky et al. (1979), when considering the magnitude of the seismic event, i.e. Mw7.8. We have applied the terminator time (TT) method to make evident the presence of sunrise and sunset time shifts at terminators one week to ten days before EQs. We discuss essentially the anomalies, in the phase and the amplitude of TBB transmitter, which are probably linked to the electron density variations at the formation and the destruction of the ionospheric D-E-layers

EFD experiment onboard CSES satellite: Characterization of hiss and chorus whistler emissions during geomagnetic activity

International audienceWe study the geomagnetic activity effects on whistler emissions recorded by the Electric Field Detector (EFD) experiment onboard the China Seismo-Electromagnetic Satellite (CSES). This mission is devoted to investigate the ionospheric disturbances linked to the seismic activity. The satellite has a circular sun-synchronous orbit with a descending node at 14 LT and an altitude of 507 km [1]. Four probes are used to measure the electric field recorded by EDF instrument covering a frequency range from DC up to 3.5 MHz [2]. We consider in this analysis geomagnetic events which occurred in the year 2018 after the launch of the CSES satellite, i.e. on 02nd February 2018. The Kp-index leads us to estimate the variation of the geomagnetic activity which is found to have sudden enhancements on the following days: 21st April, 05th May, 26th Aug. and 10th Sept. We show in this analysis that the whistler emissions, i.e. hiss and chorus occurring in the frequency bandwidth 1 kHz to 20 kHz, are influenced by the Earth's magnetic activity. Hence whistler spectral shapes are globally found to develop towards higher frequencies. Two aspects are discussed: (a) the way to characterize an ionospheric disturbance index taking into consideration the CSES geographical configuration orbit and (b) the comparison of the electric field power levels as derived from EFD/CSES instrument and from ICE/DEMETER experiment [3]

Ionospheric Layer Variability Prior to Strong Earthquakes During Quiet Geomagnetic Conditions

International audienceWe report on electric field measurements recorded by the Electric Field Detector (EFD) and the Instrument Champ Electrique (ICE) onboard, respectively, CSES and DEMETER satellites. We study the variations of Very Low Frequency (VLF) ground-based transmitter signals detected by both satellites during periods of low solar and geomagnetic activities. We consider the variation of VLF power spectra density in the frequency range between few Hertz to 20 kHz. We emphasize on ionospheric disturbances associated to earthquakes occurrences. Such disturbances are linked to waves generated by coupling of neutral particles and electrons related, through the atmosphere, to lithospheric ground displacements. The main peculiarities of seismic ionospheric anomalies are summarized taken into consideration technical complementary of both satellites

Analysis of VLF/LF transmitter signals during the minimum of solar activity in the year 2018

International audienceWe report on VLF/LF transmitter signals observed in the year 2018 during the minimum of solar activity. Those signals were recorded in Graz (Austria) using INFREP (Biagi et al., Nat. Hazards Earth Syst. Sci., 11, 2011) and UltraMSK (Schwingenschuh et al., Nat. Hazards Earth Syst. Sci., 11, 2011) systems. This leads us to record fourteen transmitter signals in the frequency range between 19 kHz and up to 270 kHz. Six transmitter channels are common to both systems and are localized in Great-Britain (Anthorn, GBZ, 19.58kHz), Italy (Tavolara, ICV, 20.27kHz), Germany (Rhauderfehn, 23.4kHz,) and Island (Keflavik, NRK, 37.5kHz). Others are mainly LF broadcasting transmitters from Romania (Brasov, 153kHz), Luxembourg (Felsberg-Berus, 183kHz), Algeria (Berkaoui, 198kHz), Monte-Carlo (Roumoules, 216kHz) and Tchecki (Lualualei, 270kHz). In the year 2018, the solar activity decreased reaching its minimum in the end of 2019. We emphasize in this work on three aspects: (a) C-flares related to the solar activity, (b) Kp-index linked to the geomagnetic activity, and (c) seismic events in the southern part of Europe, i.e. Greece and Italy.  The dominant patterns observed on almost all transmitters are due to the solar flares. Geomagnetic activity is found to depend on the seasonal effect and mainly observed few weeks before and after the summer solstice in the northern hemisphere.  Few earthquakes occurred in the southern part of Europe, in Greece (6 events) and in Italy (2 events) with a magnitude of 5.5 Mw and depths less than 10 km. We discuss the disturbances of VLF/LF transmitter signals prior to EQs occurrences, and their links to external effects. Our results are compared to recent investigations of Zhang et al. (Radio Sci., 52, 2017) and Rozhnoi et al. (Ann. Geophys., 37, 2019) concerning, respectively, the spatial distribution of VLF transmitter signals recorded by Demeter satellite, and the solar X-flare effects on VLF/LF transmitter signals

Satellite and Ground Based Measured Ionospheric Variations Over Seismic Active Areas

International audienceIn this study we investigate ionospheric disturbances over earthquake prone areas with two methods.The satellite based approach - in our case magnetic field measurements from CSES-01 and Swarm mission - shed light on ionospheric F-region plasma variations at low-earth orbit (LEO) altitudes around 500 km. The complemen-tary second technique is based on variations of the so-called Earth-ionosphere waveguide, the cavity between Earth’s surface and the lower ionospheric D/E (day/night) upper boundary at approx. 70-90 km altitude. Electric field ampli-tude and phase perturbations of paths between several narrowband VLF/LF transmitter and a receiver network are continuously recorded.In both cases the lithosphere-atmosphere-ionosphere coupling (LAIC) is a key area and of vital importance in order to establish the propagation char-acteristics from the seismic zone up to high altitudes. Possible mechanisms are discussed in the literature, e.g. [1], [2]. In this presentation we focus on acous-tic waves and atmospheric gravity waves (AGW) as energy-momentum trans-port channel (and filter) to connect the different regions from bottom to top.We examine events form the United States Geological Survey (USGS) earthquake catalog, assign a spatial box of a few degrees in latitude and lon-gitude around the epicenter, investigate measurements from satellite- and/or VLF/LF paths which crosses the box, and report on differences in variations prior and after the events.These findings could point to regular automated procedures in order to disentangle seismic from nonseismic ionospheric pattern and are equally important for upcoming satellite missions and extended ground based networks