14,593 research outputs found
Performance evaluation of carrier interferometry implementations of MC-CDMA over a wideband channel suffering phase noise
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Long reaction times are associated with delayed brain activity in Lewy body dementia
A significant symptom of Lewy body dementia (LBD) is slow cognitive processing or bradyphrenia. In a previous fMRI task-based study, we found slower responses in LBD, accompanied by greater deactivation in the default mode network. In this study, we investigated the timing and magnitude of the activations and deactivations with respect to reaction time to determine whether the slower responses in LBD were associated with delayed neuronal activity. Using fMRI, we examined the magnitude and latency of activations and deactivations during an event-related attention task in 32 patients with LBD and 23 healthy controls using predefined regions of interest. Default mode network deactivations did not significantly differ in their timing between groups or task conditions, while the task-related activations in the parietal, occipital, frontal, and motor cortex were all significantly later in the LBD group. Repeating the analysis with reaction time as a parametric modulator of activation magnitude produced similar findings, with the reaction time modulator being significant in a number of regions including the default mode network, suggesting that the increased deactivation in LBD is partly explained by slower task completion. Our data suggest that the default mode network deactivation is initiated at the start of the task, and remains deactivated until its end, with the increased magnitude of deactivation in LBD reflecting the more prolonged cognitive processing in these patients. These data add substantially to our understanding of the neural origins of bradyphrenia, which will be essential for determining optimum therapeutic strategies for cognitive impairment in LBD.Funded by: National Institute for Health Research, Newcastle Biomedical Research Unit based at Newcastle Hospitals NHS Foundation Trust, Newcastle University, Wellcome Trust. Grant Number: WT088441M
The host galaxies of luminous radio-quiet quasars
We present the results of a deep K-band imaging study which reveals the host
galaxies around a sample of luminous radio-quiet quasars. The K-band images,
obtained at UKIRT, are of sufficient quality to allow accurate modelling of the
underlying host galaxy. Initially, the basic structure of the hosts is revealed
using a modified Clean deconvolution routine optimised for this analysis. 2 of
the 14 quasars are shown to have host galaxies with violently disturbed
morphologies which cannot be modelled by smooth elliptical profiles. For the
remainder of our sample, 2D models of the host and nuclear component are fitted
to the images using the chi-squared statistic to determine goodness of fit.
Host galaxies are detected around all of the quasars. The reliability of the
modelling is extensively tested, and we find the host luminosity to be well
constrained for 9 quasars. The derived average K-band absolute K-corrected host
galaxy magnitude for these luminous radio-quiet quasars is =-25.15+/-0.04,
slightly more luminous than an L* galaxy. The spread of derived host galaxy
luminosities is small, although the spread of nuclear-to-host ratios is not.
These host luminosities are shown to be comparable to those derived from
samples of quasars of lower total luminosity and we conclude that there is no
correlation between host and nuclear luminosity for these quasars.
Nuclear-to-host ratios break the lower limit previously suggested from studies
of lower nuclear luminosity quasars and Seyfert galaxies. Morphologies are less
certain but, on the scales probed by these images, some hosts appear to be
dominated by spheroids but others appear to have disk-dominated profiles.Comment: 16 pages, 8 figures, revised version to be published in MNRA
Efficacy of Etoricoxib, Celecoxib, Lumiracoxib, Non-Selective NSAIDs, and Acetaminophen in Osteoarthritis: A Mixed Treatment Comparison
Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag
The tetrapod neuronal protein ARC and its Drosophila melanogaster homolog, dARC1, have important but differing roles in neuronal development. Both are thought to originate through exaptation of ancient Ty3/Gypsy retrotransposon Gag, with their novel function relying on an original capacity for self-assembly and encapsidation of nucleic acids. Here, we present the crystal structure of dARC1 CA and examine the relationship between dARC1, mammalian ARC, and the CA protein of circulating retroviruses. We show that while the overall architecture is highly related to that of orthoretroviral and spumaretroviral CA, there are substantial deviations in both amino- and carboxyl-terminal domains, potentially affecting recruitment of partner proteins and particle assembly. The degree of sequence and structural divergence suggests that Ty3/Gypsy Gag has been exapted on two separate occasions and that, although mammalian ARC and dARC1 share functional similarity, the structures have undergone different adaptations after appropriation into the tetrapod and insect genomes
Divergent functional network deficits during an attention-executive task in Lewy body dementia and Alzheimer’s disease
Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505.
African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs. There are conflicting reports on the role of interferon in ASFV infection. We therefore analysed the interaction of ASFV with porcine interferon, in vivo and in vitro. Virulent ASFV induced biologically active IFN in the circulation of pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes from multigene family (MGF) 360 and MGF505, did not. Infection of porcine leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels of interferon, suggesting a potential source of interferon in animals undergoing acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in interferon pretreated macrophages and a recombinant virus lacking similar genes to those absent in OUR T88/3 was also inhibited. These findings suggest that as well as inhibiting the induction of interferon, MGF360 and MGF505 genes also enable ASFV to overcome the antiviral state
Supraspinal fatigue in human inspiratory muscles with repeated sustained maximal efforts
To investigate the involvement of supraspinal fatigue in the loss of maximal inspiratory pressure (PImax), we fatigued the inspiratory muscles. Six participants performed 5 sustained maximal isometric inspiratory efforts (15-s contractions, duty cycle ~75%) which reduced PImax, as measured from esophageal and mouth pressure, to around half of their initial maximums. Transcranial magnetic stimulation (TMS) delivered over the motor cortex near the beginning and end of each maximal effort evoked superimposed twitch-like increments in the ongoing PImax, increasing from ~1.0% of PImax in the unfatigued contractions to ≥40% of ongoing PImax for esophageal and mouth pressures. The rate of increase in the superimposed twitch as PImax decreased with fatigue was not significantly different between the esophageal and mouth pressure measures. The inverse relationship between superimposed twitch pressure and PImax indicates a progressive decline in the ability of motor cortical output to drive the inspiratory muscles maximally, leading to the development of supraspinal fatigue. TMS also evoked silent periods in the electromyographic recordings of diaphragm, scalenes, and parasternal intercostal. The duration of the silent period increased with fatigue in all three muscles, which suggests greater intracortical inhibition, with the largest change observed in the diaphragm. The peak rate of relaxation in pressure during the silent period slowed as fatigue developed, indicating peripheral contractile changes in the active inspiratory muscles. These changes in the markers of fatigue show that both central and peripheral fatigue contribute to the loss in PImax when inspiratory muscles are fatigued with repeated sustained maximal efforts. NEW & NOTEWORTHY When the inspiratory muscles are fatigued with repeated sustained maximal efforts, supraspinal fatigue, a component of central fatigue, contributes to the loss in maximal inspiratory pressure. The presence of supraspinal fatigue was confirmed by the increase in amplitude of twitch-like increments in pressure evoked by motor cortical stimulation during maximal efforts, indicating that motor cortical output was not maximal as extra muscle force could be generated to increase inspiratory pressure
Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice
The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans
Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts
Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al
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