Vaccinia protein C16 blocks innate immune sensing of DNA by binding the Ku complex

VACV gene C16L encodes a 37-kDa protein that is highly conserved in orthopoxviruses and functions as an immunomodulator. Intranasal infection of mice with a virus lacking C16L (vΔC16) induced less weight loss, fewer signs of illness and increased infiltration of leukocytes to the lungs compared with wild-type virus. To understand C16’s mechanism of action, tandem affinity purification and mass spectrometry were used to identify C16 binding partners. This revealed that Ku70, Ku80 and PHD2 interact with C16 in cells. Ku70 and Ku80 constitute the Ku heterodimer, a well characterised DNA repair complex. MEFs lacking Ku, or the other component of the DNA-dependent protein kinase (DNA-PK) complex, the catalytic subunit of DNA-PK (DNA-PKcs), were shown to be deficient in the upregulation of IRF-3-dependent genes such as Cxcl10, Il6 and Ifnb in response to transfection of DNA, but not poly (I:C). Furthermore, following infection of MEFs with VACV strain MVA the activation of Cxcl10 or Il6 transcription was dependent on DNA-PK. Therefore, DNA-PK is a DNA sensor capable of detecting poxvirus DNA and activating IRF-3-dependent innate immunity. C16 inhibited the binding of Ku to DNA, and therefore inhibited DNA-mediated induction of Cxcl10 and Il-6 in MEFs. The role of C16 in vivo was also examined: infection with vΔC16 led to increased production of Cxcl10 and Il-6 following intranasal infection of mice compared with wild-type virus. C16 is therefore an inhibitor of DNA-PK-mediated DNA sensing and innate immune activation. C16 was also shown to bind to PHD2, an enzyme involved in regulation of hypoxic signalling. VACV was found to activate the transcription of hypoxia-related genes, and C16 expression in cells was also capable of doing this. The role of hypoxic signalling in VACV infection remains poorly understood

The Sacrements and Sacremental Actions in the Works of August Friedrich Chrisitan Vilmar

This paper is limited in its main part to what August Vilmar had to say about the Sacraments and what he termed “sacramental actions ( sakramentale Handlungen). It is difficult, in a few words, to determine just what Vilmar included under these terms because in keeping with the Lutheran Symbols he did not categorically limit the Sacraments to a certain number and exclude all other acts of the Church. In certain contexts he spoke of seven and more Sacraments, and in other contexts, of only two Sacraments, placing the lesser acts of the Church into the category “sacramental” actions. In general, one might say that he thought of three Sacraments-Holy Baptism, the Holy Eucharist, and Holy ,Absolution-as genuinely Sacraments, and that he called some of the other actions of the Church, such as Holy Ordination, Holy Matrimony, Holy Confirmation, and Holy Unction, “sacramental actions. Vilmar’s- numbering or the Sacraments will be discussed in greater detail in Chapter V

Henry Charles Lea: Jurisprudence and Civilization

During the same nineteenth century when the modern study of legal history got underway in Europe, from Savigny to the Codex Iuris Canonici of 1917, Henry Charles Lea (1825-1909), an ocean away and without a serious library in sight, undertook the study of several aspects of ecclesiastical and legal history that brought him into contact with canon law at virtually every turn. This talk will deal with Lea\u27s encounter with canon law - in and out of historical study proper - in the young and library-thin America of the 1850s and 60s. That is, I will focus on Lea\u27s early work - Superstition and Force (1866), An Historical Sketch of Sacerdotal Celibacy (1867), Studies in Church History (1869), and the beginning of his work on the various inquisitions. In the preface to the second edition of Superstition and Force (1870) Lea remarked that The history of jurisprudence is the history of civilization. For Lea, that jurisprudence included canon law

Bollworm (Lepidoptera: Noctuidae) production from alternate host crops and their contribution to a non-Bollgard cotton refuge

The bollworm’s, Helicoverpa zea (Boddie), inherent tolerance to the Bacillus thuringiensis toxin expressed in Bollgard® cotton and its ability to exploit numerous hosts has caused the Environmental Protection Agency to re-evalute the refuge component of the resistance management strategy. The goal of this project was to evaluate selected alternate host crops as supplemental non-cotton refuges for bollworm. The relative density, temporal occurrence, and life stage synchrony for bollworm larvae and adults was studied in Bollgard® cotton, Bollgard® cotton non-Bollgard® cotton, field corn, grain sorghum, and soybean. Native populations of bollworm larvae were monitored June to September during 2002 and 2003 in 0.1011-hectare plots in Northeast Louisiana and in commercial fields in Rapides, Concordia, Richland, and Tensas parishes. Bollworm larval occurrence varied considerably among all sites and crops based upon crop phenology, local environment, cultural production practices, and pest management strategies. Records of larval collection ranged from entirely absent in a sample to collections over a period of seven weeks. Peak densities in Bollgard® cotton were recorded from the 5 nodes above white flower (NAWF) to 1 node above cracked boll (NACB) growth stages, in non-Bollgard® cotton during the 7 NAWF to 1 NACB stages, in field corn during the R2-R5 growth stages, in grain sorghum during growth stages 4 to 9, and in maturity group (MG) 6 soybean during the R1-R6 growth stages. No larvae were observed in MG 4 soybean or in Bollgard® 2 cotton. Larval productivity was generally lowest in Bollgard® cotton fields and highest in grain sorghum and field corn, but larval development in the latter host crops was not consistently in temporal synchrony with that in Bollgard® cotton. The only host crops that exhibited temporal synchrony of larvae to that in Bollgard® cotton was non-Bollgard® cotton and MG 6 soybean. Bollworm adults were monitored with pheromone-baited wire cone traps at the interfaces of Bollgard® cotton and alternate crop hosts at the commercial field sites. During 2002 and 2003, totals of 39,356 and 42,552 adults were collected across all sample sites. Bollworm adult occurrence and total densities were generally similar among traps at all crop interfaces

The Significance of the P46 in the Second Epistle of St Paul to the Corinthians According to the Nestle Text

The purpose of this paper is to try to determine, to a certain extent, the significance of one of these Chester Beatty Papyri, namely P46, in St. Paul\u27s Second Epistle to the Corinthians. It tries to answer some of the questions that are being asked and which must be answered before critics are able to give P46 a final slot in the complicated maze of the history of the New Testament text

Luther and the Principle: Outside of the Use There Is No Sacrament

On the basis of a thorough search of the Weimar Edition and other pertinent materials the author argues that Luther taught that a valid celebration of the Sacrament of the Altar requires the acts of consecration, distribution, and reception, but that the presence of Christ\u27s body and blood is not limited to the moment of reception

Effect of antiscalants during eutectic freeze crystallization of a reverse osmosis retentate

Includes bibliography.Eutectic Freeze Crystallization (EFC) is a separation technique which involves simultaneous crystallization of water and solute under eutectic conditions. It can be applied to treatment of various industrial aqueous streams containing dissolved organic and inorganic contaminants, such as reverse osmosis (RO) retentate brine streams. Since antiscalants are dosed in RO feed streams, these become concentrated in the retentate brine stream and could have an undesirable effect on crystallization kinetics of both ice and salt in EFC. In this study, the impact of a phosphonate antiscalant on the kinetic processes of nucleation and growth in EFC was investigated. Firstly, the effect of an antiscalant on the thermodynamic phase equilibria of a binary Na2SO4 aqueous solution was experimentally determined. The effect of the antiscalant on the nucleation and growth rates of both ice and salt in a continuous EFC process was then established for concentrations of 200, 350 and 500 mg/L of antiscalant. Product quality parameters such as the Crystal Size Distribution (CSD), morphology and purity of crystals were also measured since they are directly affected by the kinetic rate processes investigated

Notes on the Mount Lyell mine

The western coast of Tasmania possesses but few indentations that can serve as reasonable harbours. Of these the most important one, commercially speaking, is Macquarie Harbour, on which is situated the port of Strahan. The country north of Strahan was subject to enormous fluctuations of level during early Silurian days, and deep seas alternated with wide, but shallow, lagoons, which in time rose into rugged hills, only again to disappear beneath the waters and lose their identity under the mud and pebbles that filled up the depressions and levelled the sea floor as with a smoothing iron. The mud and silt brought down by the ancient rivers, hardened into clay, slate, and schist, the pebbles were cemented into the ubiquitous conglomerate ; the blanketed sea floor, unable to lose its heat by radiation, sank deeper and deeper, causing the crumpling and upheaving that led to the last cycle of mountain-building, and the general configuration of the country became perhaps something as we now see it, though no doubt much lowered and scored, as well as filled up, by erosion and glacial action