88 research outputs found

    An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids

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    We describe the identification in aphids of a unique heterodimeric voltage-gated sodium channel which has an atypical ion selectivity filter and, unusually for insect channels, is highly insensitive to tetrodotoxin. We demonstrate that this channel has most likely arisen by adaptation (gene fission or duplication) of an invertebrate ancestral mono(hetero)meric channel. This is the only identifiable voltage-gated sodium channel homologue in the aphid genome(s), and the channel’s novel selectivity filter motif (DENS instead of the usual DEKA found in other eukaryotes) may result in a loss of sodium selectivity, as indicated experimentally in mutagenised Drosophila channels

    Magnetic properties of the frustrated AFM spinel ZnCr_2O_4 and the spin-glass Zn_{1-x}Cd_xCr_2O_4 (x=0.05,0.10)

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    The TT-dependence (2- 400 K) of the electron paramagnetic resonance (EPR), magnetic susceptibility, χ(T)\chi (T), and specific heat, Cv(T)C_{v}(T), of the normalnormal antiferromagnetic (AFM) spinel ZnCr2_{2}O4_{4} and the spin-glass (SG) Zn1−x_{1-x}Cdx_{x}Cr2_{2}O4_{4} (x=0.05,0.10x=0.05,0.10) is reported. These systems behave as a strongly frustrated AFM and SG with % T_{N} ≈TG≈12 \approx T_{G}\approx 12 K and -400 K ≳ΘCW≳−500\gtrsim \Theta_{CW}\gtrsim -500 K. At high-TT the EPR intensity follows the χ(T)\chi (T) and the gg-value is TT-independent. The linewidth broadens as the temperature is lowered, suggesting the existence of short range AFM correlations in the paramagnetic phase. For ZnCr2_{2}O4_{4} the EPR intensity and χ(T)\chi (T) decreases below 90 K and 50 K, respectively. These results are discussed in terms of nearest-neighbor Cr3+^{3+} (S =3/2=3/2%) spin-coupled pairs with an exchange coupling of ∣J/k∣≈| J/k| \approx 50 K. The appearance of small resonance modes for Tâ‰Č17T\lesssim 17 K, the observation of a sharp drop in χ(T)\chi (T) and a strong peak in Cv(T)C_{v}(T) at TN=12T_{N}=12 K confirms, as previously reported, the existence of long range AFM correlations in the low-TT phase. A comparison with recent neutron diffraction experiments that found a near dispersionless excitation at 4.5 meV for Tâ‰ČTNT\lesssim T_{N} and a continuous gapless spectrum for T≳TNT\gtrsim T_{N}, is also given.Comment: 17 pages, 8 figures, 1 Table. Submitted to Physical Review

    All-sky search for long-duration gravitational wave transients with initial LIGO

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    We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

    All-sky search for long-duration gravitational wave transients with initial LIGO

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    We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

    Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

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    We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

    Basement membrane proteoglycans: Modulators Par Excellence of cancer growth and angiogenesis

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    Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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    Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    On the progenitor of binary neutron star merger GW170817

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    On 2017 August 17 the merger of two compact objects with masses consistent with two neutron stars was discovered through gravitational-wave (GW170817), gamma-ray (GRB 170817A), and optical (SSS17a/AT 2017gfo) observations. The optical source was associated with the early-type galaxy NGC 4993 at a distance of just ∌40 Mpc, consistent with the gravitational-wave measurement, and the merger was localized to be at a projected distance of ∌2 kpc away from the galaxy's center. We use this minimal set of facts and the mass posteriors of the two neutron stars to derive the first constraints on the progenitor of GW170817 at the time of the second supernova (SN). We generate simulated progenitor populations and follow the three-dimensional kinematic evolution from binary neutron star (BNS) birth to the merger time, accounting for pre-SN galactic motion, for considerably different input distributions of the progenitor mass, pre-SN semimajor axis, and SN-kick velocity. Though not considerably tight, we find these constraints to be comparable to those for Galactic BNS progenitors. The derived constraints are very strongly influenced by the requirement of keeping the binary bound after the second SN and having the merger occur relatively close to the center of the galaxy. These constraints are insensitive to the galaxy's star formation history, provided the stellar populations are older than 1 Gyr

    A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

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    We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers
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