Conference Report: Third European Nowcasting Conference

The third European Nowcasting Conference took place in Madrid, Spain, from 24 to 26 April 2019. The conference was structured into four thematic sessions i) observations as basis for nowcasting, ii) seamless prediction, iii) nowcasting techniques, systems and products, iv) verification, societal impacts, applications and user aspects. This report summarizes the scientific contributions presented and the discussed scientific questions

Conference Report: Fourth European Nowcasting Conference

The fourth European Nowcasting Conference took place as an online event from 21 to 24 March 2022, organized by the EUMETNET (European National Meteorological and Hydrological Services Network) Nowcasting Program (E-NWC), and kindly supported by EUMETCAL (EUMETNET Education and Training Collaborative Network of the National Meteorological Services within Europe). More than 110 participants attended the conference. 46 conference’s presentations were given within the 0) opening session, a session on 1) observation as a basis for nowcasting, 2) seamless prediction with a special focus on Artificial Intelligence (AI), 3) nowcasting systems, products, and techniques and 4) verification, impacts on society, as well as applications and aspects of users. This report summarizes the scientific contributions presented and the discussed scientific questions

Cellular dynamics and molecular mechanisms underlying the 3D organization and connectivity of the statoacoustic ganglion

The statoacoustic ganglion (SAG) is a complex 3D structure composed by neurons in charge of transmitting the information from inner ear hair cells to the CNS. During development, SAG copes with otic tissue demands to maintain functionality. However, SAG development in coordination with otic development has not been addressed in detail. We use high resolution confocal imaging of otic neuroblasts (NB), photoconversion, photoablation, transgenic lines, CRISPR/Cas9 and Cas13 to address SAG development at the molecular and cellular levels. We find a population of pioneer SAG neurons specified outside the otic placode, which play an attracting role over delaminating NB affecting its coalescence. NB from the otic epithelium delaminate in an EMT-like manner, and non-collectively and actively migrate depending on RhoGTPases to establish the anterior SAG lobe. Followingly, NB crawl onto pioneer axons to form the posterior SAG lobe. Lack of both pioneer SAG neurons and pioneer axons alters SAG shape. Finally, we uncover the cell adhesion molecule Cntn2 and the chemokine Cxcl14 as two new molecules required for correct pioneer axon targeting to HC and posterior lobe formation. We confirm that HC and neurotrophin signaling is not required for directed axon targeting but stabilization and neuronal survival. In conclusion, SAG development is a complex process in which several mechanisms interplay, prime and scaffold further SAG developmental steps.El gangli estatoacústic (SAG) és una estructura 3D altament complexa formada per neurones que transmeten la informació rebuda de les cèl·lules ciliades (HC) del l’oïda interna al sistema nerviós central (CNS). Durant el desenvolupament, el SAG s’organitza en coordinació amb l’oïda interna per tal de mantenir la seva funcionalitat. No obstant això, es té un lleu coneixement com aquest s’organitza en 3D. Per tal d’analitzar a nivell molecular i cel·lular la formació del SAG, hem emprat microscopia confocal d’alta resolució amb marcatges de neuroblasts (NB) individuals, fotoconversió, fotoablació, CRISPR/Cas9 i Cas13. Aquí descrivim el paper de les neurones pioneres del SAG, que atrauen els NB que delaminen de l’epiteli òtic. Els NB delaminen fora de l’epiteli seguint un procés EMT. Un cop fora, els NB migren activament dependent de RhoGTPases i no col·lectiva per tal de formar un lòbul anterior del SAG. Seguidament, els NB migren sobre axons pioners per tal de formar un lòbul posterior del SAG. La manca de neurones pioneres i d’axons pioners altera la formació del SAG. Finalment, hem descobert que la molècula d’adhesió Cntn2 i la quemoquina Cxcl14 son relevants per a la correcta extensió i orientació dels axons pioners a les HC de l’oïda i la formació del lòbul posterior. Confirmem que les HC i la senyalització per neurotrofines no és requerida per a la correcta formació dels axons pioners, però sí per a estabilitzar-los i promoure la supervivència neuronal. En conclusió, l’estudi proporciona nova informació sobre els comportaments que permeten als NB establir un gangli estructurat i les claus moleculars implicades en la formació de connexions neuronals amb l’oïda interna

Pioneer statoacoustic neurons guide neuroblast behaviour during otic ganglion assembly

Cranial ganglia are aggregates of sensory neurons that mediate distinct types of sensation. The statoacoustic ganglion (SAG) develops into several lobes that are spatially arranged to connect appropriately with hair cells of the inner ear. To investigate the cellular behaviours involved in the 3D organization of the SAG, we use high-resolution confocal imaging of single-cell, labelled zebrafish neuroblasts (NBs), photoconversion, photoablation, and genetic perturbations. We show that otic NBs delaminate out of the otic epithelium in an epithelial-mesenchymal transition-like manner, rearranging apical polarity and primary cilia proteins. We also show that, once delaminated, NBs require RhoGTPases in order to perform active migration. Furthermore, tracking of recently delaminated NBs revealed their directed migration and coalescence around a small population of pioneer SAG neurons. These pioneer SAG neurons, not from otic placode origin, populate the coalescence region before otic neurogenesis begins and their ablation disrupts delaminated NB migratory pathways, consequentially affecting SAG shape. Altogether, this work shows for the first time the role of pioneer SAG neurons in orchestrating SAG development

Polyphosphate degradation by Nudt3-Zn 2+ mediates oxidative stress response

Polyphosphate (polyP) is a polymer of hundreds of phosphate residues present in all organisms. In mammals, polyP is involved in crucial physiological processes, including coagulation, inflammation, and stress response. However, after decades of research, the metabolic enzymes are still unknown. Here, we purify and identify Nudt3, a NUDIX family member, as the enzyme responsible for polyP phosphatase activity in mammalian cells. We show that Nudt3 shifts its substrate specificity depending on the cation; specifically, Nudt3 is active on polyP when Zn2+ is present. Nudt3 has in vivo polyP phosphatase activity in human cells, and importantly, we show that cells with altered polyP levels by modifying Nudt3 protein amount present reduced viability upon oxidative stress and increased DNA damage, suggesting that polyP and Nudt3 play a role in oxidative stress protection. Finally, we show that Nudt3 is involved in the early stages of embryo development in zebrafish.This work was supported by and is part of the I+D+i grant ref. PGC2018-096597-B-I00 (to J.J.) by the Spanish Ministerio de Ciencia e Innovación (MCIN). B.S.-M. was the recipient of a grant from the Agència de Gestió d’Ajuts Universitaris i de Recerca AGAUR ref. 2016FI_B 00025. H.J.J. was supported by the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy (CIBBS, EXC-2189, Project ID 390939984)