Amino-terminal sequences of the bacillus anthracis exosporium proteins BCLA and BCLB important for localization and attachment to the spore surface

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file."August 2008"Thesis (M.S.) University of Missouri-Columbia 2008.The exosporium is the outermost layer of the Bacillus anthracis spore. The predominant protein on the exosporium surface is BclA, a collagen-like glycoprotein. BclA is incorporated on the spore surface late in the B. anthracis sporulation pathway. A second collagen-like protein, BclB, has been shown to be surface exposed on anthrax spores. We have identified sequences near the N-terminus of the BclA and BclB glycoproteins responsible for the incorporation of these proteins into the exosporium layer of the spore and used these targeting domains to incorporate reporter fluorescent proteins onto the spore surface. The BclA and BclB proteins are expressed in the mother cell cytoplasm and become spore-associated in a two step process involving first association of the protein with the spore surface followed by attachment of the protein in a process that involves a proteolytic cleavage event. Protein domains associated with each of these events have been identified. This novel targeting system can be exploited to incorporate foreign proteins into the exosporium of B. anthracis resulting in the surface display of recombinant immunogens for use as a potential vaccine delivery system.Includes bibliographical references

Dietary Prebiotics and Bioactive Milk Fractions Improve NREM Sleep, Enhance REM Sleep Rebound and Attenuate the Stress-Induced Decrease in Diurnal Temperature and Gut Microbial Alpha Diversity.

Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin (Lf) and milk fat globule membrane (MFGM) will reduce the negative physiological impacts of stress. Male F344 rats, postnatal day (PND) 24, received a diet with prebiotics, Lf and MFGM (test) or a calorically matched control diet. Fecal samples were collected on PND 35/70/91 for 16S rRNA sequencing to examine microbial composition and, in a subset of rats; Lactobacillus rhamnosus was measured using selective culture. On PND 59, biotelemetry devices were implanted to record sleep/wake electroencephalographic (EEG). Rats were exposed to an acute stressor (100, 1.5 mA, tail shocks) on PND 87 and recordings continued until PND 94. Test diet, compared to control diet, increased fecal Lactobacillus rhamnosus colony forming units (CFU), facilitated non-rapid eye movement (NREM) sleep consolidation (PND 71/72) and enhanced rapid eye movement (REM) sleep rebound after stressor exposure (PND 87). Rats fed control diet had stress-induced reductions in alpha diversity and diurnal amplitude of temperature, which were attenuated by the test diet (PND 91). Stepwise multiple regression analysis revealed a significant linear relationship between early-life Deferribacteres (PND 35) and longer NREM sleep episodes (PND 71/72). A diet containing prebiotics, Lf and MFGM enhanced sleep quality, which was related to changes in gut bacteria and modulated the impact of stress on sleep, diurnal rhythms and the gut microbiota

Iris: an Extensible Application for Building and Analyzing Spectral Energy Distributions

Iris is an extensible application that provides astronomers with a user-friendly interface capable of ingesting broad-band data from many different sources in order to build, explore, and model spectral energy distributions (SEDs). Iris takes advantage of the standards defined by the International Virtual Observatory Alliance, but hides the technicalities of such standards by implementing different layers of abstraction on top of them. Such intermediate layers provide hooks that users and developers can exploit in order to extend the capabilities provided by Iris. For instance, custom Python models can be combined in arbitrary ways with the Iris built-in models or with other custom functions. As such, Iris offers a platform for the development and integration of SED data, services, and applications, either from the user's system or from the web. In this paper we describe the built-in features provided by Iris for building and analyzing SEDs. We also explore in some detail the Iris framework and software development kit, showing how astronomers and software developers can plug their code into an integrated SED analysis environment.Comment: 18 pages, 8 figures, accepted for publication in Astronomy & Computin

On the Conditions for Neutron-Rich Gamma-Ray Burst Outflows

We calculate the structure and neutron content of neutrino-heated MHD winds driven from the surface of newly-formed magnetars (``proto-magnetars'') and from the midplane of hyper-accreting disks, two of the possible central engines for gamma-ray bursts (GRBs) and hyper-energetic supernovae (SNe). Both the surface of proto-magnetars and the midplane of neutrino-cooled accretion flows (NDAFs) are electron degenerate and neutron-rich (neutron-to-proton ratio n/p >> 1). If this substantial free neutron excess is preserved to large radii in ultra-relativistic outflows, several important observational consequences may result. Weak interaction processes, however, can drive n/p to ~1 in the nondegenerate regions that obtain just above the surfaces of NDAFs and proto-magnetars. Our calculations show that mildly relativistic neutron-rich outflows from NDAFs are possible in the presence of a strong poloidal magnetic field. However, we find that neutron-rich winds possess a minimum mass-loss rate that likely precludes simultaneously neutron-rich and ultra-relativistic (Lorentz factor > 100) NDAF winds accompanying a substantial accretion power. In contrast, proto-magnetars are capable of producing neutron-rich long-duration GRB outflows ~10-30 seconds following core bounce for sub-millisecond rotation periods; such outflows would, however, accompany only extremely energetic events, in which the GRB + SN energy budget exceeds ~ 4e52 ergs. Neutron-rich highly relativistic outflows may also be produced during some short-duration GRBs by geometrically thick accretion disks formed from compact object mergers. The implications for r-process nucleosynthesis, optical transients due to non-relativistic neutron-rich winds, and Nickel production in proto-magnetar and NDAF winds are also briefly discussed.Comment: 24 pages, 7 figures, submitted to Ap

Price Discovery and the Accuracy of Consolidated Data Feeds in the U.S. Equity Markets

Both the scientific community and the popular press have paid much attention to the speed of the Securities Information Processor, the data feed consolidating all trades and quotes across the US stock market. Rather than the speed of the Securities Information Processor, or SIP, we focus here on its accuracy. Relying on Trade and Quote data, we provide various measures of SIP latency relative to high-speed data feeds between exchanges, known as direct feeds. We use first differences to highlight not only the divergence between the direct feeds and the SIP, but also the fundamental inaccuracy of the SIP. We find that as many as 60 percent or more of trades are reported out of sequence for stocks with high trade volume, therefore skewing simple measures such as returns. While not yet definitive, this analysis supports our preliminary conclusion that the underlying infrastructure of the SIP is currently unable to keep pace with the trading activity in today's stock market.Comment: 18 pages, 20 figures, 2 table

Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion

The most lethal form of malaria in humans is caused by Plasmodium falciparum. These parasites invade erythrocytes, a complex process involving multiple ligand-receptor interactions. The parasite makes initial contact with the erythrocyte followed by dramatic deformations linked to the function of the Erythrocyte binding antigen family and P. falciparum reticulocyte binding-like families. We show EBA-175 mediates substantial changes in the deformability of erythrocytes by binding to glycophorin A and activating a phosphorylation cascade that includes erythrocyte cytoskeletal proteins resulting in changes in the viscoelastic properties of the host cell. TRPM7 kinase inhibitors FTY720 and waixenicin A block the changes in the deformability of erythrocytes and inhibit merozoite invasion by directly inhibiting the phosphorylation cascade. Therefore, binding of P. falciparum parasites to the erythrocyte directly activate a signaling pathway through a phosphorylation cascade and this alters the viscoelastic properties of the host membrane conditioning it for successful invasion

Environmental impact analysis with the airspace concept evaluation system

The National Aeronautics and Space Administration (NASA) Ames Research Center has developed the Airspace Concept Evaluation System (ACES), which is a fast-time simulation tool for evaluating Air Traffic Management (ATM) systems. This paper describes linking a capability to ACES which can analyze the environmental impact of proposed future ATM systems. This provides the ability to quickly evaluate metrics associated with environmental impacts of aviation for inclusion in multi-dimensional cost-benefit analysis of concepts for evolution of the National Airspace System (NAS) over the next several decades. The methodology used here may be summarized as follows: 1) Standard Federal Aviation Administration (FAA) noise and emissions-inventory models, the Noise Impact Routing System (NIRS) and the Emissions and Dispersion Modeling System (EDMS), respectively, are linked to ACES simulation outputs; 2) appropriate modifications are made to ACES outputs to incorporate all information needed by the environmental models (e.g., specific airframe and engine data); 3) noise and emissions calculations are performed for all traffic and airports in the study area for each of several scenarios, as simulated by ACES; and 4) impacts of future scenarios are compared to the current NAS baseline scenario. This paper also provides the results of initial end-to-end, proof-of-concept runs of the integrated ACES and environmental-modeling capability. These preliminary results demonstrate that if no growth is likely to be impeded by significant environmental impacts that could negatively affect communities throughout the nation

A Nova Outburst Powered by Shocks

Classical novae are runaway thermonuclear burning events on the surfaces of accreting white dwarfs in close binary star systems, sometimes appearing as new naked-eye sources in the night sky. The standard model of novae predicts that their optical luminosity derives from energy released near the hot white dwarf which is reprocessed through the ejected material. Recent studies with the Fermi Large Area Telescope have shown that many classical novae are accompanied by gigaelectronvolt gamma-ray emission. This emission likely originates from strong shocks, providing new insights into the properties of nova outflows and allowing them to be used as laboratories to study the unknown efficiency of particle acceleration in shocks. Here we report gamma-ray and optical observations of the Milky Way nova ASASSN-16ma, which is among the brightest novae ever detected in gamma-rays. The gamma-ray and optical light curves show a remarkable correlation, implying that the majority of the optical light comes from reprocessed emission from shocks rather than the white dwarf. The ratio of gamma-ray to optical flux in ASASSN-16ma directly constrains the acceleration efficiency of non-thermal particles to be ~0.005, favouring hadronic models for the gamma-ray emission. The need to accelerate particles up to energies exceeding 100 gigaelectronvolts provides compelling evidence for magnetic field amplification in the shocks.Comment: Published in Nature Astronomy. This is the authors' version with 55 pages, 8 figures, and 3 table