Augmentation Is a Potentiation of the Exocytotic Process

AbstractShort-term synaptic enhancement is caused by an increase in the probability with which synaptic terminals release transmitter in response to presynaptic action potentials. Since exocytosed vesicles are drawn from a readily releasable pool of packaged transmitter, enhancement must result either from an increase in the size of the pool or an elevation in the fraction of releasable vesicles that undergoes exocytosis with each action potential. We show here that at least one major component of enhancement, augmentation, is not caused by an increase in the size of the readily releasable pool but is instead associated with an increase in the efficiency with which action potentials induce the exocytosis of readily releasable vesicles

Alternative reproductive tactics, sperm mobility and oxidative stress in Carollia perspicillata (Seba's short-tailed bat)

In social systems with alternative reproductive tactics, sneakers face a higher level of sperm competition than harem males and hence are predicted to allocate more resources to ejaculates. Antioxidants can protect sperm against oxidative stress, and thus, their allocation to the ejaculate may depend on mating tactic. In this study on the frugivorous bat Carollia perspicillata, we assessed, for harem and sneaker males, four spermmobility traits, blood and ejaculatemarkers of the redox balance and the ejaculate to blood ratios of the redox markers. Under higher sperm competition, sneaker males should allocate proportionally more antioxidant resources to the protection of sperm than harem males. In contrast, harem males should favour pre-copulatory functions, which comprise the protection of blood. We found significantly higher sperm velocity and sperm survival in sneakers. There was no correlation between spermmobility and spermenzymatic antioxidant activity or ejaculate levels of lipid peroxidation (oxidative damage). Ejaculate levels of lipid peroxidation and sperm survival showed a significantly positive correlation, which could be attributed to the role of reactive oxygen species for sperm capacitation. Harem and sneaker males showed similar levels of redox balance markers in ejaculate and blood. However, harem males showed a higher ratio of oxidized over reduced glutathione in blood, which may indicate higher cellular stress due to higher metabolism. Overall, our findings suggest that sneakers of C. perspicillata compensate for a higher level of sperm competition by higher sperm mobility. Significance statement In social systems with alternative reproductive tactics, sneakers face higher level of sperm competition than harem males and hence are predicted to allocate more resources to ejaculates. Antioxidants can protect sperm against oxidative stress, and thus, their allocation to the ejaculate may depend on mating tactic. In this study on the frugivorous bat Carollia perspicillata, we found sperm swimming significantly faster and longer in sneaker males compared to harem males. However, traits other than the investigated antioxidant may favour higher sperm mobility. Measured redox pattern in blood of harem males may indicate higher cellular stress due to higher metabolism. Our results provide support to the current sperm competition models at the intraspecific level, which is still debated for internal fertilizers. This study contributes to better understanding the trade-offs and adaptations resulting from alternative reproductive tactics in mammals

A multi-scale modelling framework combining musculoskeletal rigid-body simulations with adaptive finite element analyses, to evaluate the impact of femoral geometry on hip joint contact forces and femoral bone growth

Multi-scale simulations, combining muscle and joint contact force (JCF) from musculoskeletal simulations with adaptive mechanobiological finite element analysis, allow to estimate musculoskeletal loading and predict femoral growth in children. Generic linearly scaled musculoskeletal models are commonly used. This approach, however, neglects subject- and age-specific musculoskeletal geometry, e.g. femoral neck-shaft angle (NSA) and anteversion angle (AVA). This study aimed to evaluate the impact of proximal femoral geometry, i.e. altered NSA and AVA, on hip JCF and femoral growth simulations. Musculoskeletal models with NSA ranging from 120° to 150° and AVA ranging from 20° to 50° were created and used to calculate muscle and hip JCF based on the gait analysis data of a typically developing child. A finite element model of a paediatric femur was created from magnetic resonance images. The finite element model was morphed to the geometries of the different musculoskeletal models and used for mechanobiological finite element analysis to predict femoral growth trends. Our findings showed that hip JCF increase with increasing NSA and AVA. Furthermore, the orientation of the hip JCF followed the orientation of the femoral neck axis. Consequently, the osteogenic index, which is a function of cartilage stresses and defines the growth rate, barely changed with altered NSA and AVA. Nevertheless, growth predictions were sensitive to the femoral geometry due to changes in the predicted growth directions. Altered NSA had a bigger impact on the growth results than altered AVA. Growth simulations based on mechanobiological principles were in agreement with reported changes in paediatric populations

Tyrosine Phosphorylation Regulates the Endocytosis and Surface Expression of GluN3A-Containing NMDA Receptors

Selective control of receptor trafficking provides a mechanism for remodeling the receptor composition of excitatory synapses, and thus supports synaptic transmission, plasticity, and development. GluN3A (formerly NR3A) is a nonconventional member of the NMDA receptor (NMDAR) subunit family, which endows NMDAR channels with low calcium permeability and reduced magnesium sensitivity compared with NMDARs comprising only GluN1 and GluN2 subunits. Because of these special properties, GluN3A subunits act as a molecular brake to limit the plasticity and maturation of excitatory synapses, pointing toward GluN3A removal as a critical step in the development of neuronal circuitry. However, the molecular signals mediating GluN3A endocytic removal remain unclear. Here we define a novel endocytic motif (YWL), which is located within the cytoplasmic C-terminal tail of GluN3A and mediates its binding to the clathrin adaptor AP2. Alanine mutations within the GluN3A endocytic motif inhibited clathrin-dependent internalization and led to accumulation of GluN3A-containing NMDARs at the cell surface, whereas mimicking phosphorylation of the tyrosine residue promoted internalization and reduced cell-surface expression as shown by immunocytochemical and electrophysiological approaches in recombinant systems and rat neurons in primary culture. We further demonstrate that the tyrosine residue is phosphorylated by Src family kinases, and that Src-activation limits surface GluN3A expression in neurons. Together, our results identify a new molecular signal for GluN3A internalization that couples the functional surface expression of GluN3A-containing receptors to the phosphorylation state of GluN3A subunits, and provides a molecular framework for the regulation of NMDAR subunit composition with implications for synaptic plasticity and neurodevelopment

Tips for implementing multigrid methods on domains containing holes

As part of our development of a computer code to perform 3D `constrained evolution' of Einstein's equations in 3+1 form, we discuss issues regarding the efficient solution of elliptic equations on domains containing holes (i.e., excised regions), via the multigrid method. We consider as a test case the Poisson equation with a nonlinear term added, as a means of illustrating the principles involved, and move to a "real world" 3-dimensional problem which is the solution of the conformally flat Hamiltonian constraint with Dirichlet and Robin boundary conditions. Using our vertex-centered multigrid code, we demonstrate globally second-order-accurate solutions of elliptic equations over domains containing holes, in two and three spatial dimensions. Keys to the success of this method are the choice of the restriction operator near the holes and definition of the location of the inner boundary. In some cases (e.g. two holes in two dimensions), more and more smoothing may be required as the mesh spacing decreases to zero; however for the resolutions currently of interest to many numerical relativists, it is feasible to maintain second order convergence by concentrating smoothing (spatially) where it is needed most. This paper, and our publicly available source code, are intended to serve as semi-pedagogical guides for those who may wish to implement similar schemes.Comment: 18 pages, 11 figures, LaTeX. Added clarifications and references re. scope of paper, mathematical foundations, relevance of work. Accepted for publication in Classical & Quantum Gravit