Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles.

Acid-degradable cationic nanoparticles encapsulating a model antigen (i.e., ovalbumin) were prepared by inverse microemulsion polymerization with acid-cleavable acetal cross-linkers. Incubation of these degradable nanoparticles with dendritic cells derived from bone marrow (BMDCs) resulted in the enhanced presentation of ovalbumin-derived peptides, as quantified by B3Z cells, a CD8+ T cell hybridoma. The cationic nature of the particles contributed to the increased surface endocytosis (or phagocytosis) observed with BMDCs, which is the first barrier to overcome for successful antigen delivery. The acid sensitivity of the particles served to direct more ovalbumin antigens to be processed into the appropriately trimmed peptide fragments and presented via the major histocompatibility complex (MHC) class I pathway following hydrolysis within the acidic lysosomes. It was also shown that adjuvant molecules such as unmethylated CpG oligonucleotides (CpG ODN) and anti-interleukin-10 oligonucleotides (AS10 ODN) could be co-delivered with the protein antigen for maximized cellular immune response

Correlated responses in tissue weights measured in vivo by computer tomography in Dorset Down sheep selected for lean tissue growth

The aim of this study was to estimate correlated responses in lean, fat and bone weights in vivo in Dorset Down sheep selected for lean tissue growth. Over the period 1986-1992 inclusive, the lean tissue growth line had been selected using two economic indices for an increased aggregate breeding value incorporating predicted lean and fat weights with positive and negative economic weightings, respectively. The control line was selected for no change in lean tissue growth each year. Animals were born and run on pasture all year round. X-ray computer tomography was used to estimate the weights of lean, fat and bone in vivo in the 1994-born sheep, aged 265-274 days and selected randomly into 12 rams and 12 ewes from the selected line and 10 rams and 9 ewes from the control line. The lean tissue growth line had significantly greater responses in lean weight (+0.65 + 0.10 kg) and lean percentage (+1.19 + 0.17%) and significantly lesser fat weight (-0.36 + 0.08 kg) and fat percentage (-1.88 + 0.20%) compared to the control line. There was a significant increase in bone weight (+0.27 + 0.03 kg) and bone percentage (+0.69 + 0.09%) in the lean tissue growth line compared to the control line. Responses differed significantly between sexes of the lean tissue growth line, rams having a greater response in weight of lean (+1.22 + 0.20 vs. +0.08 + 0.22 kg) and bone (+0.45 + 0.06 vs. +0.09 + 0.07 kg), and a lesser response in weight of fat (-0.03 + 0.15 vs. -0.70 + 0.16 kg) than the ewes. Selection led to significant changes in lean (increase) and fat weights (decrease), and bone weight increased. Although responses in the lean tissue growth line differed significantly between sexes, there were confounding factors due to differences in management and lack of comparison at equal stage of development. Therefore, to assess real genetic differences further studies should be conducted taking these factors into consideration. Keywords: Lean tissue growth, Computer tomography, Selection index, Responses, Sheep South African Journal of Animal Science Vol.33(3) 2003: 176-18

Field plate optimization in low-power high-gain source-gated transistors

Source-gated transistors (SGTs) have potentially very high output impedance and low saturation voltages, which make them ideal as building blocks for high-performance analog circuits fabricated in thin-film technologies. The quality of saturation is greatly influenced by the design of the field-relief structure incorporated into the source electrode. Starting from measurements on self-aligned polysilicon structures, we show through numerical simulations how the field plate (FP) design can be improved. A simple source FP around 1 μm long situated several tens of nanometers above the semiconductor can increase the low-voltage intrinsic gain by more than two orders of magnitude and offers adequate tolerance to process variations in a moderately scaled thin-film SGT. © 2012 IEEE

The transcript cleavage factor paralogue TFS4 is a potent RNA polymerase inhibitor

TFIIS-like transcript cleavage factors enhance the processivity and fidelity of archaeal and eukaryotic RNA polymerases. Sulfolobus solfataricus TFS1 functions as a bona fide cleavage factor, while the paralogous TFS4 evolved into a potent RNA polymerase inhibitor. TFS4 destabilises the TBP-TFB-RNAP pre-initiation complex and inhibits transcription initiation and elongation. All inhibitory activities are dependent on three lysine residues at the tip of the C-terminal zinc ribbon of TFS4; the inhibition likely involves an allosteric component and is mitigated by the basal transcription factor TFEα/β. A chimeric variant of yeast TFIIS and TFS4 inhibits RNAPII transcription, suggesting that the molecular basis of inhibition is conserved between archaea and eukaryotes. TFS4 expression in S. solfataricus is induced in response to infection with the S ulfolobus turreted icosahedral virus. Our results reveal a compelling functional diversification of cleavage factors in archaea, and provide novel insights into transcription inhibition in the context of the host-virus relationship

Mobility, functionality and functional mobility: A review and application for canine veterinary patients

Mobility is an essential aspect of a dog’s daily life. It is defined as the ability to move freely and easily and deviations from an animals’ normal mobility capabilities are often an indicator of disease, injury or pain. When a dog’s mobility is compromised, often functionality (ability to perform activities of daily living; ADL), is also impeded, which can diminish an animal’s quality of life. Given this, it is necessary to understand the extent to which conditions impact a dog’s physiological ability to freely move around their environment to carry out ADL, a concept termed functional mobility. In contrast to human medicine, validated measures of canine functional mobility are currently limited. The aim of this review is to summarise the extent to which canine mobility and functionality are associated with various diseases and how mobility and functional mobility are currently assessed within veterinary medicine. Future work should focus on developing a standardised method of assessing functional mobility in dogs, which can contextualise how a wide range of conditions impact a dog’s daily life. However, for a true functional mobility assessment to be developed, a greater understanding of what activities dogs do on a daily basis and movements underpinning these activities must first be established

Failure to activate the IFN-beta promoter by a paramyxovirus lacking an interferon antagonist

It is generally thought that pathogen-associated molecular patterns (PAMPs) responsible for triggering interferon (IFN) induction are produced during virus replication and, to limit the activation of the IFN response by these PAMPs, viruses encode antagonists of IFN induction. Here we have studied the induction of IFN by parainfluenza virus type 5 (PIV5) at the single-cell level, using a cell line expressing GFP under the control of the IFN-β promoter. We demonstrate that a recombinant PIV5 (termed PIV5-VΔC) that lacks a functional V protein (the viral IFN antagonist) does not activate the IFN-β promoter in the majority of infected cells. We conclude that viral PAMPs capable of activating the IFN induction cascade are not produced or exposed during the normal replication cycle of PIV5, and suggest instead that defective viruses are primarily responsible for inducing IFN during PIV5 infection in this syste