Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly.

Non-structural protein 2 (NS2) plays an important role in hepatitis C virus (HCV) assembly, but neither the exact contribution of this protein to the assembly process nor its complete structure are known. In this study we used a combination of genetic, biochemical and structural methods to decipher the role of NS2 in infectious virus particle formation. A large panel of NS2 mutations targeting the N-terminal membrane binding region was generated. They were selected based on a membrane topology model that we established by determining the NMR structures of N-terminal NS2 transmembrane segments. Mutants affected in virion assembly, but not RNA replication, were selected for pseudoreversion in cell culture. Rescue mutations restoring virus assembly to various degrees emerged in E2, p7, NS3 and NS2 itself arguing for an interaction between these proteins. To confirm this assumption we developed a fully functional JFH1 genome expressing an N-terminally tagged NS2 demonstrating efficient pull-down of NS2 with p7, E2 and NS3 and, to a lower extent, NS5A. Several of the mutations blocking virus assembly disrupted some of these interactions that were restored to various degrees by those pseudoreversions that also restored assembly. Immunofluorescence analyses revealed a time-dependent NS2 colocalization with E2 at sites close to lipid droplets (LDs) together with NS3 and NS5A. Importantly, NS2 of a mutant defective in assembly abrogates NS2 colocalization around LDs with E2 and NS3, which is restored by a pseudoreversion in p7, whereas NS5A is recruited to LDs in an NS2-independent manner. In conclusion, our results suggest that NS2 orchestrates HCV particle formation by participation in multiple protein-protein interactions required for their recruitment to assembly sites in close proximity of LDs.

Photographic rectification of the graphic documentation of historical and archaeological heritage: The case of the southern facade of the Praetorium tower in Tarragona (Tarraco, Hispania Citerior)

This article details the use of photographic rectification as support for the graphic documentation of historical and archaeological heritage and specifically the southern facade of the Torre del Pretori (Praetorium Tower) in Tarragona. The Praetorium Tower is part of a larger monumental complex and one of the towers that connected different parts of the Tarraco Provincial Forum, the politic-administrative centre of the ancient capital of Hispania Citerioris. It is therefore a valuable example of the evolution of Roman urban architecture. The aim of this project is to provide accurate graphic documentation of the structure to facilitate the restoration and conservation of the tower, as well as to provide a more profound architectural and archaeological understanding of the Roman forum. The use of photographic rectification enabled us to overcome the spatial and time difficulties involved in collecting data caused by the size and location of the building. Specific software made it easier to obtain accurate two-dimensional images. For this reason, in our case, photographic rectification helped us to make a direct analysis of the monument and facilitated interpretation of the architectural stratigraphy. We currently separate the line of research into two concepts: the construction processes and the architecture of the building. The documentation collected permitted various analyses: the characterisation of the building modules, identification of the tools used to work the building materials, etc. In conclusion, the use of orthoimages is a powerful tool that permits the systematic study of a Roman building that has evolved over the centuries and is now in a modern urban context.

Variability of the nucleolar organizer activity in human lymphocytes via Ag-staining.

Chromosomes with Ag staining that varies from one metaphase to the other can be distinguished from those with an Ag-staining that is the same in all metaphases. The intercellular variation of an Ag-NOR can be attributed to many different factors. Whatever the importance of technical factors, they do not seem to account for the large variations in Ag-staining which were observed for each ac. This suggests the existence of a natural intercellular variability of the NOR's activity. The variation of the Ag-stainability of a given NOR, the diversity of Ag-stainings observed on the ten ac of one individual and the differences that exist between individuals raise the question of the existence of a compensation of activity between nucleolar organizers. The study, for each individual, of the mean sum of staining per metaphase reveals that this value is not absolutely constant from one individual to another; in the carriers of Robertsonian fusions it is smaller than in chromosomally normal individuals. The analysis of the transmission shows that inactive NORs remain inactive and that active NORs present a variation in the activity from one generation to the next.

Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer

Background: The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. Results: In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. Conclusions: The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations.

Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer

Background: The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. Results: In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. Conclusions: The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations.

The Comprehensive Standardization of the Graphic Industry Production Chain in the Printing House

The purpose of this thesis was to investigate Job Definition Format (JDF) and how it could be used in printing house's systems. JDF is a very new information exchange standard, and it gives a lot of opportunities to the printing industry. JDF is the first standard, that has an ability to carry a print job from genesis through completion. Besides, JDF has an ability to bridge the communication gap between production and management information services. In the study of JDF we focused on examining how JDF will effect on printing industry .The thesis also examines printing houses's systems ability to work with JDF standard. The result of the study is a comprehensive picture, what is JDF. We also researched the system developers' visions, how JDF will effect on their products in the future.

A graphic explanation on how a tax on exports neutralizes the Dutch disease without costs to exporters

The adequate way of neutralizing the Dutch disease is the imposition of a variable tax on the export of the commodity that originates the disease. If such tax is equivalent to the "size" of the Dutch disease, it will shifts to the right its supply curve of the commodity in relation to the exchange rate, giving the existing domestic supply and the international demand, the exchange rate will depreciate at the value of the tax, and the equilibrium exchange rate will move from the "current" to the "industrial" equilibrium.

Comics carnet : the graphic novelist as global nomad

An interdisciplinary approach is used to identify a new graphic novel genre, 'comics camet', and its key features. The study situates comics camet in a historical context and shows it to be the result of a cross-pollination between the American and French comics traditions. Comics camet incorporates features from other literary genres: journalism, autobiography, ethnography and travel writing. Its creators, primarily European rriales, document their experiences visiting countries that Europe has traditionally defined as belonging to the 'East'. A visual and narrative analysis, using theoretical perspectives derived from cultural and postcolonial studies, examines how comics camet represents the non-European other and identifies the genre's ideological assumptions. Four representative texts are examined: Joe Sacco's Palestine (2001), Craig Thompson's, Camet de Voyage (2004), Guy Delisle's Pyongyang (2005) and Mrujane Satrpi's Persespolis 2 (2004). The study concludes that the comics camet genre simultaneously reinforces and challenges stereotypical assumptions about non-European people and places.

Graphic medicine from library to classroom

Introduction. Graphic medicine is defined as the use of comics in health sciences education and patient care. Graphic stories about personal experiences of illness from patients and their families can be used to illustrate distress, empathy and collaboration between family members and health professionals and thus give students a broader experience of disease. We present a collection of graphic novels and outline collaboration with professors from various faculties in order to use comics as teaching material in health sciences. Method. The university has health sciences faculties of Nursing, Medicine, Pharmacy, Dentistry, Veterinary Medicine and schools of Public Health, Optometry and Kinesiology. The Health Library is offering its patrons a collection of 40 comics mainly on the theme of patient and family illness experience. An ongoing survey gathers feedback from users; results will help us promote the collection. A librarian is working with professors from the facultiesof Nursing, Medicine and Pharmacy in order to integrate comics’ excerpts into e-learning modules for three health and social services interprofessional courses reaching more than 1000 students annually. Other courses teaching empathy and partnership with patients will be identified and professors will be approached to raise awareness of the collection’s potential as teaching material. Results. The collection has been available to patrons since October 2012. Survey responses collected so far are very positive and titles are regularly borrowed. The collection has been added as suggested reading in a physiotherapy course outline. Discussion. The comics’ collection is already widely used by our patrons. Steps are being taken to integrate the collection into more health sciences courses and thus define graphic medicine as teaching material in health sciences education at the university.

The problem of the graphic artist

'The problem of the graphic artist' is a small example of applying elementary mathematics (divisibility of natural numbers) to a real problem which we ourselves have actually experienced. It deals with the possibilities for partitioning a sheet of paper into strips. In this contribution we report on a teaching unit in grade 6 as well as on informal tests with students in school and university. Finally we analyse this example methodologically, summarise our observations with pupils and students, and draw some didactical conclusions.

Introduction to graphic arts history

An introductory 1 hour lecture given in wk2 to x50 year 1 Graphic Arts students at Winchester School of Art. The aims of the lecture are: 1. Explore how to use historical sources appropriately 
to inform design practice
 2. Make connections between contemporary 
designs and the past

Ethics and Graphic Arts

Discussion of ethical issues pertaining to communication design