The Konkoly Blazhko Survey: Is light-curve modulation a common property of RRab stars?

A systematic survey to establish the true incidence rate of the Blazhko modulation among short-period, fundamental-mode, Galactic field RR Lyrae stars has been accomplished. The Konkoly Blazhko Survey (KBS) was initiated in 2004. Since then more than 750 nights of observation have been devoted to this project. A sample of 30 RRab stars was extensively observed, and light-curve modulation was detected in 14 cases. The 47% occurrence rate of the modulation is much larger than any previous estimate. The significant increase of the detected incidence rate is mostly due to the discovery of small-amplitude modulation. Half of the Blazhko variables in our sample show modulation with so small amplitude that definitely have been missed in the previous surveys. We have found that the modulation can be very unstable in some cases, e.g. RY Com showed regular modulation only during one part of the observations while during two seasons it had stable light curve with abrupt, small changes in the pulsation amplitude. This type of light-curve variability is also hard to detect in other Survey's data. The larger frequency of the light-curve modulation of RRab stars makes it even more important to find the still lacking explanation of the Blazhko phenomenon. The validity of the [Fe/H](P,phi_{31}) relation using the mean light curves of Blazhko variables is checked in our sample. We have found that the formula gives accurate result for small-modulation-amplitude Blazhko stars, and this is also the case for large-modulation-amplitude stars if the light curve has complete phase coverage. However, if the data of large-modulation-amplitude Blazhko stars are not extended enough (e.g. < 500 data points from < 15 nights), the formula may give false result due to the distorted shape of the mean light curve used.Comment: Accepted for publication in MNRAS, 14 pages, 7 Figure

On the Spectral Evolution of Cool, Helium-Atmosphere White Dwarfs: Detailed Spectroscopic and Photometric Analysis of DZ Stars

We present a detailed analysis of a large spectroscopic and photometric sample of DZ white dwarfs based on our latest model atmosphere calculations. We revise the atmospheric parameters of the trigonometric parallax sample of Bergeron, Leggett, & Ruiz (12 stars) and analyze 147 new DZ white dwarfs discovered in the Sloan Digital Sky Survey. The inclusion of metals and hydrogen in our model atmosphere calculations leads to different atmospheric parameters than those derived from pure helium models. Calcium abundances are found in the range from log (Ca/He) = -12 to -8. We also find that fits of the coolest objects show peculiarities, suggesting that our physical models may not correctly describe the conditions of high atmospheric pressure encountered in the coolest DZ stars. We find that the mean mass of the 11 DZ stars with trigonometric parallaxes, = 0.63 Mo, is significantly lower than that obtained from pure helium models, = 0.78 Mo, and in much better agreement with the mean mass of other types of white dwarfs. We determine hydrogen abundances for 27% of the DZ stars in our sample, while only upper limits are obtained for objects with low signal-to-noise ratio spectroscopic data. We confirm with a high level of confidence that the accretion rate of hydrogen is at least two orders of magnitude smaller than that of metals (and up to five in some cases) to be compatible with the observations. We find a correlation between the hydrogen abundance and the effective temperature, suggesting for the first time empirical evidence of a lower temperature boundary for the hydrogen screening mechanism. Finally, we speculate on the possibility that the DZA white dwarfs could be the result of the convective mixing of thin hydrogen-rich atmospheres with the underlying helium convection zone.Comment: 67 pages, 32 figures, accepted for publication in Ap

Substructure revealed by RR Lyraes in SDSS Stripe 82

We present an analysis of the substructure revealed by 407 RR Lyraes in Sloan Digital Sky Survey (SDSS) Stripe 82. Period estimates are determined to high accuracy using a string-length method. A subset of 178 RR Lyraes with spectrally derived metallicities are employed to derive metallicity-period-amplitude relations, which are then used to find metallicities and distances for the entire sample. The RR Lyraes lie between 5 and 115 kpc from the Galactic center. They are divided into subsets of 316 RRab types and 91 RRc types based on their period, colour and metallicity. The density distribution is not smooth, but dominated by clumps and substructure. Samples of 55 and 237 RR Lyraes associated with the Sagittarius Stream and the Hercules-Aquila Cloud respectively are identified. Hence, ~ 70 % of the RR Lyraes in Stripe 82 belong to known substructure. There is a sharp break in the density distribution at Galactocentric radii of 40 kpc, reflecting the fact that the dominant substructure in Stripe 82 - the Hercules-Aquila Cloud and the Sagittarius Stream - lies within 40 kpc. In fact, almost 60 % of all the RR Lyraes in Stripe 82 are associated with the Hercules-Aquila Cloud alone, which emphasises its pre-eminence. Additionally, evidence of a new and distant substructure - the Pisces Overdensity - is found, consisting of 28 faint RR Lyraes centered on Galactic coordinates (80 deg, -55 deg) and with distances of ~ 80 kpc. The total stellar mass in the Pisces Overdensity is ~10000 solar masses and its metallicity is [Fe/H] ~ -1.5.Comment: 15 pages, submitted to MNRA

ESA can be a society for all ecologists

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117231/1/fee201412291.pd

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Context Dependent Neuroprotective Properties of Prion Protein (Prp)

Although it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure—independent of infectious prion conformation—to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-β, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer’s disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP’s neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson’s disease or tauopathy. Deletion of PrP in one of two Huntington’s disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington’s motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein.Ellison Medical FoundationWhitaker Health Sciences Fund Fellowshi

Defining the Conformational Features of Anchorless, Poorly Neuroinvasive Prions

Infectious prions cause diverse clinical signs and form an extraordinary range of structures, from amorphous aggregates to fibrils. How the conformation of a prion dictates the disease phenotype remains unclear. Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectious prion develop fibrillar or nonfibrillar aggregates, respectively, and show a striking divergence in the disease pathogenesis. To better understand how a prion's physical properties govern the pathogenesis, infectious anchorless prions were passaged in mice expressing anchorless prion protein and the resulting prions were biochemically characterized. Serial passage of anchorless prions led to a significant decrease in the incubation period to terminal disease and altered the biochemical properties, consistent with a transmission barrier effect. After an intraperitoneal exposure, anchorless prions were only weakly neuroinvasive, as prion plaques rarely occurred in the brain yet were abundant in extracerebral sites such as heart and adipose tissue. Anchorless prions consistently showed very high stability in chaotropes or when heated in SDS, and were highly resistant to enzyme digestion. Consistent with the results in mice, anchorless prions from a human patient were also highly stable in chaotropes. These findings reveal that anchorless prions consist of fibrillar and highly stable conformers. The additional finding from our group and others that both anchorless and anchored prion fibrils are poorly neuroinvasive strengthens the hypothesis that a fibrillar prion structure impedes efficient CNS invasion

Plague Circulation and Population Genetics of the Reservoir Rattus rattus: The Influence of Topographic Relief on the Distribution of the Disease within the Madagascan Focus.

International audienceBACKGROUND: Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. METHODOLOGYPRINCIPAL FINDINGS: We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2) within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. CONCLUSIONSSIGNIFICANCE: Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations

Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is beta-sheet rich, infectious and self-perpetuating in nature. These infectious proteins show several remarkable biological activities, including the ability to form multiple infectious prion conformations, also known as strains or variants, encoding unique biological phenotypes, and to establish and overcome prion species (transmission) barriers. In this Perspective, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher such biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and we propose approaches to accelerate the understanding of these enigmatic, infectious conformers

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics