\u3cem\u3eIn Vivo\u3c/em\u3e Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model

Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNγ) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNγ responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs

Transcription analysis on response of swine lung to H1N1 swine influenza virus

<p>Abstract</p> <p>Background</p> <p>As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs.</p> <p>Results</p> <p>At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p < 0.05). The DE genes were involved in many vital functional classes, mainly including signal transduction, immune response, inflammatory response, cell adhesion and cell-cell signalling. Noticeably, the genes associated with immune and inflammatory response showed highly overexpressed. Through the pathway analysis, the significant pathways mainly concerned with Cell adhesion molecules, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway and MAPK signaling pathway, suggesting that the host took different strategies to activate these pathways so as to prevent virus infections at the early stage. However, on PID 7, the predominant function classes of DE genes included signal transduction, metabolism, transcription, development and transport. Furthermore, the most significant pathways switched to PPAR signaling pathway and complement and coagulation cascades, showing that the host might start to repair excessive tissue damage by anti-inflammatory functions. These results on PID 7 demonstrated beneficial turnover for host to prevent excessive inflammatory damage and recover the normal state by activating these clusters of genes.</p> <p>Conclusions</p> <p>This study shows how the target organ responds to H1N1 swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.</p

Observation of a temperature dependent asymmetry in the domain structure of a Pd-doped FeRh epilayer

Using X-ray photoelectron emission microscopy we have observed the coexistence of ferromagnetic and antiferromagnetic phases in a (3 at.%)Pd-doped FeRh epilayer. By quantitatively analyzing the resultant images we observe that as the epilayer transforms there is a change in magnetic domain symmetry from predominantly twofold at lower temperatures through to an equally weighted combination of both four and twofold symmetries at higher temperature. It is postulated that the lowered symmetry Ising-like nematic phase resides at the near-surface of the epilayer. This behavior is different to that of undoped FeRh suggesting that the variation in symmetry is driven by the competing structural and electronic interactions in the nanoscale FeRh film coupled with the effect of the chemical doping disorder.Comment: 10 pages, 8 figures, 1 tabl

Asymmetric “melting” and “freezing” kinetics of the magnetostructural phase transition in B2-ordered FeRh epilayers

Synchrotron X-ray diffraction was used to study the phase transformation processes during the magnetostructural transition in a B2-ordered FeRh (001)-oriented epilayer grown on MgO by sputtering. Out-of-plane lattice constant measurements within the hysteretic regime of the transition reveal a microstructure consistent with the coexistence of lattice-expanded and contracted phases in spatially distinct regions. It was found that the phase separation is more pronounced during cooling than heating. Furthermore, whilst lattice-expanded domains that span the height of the film can be undercooled by several kelvins, there is no equivalent superheating. This asymmetry between the cooling and heating processes in FeRh is consistent with the difference in the kinetics of generic freezing and melting transitions

The Circadian Response of Intrinsically Photosensitive Retinal Ganglion Cells

Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or intrinsic (retinal) network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18–30 years) with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux). Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO) was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells mediate this circadian variation

Inflammasome Sensor Nlrp1b-Dependent Resistance to Anthrax Is Mediated by Caspase-1, IL-1 Signaling and Neutrophil Recruitment

Bacillus anthracis infects hosts as a spore, germinates, and disseminates in its vegetative form. Production of anthrax lethal and edema toxins following bacterial outgrowth results in host death. Macrophages of inbred mouse strains are either sensitive or resistant to lethal toxin depending on whether they express the lethal toxin responsive or non-responsive alleles of the inflammasome sensor Nlrp1b (Nlrp1bS/S or Nlrp1bR/R, respectively). In this study, Nlrp1b was shown to affect mouse susceptibility to infection. Inbred and congenic mice harboring macrophage-sensitizing Nlrp1bS/S alleles (which allow activation of caspase-1 and IL-1β release in response to anthrax lethal toxin challenge) effectively controlled bacterial growth and dissemination when compared to mice having Nlrp1bR/R alleles (which cannot activate caspase-1 in response to toxin). Nlrp1bS-mediated resistance to infection was not dependent on the route of infection and was observed when bacteria were introduced by either subcutaneous or intravenous routes. Resistance did not occur through alterations in spore germination, as vegetative bacteria were also killed in Nlrp1bS/S mice. Resistance to infection required the actions of both caspase-1 and IL-1β as Nlrp1bS/S mice deleted of caspase-1 or the IL-1 receptor, or treated with the Il-1 receptor antagonist anakinra, were sensitized to infection. Comparison of circulating neutrophil levels and IL-1β responses in Nlrp1bS/S,Nlrp1bR/R and IL-1 receptor knockout mice implicated Nlrp1b and IL-1 signaling in control of neutrophil responses to anthrax infection. Neutrophil depletion experiments verified the importance of this cell type in resistance to B. anthracis infection. These data confirm an inverse relationship between murine macrophage sensitivity to lethal toxin and mouse susceptibility to spore infection, and establish roles for Nlrp1bS, caspase-1, and IL-1β in countering anthrax infection

Hall-effect characterization of the metamagnetic transition in FeRh

The antiferromagnetic ground state and the metamagnetic transition to the ferromagnetic state of CsCl-ordered FeRh epilayers have been characterized using Hall and magnetoresistance measurements. On cooling into the ground state, the metamagnetic transition is found to coincide with a suppression in carrier density of at least an order of magnitude below the typical metallic level that is shown by the ferromagnetic state. The carrier density in the antiferromagnetic state is limited by intrinsic doping from Fe/Rh substitution defects, with approximately two electrons per pair of atoms swapped, showing that the decrease in carrier density could be even larger in more perfect specimens. The surprisingly large change in carrier density is a clear quantitative indication of the extent of change at the Fermi surface at the metamagnetic transition, confirming that entropy release at the transition is of electronic origin, and hence that an electronic transition underlies the metamagnetic transition. Regarding the nature of this electronic transition, it is suggested that an orbital selective Mott transition, selective to strongly-correlated Fe 3d electrons, could cause the reduction in the Fermi surface and change in sign of the magnetic exchange from FM to AF on cooling

Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing

Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS

Strain-tuning of the magnetocaloric transition temperature in model FeRh films

The chemically ordered B2 phase of equiatomic FeRh is known to absorb or evolve a significant latent heat as it traverses its first-order phase transition in response to thermal, magnetic, and mechanical drivers. This attribute makes FeRh an ideal magnetocaloric material testbed for investigation of relationships between the crystalline lattice and the magnetic spins, which are especially experimentally accessible in thin films. In this work, epitaxial FeRh films of nominal 30 nm and 50 nm thicknesses with out-of-plane c-axis orientation were sputter-deposited at high temperature onto (0 0 1)-MgO or (0 0 0 1)-Al2O3 substrates and capped with Al, Au, Cr, or W after in situ annealing at 973 K to promote CsCl-type chemical order. In this manner a controlled strain state was invoked. Experimental results derived from laboratory and synchrotron x-ray diffraction combined with magnetometry indicate that the antiferromagnetic (AF)—ferromagnetic (FM) magnetostructural phase transformation in these films may be tuned over an ~50° range (373 K–425 K) through variation in the c/a ratio derived from lattice strain delivered by the substrate and the capping layers. These results supply fundamental information that might be used to engineer the magnetocaloric working material in new system designs by introducing targeted values of passive strain to the system

Personality profiles of cultures: aggregate personality traits

Personality profiles of cultures can be operationalized as the mean trait levels of culture members. College students from 51 cultures rated an individual from their country whom they knew well (N = 12, 156). Aggregate scores on Revised NEO Personality Inventory scales generalized across age and gender groups, approximated the individual-level Five-Factor Model, and correlated with aggregate self-report personality scores and other culture-level variables. Results were not attributable to national differences in economic development or to acquiescence. Geographical differences in scale variances and mean levels were replicated, with Europeans and Americans generally scoring higher in Extraversion than Asians and Africans. Findings support the rough scalar equivalence of NEO-PI-R factors and facets across cultures, and suggest that aggregate personality profiles provide insight into cultural differences