Galanin pathogenic mutations in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatmen

Galanin pathogenic mutations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment

Efficiency of ambient vibration HVSR investigations in soil engineering studies : backfill study in the Algiers (Algeria) harbor container terminal

This paper deals with the contribution of the ambient vibration horizontal-to-vertical spectral ratio (HVSR) method in soil engineering studies, particularly in backfill compactness assessment. The study is based on 60 ambient vibration recordings performed in 2015 at the container terminal of Algiers harbor, subjected a year before to a geotechnical study based on 23 boreholes and 13 cone penetration tests (CPT) for backfill improvement. To highlight the contribution of the HVSR method, the results of the geotechnical and HVSR studies are first analyzed separately and then in combination. The HVSR method provides a compactness zonation map based on peak amplitude variation. Both methods define the same pattern: a southern section where the backfill is more compact, and a northern section where the backfill is less compact. This shows that the HVSR peak amplitudes are sensitive to compactness variations, which may be sufficient for qualitative zonation. In addition, with the combination of the two methods, rough estimations of shear-wave velocity and thickness of the backfill can be retrieved. This study shows that the HVSR method can be a very useful investigative tool in soil engineering studies. When the HVSR method is deployed before any conventional technique, a geotechnical investigation campaign can be significantly optimized. Moreover the combined interpretation brings complementary quantitative soil information

Smooth bumps in H/V curves over a broad area from single-station ambient noise recordings are meaningful and reveal the importance of Q in array processing: The Boumerdes (Algeria) case

International audienceSingle-station H/V curves from ambient noise recordings in Boumerdes (Algeria) show smooth bumps around 1 and 3 Hz. A complementary microtremor study, based on two 34 and 134-meter aperture arrays, evidences that these bumps are indeed real peaks produced by two strong VS contrasts at 37 and 118 meters depth, strongly smoothed by very high S-wave attenuation in the two sedimentary layers. These two H/V bumps, observed over a broad area, are meaningful and reveal the importance of Q in S-wave velocity modeling from microtremor array data processing. It also appears that Tertiary rocks should be, at least in some cases, taken into account, together with the Quaternary sediments, to explain single-station H/V frequency peaks, and therefore that considering only the first 30 m of soil for VS amplification evaluation, as usually recommended, sometimes leads to flaky results by artificially eliminating non-explained low-frequency peaks from the analysis

Examples of geomorphologic and geological hazards in Algeria

We present three geomorphologic and geological phenomena that have occurred in Algeria in recent years: (i) the Bab El Oued mudflow on 11 November 2001, which claimed several hundred lives, (ii) a soil collapse induced by sand liquefaction triggered by the Boumerdes earthquake (M-w = 6.8) on 21 May 2003, and (iii) landslides that are threatening Constantine city, for which a hazard map is presented using a qualitative approach. We briefly describe and analyze these natural disasters, and in the first two cases propose the application of geophysical techniques such as ambient noise recordings and electrical imagery to help evaluate their extent and potential threat. Finally a landslide hazard map of Constantine is proposed

Mediterranean Sea and anthropogenic influences on ambient vibration amplitudes in the low-frequency and high-frequency domains in the Algiers region

Ambient vibrations have been continuously recorded at Dar El Beida, about 20 km from Algiers (Algeria). This data set allows determining that, in the low-frequency domain (<1 Hz), ambient vibration sources are mainly linked to Mediterranean Sea effects, while in the high-frequency domain, they are closely related to anthropogenic activity. Climatic conditions have an influence on the ambient vibration spectral amplitudes in the low-frequency domain, which is not the case in the high-frequency domain. The limit between the low-frequency and high-frequency domain, based on natural versus anthropogenic activity, is not clear cut and lies between 1.25 and 1.50 Hz. Variations of H/V peak amplitudes in the low-frequency domain are clearly linked to the climatic conditions. In the high-frequency domain, H/V peaks are not related to climatic conditions and cannot be clearly related to anthropogenic source changes