The Combined Impact Of IgLON Family Proteins Lsamp And Neurotrimin On Developing Neurons And Behavioral Profiles In Mouse

Cell surface neural adhesion proteins are critical components in the complex orchestration of cell proliferation, apoptosis, and neuritogenesis essential for proper brain construction and behavior. We focused on the impact of two plasticity-associated IgLON family neural adhesion molecules, Neurotrimin (Ntm) and Limbic system associated membrane protein (Lsamp), on mouse behavior and its underlying neural development. Phenotyping neurons derived from the hippocampi of Lsamp−/−, Ntm−/− and Lsamp−/−Ntm−/− mice was performed in parallel with behavioral testing. While the anatomy of mutant brains revealed no gross changes, the Ntm−/− hippocampal neurons exhibited premature sprouting of neurites and manifested accelerated neurite elongation and branching. We propose that Ntm exerts an inhibitory impact on neurite outgrowth, whereas Lsamp appears to be an enhancer of the said process as premature neuritogenesis in Ntm−/− neurons is apparent only in the presence of Lsamp. We also show interplay between Lsamp and Ntm in regulating tissue homeostasis: the impact of Ntm on cellular proliferation was dependent on Lsamp, and Lsamp appeared to be a positive regulator of apoptosis in the presence of Ntm. Behavioral phenotyping indicated test-specific interactions between Lsamp and Ntm. The phenotypes of single mutant lines, such as reduced swimming speed in Morris water maze and increased activity in the elevated plus maze, were magnified in Lsamp−/−Ntm−/− mice. Altogether, evidence both from behavioral experiments and cultured hippocampal cells show combined and differential interactions between Ntm and Lsamp in the formation of hippocampal circuits and behavioral profiles. We demonstrate that mutual interactions between IgLON molecules regulate the initiation of neurite sprouting at very early ages, and even cell-autonomously, independent of their regulation of cell-cell adhesion

Vectorial Loading of Processive Motor Proteins: Implementing a Landscape Picture

Individual processive molecular motors, of which conventional kinesin is the most studied quantitatively, move along polar molecular tracks and, by exerting a force ${\bm F} = (F_x,F_y,F_z)$ on a tether, drag cellular cargoes, {\em in vivo}, or spherical beads, {\em in vitro}, taking up to hundreds of nanometer-scale steps. From observations of velocities and the dispersion of displacements with time, under measured forces and controlled fuel supply (typically ATP), one may hope to obtain insight into the molecular motions undergone in the individual steps. In the simplest situation, the load force ${\bm F}$ may be regarded as a scalar resisting force, $F_x < 0$, acting parallel to the track: however, experiments, originally by Gittes {\em et al.} (1996), have imposed perpendicular (or vertical) loads, $F_z > 0$, while more recently Block and coworkers (2002, 2003) and Carter and Cross (2005) have studied {\em assisting} (or reverse) loads, $F_x > 0$, and also sideways (or transverse) loads $F_y \neq 0$

Anderson Transition in Disordered Graphene

We use the regularized kernel polynomial method (RKPM) to numerically study the effect disorder on a single layer of graphene. This accurate numerical method enables us to study very large lattices with millions of sites, and hence is almost free of finite size errors. Within this approach, both weak and strong disorder regimes are handled on the same footing. We study the tight-binding model with on-site disorder, on the honeycomb lattice. We find that in the weak disorder regime, the Dirac fermions remain extended and their velocities decrease as the disorder strength is increased. However, if the disorder is strong enough, there will be a {\em mobility edge} separating {\em localized states around the Fermi point}, from the remaining extended states. This is in contrast to the scaling theory of localization which predicts that all states are localized in two-dimensions (2D).Comment: 4 page

Flexible Lipid Bilayers in Implicit Solvent

A minimalist simulation model for lipid bilayers is presented. Each lipid is represented by a flexible chain of beads in implicit solvent. The hydrophobic effect is mimicked through an intermolecular pair potential localized at the ``water''/hydrocarbon tail interface. This potential guarantees realistic interfacial tensions for lipids in a bilayer geometry. Lipids self assemble into bilayer structures that display fluidity and elastic properties consistent with experimental model membrane systems. Varying molecular flexibility allows for tuning of elastic moduli and area/molecule over a range of values seen in experimental systems.Comment: 5 pages, 5 figure

Wfs1 Is Expressed In Dopaminoceptive Regions Of The Amniote Brain And Modulates Levels Of D1-Like Receptors

During amniote evolution, the construction of the forebrain has diverged across different lineages, and accompanying the structural changes, functional diversification of the homologous brain regions has occurred. This can be assessed by studying the expression patterns of marker genes that are relevant in particular functional circuits. In all vertebrates, the dopaminergic system is responsible for the behavioral responses to environmental stimuli. Here we show that the brain regions that receive dopaminergic input through dopamine receptor D1 are relatively conserved, but with some important variations between three evolutionarily distant vertebrate lines–house mouse (Mus musculus), domestic chick (Gallus gallus domesticus) / common quail (Coturnix coturnix) and red-eared slider turtle (Trachemys scripta). Moreover, we find that in almost all instances, those brain regions expressing D1-like dopamine receptor genes also express Wfs1. Wfs1 has been studied primarily in the pancreas, where it regulates the endoplasmic reticulum (ER) stress response, cellular Ca2+ homeostasis, and insulin production and secretion. Using radioligand binding assays in wild type and Wfs1-/- mouse brains, we show that the number of binding sites of D1-like dopamine receptors is increased in the hippocampus of the mutant mice. We propose that the functional link between Wfs1 and D1-like dopamine receptors is evolutionarily conserved and plays an important role in adjusting behavioral reactions to environmental stimuli

A programmable two-qubit quantum processor in silicon

With qubit measurement and control fidelities above the threshold of fault-tolerance, much attention is moving towards the daunting task of scaling up the number of physical qubits to the large numbers needed for fault tolerant quantum computing. Here, quantum dot based spin qubits may offer significant advantages due to their potential for high densities, all-electrical operation, and integration onto an industrial platform. In this system, the initialisation, readout, single- and two-qubit gates have been demonstrated in various qubit representations. However, as seen with other small scale quantum computer demonstrations, combining these elements leads to new challenges involving qubit crosstalk, state leakage, calibration, and control hardware which provide invaluable insight towards scaling up. Here we address these challenges and demonstrate a programmable two-qubit quantum processor in silicon by performing both the Deutsch-Josza and the Grover search algorithms. In addition, we characterise the entanglement in our processor through quantum state tomography of Bell states measuring state fidelities between 85-89% and concurrences between 73-80%. These results pave the way for larger scale quantum computers using spins confined to quantum dots

Efficient magneto-optical trapping of a metastable helium gas

This article presents a new experiment aiming at BEC of metastable helium atoms. It describes the design of a high flux discharge source of atoms and a robust laser system using a DBR diode coupled with a high power Yb doped fiber amplifier for manipulating the beam of metastable atoms. The atoms are trapped in a small quartz cell in an extreme high vacuum. The trapping design uses an additional laser (repumper) and allows the capture of a large number of metastable helium atoms (approximately $10^9$) in a geometry favorable for loading a tight magnetostatic trap.Comment: 12 pages, 7 figures, Late

Alternative Promoter Use Governs The Expression Of IgLON Cell Adhesion Molecules In Histogenetic Fields Of The Embryonic Mouse Brain

The members of the IgLON superfamily of cell adhesion molecules facilitate fundamental cellular communication during brain development, maintain functional brain circuitry, and are associated with several neuropsychiatric disorders such as depression, autism, schizophrenia, and intellectual disabilities. Usage of alternative promoter-specific 1a and 1b mRNA isoforms in Lsamp, Opcml, Ntm, and the single promoter of Negr1 in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of Lsamp, Opcml, Ntm isoforms, and Negr1, in the developing brain, we generated isoform-specific RNA probes and carried out in situ hybridization in the developing (embryonic, E10.5, E11.5, 13.5, 17; postnatal, P0) and adult mouse brains. We show that promoter-specific expression of IgLONs is established early during pallial development (at E10.5), where it remains throughout its differentiation through adulthood. In the diencephalon, midbrain, and hindbrain, strong expression patterns are initiated a few days later and begin fading after birth, being only faintly expressed during adulthood. Thus, the expression of specific IgLONs in the developing brain may provide the means for regionally specific functionality as well as for specific regional vulnerabilities. The current study will therefore improve the understanding of how IgLON genes are implicated in the development of neuropsychiatric disorders

Asynchronous Non-Invasive Brain-Actuated Control of an Intelligent Wheelchair

In this paper we present further results of our asynchronous and non-invasive BMI for the continuous control of an intelligent wheelchair. Three subjects participated in two experiments where they steered the wheelchair spontaneously, without any external cue. To do so the users learn to voluntary modulate EEG oscillatory rhythms by executing three mental tasks (i.e., mental imagery) that are associated to different steering commands. Importantly, we implement shared control techniques between the BMI and the intelligent wheelchair to assist the subject in the driving task. The results show that the three subjects could achieve a significant level of mental control, even if far from optimal, to drive an intelligent wheelchair

Excitation of the molecular gas in the nuclear region of M82

We present high resolution HIFI spectroscopy of the nucleus of the archetypical starburst galaxy M82. Six 12CO lines, 2 13CO lines and 4 fine-structure lines are detected. Besides showing the effects of the overall velocity structure of the nuclear region, the line profiles also indicate the presence of multiple components with different optical depths, temperatures and densities in the observing beam. The data have been interpreted using a grid of PDR models. It is found that the majority of the molecular gas is in low density (n=10^3.5 cm^-3) clouds, with column densities of N_H=10^21.5 cm^-2 and a relatively low UV radiation field (GO = 10^2). The remaining gas is predominantly found in clouds with higher densities (n=10^5 cm^-3) and radiation fields (GO = 10^2.75), but somewhat lower column densities (N_H=10^21.2 cm^-2). The highest J CO lines are dominated by a small (1% relative surface filling) component, with an even higher density (n=10^6 cm^-3) and UV field (GO = 10^3.25). These results show the strength of multi-component modeling for the interpretation of the integrated properties of galaxies.Comment: Accepted for publication in A&A Letter