Comparing the Ancient Star Formation Histories of the Magellanic Clouds

We present preliminary results from a new HST archival program aimed at tightly constraining the ancient (>4 Gyr ago) star formation histories (SFHs) of the field populations of the SMC and LMC. We demonstrate the quality of the archival data by constructing HST/WFPC2-based color-magnitude diagrams (CMDs; M_{F555W} ~ +8) for 7 spatially diverse fields in the SMC and 8 fields in the LMC. The HST-based CMDs are >2 magnitudes deeper than any from ground based observations, and are particularly superior in high surface brightness regions, e.g., the LMC bar, which contain a significant fraction of star formation and are crowding limited from ground based observations. To minimize systematic uncertainties, we derive the SFH of each field using an identical maximum likelihood CMD fitting technique. We then compute an approximate mass weighted average SFH for each galaxy. We find that both galaxies lack a dominant burst of early star formation, which suggests either a suppression or an under-fueling of early star formation. From 10-12 Gyr ago, the LMC experienced a period of enhanced stellar mass growth relative to the SMC. Similar to some previous studies, we find two notable peaks in the SFH of the SMC at ~4.5 and 9 Gyr ago, which could be due to repeated close passages with the LMC, implying an interaction history that has persisted for at least 9 Gyr. We find little evidence for strong periodic behavior in the lifetime SFHs of both MCs, suggesting that repeated encounters with the Milky Way are unlikely. Beginning ~3.5 Gyr ago, both galaxies show increases in their SFHs, in agreement with previous studies, and thereafter, track each other remarkably well. (abridged)Comment: 9 pages, 5 Figures, Accepted for Publication in MNRA

Mixed Dark Matter from Axino Distribution

We study the possibility of mixed dark matter obtained through the phase space distribution of a single particle. An example is offered in the context of SUSY models with a Peccei-Quinn symmetry. Axinos in the 100 keV range can naturally have both thermal and non-thermal components. The latter one arises from the lightest neutralino decays and derelativizes at z ~ 10^4.Comment: Figures added, references fixed. Version accepted for publication on Phys. Rev. D. LaTeX. 9 pages, 3 figures, uses epsfig.st

A heterotrimeric G protein, G alpha i-3, on Golgi membranes regulates the secretion of a heparan sulfate proteoglycan in LLC-PK1 epithelial cells

A heterotrimeric G-alpha-i subunit, alpha-i-3, is localized on Golgi membranes in LLC-PK1 and NRK epithelial cells where it colocalizes with mannosidase II by immunofluorescence. The alpha-i-3 was found to be localized on the cytoplasmic face of Golgi cisternae and it was distributed across the whole Golgi stack. The alpha-i-3 subunit is found on isolated rat liver Golgi membranes by Western blotting and G-alpha-i-3 on the Golgi apparatus is ADP ribosylated by pertussis toxin. LLC-PK1 cells were stably transfected with G-alpha-i-3 on an MT-1, inducible promoter in order to overexpress alpha-i-3 on Golgi membranes. The intracellular processing and constitutive secretion of the basement membrane heparan sulfate proteoglycan (HSPG) was measured in LLC-PK1 cells. Overexpression of alpha-i-3 on Golgi membranes in transfected cells retarded the secretion of HSPG and accumulated precursors in the medial-trans-Golgi. This effect was reversed by treatment of cells with pertussis toxin which results in ADP-ribosylation and functional uncoupling of G-alpha-i-3 on Golgi membranes. These results provide evidence for a novel role for the pertussis toxin sensitive G-alpha-i-3 protein in Golgi trafficking of a constitutively secreted protein in epithelial cells

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

BEAMS: separating the wheat from the chaff in supernova analysis

We introduce Bayesian Estimation Applied to Multiple Species (BEAMS), an algorithm designed to deal with parameter estimation when using contaminated data. We present the algorithm and demonstrate how it works with the help of a Gaussian simulation. We then apply it to supernova data from the Sloan Digital Sky Survey (SDSS), showing how the resulting confidence contours of the cosmological parameters shrink significantly.Comment: 23 pages, 9 figures. Chapter 4 in "Astrostatistical Challenges for the New Astronomy" (Joseph M. Hilbe, ed., Springer, New York, forthcoming in 2012), the inaugural volume for the Springer Series in Astrostatistic

Human central nervous system (CNS) ApoE isoforms are increased by age, differentially altered by amyloidosis, and relative amounts reversed in the CNS compared with plasma

The risk of Alzheimer's disease (AD) is highly dependent on apolipoprotein-E (apoE) genotype. The reasons for apoE isoform-selective risk are uncertain; however, both the amounts and structure of human apoE isoforms have been hypothesized to lead to amyloidosis increasing the risk for AD. To address the hypothesis that amounts of apoE isoforms are different in the human CNS, we developed a novel isoform-specific method to accurately quantify apoE isoforms in clinically relevant samples. The method utilizes an antibody-free enrichment step and isotope-labeled physiologically relevant lipoprotein particle standards produced by immortalized astrocytes. We applied this method to a cohort of well characterized clinical samples and observed the following findings. The apoE isoform amounts are not different in cerebrospinal fluid (CSF) from young normal controls, suggesting that the amount of apoE isoforms is not the reason for risk of amyloidosis prior to the onset of advanced age. We did, however, observe an age-related increase in both apoE isoforms. In contrast to normal aging, the presence of amyloid increased apoE3, whereas apoE4 was unchanged or decreased. Importantly, for heterozygotes, the apoE4/apoE3 isoform ratio was increased in the CNS, although the reverse was true in the periphery. Finally, CSF apoE levels, but not plasma apoE levels, correlated with CSF β-amyloid levels. Collectively, these findings support the hypothesis that CNS and peripheral apoE are separate pools and differentially regulated. Furthermore, these results suggest that apoE mechanisms for the risk of amyloidosis and AD are related to an interaction between apoE, aging, and the amount of amyloid burden