The Adenoviridae family includes clinically important viruses associated with acute episodes of pharyngitis, conjunctivitis, diarrhea, and cystitis in immunocompetent individuals. In immunosuppressed patients, particularly pediatric transplant recipients, adenoviruses (Ads) are capable of systemic viremic spread that produces significant levels of morbidity and mortality. More than 50 human Ads have been described, of which the common species C serotypes 2 and 5 (HAdV-2 and HAdV-5) have been studied most intensively (52), and demonstrated to encode functions that act in vitro and in vivo to promote evasion of both innate and adaptive host immune responses (11). Immunomodulatory functions are concentrated in the early transcription unit E3 (33, 51). An E3 protein, E3/19K, became an immunological paradigm when it was demonstrated to impede cell surface antigen presentation by retaining the major histocompatibility class I complex (MHC-I) in the endoplasmic reticulum (ER) (1,8,10,17). E3/ 10.4K and E3/14.5K (the RID complex) together remove Fas, tumor necrosis factor-related apoptosis-inducing ligand receptors 1 and 2, and the epidermal growth factor receptor from the cell surface and promote their subsequent degradation in lysosomes (5,12,18,24,44,45,51). Moreover, E3/14.7K suppresses inflammation and cytolysis by inhibiting tumor necrosis factor alphamediated signaling independently of the RID complex (11,26).We are interested in the role of NK cells in controlling Ad infections. NK cells are a heterogeneous population of cells expressing a wide range of activating and inhibitory receptors. NKG2D is a homodimeric activating receptor that is ubiquitously expressed on NK cells, ␥␦ T cells, and NKT cells and also on certain ␣ T-cell subsets (3). To date, seven human cellular NKG2D ligands (NKG2DLs) have been identified: the MHC-I chain-related A (MICA) and B (MICB) proteins, the UL16 binding proteins ULBP1 to -3, and the retinoic acid early inducible proteins E (ULBP4) and G (2, 3, 16). While MICA and MICB are closely related, sharing 84% amino acid (aa) identity and similar tertiary structures (25, 32), they are also highly polymorphic, with 61 MICA and 30 MICB alleles having been described (IMGT;
Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I–like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substitutions with little functional defects implied that E3/19K may have additional cellular target molecules. Indeed, when assessing MICA/B cell-surface expression we found that mutation of T14 and M82 selectively compromised MICA/B downregulation with essentially no effect on HLA-I modulation. In general, downregulation of HLA-I was more severely affected than that of MICA/B; for example, substitutions W52, M87, and W96 essentially abrogated HLA-I modulation while largely retaining the ability to sequester MICA/B. Thus, distinct conserved amino acids seem preferentially important for a particular functional activity of E3/19K.
The demand for consistent and enhanced injection moulded product quality continues to rise. Modern injection moulding machines come with extensive control and measurement systems for machine control which are generally not available to the user. However, it is desired to actually measure variables that are closely related to the process itself. Sensors normally used to do this are typically invasive. However, as a result of the breadth of application of injection moulding machines, there remains a desire by the process user to be able to monitor some aspects of the process preferably in a non-invasive manner, in order to monitor, control and improve the output.In this paper, the potential for process and production measurement on injection moulding machines using non-invasive, energy measurements is presented. In addition, a comparison of electric and hydraulic injection moulding machines is given, that highlights the benefits of energy measurement to the process user. Finally, it is concluded that energy monitoring can provide a 'fingerprint' of a process, and hence can be used for product quality control.
Editorial NoteHere are two short pieces concerning aspects of industrial relations and the nature of control. We received these pieces co-incidentally and coincidentally they both have a character called Bannister. They share the medium of the short story to present industrial relations in a culture where information about this part of working life is either transmitted through the dry statistics and legal language of the academic or the melodramatic headlines of the daily papers. These short storiesone stemming from the dramatic circumstances of a colliery explosion, and one from the mundane drama surrounding working rulesillustrate some things which neither the academic nor the melodramatic succeed in doing. We can all relate to the central characters in these dramas; we can ponder on their practical and ethical dilemmas; we can wonder what we would have done in these circumstances. For there is nothing black and white hereno right answers or infallible procedures to follow when problems such as these present themselves. We get some clear messages nevertheless about the nature of authority, both personal and institutional, and how the one strains or supports the other in that field of tension which we call industrial relations. MIKE PEDLER
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.