Abnormal Action Potentials Associated with the Shaker Complex Locus of Drosophila

Intracellular recordings of action potentials were made from the cervical giant axon in Shaker (Sh) mutants and normal Drosophila. The mutants showed abnormally long delays in repolarization. The defect is not due to abnormal Ca2+ channels, because it persists in the presence of Co2+, a Ca2+-channel blocker. On the other hand, the K+-channel blocker 4-aminopyridine causes a similar effect in normal animals, suggesting that the Sh mutant may have abnormal K+ conductance. Gene-dosage analysis of Sh shows that the defect is not due to underproduction of an otherwise normal molecule; it may be due to an abnormal molecule produced by the mutated gene. Gel electrophoresis failed to detect an abnormal protein, suggesting that, if Sh codes for a nervous system protein, it is rare. Genetic analysis of the Sh locus indicates three regions. Mutations or chromosome breaks in the two flanking regions cause Sh mutant physiology; the central region shows a "haplolethal effect"--i.e., heterozygous females are lethal

The Ubiquitin Ligase Ariadne-1 Regulates Neurotransmitter Release Via Ubiquitination of NSF

Ariadne-1 (Ari-1) is an E3 ubiquitin-ligase essential for neuronal development, but whose neuronal substrates are yet to be identified. To search for putative Ari-1 substrates, we used an in vivo ubiquitin biotinylation strategy coupled to quantitative proteomics of Drosophila heads. We identified sixteen candidates that met the established criteria: a significant change of at least two-fold increase on ubiquitination, with at least two unique peptides identified. Amongst those candidates, we identified Comatose (Comt), the homologue of the N-ethylmaleimide sensitive factor (NSF), which is involved in neurotransmitter release. Using a pulldown approach that relies on the overexpression and stringent isolation of a GFP-fused construct, we validate Comt/NSF to be an ubiquitination substrate of Ari-1 in fly neurons, resulting in the preferential monoubiquitination of Comt/NSF. We tested the possible functional relevance of this modification using Ari-1 loss of function mutants, which displayed a lower rate of spontaneous neurotransmitter release due to failures at the pre-synaptic side. By contrast, evoked release in Ari-1 mutants was enhanced compared to controls in a Ca2+ dependent manner without modifications in the number of active zones, indicating that the probability of release per synapse is increased in these mutants. This phenotype distinction between spontaneous versus evoked release suggests that NSF activity may discriminate between these two types of vesicle fusion. Our results thus provide a mechanism to regulate NSF activity in the synapse through Ari-1-dependent ubiquitinationThis research was funded by grants BFU2015-65685 and PGC2018-094630-B-100 from the Spanish Ministry of Economy to A. F. and grant SAF2016-76898-P from the Spanish Ministry of Economy cofinanced with FEDER funds to U. M. J. R. was supported with a postdoctoral research fellowship from the University of the Basque Country (UPV/EHU

Mechanisms and mechanics of cell competition in epithelia

When fast-growing cells are confronted with slow-growing cells in a mosaic tissue, the slow-growing cells are often progressively eliminated by apoptosis through a process known as cell competition. The underlying signalling pathways remain unknown, but recent findings have shown that cell crowding within an epithelium leads to the eviction of cells from the epithelial sheet. This suggests that mechanical forces could contribute to cell elimination during cell competition

Origin of a restraining bend in an evolving strike-slip system: The Cenozoic As Pontes basin (NW Spain)

The As Pontes basin (12 km2), NW Iberian Peninsula, is bounded by a double restraining bend of a dextral strike-slip fault, which is related to the western onshore end of the Pyrenean belt. Surface and subsurface data obtained from intensive coal exploration and mining in the basin since the 1960s together with additional structural and stratigraphic sequence analysis allowed us to determine the geometric relationships between tectonic structures and stratigraphic markers. The small size of the basin and the large amount of quality data make the As Pontes basin a unique natural laboratory for improving our understanding of the origin and evolution of restraining bends. The double restraining bend is the end stage of the structural evolution of a compressive underlapping stepover, where the basin was formed. During the first stage (stepover stage), which began ca. 30 Ma ago (latest Rupelian) and lasted 3.4 My, two small isolated basins bounded by thrusts and normal faults were formed. For 1.3 My, the strike-slip faults, which defined the stepover, grew towards each other until joining and forming the double restraining bend, which bounds one large As Pontes basin (transition stage). The history of the basin was controlled by the activity of the double restraining bend for a further 3.4 My (restraining bend stage) and ended in mid-Aquitanian times (ca. 22 Ma)

Without bounds: a scientific canvas of nonlinearity and complex dynamics

Bringing together over fifty contributions on all aspects of nonlinear and complex dynamics, this impressive topical collection is both a scientific and personal tribute, on the occasion of his 70th birthday, by many outstanding colleagues in the broad fields of research pursued by Prof. Manuel G Velarde. The topics selected reflect the research areas covered by the famous Instituto Pluridisciplinar at the Universidad Complutense of Madrid, which he co-founded over two decades ago, and include: fluid physics and related nonlinear phenomena at interfaces and in other geometries, wetting and spreading dynamics, geophysical and astrophysical flows, and novel aspects of electronic transport in anharmonic lattices, as well as topics in neurodynamics and robotics

Without Bounds: A Scientific Canvas of Nonlinearity and Complex Dynamics

XIII, 799 p. 369 illus., 195 illus. in color.onli