Mutant glycyl-tRNA synthetase (Gars) ameliorates SOD1G93A motor neuron degeneration phenotype but has little affect on Loa dynein heavy chain mutant mice

Background: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system, and clinical phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions in addition to its canonical role in protein synthesis through catalyzing the addition of glycine to cognate tRNAs. Methodology/Principal findings: We have recently described a new mouse model with a point mutation in the Gars gene resulting in a cysteine to arginine change at residue 201. Heterozygous Gars^{C201R/+} mice have locomotor and sensory deficits. In an investigation of genetic mutations that lead to death of motor and sensory neurons, we have crossed the Gars^{C201R/+} mice to two other mutants: the TgSOD1^{G93A} model of human amyotrophic lateral sclerosis and the Legs at odd angles mouse (Dync1h1^{Loa}) which has a defect in the heavy chain of the dynein complex. We found the Dync1h1^{Loa/+}; Gars^{C201R/+} double heterozygous mice are more impaired than either parent, and this is may be an additive effect of both mutations. Surprisingly, the Gars^{C201R} mutation significantly delayed disease onset in the SOD1^{G93A}; Gars^{C201R/+} double heterozygous mutant mice and increased lifespan by 29% on the genetic background investigated. Conclusions/Significance: These findings raise intriguing possibilities for the study of pathogenetic mechanisms in all three mouse mutant strains

Diurnal Variations in Vascular Endothelial Vasodilation Are Influenced by Chronotype in Healthy Humans

Introduction: The time of day when cardiovascular events are most likely to occur is thought to be aligned with the circadian rhythm of physiological variables. Chronotype has been shown to influence the time of day when cardiovascular events happen, with early chronotypes reported to be more susceptible in the morning and late chronotypes in the evening. However, no studies have investigated the influence of chronotype on physiological variables responsible for cardiovascular regulation in healthy individuals. Methods: 312 individuals completed the Munich ChronoType Questionnaire to assess chronotype. Twenty participants were randomly selected to continue into the main study. In a repeated-measures experiment, participants were tested between 08:00 and 10:00 h and again between 18:00 and 20:00 h. Measurements of mean arterial pressure, heart rate and vascular endothelial vasodilation via flow-mediated dilatation (FMD) were obtained at each session. Results: Individual diurnal differences in mean arterial pressure and heart rate show no significant relationship with chronotype. Diurnal differences in FMD showed a significant correlation (p = 0.010), driven by a clear significant relationship in the evening and not the morning (p < 0.001). Conclusion: These preliminary data indicate that chronotype influences the diurnal variation of endothelial vasodilation measured using flow-mediated dilatation. Furthermore, we show that the influence of chronotype is much stronger in the evening, highlighting an increased susceptibility for later types. These findings are consistent with the diurnal rhythm in cardiovascular events and uncover potential mechanisms of local mediators that may underpin the influence of chronotype in the onset of these events

Classification of human chronotype based on fMRI network-based statistics

Chronotype—the relationship between the internal circadian physiology of an individual and the external 24-h light-dark cycle—is increasingly implicated in mental health and cognition. Individuals presenting with a late chronotype have an increased likelihood of developing depression, and can display reduced cognitive performance during the societal 9–5 day. However, the interplay between physiological rhythms and the brain networks that underpin cognition and mental health is not well-understood. To address this issue, we use rs-fMRI collected from 16 people with an early chronotype and 22 people with a late chronotype over three scanning sessions. We develop a classification framework utilizing the Network Based-Statistic methodology, to understand if differentiable information about chronotype is embedded in functional brain networks and how this changes throughout the day. We find evidence of subnetworks throughout the day that differ between extreme chronotypes such that high accuracy can occur, describe rigorous threshold criteria for achieving 97.3% accuracy in the Evening and investigate how the same conditions hinder accuracy for other scanning sessions. Revealing differences in functional brain networks based on extreme chronotype suggests future avenues of research that may ultimately better characterize the relationship between internal physiology, external perturbations, brain networks, and disease

Many-body spin related phenomena in ultra-low-disorder quantum wires

Zero length quantum wires (or point contacts) exhibit unexplained conductance structure close to 0.7 X 2e^2/h in the absence of an applied magnetic field. We have studied the density- and temperature-dependent conductance of ultra-low-disorder GaAs/AlGaAs quantum wires with nominal lengths l=0 and 2 mu m, fabricated from structures free of the disorder associated with modulation doping. In a direct comparison we observe structure near 0.7 X 2e^2/h for l=0 whereas the l=2 mu m wires show structure evolving with increasing electron density to 0.5 X 2e^2/h in zero magnetic field, the value expected for an ideal spin-split sub-band. Our results suggest the dominant mechanism through which electrons interact can be strongly affected by the length of the 1D region.Comment: 5 Pages, 4 figure

Magnetoresistance and electronic structure of asymmetric GaAs/AlGaAs double quantum wells in the in-plane/tilted magnetic field

Bilayer two-dimensional electron systems formed by a thin barrier in the GaAs buffer of a standard heterostructure were investigated by magnetotransport measurements. In magnetic fields oriented parallel to the electron layers, the magnetoresistance exhibits an oscillation associated with the depopulation of the higher occupied subband and the field-induced transition into a decoupled bilayer. Shubnikov-de Haas oscillations in slightly tilted magnetic fields allow to reconstruct the evolution of the electron concentration in the individual subbands as a function of the in-plane magnetic field. The characteristics of the system derived experimentally are in quantitative agreement with numerical self-consistent-field calculations of the electronic structure.Comment: 6 pages, 5 figure

Suppression of non-Poissonian shot noise by Coulomb correlations in ballistic conductors

We investigate the current injection into a ballistic conductor under the space-charge limited regime, when the distribution function of injected carriers is an arbitrary function of energy F_c(epsilon). The analysis of the coupled kinetic and Poisson equations shows that the injected current fluctuations may be essentially suppressed by Coulomb correlations, and the suppression level is determined by the shape of F_c(epsilon). This is in contrast to the time-averaged quantities: the mean current and the spatial profiles are shown to be insensitive to F_c(epsilon) in the leading-order terms at high biases. The asymptotic high-bias behavior for the energy resolved shot-noise suppression has been found for an arbitrary (non-Poissonian) injection, which may suggest a new field of investigation on the optimization of the injected energy profile to achieve the desired noise-suppression level.Comment: extended version 4 -> 8 pages, examples and figure adde

Suppression of non-Poissonian shot noise by Coulomb correlations in ballistic conductors

We investigate the current injection into a ballistic conductor under the space-charge limited regime, when the distribution function of injected carriers is an arbitrary function of energy F_c(epsilon). The analysis of the coupled kinetic and Poisson equations shows that the injected current fluctuations may be essentially suppressed by Coulomb correlations, and the suppression level is determined by the shape of F_c(epsilon). This is in contrast to the time-averaged quantities: the mean current and the spatial profiles are shown to be insensitive to F_c(epsilon) in the leading-order terms at high biases. The asymptotic high-bias behavior for the energy resolved shot-noise suppression has been found for an arbitrary (non-Poissonian) injection, which may suggest a new field of investigation on the optimization of the injected energy profile to achieve the desired noise-suppression level.Comment: extended version 4 -> 8 pages, examples and figure adde

Ring-shaped spatial pattern of exciton luminescence formed due to the hot carrier transport in a locally photoexcited electron-hole bilayer

A consistent explanation of the formation of a ring-shaped pattern of exciton luminescence in GaAs/AlGaAs double quantum wells is suggested. The pattern consists of two concentric rings around the laser excitation spot. It is shown that the luminescence rings appear due to the in-layer transport of hot charge carriers at high photoexcitation intensity. Interestingly, one of two causes of this transport might involve self-organized criticality (SOC) that would be the first case of the SOC observation in semiconductor physics. We test this cause in a many-body numerical model by performing extensive molecular dynamics simulations. The results show good agreement with experiments. Moreover, the simulations have enabled us to identify the particular kinetic processes underlying the formation of each of these two luminescence rings.Comment: 14 pages, 16 figures. Final versio