Does Epileptiform Activity Contribute to Cognitive Impairment in Alzheimer's Disease?

Alzheimer's disease is a devastating neurological disorder. The role of hyperexcitability in the disease's cognitive decline is not completely understood. In this issue of Neuron, Palop et al. report both limbic seizures and presumed homeostatic responses to seizures in an animal model of Alzheimer's

GRANAT/WATCH catalogue of cosmic gamma-ray bursts: December 1989 to September 1994

We present the catalogue of gamma-ray bursts observed with the WATCH all-sky monitor on board the GRANAT satellite during the period December 1989 to September 1994. The cosmic origin of 95 bursts comprising the catalogue is confirmed either by their localization with WATCH or by their detection with other GRB experiments. For each burst its time history and information on its intensity in the two energy ranges 8-20 keV and 20-60 keV are presented. Most events show hardening of the energy spectrum near the burst peak. In part of the bursts an X-ray precursor or a tail is seen at 8-20 keV. We have determined the celestial positions of the sources of 47 bursts. Their localization regions (at 3-sigma confidence level) are equivalent in area to circles with radii ranging from 0.2 to 1.6 deg. The burst sources appear isotropically distributed on the sky on large angular scales.Comment: 18 pages (including 3 tables and 7 figures), LaTeX, l-aa style. Accepted by Astronomy and Astrophysics Suppl. Serie

A Gyrochronology and Microvariability Survey of the Milky Way's Older Stars Using Kepler's Two-Wheels Program

Even with the diminished precision possible with only two reaction wheels, the Kepler spacecraft can obtain mmag level, time-resolved photometry of tens of thousands of sources. The presence of such a rich, large data set could be transformative for stellar astronomy. In this white paper, we discuss how rotation periods for a large ensemble of single and binary main- sequence dwarfs can yield a quantitative understanding of the evolution of stellar spin-down over time. This will allow us to calibrate rotation-based ages beyond ~1 Gyr, which is the oldest benchmark that exists today apart from the Sun. Measurement of rotation periods of M dwarfs past the fully-convective boundary will enable extension of gyrochronology to the end of the stellar main-sequence, yielding precise ages ({\sigma} ~10%) for the vast majority of nearby stars. It will also help set constraints on the angular momentum evolution and magnetic field generation in these stars. Our Kepler-based study would be supported by a suite of ongoing and future ground-based observations. Finally, we briefly discuss two ancillary science cases, detection of long-period low-mass eclipsing binaries and microvariability in white dwarfs and hot subdwarf B stars that the Kepler Two-Wheels Program would facilitate.Comment: Kepler white pape

Cytokines in Pigs Bred Selectively for High and Low Immune Response [abstract only]

Yorkshire pigs have been bred for high (H) and low (L) immune response based on selection for multiple antibody (Ab) and cell mediated immune response traits. High responders have better production and larger litter size when compared with controls and low responders. The ability of high and low line pigs to resist M. hyorhinis infection has been tested. The high responders had more rapid and higher Ab response and the severity of the disease was less, as judged by clinical and postmortem signs. However, arthritis was found to be relatively more severe in high responders. We hypothesized that the immune response differences between genetically different lines could be attributed to either dominant or differential cytokine expression. To test the above hypothesis, quantitative RNA PCR (Q.RNA PCR), to quantitate the porcine cytokines at the mRNA level, was developed by constructing an internal control. Two synthetic oligos, namely 5\u27 construct (FPC) and 3\u27 construct (TPC), were designed based on the nt sequences of porcine cytokine genes. FPC represented the upstream primer sequences of nine cytokines sequentially in the order IL-1, IL-4, IL-6, IL-8, IL-2, IL-1O, TNF-α, TNF-β and IFN-γ, and TPC, the downstream primer sequences in the same order. The primers were designed such that when cRNA and target RNA were amplified, they give two non-overlapping products. FPCs and TPCs were constructed by overlapping and the extension method of PCR amplification utilizing six oligos for each, and were cloned into pSP 64 poly A vector. The application of Q.RNA PCR has been tested for determining quantitatively the cytokines in peripheral blood mononuclear cells in H-L line pigs. Preliminary study indicated differential expression of cytokines, namely IL-1, IL-6, IL-1O, TNF-α and IFN-γ, in naive animals. Expression of other cytokines, namely IL-2, IL-4, IL-8 and TNF-β, was absent in the pigs tested. Future studies involve the determination of cytokines in the context of immunization to the antigens (HEWL, BCG, etc.) as well as during infection (ex: M. hyorhinis) in conjunction with cytokine expression regulation strategies, namely MAbs and/or antisense ODNs or gene therapy

Ischemia and reperfusion injury in kidney transplantation : relevant mechanisms in injury and repair

Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to interstitial fibrosis and tubular atrophy. Recently, more insight has been gained in the underlying molecular pathways and signalling cascades involved, which opens the door to new therapeutic opportunities aiming to reduce IRI and improve graft survival. This review systemically discusses the specific molecular pathways involved in the pathophysiology of IRI and highlights new therapeutic strategies targeting these pathways

A Young Globular Cluster in the Galaxy NGC 6946

A globular cluster ~15 My old that contains 5x10^5 Msun of stars inside an 11 pc radius has been found in the nearby spiral galaxy NGC 6946, surrounded by clouds of dust and smaller young clusters inside a giant circular bubble 300 pc in radius. At the edge of the bubble is an arc of regularly-spaced clusters that could have been triggered during the bubble's formation. The region is at the end of a spiral arm, suggesting an origin by the asymmetric collapse of spiral arm gas. The globular is one of the nearest examples of a cluster that is similar to the massive old globulars in the Milky Way. We consider the energetics of the bubble and possible formation mechanisms for the globular cluster, including the coalescence of smaller clusters.Comment: 20 pages, 7 figures, accepted for Astrophysical Journal Vol 535, June 1 200

Topoisomerase IB: a relaxing enzyme for stressed DNA

DNA topoisomerase I enzymes relieve the torsional strain in DNA; they are essential for fundamental molecular processes such as DNA replication, transcription, recombination, and chromosome condensation; and act by cleaving and then religating DNA strands. Over the past few decades, scientists have focused on the DNA topoisomerases biological functions and established a unique role of Type I DNA topoisomerases in regulating gene expression and DNA chromosome condensation. Moreover, the human enzyme is being investigated as a target for cancer chemotherapy. The active site tyrosine is responsible for initiating two transesterification reactions to cleave and then religate the DNA backbone, allowing the release of superhelical tension. The different steps of the catalytic mechanism are affected by various inhibitors; some of them prevent the interaction between the enzyme and the DNA while others act as poisons, leading to TopI-D NA lesions, breakage of DNA, and eventually cellular death. In this review, our goal is to provide an overview of mechanism of human topoisomerase IB action together with the different types of inhibitors and their effect on the enzyme functionality

Evolved Eclipsing Binaries and the Age of the Open Cluster NGC 752

We present analyses of improved photometric and spectroscopic observations for two detached eclipsing binaries at the turnoff of the open cluster NGC 752: the 1.01 day binary DS And and the 15.53 d BD $+$37 410. For DS And, we find $M_1 = 1.692\pm0.004\pm0.010 M_\odot$, $R_1 = 2.185\pm0.004\pm0.008 R_\odot$, $M_2 = 1.184\pm0.001\pm0.003 M_\odot$, and $R_2 = 1.200\pm0.003\pm0.005 R_\odot$. We either confirm or newly identify unusual characteristics of both stars in the binary: the primary star is found to be slightly hotter than the main sequence turn off and there is a more substantial discrepancy in its luminosity compared to models (model luminosities are too large by about 40%), while the secondary star is oversized and cooler compared to other main sequence stars in the same cluster. The evidence points to non-standard evolution for both stars, but most plausible paths cannot explain the low luminosity of the primary star. BD $+$37 410 only has one eclipse per cycle, but extensive spectroscopic observations and the TESS light curve constrain the stellar masses well: $M_1 = 1.717\pm0.011 M_\odot$ and $M_2 = 1.175\pm0.005 M_\odot$. The radius of the main sequence primary star near $2.9R_\odot$ definitively requires large convective core overshooting ($> 0.2$ pressure scale heights) in models for its mass, and multiple lines of evidence point toward an age of $1.61\pm0.03\pm0.05$ Gyr (statistical and systematic uncertainties). Because NGC 752 is currently undergoing the transition from non-degenerate to degenerate He ignition of its red clump stars, BD $+$37 410 A directly constrains the star mass where this transition occurs.Comment: 34 pages, 23 figures, accepted for Astronomical Journa