Evaluating the effects of bilingual traffic signs on driver performance and safety

Variable Message Signs (VMS) can provide immediate and relevant information to road users and bilingual VMS can provide great flexibility in countries where a significant proportion of the population speak an alternative language to the majority. The study reported here evaluates the effect of various bilingual VMS configurations on driver behaviour and safety. The aim of the study was to determine whether or not the visual distraction associated with bilingual VMS signs of different configurations (length, complexity) impacted on driving performance. A driving simulator was used to allow full control over the scenarios, road environment and sign configuration and both longitudinal and lateral driver performance was assessed. Drivers were able to read one and two-line monolingual signs and two-line bilingual signs without disruption to their driving behaviour. However, drivers significantly reduced their speed in order to read four-line monolingual and four-line bilingual signs, accompanied by an increase in headway to the vehicle in front. This implies that drivers are possibly reading the irrelevant text on the bilingual sign and various methods for reducing this effect are discussed

POLG1 p.R722H mutation associated with multiple mtDNA deletions and a neurological phenotype

<p>Abstract</p> <p>Background</p> <p>The c.2447G>A (p.R722H) mutation in the gene <it>POLG1 </it>of the catalytic subunit of human mitochondrial polymerase gamma has been previously found in a few occasions but its pathogenicity has remained uncertain. We set out to ascertain its contribution to neuromuscular disease.</p> <p>Methods</p> <p>Probands from two families with probable mitochondrial disease were examined clinically, muscle and buccal epithelial DNA were analyzed for mtDNA deletions, and the <it>POLG1, POLG2, ANT1 </it>and <it>Twinkle </it>genes were sequenced.</p> <p>Results</p> <p>An adult proband presented with progressive external ophthalmoplegia, sensorineural hearing impairment, diabetes mellitus, dysphagia, a limb myopathy and dementia. Brain MRI showed central and cortical atrophy, and ¹⁸F-deoxyglucose PET revealed reduced glucose uptake. Histochemical analysis of muscle disclosed ragged red fibers and cytochrome c oxidase-negative fibers. Electron microscopy showed subsarcolemmal aggregates of morphologically normal mitochondria. Multiple mtDNA deletions were found in the muscle, and sequencing of the <it>POLG1 </it>gene revealed a homozygous c.2447G>A (p.R722H) mutation. His two siblings were also homozygous with respect to the p.R722H mutation and presented with dementia and sensorineural hearing impairment. In another family the p.R722H mutation was found as compound heterozygosity with the common p.W748S mutation in two siblings with mental retardation, ptosis, epilepsy and psychiatric symptoms. The estimated carrier frequency of the p.R722H mutation was 1:135 in the Finnish population. No mutations in <it>POLG2</it>, <it>ANT1 </it>and <it>Twinkle </it>genes were found. Analysis of the POLG1 sequence by homology modeling supported the notion that the p.R722H mutation is pathogenic.</p> <p>Conclusions</p> <p>The recessive c.2447G>A (p.R722H) mutation in the linker region of the <it>POLG1 </it>gene is pathogenic for multiple mtDNA deletions in muscle and is associated with a late-onset neurological phenotype as a homozygous state. The onset of the disease can be earlier in compound heterozygotes.</p

Disruption of Mitochondrial DNA Replication in Drosophila Increases Mitochondrial Fast Axonal Transport In Vivo

Mutations in mitochondrial DNA polymerase (pol γ) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol γ leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol γ deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol γ−α mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases

Replication Pauses of the Wild-Type and Mutant Mitochondrial DNA Polymerase Gamma: A Simulation Study

The activity of polymerase γ is complicated, involving both correct and incorrect DNA polymerization events, exonuclease activity, and the disassociation of the polymerase:DNA complex. Pausing of pol-γ might increase the chance of deletion and depletion of mitochondrial DNA. We have developed a stochastic simulation of pol-γ that models its activities on the level of individual nucleotides for the replication of mtDNA. This method gives us insights into the pausing of two pol-γ variants: the A467T substitution that causes PEO and Alpers syndrome, and the exonuclease deficient pol-γ (exo−) in premature aging mouse models. To measure the pausing, we analyzed simulation results for the longest time for the polymerase to move forward one nucleotide along the DNA strand. Our model of the exo− polymerase had extremely long pauses, with a 30 to 300-fold increase in the time required for the longest single forward step compared to the wild-type, while the naturally occurring A467T variant showed at most a doubling in the length of the pauses compared to the wild-type. We identified the cause of these differences in the polymerase pausing time to be the number of disassociations occurring in each forward step of the polymerase

Silencing of PINK1 Expression Affects Mitochondrial DNA and Oxidative Phosphorylation in DOPAMINERGIC Cells

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD). Impairment of the mitochondrial electron transport chain (ETC) and an increased frequency in deletions of mitochondrial DNA (mtDNA), which encodes some of the subunits of the ETC, have been reported in the substantia nigra of PD brains. The identification of mutations in the PINK1 gene, which cause an autosomal recessive form of PD, has supported mitochondrial involvement in PD. The PINK1 protein is a serine/threonine kinase localized in mitochondria and the cytosol. Its precise function is unknown, but it is involved in neuroprotection against a variety of stress signalling pathways.Methodology/Principal Findings: In this report we have investigated the effect of silencing PINK1 expression in human dopaminergic SH-SY5Y cells by siRNA on mtDNA synthesis and ETC function. Loss of PINK1 expression resulted in a decrease in mtDNA levels and mtDNA synthesis. We also report a concomitant loss of mitochondrial membrane potential and decreased mitochondrial ATP synthesis, with the activity of complex IV of the ETC most affected. This mitochondrial dysfunction resulted in increased markers of oxidative stress under basal conditions and increased cell death following treatment with the free radical generator paraquat.Conclusions: This report highlights a novel function of PINK1 in mitochondrial biogenesis and a role in maintaining mitochondrial ETC activity. Dysfunction of both has been implicated in sporadic forms of PD suggesting that these may be key pathways in the development of the disease

Nanosecond-Scale Proton Emission from Strongly Oblate-Deformed Lu-149

Using the fusion-evaporation reaction 96Ru(58Ni,p4n)149Lu and the MARA vacuum-mode recoil separator, a new proton-emitting isotope 149Lu has been identified. The measured decay Q value of 1920(20) keV is the highest measured for a ground-state proton decay, and it naturally leads to the shortest directly measured half-life of 450+170−100 ns for a ground-state proton emitter. The decay rate is consistent with lp=5 emission, suggesting a dominant πh11/2 component for the wave function of the proton-emitting state. Through nonadiabatic quasiparticle calculations it was concluded that 149Lu is the most oblate deformed proton emitter observed to date.peerReviewe

Probing triaxiality beyond the proton drip line: Spectroscopy of 147Tm

Two triaxial states of the proton-decaying nucleus Tm147 were studied via a comparison of experimental data to results obtained through nonadiabatic quasiparticle calculations. The experimental data were collected in a recoil-decay tagging study using the vacuum-mode recoil separator MARA coupled with the JUROGAM3 γ-ray spectrometer. The previously proposed level scheme above the triaxial 11/2- (πh11/2) ground state was confirmed, and the level structure was expanded to cover the states above the weakly populated proton-emitting 5/2+ (πd5/2) isomeric state. It was found that the isomeric state is also triaxial, and possibly more deformed than the ground state

Prediction and prevention of suicide in patients with unipolar depression and anxiety

Epidemiological data suggest that between 59 and 87% of suicide victims suffered from major depression while up to 15% of these patients will eventually commit suicide. Male gender, previous suicide attempt(s), comorbid mental disorders, adverse life-situations, acute psycho-social stressors etc. also constitute robust risk factors. Anxiety and minor depression present with a low to moderate increase in suicide risk but anxiety-depression comorbidity increases this risk dramatically Contrary to the traditional psychoanalytic approach which considers suicide as a retrospective murder or an aggression turned in-wards, more recent studies suggest that the motivations to commit suicide may vary and are often too obscure. Neurobiological data suggest that low brain serotonin activity might play a key role along with the tryptophan hydroxylase gene. Social factors include social support networks, religion etc. It is proven that most suicide victims had asked for professional help just before committing suicide, however they were either not diagnosed (particularly males) or the treatment they received was inappropriate or inadequate. The conclusion is that promoting suicide prevention requires the improving of training and skills of both psychiatrists and many non-psychiatrists and especially GPs in recognizing and treating depression and anxiety. A shift of focus of attention is required in primary care to detect potentially suicidal patients presenting with psychological problems. The proper use of antidepressants, after a careful diagnostic evaluation, is important and recent studies suggest that successful acute and long-term antidepressant pharmacotherapy reduces suicide morbidity and mortality

Intergenerational Transmission of Multiple Problem Behaviors: Prospective Relationships between Mothers and Daughters

Much of the research examining intergenerational continuity of problems from mother to offspring has focused on homotypic continuity (e.g., depression), despite the fact that different types of mental health problems tend to cluster in both adults and children. It remains unclear whether mothers with multiple mental health problems compared to mothers with fewer or no problems are more likely to have daughters with multiple mental health problems during middle childhood (ages 7 to 11). Six waves of maternal and child data from the Pittsburgh Girls Study (n = 2,451) were used to examine the specificity of effects of maternal psychopathology on child adjustment. Child multiple mental health problems comprised disruptive behavior, ADHD symptoms, depressed mood, anxiety symptoms and somatic complaints, while maternal multiple mental health problems consisted of depression, prior conduct problems and somatic complaints. Generalized Estimating Equations (GEE) was used to examine the prospective relationships between mother’s single and multiple mental health problems and their daughter’s single and multiple mental health problems across the elementary school-aged period (ages 7–11 years). The results show that multiple mental health problems in the mothers predicted multiple mental health problems in the daughters even when earlier mental health problem of the daughters, demographic factors, and childrearing practices were controlled. Maternal low parental warmth and harsh punishment independently contributed to the prediction of multiple mental health problems in their daughter, but mediation analyses showed that the contribution of parenting behaviors to the explanation of girls’ mental health problems was small