Spatial Tapping Interferes With the Processing of Linguistic Spatial Relations

Simple spatial relations may be represented either in a propositional format that is dependent on verbal rehearsal or in a picture-like format that is maintained by visual-spatial rehearsal. In sentence-picture and picture-picture verification tasks, we examined the effect of an articulatory suppression and a spatial tapping dual task on the encoding of simple spatial relations (e.g., triangle left of circle). Articulatory suppression did not interfere, while spatial tapping lowered performance in both tasks. Apparently, both linguistic and perceptual inputs of simple spatial relations engaged the visual-spatial working memory. In the sentence-picture verification experiments, spatial tapping only hampered performance of participants who were classified on the basis of their RT patterns as having used a visual-spatial strategy, while it had no effect for those who were classified as having applied a verbal strategy. Therefore, this study provides converging evidence, using a dual-task methodology, that both separate verbal and visual-spatial strategies exist for the processing of simple spatial sentences

Rat-to-Human Transmission of Cowpox Infection

We isolated Cowpox virus (CPXV) from the ulcerative eyelid lesions of a 14-year-old girl, who had cared for a clinically ill wild rat that later died. CPXV isolated from the rat (Rattus norvegicus) showed complete homology with the girl’s virus. Our case is the first proven rat-to-human transmission of cowpox

QCD Corrections to QED Vacuum Polarization

We compute QCD corrections to QED calculations for vacuum polarization in background magnetic fields. Formally, the diagram for virtual $e\bar{e}$ loops is identical to the one for virtual $q\bar{q}$ loops. However due to confinement, or to the growth of $\alpha_s$ as $p^2$ decreases, a direct calculation of the diagram is not allowed. At large $p^2$ we consider the virtual $q\bar{q}$ diagram, in the intermediate region we discuss the role of the contribution of quark condensates \left and at the low-energy limit we consider the $\pi^0$, as well as charged pion $\pi^+\pi^-$ loops. Although these effects seem to be out of the measurement accuracy of photon-photon laboratory experiments they may be relevant for $\gamma$-ray burst propagation. In particular, for emissions from the center of the galaxy (8.5 kpc), we show that the mixing between the neutral pseudo-scalar pion $\pi_0$ and photons renders a deviation from the power-law spectrum in the $TeV$ range. As for scalar quark condensates \left and virtual $q\bar{q}$ loops are relevant only for very high radiation density $\sim 300 MeV/fm^3$ and very strong magnetic fields of order $\sim 10^{14} T$.Comment: 15 pages, 4 figures; Final versio

Background Dependent Lorentz Violation: Natural Solutions to the Theoretical Challenges of the OPERA Experiment

To explain both the OPERA experiment and all the known phenomenological constraints/observations on Lorentz violation, the Background Dependent Lorentz Violation (BDLV) has been proposed. We study the BDLV in a model independent way, and conjecture that there may exist a "Dream Special Relativity Theory", where all the Standard Model (SM) particles can be subluminal due to the background effects. Assuming that the Lorentz violation on the Earth is much larger than those on the interstellar scale, we automatically escape all the astrophysical constraints on Lorentz violation. For the BDLV from the effective field theory, we present a simple model and discuss the possible solutions to the theoretical challenges of the OPERA experiment such as the Bremsstrahlung effects for muon neutrinos and the pion decays. Also, we address the Lorentz violation constraints from the LEP and KamLAMD experiments. For the BDLV from the Type IIB string theory with D3-branes and D7-branes, we point out that the D3-branes are flavour blind, and all the SM particles are the conventional particles as in the traditional SM when they do not interact with the D3-branes. Thus, we not only can naturally avoid all the known phenomenological constraints on Lorentz violation, but also can naturally explain all the theoretical challenges. Interestingly, the energy dependent photon velocities may be tested at the experiments.Comment: RevTex4, 14 pages, minor corrections, references adde

Particle Acceleration in Cosmic Sites - Astrophysics Issues in our Understanding of Cosmic Rays

Laboratory experiments to explore plasma conditions and stimulated particle acceleration can illuminate aspects of the cosmic particle acceleration process. Here we discuss the cosmic-ray candidate source object variety, and what has been learned about their particle-acceleration characteristics. We identify open issues as discussed among astrophysicists. -- The cosmic ray differential intensity spectrum is a rather smooth power-law spectrum, with two kinks at the "knee" (~10^15 eV) and at the "ankle" (~3 10^18 eV). It is unclear if these kinks are related to boundaries between different dominating sources, or rather related to characteristics of cosmic-ray propagation. We believe that Galactic sources dominate up to 10^17 eV or even above, and the extragalactic origin of cosmic rays at highest energies merges rather smoothly with Galactic contributions throughout the 10^15--10^18 eV range. Pulsars and supernova remnants are among the prime candidates for Galactic cosmic-ray production, while nuclei of active galaxies are considered best candidates to produce ultrahigh-energy cosmic rays of extragalactic origin. Acceleration processes are related to shocks from violent ejections of matter from energetic sources such as supernova explosions or matter accretion onto black holes. Details of such acceleration are difficult, as relativistic particles modify the structure of the shock, and simple approximations or perturbation calculations are unsatisfactory. This is where laboratory plasma experiments are expected to contribute, to enlighten the non-linear processes which occur under such conditions.Comment: accepted for publication in EPJD, topical issue on Fundamental physics and ultra-high laser fields. From review talk at "Extreme Light Infrastructure" workshop, Sep 2008. Version-2 May 2009: adjust some wordings and references at EPJD proofs stag

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy

Background: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells. We hypothesized that this would lead to cell-to-cell variation in cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3 gene) protein levels. Methods: Twelve HCM patients were included (six had no sarcomere mutations (HCMsmn) and served as the control group and six harbored mutations in the MYBPC3 gene (MYBPC3mut). Western blot and RNA sequencing analysis of cardiac tissue lysates were performed to detect overall cMyBP-C protein and mRNA levels. Cellular expression of cMyBP-C and α-actin was obtained by immunofluorescence staining. Quantification of cell-to-cell variation of cMyBP-C expression between cardiomyocytes was measured by determining the ratio of cMyBP-C:α-actin stained area of each cell. Results: Protein and mRNA analysis revealed significantly reduced cMyBP-C levels in MYBPC3mut patients compared with HCMsmn patients (0.73 ± 0.09 vs. 1.0 ± 0.15, p <.05; 162.3 ± 16.4 vs. 326.2 ± 41.9 RPKM, p =.002), without any sign of truncated proteins. Immunofluorescence staining of individual cardiomyocytes in HCMsmn patients demonstrated homogenous and equal cMyBP-C:α-actin staining ratio. In contrast, MYBPC3mut patients demonstrated inhomogeneous staining patterns with a large intercellular variability per patient. Coefficient of variance for cMyBP-C/α-actin staining for each patient showed a significant difference between both groups (17.30 ± 4.08 vs. 5.18 ± 0.65% in MYBPC3mut vs. HCMsmn, p =.02). Conclusion: This is the first study to demonstrate intercellular variation of myofilament cMyBP-C protein expression within the myocardium from HCM patients with heterozygous MYBPC3 mutations

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium

Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints