Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities.

Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the molecular motor protein complex dynein. Reduced levels of DCTN1 mRNA and protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this protein in disease pathogenesis is still unknown. We characterized a Dynactin1a depletion model in the zebrafish embryo and combined in vivo molecular analysis of primary motor neuron development with live in vivo axonal transport assays in single cells to investigate ALS-related defects. To probe neuromuscular junction (NMJ) function and organization we performed paired motor neuron-muscle electrophysiological recordings and GCaMP calcium imaging in live, intact larvae, and the synapse structure was investigated by electron microscopy. Here we show that Dynactin1a depletion is sufficient to induce defects in the development of spinal cord motor neurons and in the function of the NMJ. We observe synapse instability, impaired growth of primary motor neurons, and higher failure rates of action potentials at the NMJ. In addition, the embryos display locomotion defects consistent with NMJ dysfunction. Rescue of the observed phenotype by overexpression of wild-type human DCTN1-GFP indicates a cell-autonomous mechanism. Synaptic accumulation of DCTN1-GFP, as well as ultrastructural analysis of NMJ synapses exhibiting wider synaptic clefts, support a local role for Dynactin1a in synaptic function. Furthermore, live in vivo analysis of axonal transport and cytoskeleton dynamics in primary motor neurons show that the phenotype reported here is independent of modulation of these processes. Our study reveals a novel role for Dynactin1 in ALS pathogenesis, where it acts cell-autonomously to promote motor neuron synapse stability independently of dynein-mediated axonal transport

A Comparison of Airborne In Situ Cloud Microphysical Measurement with Ground-Based C-Band Radar Observations in Deep Stratiform Regions of African Squall Lines

This study addresses clouds with significant ice water content (IWC) in the stratiform regions downwind of the convective cores of African squall lines in the framework of the French–Indian satellite Megha-Tropiques project, observed in August 2010 next to Niamey (13.5°N, 2°E) in the southwestern part of Niger. The objectives included comparing the IWC–Z reflectivity relationship for precipitation radars in deep stratiform anvils, collocating reflectivity observed from ground radar with the calculated reflectivity from in situ microphysics for all aircraft locations inside the radar range, and interpreting the role of large ice crystals in the reflectivity of centimeter radars through analysis of their microphysical characteristics as ice crystals larger than 5 mm frequently occurred. It was found that, in the range of 20–30 dBZ, IWC and C-band reflectivity are not really correlated. Cloud regions with high IWC caused by important crystal number concentrations can lead to the same reflectivity factor as cloud regions with low IWC formed by a few millimeter-sized ice crystals

Study of the diffraction pattern of cloud particles and the respective responses of optical array probes

Optical array probes (OAPs) are classical instrumental means to derive shape, size, and number concentration of cloud and precipitation particles from 2-D images. However, recorded 2-D images are subject to distortion based on the diffraction of light when particles are imaged out of the object plane of the optical device. This phenomenon highly affects retrievals of microphysical properties of cloud particles. Previous studies of this effect mainly focused on spherical droplets. In this study we propose a theoretical method to compute diffraction patterns of all kinds of cloud particle shapes in order to simulate the response recorded by an OAP. To check the validity of this method, a series of experimental measurements have been performed with a 2D-S probe mounted on a test bench. Measurements are performed using spinning glass discs with imprinted non-circular opaque particle shapes.</p

Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation.

Dysregulated transforming growth factor TGF-β signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-β-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-β signaling, ipo8-/- zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8-/- zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-β signaling during development and reinforces the existing link between TGF-β signaling and connective tissue defects

INFLUENCE DE LA RUGOSITE DU GIVRE SUR SA CROISSANCE PAR LA CAPTATION DES GOUTTES D'EAU SURFONDUE : APPLICATION AU GIVRAGE DES CABLES ELECTRIQUES

L'effet de la rugosité des dépôts de givre sur la captation des gouttes est étudié. Une paramétrisation du coefficient de captation est proposée. Pour utiliser cette paramétrisation, l'évolution de la rugosité relative a été simulée. La formulation du coefficient de captation a été utilisée dans le cas du givrage des câbles électriques.The collection efficiency of droplets is studied as a function of the ice deposit roughness. A parameterization of this efficiency is suggested. In order to apply this parameterization, the evolution of the relative roughness is simulated. The equation is confirmed in the case of ice accretion on transmission lines

MODELISATION DE LA CROISSANCE DU GIVRE DE FAIBLE DENSITE

Un modèle balistique d'empilage de particules sphériques est utilisé pour simuler la croissance du givre par captation de gouttelettes d'eau surfondue. Les mécanismes intervenant dans la formation du givre en forme de plumes et de la neige roulée conique sont étudiés à l'aide de ce modèle. Le givre en forme de plumes a pu être reproduit en supposant que la captation des gouttes se produit sur les irrégularités de surface. La forme des particules de neige roulée a été étudiée en fonction de l'amplitude des oscillations de la particule au cours de sa chute.A ballistic deposition model with aggregation of spherical particles is used to simulate the soft rime growth by collection of supercooled droplets. With this model we have studied the main accretion mechanisms of "feather" rime and conical graupels. The shape of feathers is reproduced assuming that the collection of droplets occurs on the surface roughness. We have also studied the shape of graupels as a function of the graupel oscillations during their fall down

The metallic state of the organic conductor TMTSF-DMTCNQ at low temperature under pressure

We present experimental evidences for a high conductivity state (σ > 105 (Ω.cm)-1) stabilized by high pressure (P > 10 kbar) at low temperature in the quasi one-dimensional organic conductor TMTSF-DMTCNQ. The magnetoresistance investigations suggest among several possible interpretations of the metallic state, the existence of a quasi 1-D BCS-like superconductivity remaining up to ~ 30 K.Nous présentons la mise en évidence d'un état de conductivité élevée (σ > 105 (Ω.cm)-1) à basse température, stabilisé sous haute pression (P > 10 kbar) dans le conducteur organique quasi unidimensionnel TMTSF-DMTCNQ. L'étude de la magnétorésistance suggère que parmi plusieurs interprétations de l'état métallique l'hypothèse d'une supraconductibilité quasi unidimensionnelle de type BCS persistant jusqu'à 30 K environ pourrait être retenue