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The result of work of an interdisciplinary group of researchers of the French Workshop Zone Network (Réseau des Zones Ateliers, CNRS), this article focuses on the implementation of restoration projects aiming to restore ecological connectivity of rivers. These projects are at the center of an important controversy taking place in the French public space since several years. Thus certain actors put into question the pertinence of the public policy aiming at removal of hydraulic structures contributing to connectivity interruption. Here, we first synthesize the currently known effects of the connectivity interruption in its longitudinal, lateral and vertical dimensions on a row of biophysical and socio-economic processes. Spotlighting the complexity of processes linked to river connectivity, the variablity of territorial contexts and the associated uncertainties, our analysis reveals the necessity of inscribing restoration projects within a larger project of water ressource management conducted at the scale of a territory and rooted in a participatory decision process. The decision to restore or not restore connectivity cannot be based exclusively on science and technical expertise. With this in mind, we propose an action strategy to address challenges related to river connectivity restoration. We identify ten critical points to take into account for implementing restoration projects that would be both supported by different stakeholders, and efficient in regard to their defined objectives.

Abstract A minequake of magnitude ML 4.1 occurred on 18 May 2020 early in the morning at the LKAB underground iron ore mine in Kiruna, Sweden. This is the largest mining‐induced earthquake in Scandinavia. It generated acoustic signals observed at three infrasound arrays at 9.3 (KRIS, Sweden), 155 (IS37, Norway), and 286 km (ARCI, Norway) distance. We perform full‐waveform focal mechanism inversion based on regional seismic data and local infrasound data. These independently highlight that this event was dominated by a shallow‐depth collapse in agreement with in‐mine seismic station data. However, regional infrasound data cannot inform the inversion process without an accurate model of atmospheric winds and temperatures. Yet, our numerical simulations demonstrate a potential of using local and regional infrasound data to constrain an event's focal mechanism and depth.

Abstract Neurological side effects arising from chemotherapy, such as severe pain and cognitive impairment, are a major concern for cancer patients. These major side effects can lead to reduction or termination of chemotherapy medication in patients, negatively impacting their prognoses. With cancer survival rates improving dramatically, addressing side effects of cancer treatment has become pressing. Here, we use iPSC-derived human neurons to investigate the molecular mechanisms that lead to neurotoxicity induced by vincristine, a common chemotherapeutic used to treat solid tumors. Our results uncover a novel mechanism by which vincristine causes a local increase in mitochondrial proteins that produce reactive oxygen species (ROS) in the axon. Vincristine triggers a cascade of axon pathology, causing mitochondrial dysfunction that leads to elevated axonal ROS levels and SARM1-dependent axon degeneration. Importantly, we show that the neurotoxic effect of increased axonal ROS can be mitigated by the small molecule mitochondrial division inhibitor 1 (mdivi-1) and antioxidants glutathione and mitoquinone, identifying a novel therapeutic avenue to treat the neurological effects of chemotherapy.

IMPORTANCE: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders. OBSERVATIONS: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings. CONCLUSIONS AND RELEVANCE: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

The International Monitoring System (IMS) was established in the late 1990s for verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT). Upon completion, 60 infrasound stations distributed over the globe will monitor the Earth's atmosphere for low-frequency pressure waves. In this study, we present advanced infrasound data products of the 53 currently certified IMS infrasound stations for atmospheric studies and civilian applications. For this purpose, 18 years of raw IMS infrasound waveform data (2003–2020) were reprocessed using the Progressive Multi-Channel Correlation (PMCC) method. A one-third octave frequency band configuration between 0.01 and 4 Hz was chosen to run this array-processing algorithm which detects coherent infrasound waves within the background noise. From the comprehensive detection lists, four products were derived for each of the certified 53 IMS infrasound stations. The four products cover different frequency ranges and are provided at the following different temporal resolutions: a very low-frequency set (0.02–0.07 Hz, 30 min; https://doi.org/10.25928/bgrseis_bblf-ifsd, Hupe et al., 2021a), two so-called microbarom frequency sets – covering both the lower (0.15–0.35 Hz, 15 min; https://doi.org/10.25928/bgrseis_mblf-ifsd, Hupe et al., 2021b) and a higher (0.45–0.65 Hz, 15 min; https://doi.org/10.25928/bgrseis_mbhf-ifsd, Hupe et al., 2021c) part – named after the dominant ambient noise of interacting ocean waves that are quasi-continuously detected at IMS stations, and observations with center frequencies of 1 to 3 Hz (5 min), called the high-frequency product (https://doi.org/10.25928/bgrseis_bbhf-ifsd, Hupe et al., 2021d). Within these frequency ranges and time windows, the dominant repetitive signal directions are summarized. Along with several detection parameters, calculated quantities for assessing the relative quality of the products are provided. The validity of the data products is demonstrated through example case studies of recent events that produced infrasound detected at IMS infrasound stations and through a global assessment and summary of the products. The four infrasound data products cover globally repeating infrasound sources such as ocean ambient noise or persistently active volcanoes, which have previously been suggested as sources for probing the winds in the middle atmosphere. Therefore, our infrasound data products open up the IMS observations also to user groups who do not have unconstrained access to IMS data or who are unfamiliar with infrasound data processing using the PMCC method. These types of data products could potentially serve as a basis for volcanic eruption early warning systems in the future.

Abstract: The two major explosive phases of the 22–23 April 2015 eruption of Calbuco volcano, Chile, produced powerful seismicity and infrasound. The eruption was recorded on seismo‐acoustic stations out to 1,540 km and on five stations (IS02, IS08, IS09, IS27, and IS49) of the International Monitoring System (IMS) infrasound network at distances from 1,525 to 5,122 km. The remote IMS infrasound stations provide an accurate explosion chronology consistent with the regional and local seismo‐acoustic data and with previous studies of lightning and plume observations. We use the IMS network to detect and locate the eruption signals using a brute‐force, grid‐search, cross‐bearings approach. After incorporating azimuth deviation corrections from stratospheric crosswinds using 3‐D ray tracing, the estimated source location is 172 km from true. This case study highlights the significant capability of the IMS infrasound network to provide automated detection, characterization, and timing estimates of global explosive volcanic activity. Augmenting the IMS with regional seismo‐acoustic networks will dramatically enhance volcanic signal detection, reduce latency, and improve discrimination capability.

Single-cell profiling has led to the identification of diverse cell types. Here, the authors generate a harmonized cell atlas of the mouse post-natal spinal cord. They also provide spatial analysis of the distribution of the identified cell types and an open-source cell type classifier.

The concept of Epilepsy Treatment Gap (ETG) refers to the proportion of people with epilepsy who are not being appropriately treated. The ETG in the USA approaches 10%, with historically underserved populations and rural populations disproportionately affected. The ETG in Low-and Middle-Income Countries (LMIC) is reported to be 5–10 times higher than in high-income countries. The growing availability of reliable internet access offers a unique opportunity to provide better care to children and adults with epilepsy. In this paper we explore various telehealth (TH) initiatives that have leveraged the availability of easy and free access to an internet connection in reducing the ETG in underserved regions of the world. We describe several interventions targeted to reach patients and providers in rural areas of the United States and in LMIC. First, we examine initiatives that were developed to improve patient access to coordinated care and education regarding epilepsy and seizures. Next, we describe an intervention designed to improve knowledge of epilepsy diagnosis and treatment for providers in LMIC. We conclude with a brief overview of the use of virtual tools in diminishing the ETG.

Abstract Stromboli Volcano is well known for its persistent explosive activity. On July 3rd and August 28th 2019, two paroxysmal explosions occurred, generating an eruptive column that quickly rose up to 5 km above sea level. Both events were detected by advanced local monitoring networks operated by Istituto Nazionale di Geofisica e Vulcanologia (INGV) and Laboratorio di Geofisica Sperimentale of the University of Firenze (LGS-UNIFI). Signals were also recorded by the Italian national seismic network at a range of hundreds of kilometres and by infrasonic arrays up to distances of 3700 km. Using state-of-the-art propagation modeling, we identify the various seismic and infrasound phases that are used for precise timing of the eruptions. We highlight the advantage of dense regional seismo-acoustic networks to enhance volcanic signal detection in poorly monitored regions, to provide timely warning of eruptions and reliable source amplitude estimate to Volcanic Ash Advisory Centres (VAAC).

This study investigates the use of a vespagram-based approach as a tool for multi-directional comparison between simulated microbarom soundscapes and infrasound data recorded at ground-based array stations. Data recorded at the IS37 station in northern Norway during 2014–2019 have been processed to generate vespagrams (velocity spectral analysis) for five frequency bands between 0.1 and 0.6 Hz. The back azimuth resolution between the vespagram and the microbarom model is harmonized by smoothing the modeled soundscapes along the back azimuth axis with a kernel corresponding to the frequency-dependent array resolution. An estimate of similarity between the output of the microbarom radiation and propagation model and infrasound observations is then generated based on the image-processing approach of the mean square difference. The analysis reveals that vespagrams can monitor seasonal variations in the microbarom azimuthal distribution, amplitude, and frequency, as well as changes during sudden stratospheric warming events. The vespagram-based approach is computationally inexpensive, can uncover microbarom source variability, and has the potential for near-real-time stratospheric diagnostics and atmospheric model assessment.

Hallmarks of chronic neurodegenerative disease include progressive synaptic loss and neuronal cell death, yet the cellular pathways that underlie these processes remain largely undefined. We provide evidence that dual leucine zipper kinase (DLK) is an essential regulator of the progressive neurodegeneration that occurs in amyotrophic lateral sclerosis and Alzheimer's disease. We demonstrate that DLK/c-Jun N-terminal kinase signaling was increased in mouse models and human patients with these disorders and that genetic deletion of DLK protected against axon degeneration, neuronal loss, and functional decline in vivo. Furthermore, pharmacological inhibition of DLK activity was sufficient to attenuate the neuronal stress response and to provide functional benefit even in the presence of ongoing disease. These findings demonstrate that pathological activation of DLK is a conserved mechanism that regulates neurodegeneration and suggest that DLK inhibition may be a potential approach to treat multiple neurodegenerative diseases.

Abstract The International Monitoring System (IMS) infrasound network has been established to detect nuclear explosions and other signals of interest embedded in the station‐specific ambient noise. The ambient noise can be separated into coherent infrasound (e.g., real infrasonic signals) and incoherent noise (such as that caused by wind turbulence). Previous work statistically and systematically characterized coherent infrasound recorded by the IMS. This paper expands on this analysis of the coherent ambient infrasound by including updated IMS data sets with data up to the end of 2020 for all 53 of the currently certified IMS infrasound stations using an updated configuration of the Progressive Multi‐Channel Correlation (PMCC) method. This paper presents monthly station‐dependent reference curves for the back azimuth, trace velocity, and root mean squared amplitude, which provides a means to determine the deviation from the nominal monthly behavior. In addition, a daily Ambient Noise Stationarity (ANS) factor based on deviations from the reference curves is determined for a quick reference to the coherent signal quality compared to the nominal situations. Newly presented histograms provide a higher resolution spectrum, including the observations of the microbarom peak, as well as additional peaks reflecting station‐dependent environmental noise. The aim of these reference curves is to identify periods of suboptimal operation (e.g., nonoperational sensor) or instances of strong abnormal signals of interest.

The full heterogeneity and different functional roles of cholinergic neurons in the adult spinal cord remain to be defined. Here the authors develop a targeted single nuclear RNA sequencing approach and use it to identify an array of cholinergic interneurons, as well as visceral and skeletal motor neurons.

Abstract Objective Patients with drug‐resistant epilepsy (DRE) pose considerable management challenges for patients, their families, and providers. Both the vagus nerve stimulator (VNS) and the ketogenic diet (KD) have been shown to be safe and effective in treating DRE. Nevertheless, information is lacking regarding treatment with combination of both modalities. This study reports the efficacy and tolerability of combining VNS and KD in a pediatric cohort with intractable epilepsy. Methods This is a retrospective review of 33 patients (0‐17 years) with DRE treated with VNS and KD at a single pediatric level IV epilepsy center. We compared seizure reduction rates for each patient at baseline and at every clinic visit for 24 months after adding the second nonpharmacological therapy. The frequency of adverse events on the combined therapy was collected to assess safety and tolerability. Results There were a total of 170 visits for all patients while on the combined therapy. At 88% (95% CI: 83%‐93%) of the visits, patients reported some reduction in seizure frequency. The proportion of patients reporting a greater than 50% seizure reduction over all visits was 62% (95% CI: 55%‐69%). The proportion of a patient's visits with at least a greater than 50% reduction in seizure frequency had a median of 71% (IQR 33%‐100%). Continued improvement was seen over time of combined treatment; for every one‐unit time unit change (one month), there was a 6% increase in the odds of having a reduction in seizure frequency of >50% (OR = 1.06, 95% CI: 1.01‐1.11). Significance This study shows that combining the VNS and KD in patients with drug‐resistant epilepsy is well tolerated and reduces seizure frequency more than either one modality used alone and that the benefits in terms of seizure reduction continue to increase with the length of treatment.

Infrasound covers frequencies of around 10−3 Hz to approximately 20 Hz and can propagate in atmospheric waveguides over long distances as a result of low absorption, depending on the state of the atmosphere. Therefore, infrasound is utilized to detect atmospheric explosions. Following the opening of the Comprehensive Nuclear-Test-Ban Treaty for signature in 1996, the International Monitoring System (IMS) was designed to detect explosions with a minimum yield of one kiloton of TNT equivalent worldwide. Currently 51 out of 60 IMS infrasound stations are recording pressure fluctuations of the order of 10−3 Pa to 10 Pa. In this study, this unique network is used to characterize infrasound signals of so-called Mountain-Associated Waves (MAWs) on a global scale. MAW frequencies range from 0.01 Hz to 0.1 Hz. Previous observations were constrained to regional networks in America and date back to the 1960s and 1970s. Since then, studies on MAWs have been rare, and the exact source generation mechanism has been poorly investigated. Here, up to 16 years of IMS infrasound data enable the determination of global and seasonal MAW source regions. A cross-bearing method is applied which combines the dominant back-azimuth directions of different stations. For better understanding the MAW generation conditions, the MAW occurrence is compared to tropospheric winds at the determined hotspots. Furthermore, ray-tracing simulations reflect middle atmosphere dynamics for describing monthly propagation characteristics. Both the geographic source regions and the meteorological conditions agree with those of orographic gravity waves (OGWs). A comparison with GW hotspots, derived from satellite data, suggests that MAW source regions match those of OGWs. Discrepancies in the respective source regions result from a stratospheric wind minimum that prevents an upward propagation of OGWs at some hotspots of MAWs. The process of breaking GWs is discussed in terms of the MAW generation.

The dynamic vertical coupling in the middle and lower thermosphere (MLT) is documented over the Maïdo observatory at La Réunion island (21°S, 55°E). The investigation uses data obtained in the framework of the Atmospheric dynamics Research InfraStructure in Europe (ARISE) project. In particular, Rayleigh lidar and nightglow measurements combined with other observations and modeling provide information on a mesospheric inversion layer (MIL) and the related gravity waves (GWs) on 9 and 10 October 2017. A Rossby wave breaking (RWB) produced instabilities in the sheared background wind and a strong tropospheric activity of GWs on 9–11 October above La Réunion. The MIL was observed on the night of 9 October when a large amount of tropospheric GWs propagated upward into the middle atmosphere and disappeared on 11 October when the stratospheric zonal wind filtering became a significant blocking. Among other results, dominant mesospheric GW modes with vertical wavelengths of about 4–6 km and 10–13 km can be traced down to the troposphere and up to the mesopause. Dominant GWs with a wavelength of ~2–3 km and 6 km also propagated upward and eastward from the tropospheric source into the stratosphere on 9–11 October. Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) temperature and OH profiles indicate that GW activity in the middle atmosphere affects the upper atmosphere with waves breaking at heights below the MIL and in the mesopause. Several techniques are illustrated on nightglow images to access GW activity and spectral characteristics at the mesopause for high and low frequency GWs on the nights of 9–10 October. In conclusion, intense tropospheric activity of GWs induced by RWB events can be linked with MILs at the subtropical barrier in the South-West Indian Ocean during austral winter.

To improve the confidence and quality of measurements produced by regional and international infrasound monitoring networks, this work investigates a methodology for propagating uncertainty associated with on-site measurement systems. We focus on the propagation of sensor calibration uncertainties. The proposed approach is applied to synthetic infrasound signals with known back azimuth and trace velocity, recorded at the array elements. Relevant input uncertainties are investigated for propagation targeting the incoming signals (noise), instrumentation (microbarometers, calibration system, wind noise reduction system), and the time-delay-of-arrival (TDOA) model (frequency band). Uncertainty propagation is performed using the Monte Carlo method to obtain the corresponding uncertainties of the relevant output quantities of interest, namely back azimuth and trace velocity. The results indicate that, at high frequencies, large sensor uncertainties are acceptable. However, at low frequencies (∘ sensor phase uncertainty can lead to errors in the back azimuth of up to 5∘ and errors in the trace velocity of 20 m/s.

A minequake of magnitude ML 4.1 occurred on 18 May 2020 early in the morning at the LKAB underground iron ore mine in Kiruna, Sweden. This is the largest mining‐induced earthquake in Scandinavia. It generated acoustic signals observed at three infrasound arrays at 9.3 (KRIS, Sweden), 155 (IS37, Norway), and 286 km (ARCI, Norway) distance. We perform full‐waveform focal mechanism inversion based on regional seismic data and local infrasound data. These independently highlight that this event was dominated by a shallow‐depth collapse in agreement with in‐mine seismic station data. However, regional infrasound data cannot inform the inversion process without an accurate model of atmospheric winds and temperatures. Yet, our numerical simulations demonstrate a potential of using local and regional infrasound data to constrain an event's focal mechanism and depth. Plain Language Summary: The largest mining‐induced earthquake in Scandinavia (ML 4.1) occurred on 18 May 2020 early in the morning at the LKAB underground iron ore mine in Kiruna, Sweden. The seismic waves coupled to the atmosphere and propagated large distances as sound waves which were observed at three infrasound arrays at 9.3 (KRIS, Sweden), 155 (IS37, Norway), and 286 km (ARCI, Norway) distance. Our seismic and acoustic modeling results highlight a strong collapse event within the northern section of the mine. The modeling of acoustic and seismic waves across the Earth‐atmosphere suggests that sound wave data can help when determining the location and properties of a seismic source. Key Points: Seismic and acoustic records indicate a strong collapse at shallow depth of 1 ± 0.5 km for the 2020 Kiruna minequakeFocal mechanisms and depths of shallow seismic sources can be retrieved from local infrasound recordsInversions using regional infrasound data is possible when accurate weather models are available [ABSTRACT FROM AUTHOR]

In this study, the dense seismo-acoustic network of the Institute of Geophysical Research (IGR), National Nuclear Centre of the Republic of Kazakhstan, is used to characterize the global ocean ambient noise. As the monitoring facilities are collocated, this allows for a joint seismo-acoustic analysis of oceanic ambient noise. Infrasonic and seismic data are processed using a correlation-based method to characterize the temporal variability of microbarom and microseism signals from 2014 to 2017. The measurements are compared with microbarom and microseism source model output that are distributed by the French Research Institute for Exploitation of the Sea (IFREMER). The microbarom attenuation is calculated using a semi-empirical propagation law in a range-independent atmosphere. The attenuation of microseisms is calculated taking into account seismic attenuation and bathymetry effect. Comparisons between the observed and predicted infrasonic and seismic signals confirm a common source mechanism for both microbaroms and microseisms. Multi-year and intra-seasonal parameter variations are analyzed, revealing the strong influence of long-range atmospheric propagation on microbarom predictions. In winter, dominating sources of microbaroms are located in the North Atlantic and in the North Pacific during sudden stratospheric warming events, while signals observed in summer could originate from sources located in the Southern Hemisphere; however, additional analyses are required to consolidate this hypothesis. These results reveal the strengths and weaknesses of seismic and acoustic methods and lead to the conclusion that a fusion of two techniques brought the investigation to a new level of findings. Summarized findings also provide a perspective for a better description of the source (localization, intensity, spectral distribution) and bonding mechanisms of the ocean–atmosphere–land interfaces.

A magnitude 7.5 earthquake occurred on 28 September 2018 at 10:02:43 UTC near the city of Palu on the Indonesian island of Sulawesi. It was a shallow, strike-slip earthquake with a rupture extending to a length of about 150 km and reaching the surface. Moreover, this earthquake was identified as one of very few events having a super-shear rupture speed. Clear and long-lasting infrasound signatures related to this event were observed by four infrasound arrays of the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organization as well as by one national infrasound station in Singapore. Although these infrasound stations SING (Singapore), I39PW (Palau), I07AU (Australia), I40PG (Papua New Guinea) and I30JP (Japan) are located at large distances of between 1800 and 4500 km from the earthquake's epicentral region, the observed infrasound signals associated with this event were intense, including both seismic and acoustic arrivals. A detailed study of the event-related infrasound observations and the potential infrasound generation mechanisms is presented, covering range-dependent infrasound transmission loss and propagation modeling and characterization of the atmospheric background conditions, as well as identification of the regions of seismoacoustic activity by applying a back-projection method from the infrasound receivers to potential source regions. This back projection of infrasonic arrivals allows one to estimate that the main infrasound source region for the Sulawesi earthquake is related to the extended rupture zone and the nearby topography. This estimation and a comparison to other super-shear as well as large regional earthquakes identify no clear connection between the earthquake's super-shear nature and the strong infrasound emission.

The immune mechanisms underlying hypersensitivity to pain after nerve injury are different in male and female mice.

Mediterranean hurricanes, or medicanes, are tropical-like cyclones forming once or twice per year over the waters of the Mediterranean Sea. These mesocyclones pose a serious threat to coastal infrastructure and lives because of their strong winds and intense rainfall. Infrasound technology has already been employed to investigate the acoustic signatures of severe weather events, and this study aims at characterizing, for the first time, the infrasound detections that can be related to medicanes. This work also contributes to infrasound source discrimination efforts in the context of the Comprehensive Nuclear-Test-Ban Treaty. We use data from the infrasound station IS48 of the International Monitoring System in Tunisia to investigate the infrasound signatures of mesocyclones using a multi-channel correlation algorithm. We discuss the detections using meteorological fields to assess the presence of stratospheric waveguides favoring propagation. We corroborate the detections by considering other datasets, such as satellite observations, a surface lightning detection network, and products mapping the simulated intensity of the swell. High- and low-frequency detections are evidenced for three medicanes at distances ranging between 250 and 1100 km from the station. Several cases of non-detection are also discussed. While deep convective systems, and mostly lightning within them, seem to be the main source of detections above 1 Hz, hotspots of swell (microbarom) related to the medicanes are evidenced between 0.1 and 0.5 Hz. In the latter case, simulations of microbarom detections are consistent with the observations. Multi-source situations are highlighted, stressing the need for more resilient detection-estimation algorithms. Cloud-to-ground lightning seems not to explain all high-frequency detections, suggesting that additional sources of electrical or dynamical origin may be at play that are related to deep convective systems.

Transmembrane AMPA receptor regulatory proteins (TARPs) play an essential role in excitatory synaptic transmission throughout the central nervous system (CNS) and exhibit subtype-specific effects on AMPA receptor (AMPAR) trafficking, gating, and pharmacology. The function of TARPs has largely been determined through work on canonical type I TARPs such as stargazin (TARP γ-2), absent in the ataxic stargazer mouse. Little is known about the function of atypical type II TARPs, such as TARP γ-7, which exhibits variable effects on AMPAR function. Because γ-2 and γ-7 are both strongly expressed in multiple cell types in the cerebellum, we examined the relative contribution of γ-2 and γ-7 to both synaptic transmission in the cerebellum and motor behavior by using both the stargazer mouse and a γ-7 knockout (KO) mouse. We found that the loss of γ-7 alone had little effect on climbing fiber (cf) responses in Purkinje neurons (PCs), yet the additional loss of γ-2 all but abolished cf responses. In contrast, γ-7 failed to make a significant contribution to excitatory transmission in stellate cells and granule cells. In addition, we generated a PC-specific deletion of γ-2, with and without γ-7 KO background, to examine the relative contribution of γ-2 and γ-7 to PC-dependent motor behavior. Selective deletion of γ-2 in PCs had little effect on motor behavior, yet the additional loss of γ-7 resulted in a severe disruption in motor behavior. Thus, γ-7 is capable of supporting a component of excitatory transmission in PCs, sufficient to maintain essentially normal motor behavior, in the absence of γ-2.

We identify long transform faults that frame the eastern Mediterranean Sea and that were active during Jurassic and probably the Early Cretaceous, during the opening of the central Atlantic Ocean. We show that the African margin of the eastern Mediterranean Sea is an 1800 km long transform fault that absorbed the Africa/Eurasia Jurassic left-lateral motion during the opening of the central Atlantic. We call this transform fault the Eastern Mediterranean South Transform fault (EMST). We identify two other transform faults that were active simultaneously and framed the eastern Mediterranean Sea during its formation. These are the Apulia Transform fault (AT) and the Eastern Mediterranean North Transform fault (EMNT). The AT, three hundred km north of the EMST, followed the southern boundary of the Apulia block. Still 300 km farther north, the EMNT formed the northern boundary of this eastern Mediterranean shear zone. This last fault has been destroyed over a large portion by the Hellenic subduction. We relate these transform faults to the kinematics of the Jurassic Africa/Eurasia motion. We conclude that the eastern Mediterranean Sea is a long pull-apart created by left-lateral shearing of the Adria block as it was structurally linked to Africa. Key words: eastern Mediterranean Sea, Eastern Mediterranean South Transform fault, Eastern Mediterranean North Transform fault, Apulia Transform fault. Nous faisons etat de longues failles transformantes qui delimitent la mer Mediterranee orientale et qui etaient actives au Jurassique et probablement au debut du Cretace, durant l'ouverture de l'ocean Atlantique central. Nous demontrons que la marge africaine de la Mediterranee orientale est une faille transformante longue de 1 800 km qui a absorbe le deplacement jurassique senestre de l'Afrique/Eurasie durant l'ouverture de l'Atlantique central. Nous designons cette faille transformante la faille transformante sud de la Mediterranee orientale (TSMO). Nous relevons deux autres failles transformantes qui etaient actives en meme temps et delimitaient la Mediterranee orientale durant sa formation. Il s'agit de la faille transformante apulienne (TA) et de la faille transformante nord de la Mediterranee orientale (TNMO). La TA, situee a 300 km au nord de la TSMO, suivait la limite sud du bloc apulien, alors que, a 300 km encore plus au nord, la TNMO formait la limite nord de cette zone de cisaillement de la Mediterranee orientale. La subduction hellenique a en bonne partie detruit cette derniere faille. Nous relions ces failles transformantes a la cinematique des deplacements de l'Afrique et de l'Eurasie au Jurassique. Nous concluons que la mer Mediterranee orientale est un long bassin de fragmentation par etirement cree par le cisaillement senestre du bloc adriatique alors que ce dernier etait lie sur le plan structural a l'Afrique. Mots-cles : mer Mediterranee orientale, faille transformante sud de la Mediterranee orientale, faille transformante nord de la Mediterranee orientale, faille transformante apulienne., Introduction The mode of formation of the eastern Mediterranean Sea and its age have been debated for tens of years and are still subjects of contention. Among those who attributed [...]

We discuss the structure of the present Hellenic subduction zone. We show that the present Hellenic subduction zone was formed at about 15 Ma when it started to consume the Mediterranean lithosphere and to form the large accretionary wedge that covers a large part of the eastern Mediterranean. We establish that there is independent evidence that the very large Hellenic Trough that it created was formed simultaneously. Shortly before, an 8-10 km thick backstop that extends 200 km southward, where it presently abuts the African margin, was put into place. We reconstruct the northern margin of the eastern Mediterranean Sea prior to the Hellenic subduction in a new and independent way. The faults recently identified by Sachpazi et al. (2016a. Geophysical Research Letters, 43: 651-658) and Sachpazi et al. (2016b. Geophysical Research Letters, 43: 9619-9626) within the Hellenic seismic slab are a key element of our reconstruction. This is because the slab, which is part of the Nubia plate, is rigid and the faults within it coincide with the lines of slip congruent with the relative motion of the Aegean block over it. These faults demonstrate that about 400 to 500 kilometers of eastern Mediterranean lithosphere have been subducted with essentially the same southwestward direction of motion during the last 15 Myr. Our reconstruction shows that before the onset of the Hellenic subduction, the northern margin of the eastern Mediterranean Sea coincided with a major Jurassic transform fault that limited the eastern Mediterranean to the north during its formation in the Jurassic and Early Cretaceous as proposed in part 1. We discuss the implications of this reconstruction on the Neogene evolution of the Anatolia-Aegea block and its geodynamics. Key words: Hellenic subduction zone, eastern Mediterranean Sea, kinematics, evolution of Anatolia-Aegea. Resume : Nous nous penchons sur la structure de l'actuelle zone de subduction hellenique. Nous demontrons qu'elle a ete formee il y a environ 15 millions d'annees alors qu'elle commencait a consommer la lithosphere mediterraneenne et a former un enorme prisme d'accretion qui couvre aujourd'hui une bonne partie de la Mediterranee orientale. Nous etablissons que des preuves independantes attestent le fait que la tres grande fosse hellenique qu'elle a creee s'est formee simultanement. Peu avant, une butee de 8-10 km d'epaisseur, s'etalant sur 200 km vers le sud, ou elle donne aujourd'hui contre la marge africaine, avait ete mise en place. Nous presentons une nouvelle reconstitution independante de la marge septentrionale de la mer Mediterranee orientale avant la subduction hellenique. Les failles recemment cernees par Sachpazi et al. (2016a. Geophysical Research Letters, 43: 651-658) et Sachpazi et al. (2016b. Geophysical Research Letters, 43: 9619-9626) dans la plaque sismique hellenique sont des elements cles de cette reconstitution puisque cette plaque, qui fait partie de la plaque nubienne, est rigide et les failles qu'elle renferme coincident avec des lignes de glissement congruentes avec le deplacement relatif du bloc egeen sur elle. Ces failles demontrent que de 400 km a 500 km environ de la lithosphere de la Mediterranee orientale ont ete subductes en suivant essentiellement la meme direction de deplacement vers le sud-ouest au cours des dernieres 15 millions d'annees. Notre reconstitution montre que, avant le debut de la subduction hellenique, la marge nord de la mer Mediterranee orientale coincidait avec une importante faille transformante qui bordait la Mediterranee orientale au nord durant sa formation au Jurassique et au Cretace inferieur, comme cela est propose dans la partie 1. Nous discutons de ce que cette reconstitution signifie en ce qui concerne l'evolution neogene du bloc Anatolie-Egee et sa geodynamique. [Traduit par la Redaction] Mots-cles: zone de subduction hellenique, mer Mediterranee orientale, cinematique, evolution de l'Anatolie-Egee., Introduction In part 1, we identified long transform faults that frame the eastern Mediterranean Sea and proposed that they were created during the Jurassic and probably Early Cretaceous when this [...]