Profit enhancing competitive pressure in vertically related industries

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing

SAXS investigations of polyethylene modified with methacrylic acid

The polyethylene/poly(methacrylic acid-co-divinylbenzene), PE/poly(MA-co-DVB), interpolymer type carboxylic membranes were studied using small-angle X-ray diffraction (SAXS) in order to deduce the effect of DVB content on their morphology. SAXS curves exhibit a maximum which indicates that the interpolymers have morphology of domain type. Using the standard theory for a two-phase system mean distance between domains and their sizes were calculated from the SAXS data. Analysis of the SAXS curves suggests a fractal behaviour of the internal surface, associated with this two-phase system. Results obtained from SAXS studies are consistent with the general model of these interpolymers revealed by microscopic investigations

Properties of Water in Prestretched Recast Nafion

NRC publication: Ye

Combining numercial and cognitive 3D modelling approaches in order to determine the structure of the Chalk in the London Basin

In order to determine the structure of the Chalk in the London Basin, a combined cognitive and numerical approach to model construction was developed. A major difficultly in elucidating the structure of the Chalk in the London Basin is that the Chalk is largely unexposed. The project had to rely on subsurface data such as boreholes and site investigation reports. Although a high density of data was available problems with the distribution of data and its quality meant that, an approach based on a numerical interpolation between data points could not be used in this case. Therefore a methodology was developed that enabled the modeller to pick out areas of possible faulting and to achieve a geologically reasonable solution even in areas where the data was sparse or uncertain. By using this combined approach, the resultant 3D model for the London Basin was more consistent with current geological observations and understanding. In essence, the methodology proposed here decreased the disparity between the digital geological model and current geological Knowledge. Furthermore, the analysis and interpretation of this model resulted in an improved understanding of how the London Basin evolved during the Cretaceous period

A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing

Epstein-Barr viral BNLF2a protein hijacks the tail-anchored protein insertion machinery to block antigen processing by the transport complex TAP

Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors

Epstein-Barr viral BNLF2a protein hijacks the tail-anchored protein insertion machinery to block antigen processing by the transport complex TAP

Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein. We demonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors