Dopamine Activation Preserves Visual Motion Perception Despite Noise Interference of Human V5/MT

Copyright © 2016 Yousif et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.When processing sensory signals, the brain must account for noise, both noise in the stimulus and that arising from within its own neuronal circuitry. Dopamine receptor activation is known to enhance both visual cortical signal-to-noise-ratio (SNR) and visual perceptual performance; however, it is unknown whether these two dopamine-mediated phenomena are linked. To assess this, we used single-pulse transcranial magnetic stimulation (TMS) applied to visual cortical area V5/MT to reduce the SNR focally and thus disrupt visual motion discrimination performance to visual targets located in the same retinotopic space. The hypothesis that dopamine receptor activation enhances perceptual performance by improving cortical SNR predicts that dopamine activation should antagonize TMS disruption of visual perception. We assessed this hypothesis via a double-blinded, placebo-controlled study with the dopamine receptor agonists cabergoline (a D2 agonist) and pergolide (a D1/D2 agonist) administered in separate sessions (separated by 2 weeks) in 12 healthy volunteers in a William's balance-order design. TMS degraded visual motion perception when the evoked phosphene and the visual stimulus overlapped in time and space in the placebo and cabergoline conditions, but not in the pergolide condition. This suggests that dopamine D1 or combined D1 and D2 receptor activation enhances cortical SNR to boost perceptual performance. That local visual cortical excitability was unchanged across drug conditions suggests the involvement of long-range intracortical interactions in this D1 effect. Because increased internal noise (and thus lower SNR) can impair visual perceptual learning, improving visual cortical SNR via D1/D2 agonist therapy may be useful in boosting rehabilitation programs involving visual perceptual training.Peer reviewe

Nebulized heparin in burn patients with inhalation trauma : safety and feasibility

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients

Preliminary Results on HAT-P-4, TrES-3, XO-2, and GJ 436 from the NASA EPOXI Mission

EPOXI (EPOCh + DIXI) is a NASA Discovery Program Mission of Opportunity using the Deep Impact flyby spacecraft. The EPOCh (Extrasolar Planet Observation and Characterization) Science Investigation will gather photometric time series of known transiting exoplanet systems from January through August 2008. Here we describe the steps in the photometric extraction of the time series and present preliminary results of the first four EPOCh targets.Comment: 4 pages, 2 figures. To appear in the Proceedings of the 253rd IAU Symposium: "Transiting Planets", May 2008, Cambridge, M

Titanite Mineralization of Microbial Bioalteration Textures in Jurassic Volcanic Glass, Coast Range Ophiolite, California

Volcanic glasses are rarely preserved in the rock record, and the quality of preservation generally declines with increasing age. Records preserved in ancient basaltic glasses therefore provide important links between processes operating in the distant past, and those that are active on the Earth today. Microbial colonization has been linked to the formation of characteristic structures in basaltic glass, including tubules and granule-filled tubules, which are thought to be produced by microbially mediated glass dissolution. Structures of similar occurrence and morphology but filled almost entirely with fine-grained titanite have been documented in some ancient metabasalts. It has been suggested that the ancient titanite-mineralized structures are mineralized equivalents of hollow tubules in modern glassy basaltic rocks, but a direct link has not been firmly established. We report the discovery of tubular bioalteration structures in fresh and minimally altered basaltic glasses of middle Jurassic (164 Ma) age from the Stonyford Volcanic Complex (SFVC), Coast Range Ophiolite, California. Tubular structures hosted in unaltered basaltic glass are typically hollow, whilst those in zones of zeolitic alteration are mineralized by titanite. Tubules are continuous across zeolite-glass interfaces, which mark an abrupt change from titanite-filled to hollow tubules, demonstrating that titanite growth occurs preferentially within pre-existing tubular structures. Titanite mineralization in the SFVC represent a link between tubular structures in modern basaltic glass and titanite-mineralized features of similar morphology and spatial distribution in ancient metabasalts. Our observations support a link between textures in modern glassy basaltic rocks and some of the oldest-known putative ichnofossils

Nebulized Heparin For Patients Under Mechanical Ventilation: An Individual Patient Data Meta-Analysis

Pulmonary coagulopathy is a characteristic feature of lung injury including ventilator-induced lung injury. The aim of this individual patient data meta-analysis is to assess the effects of nebulized anticoagulants on outcome of ventilated intensive care unit (ICU) patients. A systematic search of PubMed (1966–2014), Scopus, EMBASE, and Web of Science was conducted to identify relevant publications. Studies evaluating nebulization of anticoagulants in ventilated patients were screened for inclusion, and corresponding authors of included studies were contacted to provide individual patient data. The primary endpoint was the number of ventilator-free days and alive at day 28. Secondary endpoints included hospital mortality, ICU- and hospital-free days at day 28, and lung injury scores at day seven. We constructed a propensity score-matched cohort for comparisons between patients treated with nebulized anticoagulants and controls. Data from five studies (one randomized controlled trial, one open label study, and three studies using historical controls) were included in the meta-analysis, compassing 286 patients. In all studies unfractionated heparin was used as anticoagulant. The number of ventilator-free days and alive at day 28 was higher in patients treated with nebulized heparin compared to patients in the control group (14 [IQR 0–23] vs. 6 [IQR 0–22]), though the difference did not reach statistical significance (P = 0.459). The number of ICU-free days and alive at day 28 was significantly higher, and the lung injury scores at day seven were significantly lower in patients treated with nebulized heparin. In the propensity score-matched analysis, there were no differences in any of the endpoints. This individual patient data meta-analysis provides no convincing evidence for benefit of heparin nebulization in intubated and ventilated ICU patients. The small patient numbers and methodological shortcomings of included studies underline the need for high-quality well-powered randomized controlled trials

Multilocus haplotypes reveal variable levels of diversity and population structure of Plasmodium falciparum in Papua New Guinea, a region of intense perennial transmission

<p>Abstract</p> <p>Background</p> <p>The South West Pacific nation of Papua New Guinea has intense year round transmission of <it>Plasmodium falciparum </it>on the coast and in the low-lying inland areas. Local heterogeneity in the epidemiology of malaria suggests that parasites from multiple locations will need to be surveyed to define the population biology of <it>P. falciparum </it>in the region. This study describes the population genetics of <it>P. falciparum </it>in thirteen villages spread over four distinct catchment areas of Papua New Guinea.</p> <p>Methods</p> <p>Ten microsatellite loci were genotyped in 318 <it>P. falciparum </it>isolates from the parasite populations of two inland catchment areas, namely Wosera (number of villages (n) = 7) and Utu (n = 1) and; and two coastal catchments, Malala (n = 3) and Mugil (n = 3). Analysis of the resultant multilocus haplotypes was done at different spatial scales (2-336 km) to define the genetic diversity (allelic richness and expected heterozygosity), linkage disequilibrium and population structure throughout the study area.</p> <p>Results</p> <p>Although genetic diversity was high in all parasite populations, it was also variable with a lower allelic richness and expected heterozygosity for inland populations compared to those from the more accessible coast. This variability was not correlated with two proxy measures of transmission intensity, the infection prevalence and the proportion multiple infections. Random associations among the microsatellite loci were observed in all four catchments showing that a substantial degree of out-crossing occurs in the region. Moderate to very high levels of population structure were found but the amount of genetic differentiation (<it>F_ST</it>) did not correlate with geographic distance suggesting that parasite populations are fragmented. Population structure was also identified between villages within the Malala area, with the haplotypes of one parasite population clustering with the neighbouring catchment of Mugil.</p> <p>Conclusion</p> <p>The observed population genetics of <it>P. falciparum </it>in this region is likely to be a consequence of the high transmission intensity combined with the isolation of human and vector populations, especially those located inland and migration of parasites via human movement into coastal populations. The variable genetic diversity and population structure of <it>P. falciparum </it>has important implications for malaria control strategies and warrants further fine scale sampling throughout Papua New Guinea.</p

Loop symmetry of integrable vertex models at roots of unity

It has been recently discovered in the context of the six vertex or XXZ model in the fundamental representation that new symmetries arise when the anisotropy parameter $(q+q^{-1})/2$ is evaluated at roots of unity $q^{N}=1$. These new symmetries have been linked to an $U(A^{(1)}_1)$ invariance of the transfer matrix and the corresponding spin-chain Hamiltonian.In this paper these results are generalized for odd primitive roots of unity to all vertex models associated with trigonometric solutions of the Yang-Baxter equation by invoking representation independent methods which only take the algebraic structure of the underlying quantum groups $U_q(\hat g)$ into account. Here $\hat g$ is an arbitrary Kac-Moody algebra. Employing the notion of the boost operator it is then found that the Hamiltonian and the transfer matrix of the integrable model are invariant under the action of $U(\hat{g})$. For the simplest case $\hat g=A_1^{(1)}$ the discussion is also extended to even primitive roots of unity.Comment: tcilatex, 19 pages (minor typos corrected, one reference changed

Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis

SummaryHeme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional mitochondrial transporters and regulatory factors are predicted to be required. To discover such unknown components, we utilized a large-scale computational screen to identify mitochondrial proteins whose transcripts consistently coexpress with the core machinery of heme biosynthesis. We identified SLC25A39, SLC22A4, and TMEM14C, which are putative mitochondrial transporters, as well as C1orf69 and ISCA1, which are iron-sulfur cluster proteins. Targeted knockdowns of all five genes in zebrafish resulted in profound anemia without impacting erythroid lineage specification. Moreover, silencing of Slc25a39 in murine erythroleukemia cells impaired iron incorporation into protoporphyrin IX, and vertebrate Slc25a39 complemented an iron homeostasis defect in the orthologous yeast mtm1Δ deletion mutant. Our results advance the molecular understanding of heme biosynthesis and offer promising candidate genes for inherited anemias