A novel Netrin-1–sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching

Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1–sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion.     

Secondary biochemical and morphological consequences in lysosomal storage diseases

More than 50 hereditary lysosomal storage disorders (LSDs) are currently described. Most of these disorders are due to a deficiency of certain hydrolases/glycosidases and subsequent accumulation of nonhydrolyzable carbohydrate-containing compounds in lysosomes. Such accumulation causing hypertrophy of the lysosomal compartment is a characteristic feature of affected cells in LSDs. The investigation of biochemical and cellular parameters is of particular interest for understanding “life” of lysosomes in the normal state and in LSDs. This review highlights the wide spectrum of biochemical and morphological changes during developing LSDs that are extremely critical for many metabolic processes inside the various cells and tissues of affected persons. The data presented will help establish new complex strategies for metabolic correction of LSDs.     

Biosecurity in the age of Big Data: a conversation with the FBI

New scientific frontiers and emerging technologies within the life sciences pose many global challenges to society. Big Data is a premier example, especially with respect to individual, national, and international security. Here a Special Agent of the Federal Bureau of Investigation discusses the security implications of Big Data and the need for security in the life sciences.     

Finite elements/Taguchi method based procedure for the identification of the geometrical parameters significantly affecting the biomechanical behavior of a lumbar disc

The aim of this work is to show a quick and simple procedure able to identify the geometrical parameters of the intervertebral disc that strongly affect the behavior of the FEM model. First, we allocated a selection criterion for the minimum number of geometrical parameters that describe, with a good degree of approximation, a healthy human vertebra. Next, we carried out a sensitivity analysis using the ‘Taguchi orthogonal array’ to arrive at a quick identification of the parameters that strongly affect the behavior of the Fem model.     

Morphological variation among the inner ears of extinct and extant baleen whales (Cetacea: Mysticeti)

Living mysticetes (baleen whales) and odontocetes (toothed whales) differ significantly in auditory function in that toothed whales are sensitive to high‐frequency and ultrasonic sound vibrations and mysticetes to low‐frequency and infrasonic noises. Our knowledge of the evolution and phylogeny of cetaceans, and mysticetes in particular, is at a point at which we can explore morphological and physiological changes within the baleen whale inner ear. Traditional comparative anatomy and landmark‐based 3D‐geometric morphometric analyses were performed to investigate the anatomical diversity of the inner ears of extinct and extant mysticetes in comparison with other cetaceans. Principal component analyses (PCAs) show that the cochlear morphospace of odontocetes is tangential to that of mysticetes, but odontocetes are completely separated from mysticetes when semicircular canal landmarks are combined with the cochlear data. The cochlea of the archaeocete Zygorhiza kochii and early diverging extinct mysticetes plot within the morphospace of crown mysticetes, suggesting that mysticetes possess ancestral cochlear morphology and physiology. The PCA results indicate variation among mysticete species, although no major patterns are recovered to suggest separate hearing or locomotor regimes. Phylogenetic signal was detected for several clades, including crown Cetacea and crown Mysticeti, with the most clades expressing phylogenetic signal in the semicircular canal dataset. Brownian motion could not be excluded as an explanation for the signal, except for analyses combining cochlea and semicircular canal datasets for Balaenopteridae. J. Morphol. 277:1599–1615, 2016. © 2016 Wiley Periodicals, Inc.