318 research outputs found

    Chandra follow up of the Hectospec Cluster Survey: Comparison of Caustic and Hydrostatic Masses and Constraints on the Hydrostatic Bias

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    Clusters of galaxies are powerful probes with which to study cosmology and astrophysics. However, for many applications an accurate measurement of a cluster's mass is essential. A systematic underestimate of hydrostatic masses from X-ray observations (the so-called hydrostatic bias) may be responsible for tension between the results of different cosmological measurements. We compare X-ray hydrostatic masses with masses estimated using the caustic method (based on galaxy velocities) in order to explore the systematic uncertainties of both methods and place new constraints on the level of hydrostatic bias. Hydrostatic and caustic mass profiles were determined independently for a sample of 44 clusters based on Chandra observations of clusters from the Hectospec Cluster Survey. This is the largest systematic comparison of its kind. Masses were compared at a standardised radius (R500R_{500}) using a model that includes possible bias and scatter in both mass estimates. The systematics affecting both mass determination methods were explored in detail. The hydrostatic masses were found to be systematically higher than caustic masses on average, and we found evidence that the caustic method increasingly underestimates the mass when fewer galaxies are used to measure the caustics. We limit our analysis to the 14 clusters with the best-sampled caustics where this bias is minimised (210\ge210 galaxies), and find that the average ratio of hydrostatic to caustic mass at R500R_{500} is MX/MC=1.120.10+0.11M_X/M_C=1.12^{+0.11}_{-0.10}. We interpret this result as a constraint on the level of hydrostatic bias, favouring small or zero levels of hydrostatic bias (less than 20%20\% at the 3σ3\sigma level). However, we find systematic uncertainties associated with both mass estimation methods remain at the 1015%10-15\% level, which would permit significantly larger levels of hydrostatic bias.Comment: 15 pages plus appendices. Updated to match version accepted for publication in A&A. Updates include additional tests of systematics. Main results are unchange

    Structural Basis for α-Conotoxin Potency and Selectivity

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    Parkinson\u27s disease is a debilitating movement disorder characterized by altered levels of α6β2* nicotinic acetylcholine receptors (nAChRs) localized on presynaptic striatal catecholaminergic neurons. α-Conotoxin MII (α-CTx MII) is a highly useful ligand to probe α6ß2 nAChRs structure and function, but it does not discriminate among closely related α6* nAChR subtypes. Modification of the α-CTx MII primary sequence led to the identification of α-CTx MII[E11A], an analog with 500-5300 fold discrimination between α6* subtypes found in both human and non-human primates. α-CTx MII[E11A] binds most strongly (femtomolar dissociation constant) to the high affinity α6* nAChR, a subtype that is selectively lost in Parkinson\u27s disease. Here we present the three-dimensional solution structure for α-CTx MII[E11A] as determined by two-dimensional 1H NMR spectroscopy to 0.13 +/- 0.09 Ǻ backbone and 0.45 +/- 0.08 Ǻ heavy atom root mean square deviation from mean structure. Structural comparisons suggest that the increased hydrophobic area of α-CTx MII[E11A] relative to other members of the α-CTx family may be responsible for its exceptionally high affinity for α6α4β2* nAChR as well as discrimination between α6ß2 and α3β2 containing nAChRs. This finding may enable the rational design of novel peptide analogs that demonstrate enhanced specificity for α6* nAChR subunit interfaces and provide a means to better understand nAChR structural determinants that modulate brain dopamine levels and the pathophysiology of Parkinson\u27s disease

    Chronic testicular Chlamydia muridarum infection impairs mouse fertility and offspring development

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    With approximately 131 million new genital tract infections occurring each year, Chlamydia is the most common sexually transmitted bacterial pathogen worldwide. Male and female infections occur at similar rates and both cause serious pathological sequelae. Despite this, the impact of chlamydial infection on male fertility has long been debated, and the effects of paternal chlamydial infection on offspring development are unknown. Using a male mouse chronic infection model, we show that chlamydial infection persists in the testes, adversely affecting the testicular environment. Infection increased leukocyte infiltration, disrupted the blood:testis barrier and reduced spermiogenic cell numbers and seminiferous tubule volume. Sperm from infected mice had decreased motility, increased abnormal morphology, decreased zona-binding capacity, and increased DNA damage. Serum anti-sperm antibodies were also increased. When both acutely and chronically infected male mice were bred with healthy female mice, 16.7% of pups displayed developmental abnormalities. Female offspring of chronically infected sires had smaller reproductive tracts than offspring of noninfected sires. The male pups of infected sires displayed delayed testicular development, with abnormalities in sperm vitality, motility, and sperm-oocyte binding evident at sexual maturity. These data suggest that chronic testicular Chlamydia infection can contribute to male infertility, which may have an intergenerational impact on sperm quality

    Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

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    We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease
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