Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats

<p>Abstract</p> <p>Background</p> <p>Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of such cross-protection showed that cytotoxic T lymphocytes (CTL) protect H3N2-immune mice from a lethal H1N1 infection. More recent studies in mice demonstrate that antibodies also contribute to heterosubtypic immunity (HSI). We previously demonstrated that HSI in cotton rats (<it>Sigmodon hispidus</it>) is characterized by protection of H3N2-immune animals from influenza H1N1-induced increase in respiratory rate (tachypnea). Alternatively, H1N1-immune animals are protected from H3N2-induced tachypnea. The experiments described in this report were designed to elucidate the immune mechanism that prevents this very early sign of disease.</p> <p>Results</p> <p>Our results show that cotton rats provided with H1N1-immune serum prior to challenge with an H3N2 virus were protected from influenza-associated tachypnea, with the degree of protection correlating with the antibody titer transferred. Immunization with an inactivated preparation of virus delivered intramuscularly also provided some protection suggesting that CTL and/or mucosal antibody responses are not required for protection. Antibodies specific for conserved epitopes present on the virus exterior are likely to facilitate this protection since prophylactic treatment of cotton rats with anti-M2e (the extracellular domain of M2) but not anti-nucleoprotein (NP) reduced virus-induced tachypnea.</p> <p>Conclusion</p> <p>In the cotton rat model of heterosubtypic immunity, humoral immunity plays a role in protecting animals from influenza-induced tachypea. Partial protection against respiratory disease caused by different influenza A subtypes can be attained with either live virus administered intranasally or inactivated virus delivered intramuscularly suggesting that either vaccine regimen may provide some protection against potential pandemic outbreaks in humans.</p

Embedding Four-directional Paths on Convex Point Sets

A directed path whose edges are assigned labels "up", "down", "right", or "left" is called \emph{four-directional}, and \emph{three-directional} if at most three out of the four labels are used. A \emph{direction-consistent embedding} of an \mbox{$n$-vertex} four-directional path $P$ on a set $S$ of $n$ points in the plane is a straight-line drawing of $P$ where each vertex of $P$ is mapped to a distinct point of $S$ and every edge points to the direction specified by its label. We study planar direction-consistent embeddings of three- and four-directional paths and provide a complete picture of the problem for convex point sets.Comment: 11 pages, full conference version including all proof

Anaphase Onset does not Require the Microtubule-Dependent Depletion of Kinetochore and Centromere-Binding Proteins

Spindle checkpoint proteins, such as Mad2 and BubR1, and the motors dynein/dynactin and CENP-E usually leave kinetochores prior to anaphase onset by microtubule-dependent mechanisms. Likewise, \u27chromosome passenger proteins\u27 including INCENP are depleted from the centromeres after anaphase onset and then move to the midzone complex, an event that is essential for cytokinesis. Here we test whether the cell cycle changes that occur at anaphase onset require or contribute to the depletion of kinetochore and centromere proteins independent of microtubules. This required the development of a novel non-antibody method to induce precocious anaphase onset in vivo by using a bacterially expressed fragment of the spindle checkpoint protein Mad1 capable of activating the APC/C, called GST-Mad1F10. By injecting PtK1 cells in nocodazole with GST-Mad1F10 and processing the cells for immunofluorescence microscopy after anaphase sister chromatid separation in nocodazole we found that Mad2, BubR1, cytoplasmic dynein, CENP-E and the 3F3/2 phosphoepitope remain on kinetochores. Thus depletion of these proteins (or phosphoepitope) at kinetochores is not required for anaphase onset and anaphase onset does not produce their depletion independent of microtubules. In contrast, both microtubules and anaphase onset are required for depletion of the \u27chromosome passenger\u27 protein INCENP from centromeres, as INCENP does not leave the chromosomes prior to anaphase onset in the presence or absence of microtubules, but does leave the centromeres after anaphase onset in the presence of microtubules

Modeling Temporal Trends in Aphid Vector Dispersal and Cucumber Mosaic Virus Epidemics in Snap Bean

Cucumber mosaic virus (CMV) has become a major limiting factor in snap bean production in the Great Lakes region of North America, and epidemics have occurred more frequently since the soybean aphid, Aphis glycines Matsumura, was introduced. Major aphid vectors of CMV epidemics were identified by statistically relating their temporal dispersal trends to the incidence of CMV. Alates were monitored weekly using water pan traps in 74 snap bean fields in New York and Pennsylvania from 2002 to 2006. Plants were tested for CMV by ELISA one time during late bloom in 2002 and 2003 and weekly over the season from 2004 to 2006. Principal vectors of CMV included Acyrthosiphon pisum (Harris), A. glycines, Aphis gossypii Glover, and Therioaphis trifolii (Monell). Among these, A. glycines and T. trifolii were likely responsible for severe CMV epidemics because they were among the most abundant species captured, they efficiently transmit CMV, and their dispersal activity was positively correlated with periods when CMV incidence was highest. Moreover, because high numbers of A. glycines and T. trifolii disperse during July and August, snap bean fields planted beyond late June are at risk for infection during early vegetative stages and are subsequently more at risk for yield loss. In contrast, plantings up to late June are less likely to become infected during early developmental stages and should escape yield loss because major vectors are dispersing infrequently. CMV-resistant or tolerant snap bean varieties should be planted after late June to reduce the risk of yield los

Distribution of endemic and imperiled fauna of the Tallapoosa River system of Georgia

Proceedings of the 2003 Georgia Water Resources Conference, held April 23-24, 2003, at the University of Georgia.A proposal for a water supply reservoir in the Tallapoosa River system in Northwest Georgia has called attention to the potential effects of a large impoundment on the faunal resources of the system. The Tallapoosa and Little Tallapoosa Rivers and their tributaries support species assemblages found nowhere else, including five endemic fishes, two endemic crayfishes, and an endemic snail, in addition to a federally threatened mussel (Lampsilis altilis). We are analyzing survey data collected in 1990 and in 2002 to estimate species distributions, abundances, and changes in both of these factors relative to changes in land use. These data will be useful to the U.S. Fish and Wildlife Service and others for designing conservation strategies for the unique fauna of the Tallapoosa River system

Candida albicans repetitive elements display epigenetic diversity and plasticity

Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation