Inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal.

Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural protein p22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of p22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular protein secretion. This is the first reported function for p22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of p22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development

Novel modeling of task versus rest brain state predictability using a dynamic time warping spectrum: comparisons and contrasts with other standard measures of brain dynamics

Dynamic time warping, or DTW, is a powerful and domain-general sequence alignment method for computing a similarity measure. Such dynamic programming-based techniques like DTW are now the backbone and driver of most bioinformatics methods and discoveries. In neuroscience it has had far less use, though this has begun to change. We wanted to explore new ways of applying DTW, not simply as a measure with which to cluster or compare similarity between features but in a conceptually different way. We have used DTW to provide a more interpretable spectral description of the data, compared to standard approaches such as the Fourier and related transforms. The DTW approach and standard discrete Fourier transform (DFT) are assessed against benchmark measures of neural dynamics. These include EEG microstates, EEG avalanches, and the sum squared error (SSE) from a multilayer perceptron (MLP) prediction of the EEG time series, and simultaneously acquired FMRI BOLD signal. We explored the relationships between these variables of interest in an EEG-FMRI dataset acquired during a standard cognitive task, which allowed us to explore how DTW differentially performs in different task settings. We found that despite strong correlations between DTW and DFT-spectra, DTW was a better predictor for almost every measure of brain dynamics. Using these DTW measures, we show that predictability is almost always higher in task than in rest states, which is consistent to other theoretical and empirical findings, providing additional evidence for the utility of the DTW approach

Coerced Mechanical Coarsening of Nanoparticle Assemblies

Coarsening is a ubiquitous phenomenon [1-3] that underpins countless processes in nature, including epitaxial growth [1,3,4], the phase separation of alloys, polymers and binary fluids [2], the growth of bubbles in foams5, and pattern formation in biomembranes6. Here we show, in the first real-time experimental study of the evolution of an adsorbed colloidal nanoparticle array, that tapping-mode atomic force microscopy (TM-AFM) can drive the coarsening of Au nanoparticle assemblies on silicon surfaces. Although the growth exponent has a strong dependence on the initial sample morphology, our observations are largely consistent with modified Ostwald ripening processes [7-9]. To date, ripening processes have been exclusively considered to be thermally activated, but we show that nanoparticle assemblies can be mechanically coerced towards equilibrium, representing a new approach to directed coarsening. This strategy enables precise control over the evolution of micro- and nanostructures

Chemical Equilibrium Abundances in Brown Dwarf and Extrasolar Giant Planet Atmospheres

We calculate detailed chemical abundance profiles for a variety of brown dwarf and extrasolar giant planet atmosphere models, focusing in particular on Gliese 229B, and derive the systematics of the changes in the dominant reservoirs of the major elements with altitude and temperature. We assume an Anders and Grevesse (1989) solar composition of 27 chemical elements and track 330 gas--phase species, including the monatomic forms of the elements, as well as about 120 condensates. We address the issue of the formation and composition of clouds in the cool atmospheres of substellar objects and explore the rain out and depletion of refractories. We conclude that the opacity of clouds of low--temperature ($\le$900 K), small--radius condensibles (specific chlorides and sulfides), may be responsible for the steep spectrum of Gliese 229B observed in the near infrared below 1 \mic. Furthermore, we assemble a temperature sequence of chemical transitions in substellar atmospheres that may be used to anchor and define a sequence of spectral types for substellar objects with T$_{eff}$s from $\sim$2200 K to $\sim$100 K.Comment: 57 pages total, LaTeX, 14 figures, 5 tables, also available in uuencoded, gzipped, and tarred form via anonymous ftp at www.astrophysics.arizona.edu (cd to pub/burrows/chem), submitted to Ap.

Liver Transplantation for Advanced Liver Disease with Alpha-1antitrypsin Deficiency

ALPHA-1-antitrypsin deficiency associated with chronic obstructive airway disease was recognized in 1963 by Laurell and Ericksson.1 In 1969, Sharp2 described the first cases of alpha-1-antitrypsin-deficiency disease in children with cirrhosis. Since then, this inborn error has been recognized as one of the more common factors in cirrhosis of infancy and childhood,3 including “neonatal hepatitis.”4 Alpha-1-antitrypsin is a glycoprotein that accounts for a major portion of the alpha-1 globulin fraction of the serum.5 It is responsible for approximately 90 per cent of the antitrypsin activity6 of the serum, and it also inhibits several other plasma enzymes, including plasmin,7 elastase,8 collagenase,9 and. © 1980, Massachusetts Medical Society. All rights reserved

Aeolian sans ripples: experimental study of saturated states

We report an experimental investigation of aeolian sand ripples, performed both in a wind tunnel and on stoss slopes of dunes. Starting from a flat bed, we can identify three regimes: appearance of an initial wavelength, coarsening of the pattern and finally saturation of the ripples. We show that both initial and final wavelengths, as well as the propagative speed of the ripples, are linear functions of the wind velocity. Investigating the evolution of an initially corrugated bed, we exhibit non-linear stable solutions for a finite range of wavelengths, which demonstrates the existence of a saturation in amplitude. These results contradict most of the models.Comment: 4 pages, 5 figures, submitted to Phys. Rev. Lett. Title changed, figures corrected and simplified, more field data included, text clarifie

Simian immunodeficiency virus infection in wild-caught chimpanzees from Cameroon

Simian immunodeficiency viruses (SIVcpz) infecting chimpanzees (Pan troglodytes) in west central Africa are the closest relatives to all major variants of human immunodeficiency virus type 1 ([HIV-1]; groups M, N and O), and have thus been implicated as the source of the human infections; however, information concerning the prevalence, geographic distribution, and subspecies association of SIVcpz still remains limited. In this study, we tested 71 wild-caught chimpanzees from Cameroon for evidence of SIVcpz infection. Thirty-nine of these were of the central subspecies (Pan troglodytes troglodytes), and 32 were of the Nigerian subspecies (Pan troglodytes vellerosus), as determined by mitochondrial DNA analysis. Serological analysis determined that one P. t. troglodytes ape (CAM13) harbored serum antibodies that cross-reacted strongly with HIV-1 antigens; all other apes were seronegative. To characterize the newly identified virus, 14 partially overlapping viral fragments were amplified from fecal virion RNA and concatenated to yield a complete SIVcpz genome (9,284 bp). Phylogenetic analyses revealed that SIVcpzCAM13 fell well within the radiation of the SIVcpzPtt group of viruses, as part of a clade including all other SIVcpzPtt strains as well as HIV-1 groups M and N. However, SIVcpzCAM13 clustered most closely with SIVcpzGAB1 from Gabon rather than with SIVcpzCAM3 and SIVcpzCAM5 from Cameroon, indicating the existence of divergent SIVcpzPtt lineages within the same geographic region. These data, together with evidence of recombination among ancestral SIVcpzPtt lineages, indicate long-standing endemic infection of central chimpanzees and reaffirm a west central African origin of HIV-1. Whether P. t. vellerosus apes are naturally infected with SIVcpz requires further study