4,780 research outputs found

    Standoff Distance of Bow Shocks in Galaxy Clusters as Proxy for Mach Number

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    X-ray observations of merging clusters provide many examples of bow shocks leading merging subclusters. While the Mach number of a shock can be estimated from the observed density jump using Rankine-Hugoniot condition, it reflects only the velocity of the shock itself and is generally not equal to the velocity of the infalling subcluster dark matter halo or to the velocity of the contact discontinuity separating gaseous atmospheres of the two subclusters. Here we systematically analyze additional information that can be obtained by measuring the standoff distance, i.e. the distance between the leading edge of the shock and the contact discontinuity that drives this shock. The standoff distance is influenced by a number of additional effects, e.g. (1) the gravitational pull of the main cluster (causing acceleration/deceleration of the infalling subcluster), (2) the density and pressure gradients of the atmosphere in the main cluster, (3) the non-spherical shape of the subcluster, and (4) projection effects. The first two effects tend to bias the standoff distance in the same direction, pushing the bow shock closer to (farther away from) the subcluster during the pre- (post-)merger stages. Particularly, in the post-merger stage, the shock could be much farther away from the subcluster than predicted by a model of a body moving at a constant speed in a uniform medium. This implies that a combination of the standoff distance with measurements of the Mach number from density/temperature jumps can provide important information on the merger, e.g. differentiating between the pre- and post-merger stages.Comment: 11 pages, 12 figures. Including major revision and matched to accepted version in MNRA

    Structure and substrate selectivity of the 750-kDa α6β6 holoenzyme of geranyl-CoA carboxylase.

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    Geranyl-CoA carboxylase (GCC) is essential for the growth of Pseudomonas organisms with geranic acid as the sole carbon source. GCC has the same domain organization and shares strong sequence conservation with the related biotin-dependent carboxylases 3-methylcrotonyl-CoA carboxylase (MCC) and propionyl-CoA carboxylase (PCC). Here we report the crystal structure of the 750-kDa α6β6 holoenzyme of GCC, which is similar to MCC but strikingly different from PCC. The structures provide evidence in support of two distinct lineages of biotin-dependent acyl-CoA carboxylases, one carboxylating the α carbon of a saturated organic acid and the other carboxylating the γ carbon of an α-β unsaturated acid. Structural differences in the active site region of GCC and MCC explain their distinct substrate preferences. Especially, a glycine residue in GCC is replaced by phenylalanine in MCC, which blocks access by the larger geranyl-CoA substrate. Mutation of this residue in the two enzymes can change their substrate preferences

    Gene expression in the mouse brain following early pregnancy exposure to ethanol

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    Exposure to alcohol during early embryonic or fetal development has been linked with a variety of adverse outcomes, the most common of which are structural and functional abnormalities of the central nervous system [1]. Behavioural and cognitive deficits reported in individuals exposed to alcohol in utero include intellectual impairment, learning and memory difficulties, diminished executive functioning, attention problems, poor motor function and hyperactivity [2]. The economic and social costs of these outcomes are substantial and profound [3] and [4]. Improvement of neurobehavioural outcomes following prenatal alcohol exposure requires greater understanding of the mechanisms of alcohol-induced damage to the brain. Here we use a mouse model of relatively moderate ethanol exposure early in pregnancy and profile gene expression in the hippocampus and caudate putamen of adult male offspring. The effects of offspring sex and age on ethanol-sensitive hippocampal gene expression were also examined. All array data are available at the Gene Expression Omnibus (GEO) repository under accession number GSE87736

    Accessing the purity of a single photon by the width of the Hong-Ou-Mandel interference

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    We demonstrate a method to determine the spectral purity of single photons. The technique is based on the Hong-Ou-Mandel (HOM) interference between a single photon state and a suitably prepared coherent field. We show that the temporal width of the HOM dip is not only related to reciprocal of the spectral width but also to the underlying quantum coherence. Therefore, by measuring the width of both the HOM dip and the spectrum one can directly quantify the degree of spectral purity. The distinct advantage of our proposal is that it obviates the need for perfect mode matching, since it does not rely on the visibility of the interference. Our method is particularly useful for characterizing the purity of heralded single photon states.Comment: Extended version, 16 pages, 9 figure

    Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.

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    Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017)

    Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

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    We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE). The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [3H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP-) 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P < .05). Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P < .05) and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier

    Ancient Polyploidy and Genome Evolution in Palms

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    Mechanisms of genome evolution are fundamental to our understanding of adaptation and the generation and maintenance of biodiversity, yet genome dynamics are still poorly characterized in many clades. Strong correlations between variation in genomic attributes and species diversity across the plant tree of life suggest that polyploidy or other mechanisms of genome size change confer selective advantages due to the introduction of genomic novelty. Palms (order Arecales, family Arecaceae) are diverse, widespread, and dominant in tropical ecosystems, yet little is known about genome evolution in this ecologically and economically important clade. Here, we take a phylogenetic comparative approach to investigate palm genome dynamics using genomic and transcriptomic data in combination with a recent, densely sampled, phylogenetic tree. We find conclusive evidence of a paleopolyploid event shared by the ancestor of palms but not with the sister clade, Dasypogonales. We find evidence of incremental chromosome number change in the palms as opposed to one of recurrent polyploidy. We find strong phylogenetic signal in chromosome number, but no signal in genome size, and further no correlation between the two when correcting for phylogenetic relationships. Palms thus add to a growing number of diverse, ecologically successful clades with evidence of whole-genome duplication, sister to a species-poor clade with no evidence of such an event. Disentangling the causes of genome size variation in palms moves us closer to understanding the genomic conditions facilitating adaptive radiation and ecological dominance in an evolutionarily successful, emblematic tropical clade

    Quantitative Analysis of Outer Retinal Tubulation in Age-Related Macular Degeneration From Spectral-Domain Optical Coherence Tomography and Histology

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    Purpose: To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods: In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results: By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 ± 7.9 μm2. The average cone spacing was 7.5 ± 0.6 μm. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6% to 44% of the cones present in a healthy macula. Conclusions: These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses

    Inter-Strain Epigenomic Profiling Reveals a Candidate IAP Master Copy in C3H Mice.

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    Insertions of endogenous retroviruses cause a significant fraction of mutations in inbred mice but not all strains are equally susceptible. Notably, most new Intracisternal A particle (IAP) ERV mutagenic insertions have occurred in C3H mice. We show here that strain-specific insertional polymorphic IAPs accumulate faster in C3H/HeJ mice, relative to other sequenced strains, and that IAP transcript levels are higher in C3H/HeJ embryonic stem (ES) cells compared to other ES cells. To investigate the mechanism for high IAP activity in C3H mice, we identified 61 IAP copies in C3H/HeJ ES cells enriched with H3K4me3 (a mark of active promoters) and, among those tested, all are unmethylated in C3H/HeJ ES cells. Notably, 13 of the 61 are specific to C3H/HeJ and are members of the non-autonomous 1Δ1 IAP subfamily that is responsible for nearly all new insertions in C3H. One copy is full length with intact open reading frames and hence potentially capable of providing proteins i
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