bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonstructural Protein Precursor NS4A/B from Hepatitis C Virus Alters Function and Ultrastructure of Host Secretory Apparatus
Authors: Konan Kouacou V. , Giddings Thomas H. , Ikeda Masanori , Li Kui , Lemon Stanley M. , Kirkegaard Karla 
Published: June 2003

ABSTRACT

The nonstructural proteins of hepatitis C virus (HCV) have been shown previously to localize to the endoplasmic reticulum (ER) when expressed singly or in the context of other HCV proteins. To determine whether the expression of HCV nonstructural proteins alters ER function, we tested the effect of expression of NS2/3/4A, NS4A, NS4B, NS4A/B, NS4B/5A, NS5A, and NS5B from genotype 1b HCV on anterograde traffic from the ER to the Golgi apparatus. Only the nominal precursor protein NS4A/B affected the rate of ER-to-Golgi traffic, slowing the rate of Golgi-specific modification of the vesicular stomatitis virus G protein expressed by transfection by approximately threefold. This inhibition of ER-to-Golgi traffic was not observed upon expression of the processed proteins NS4A and NS4B, singly or in combination. To determine whether secretion of other cargo proteins was inhibited by NS4A/B expression, we monitored the appearance of newly synthesized proteins on the cell surface in the presence and absence of NS4A/B expression; levels of all were reduced in the presence of NS4A/B. This reduction is also seen in cells that contain genome length HCV replicons: the rate of appearance of major histocompatibility complex class I (MHC-I) on the cell surface was reduced by three- to fivefold compared to that for a cured cell line. The inhibition of protein secretion caused by NS4A/B does not correlate with the ultrastructural changes leading to the formation a “membranous web” (D. Egger et al., J. Virol.
76:
5974-5984, 2002), which can be caused by expression of NS4B alone. Inhibition of global ER-to-Golgi traffic could, by reducing cytokine secretion, MHC-I presentation, and transport of labile membrane proteins to the cell surface, have significant effects on the host immune response to HCV infection.
Generation of Influenza A Viruses with Chimeric (Type A/B) Hemagglutinins
Authors: Horimoto Taisuke , Takada Ayato , Iwatsuki-Horimoto Kiyoko , Hatta Masato , Goto Hideo , Kawaoka Yoshihiro 
Published: June 2003

ABSTRACT

To gain insight into the intertypic incompatibility between type A and B influenza viruses, we focused on the hemagglutinin (HA) gene, systematically studying the compatibility of chimeric (type A/B) HAs with a type A genetic background. An attempt to generate a reassortant containing an intact type B HA segment in a type A virus background by reverse genetics was unsuccessful despite transcription of the type B HA segment by the type A polymerase complex. Although a type A virus with a chimeric HA segment comprising the entire coding sequence of the type B HA flanked by the noncoding sequence of the type A HA was viable, it replicated only marginally. Other chimeric viruses contained type A/B HAs possessing the type A noncoding region together with either the signal peptide or transmembrane/cytoplasmic region of type A virus or both, with the remaining regions derived from the type B HA. Each of these viruses grew to median tissue culture infectious doses of more than 10
5
per ml, but those with more type A HA regions replicated better, suggesting protein-protein interactions or increased HA segment incorporation into virions as contributing factors in the efficient growth of this series of viruses. All of these chimeric (A/B) HA viruses were attenuated in mice compared with wild-type A or B viruses. All animals intranasally immunized with a chimeric virus survived upon challenge with a lethal dose of wild-type type B virus. These results suggest a framework for the design of a novel live vaccine virus.
Modulation of Borna Disease Virus Phosphoprotein Nuclear Localization by the Viral Protein X Encoded in the Overlapping Open Reading Frame
Authors: Kobayashi Takeshi , Zhang Guoqi , Lee Byeong-Jae , Baba Satoko , Yamashita Makiko , Kamitani Wataru , Yanai Hideyuki , Tomonaga Keizo , Ikuta Kazuyoshi 
Published: June 2003

ABSTRACT

Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the
Mononegavirales
order. Unlike other animal viruses in this order, BDV replicates and transcribes in the nucleus of infected cells. Therefore, regulation of the intracellular movement of virus components must be critical for accomplishing the BDV life cycle in mammalian cells. Previous studies have demonstrated that BDV proteins are prone to accumulate in the nucleus of cells transiently transfected with each expression plasmid of the viral proteins. In BDV infection, however, cytoplasmic distribution of the viral proteins is frequently found in cultured cells and animal brains. In this study, to understand the modulation of subcellular localization of BDV proteins, we investigated the intracellular localization of the viral phosphoprotein (P). Transient-transfection analysis with a cDNA clone corresponding to a bicistronic transcript that expresses both viral X and P revealed that P efficiently localizes in the cytoplasm only when BDV X is expressed in the cells. Furthermore, our analysis revealed that the direct binding between X and P is necessary for the cytoplasmic localization of the P. Interestingly, we showed that X is not detectably expressed in the BDV-infected cells in which P is predominantly found in the nucleus, with little or no signal in the cytoplasm. These observations suggested that BDV P can modulate their subcellular localization through binding to X and that BDV may regulate the expression ratio of each viral product in infected cells to control the intracellular movement of the viral protein complexes. The results presented here provide a new insight into the regulation of the intracellular movement of viral proteins of a unique, nonsegmented, negative-strand RNA virus.
Structure-Based Mutagenesis of Herpes Simplex Virus Glycoprotein D Defines Three Critical Regions at the gD-HveA/HVEM Binding Interface
Authors: Connolly Sarah A. , Landsburg Daniel J. , Carfi Andrea , Wiley Don C. , Cohen Gary H. , Eisenberg Roselyn J. 
Published: June 2003

ABSTRACT
Herpes simplex virus (HSV) entry into cells requires the binding of glycoprotein D (gD) to one of several cell surface receptors. The crystal structure of gD bound to one of these receptors, HveA/HVEM, reveals that the core of gD comprises an immunoglobulin fold flanked by a long C-terminal extension and an N-terminal hairpin loop. HveA is a member of the tumor necrosis factor receptor family and contains four cysteine-rich domains (CRDs) characteristic of this family. Fourteen amino acids within the gD N-terminal loop comprise the entire binding site for HveA. To determine the contribution of each gD contact residue to virus entry, we constructed gD molecules mutated in these amino acids. We determined the abilities of the gD mutants to bind receptors, facilitate virus entry, and mediate cell-cell fusion. Seven of the gD mutants exhibited wild-type levels of receptor binding and gD function. Results from the other seven gD mutants revealed three critical regions at the gD-HveA interface. (i) Several gD residues that participate in an intermolecular β-sheet with HveA were found to be crucial for HveA binding and entry into HveA-expressing cells. (ii) Two gD residues that contact HveA-Y23 contributed to HveA binding but were not required for mediating entry into cells. HveA-Y23 fits into a crevice on the surface of gD and was previously shown to be essential for gD binding. (iii) CRD2 was previously shown to contribute to gD binding, and this study shows that one gD residue that contacts CRD2 contributes to HveA binding. None of the gD mutations prevented interaction with nectin-1, another gD receptor. However, when cotransfected with the other glycoproteins required for fusion, two gD mutants gained the ability to mediate fusion of cells expressing nectin-2, a gD receptor that interacts with several laboratory-derived gD mutants but not with wild-type gD. Thus, results from this panel of gD mutants as well as those of previous studies (A. Carfi, S. H. Willis, J. C. Whitbeck, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and D. C. Wiley, Mol. Cell 8:169-179, 2001, and S. A. Connolly, D. J. Landsburg, A. Carfi, D. C. Wiley, R. J. Eisenberg, and G. H. Cohen, J. Virol. 76:10894-10904, 2002) provide a detailed picture of the gD-HveA interface and the contacts required for functional interaction. The results demonstrate that of the 35 gD and HveA contact residues that comprise the gD-HveA interface, only a handful are critical for complex formation.
The Zipper Region of Epstein-Barr Virus bZIP Transcription Factor Zta Is Necessary but Not Sufficient To Direct DNA Binding
Authors: Hicks Matthew R. , Al-Mehairi Salama S. , Sinclair Alison J. 
Published: June 2003

ABSTRACT
The viral bZIP transcription factor Zta (BZLF1, EB1, ZEBRA) mediates the switch between the latent and lytic cycles of Epstein-Barr virus (EBV). In part, its activity requires the formation of homodimers and interaction with specific DNA sequence elements (ZREs). Zta has an atypical zipper motif that has a lower stability than do typical bZIP proteins. Here we show that a synthetic peptide directed against the zipper can disrupt the DNA-binding function of Zta. This highlights the relevance of this region for the function of Zta and demonstrates that the zipper region is a potential target for therapeutic agents. We also unmask the relevance of a region adjacent to the zipper (CT region), which is required to direct the interaction of Zta with DNA and to transactivate ZRE-dependent promoters in vivo.
Theory of Accretion Disks I: Angular Momentum Transport Processes
Authors: Papaloizou J. C. B. , Lin D. N. C. 
Published: July 2003

Accretion disk flow is a common phenomenon in astrophysics. It provides the nursery for planetary system formation and the channel for mass transfer in interacting binary stars. Such flows are also associated with the central engine for active galactic nuclei. Mass is redistributed in accretion disks as a consequence of angular momentum transfer. The identification of the dominant process involved is an important task in the development of accretion disk theory. Here, we review recent theoretical investigations on several important physical processes, including: 1. the removal of angular momentum from disks through hydromagnetic winds, 2. the amplification of local viscous stress through the onset of turbulence resulting from possible hydromagnetic, convective, or shear flow instabilities, 3. the transport of angular momentum carried by propagating waves, and 4. torque resulting from the presence of nonaxisymmetric unstable modes in self-gravitating and geometrically thick disks. Because of the technical nature of this subject, we present some of the mathematical formalisms in a pedagogical manner. We focus our attention on the physical discussion of the necessary conditions for each process to operate and the efficiency of angular momentum transfer to be expected. In Part II of this review, we shall present observational evidences and discuss applications of theoretical results in different astrophysical contexts.
Metabolomics in Systems Biology
Authors: Weckwerth Wolfram 
Published: July 2003

The primary aim of “omic” technologies is the nontargeted identification of all gene products (transcripts, proteins, and metabolites) present in a specific biological sample. By their nature, these technologies reveal unexpected properties of biological systems. A second and more challenging aspect of omic technologies is the refined analysis of quantitative dynamics in biological systems. For metabolomics, gas and liquid chromatography coupled to mass spectrometry are well suited for coping with high sample numbers in reliable measurement times with respect to both technical accuracy and the identification and quantitation of small-molecular-weight metabolites. This potential is a prerequisite for the analysis of dynamic systems. Thus, metabolomics is a key technology for systems biology. The aim of this review is to (a) provide an in-depth overview about metabolomic technology, (b) explore how metabolomic networks can be connected to the underlying reaction pathway structure, and (c) discuss the need to investigate integrative biochemical networks.
When All is said and Done
Authors: Benacerraf Baruj 
Published: July 2003

Dr. Benacerraf describes his experience in training immunologists for a period of over 30 years. He then analyzes the circumstances in which selected discoveries were made in his laboratory and the events and reasoning that led to these findings. The following topics are discussed: The phagocytic activity of the reticulo-endothelial system. The pathogenesis of immune complex diseases. The impact of activated macrophages on tumor rejection. The evidence that T-cell immunity is specific for internal protein determinants generated by antigen processing. The maturation of the antibody response in terms of antibody affinity. The discovery of Ir gene control of specific immuner esponses and the role of MHC molecules as presenters of peptide antigens to T cells. The generation of alloreactivity. Lastly, he addresses the administration of science and, particularly, the problems related to the transfer of technology to industrial partners.
Bacterial Genetics
Authors: Cavalli-Sforza Luigi Luca 
Published: July 2003

Microbial genetics is still in a phase of expansion and the splitting of the subject this year has somewhat relieved the reviewer's labours. The present paper attempts to cover the developments in the genetics of bacteria which have taken place in the years 1955 and 1956, i.e., subsequent to the publication of the previous review by Zelle (181). Work on phage will be considered only insofar as directly relevant. The author is also grateful to the editors for their encouragement in suggesting that attention be focussed on selected problems. The choice of subjects to which more space and time has been dedicated is inevitably dependent on the author's taste and background. Although a general picture has been attempted, omissions may have occurred, voluntarily or involuntarily. Moreover, the tyranny of space has made it impossible to consider cytology, radiation, and biochemical genetics, except for a few selected themes. Apologies are offered in advance to readers and writers for these omissions. The following topics will be discussed: mechanisms of genetic transfer; genetic changes in individuals and populations; phenogenetics; some cytological contributions; taxonomy and the species problem.
Blood, Birds, and the Old Road
Authors: Wilkinson Denys 
Published: July 2003

This personal retrospective covers half a century of the development of our understanding of the atomic nucleus with particular reference to the writer’s involvement in it: nuclear instrumentation, nuclear photodisintegration, the early years of the shell model, nuclear symmetries, isospin, and β-decay. “. . . a breaker of stones on an old road to a not yet clearly marked destination.”
The Evolution of National Nutrition Policy
Authors: Kessler David A. 
Published: July 2003

Domestic regulatory efforts in the area of nutrition historically have focused on achieving and sustaining the highest possible level of food safety and availability. More recently, the linkages between certain dietary practices and the risk of chronic, degenerative diseases have also become a significant focus of public policy. In order to promote good nutrition practices, the Food and Drug Administration (FDA) now requires a detailed and informative Nutrition Facts food label on virtually all food packages. Other public policies promoted by the FDA and others include increasing public knowledge of the relationship between diet and health; promoting unified food and nutrition policies among all government agencies; educating the American consumer about sound dietary practices; and encouraging the development of technologies that may result in more healthful, more abundant, and more affordable foods.
Roy Markham: Pioneer in Plant Pathology
Authors: Matthews R. E. F. 
Published: July 2003

I first met Roy Markham in September 1945, when I came to Cambridge after four years in the New Zealand army to begin research for the PhD in plant virology. As far as the University was concerned Dr. K. M. Smith was my supervisor, but I very rapidly came under Roy’s influence, and he was my de facto supervisor for three years. I came back to his group for four full years from 1952 to 1956 and later made several short visits to his laboratory both in Cambridge and, after the shift, in Norwich. Thus, I knew him well for a significant portion of his working life. Roy made a number of seminal contributions to plant virology and thus to plant pathology. However, he was in no sense a plant pathologist himself. His formal training was in biochemistry, and he learned a great deal in the physical sciences on his own account. In the main thrust of his research, he was really one of the pioneers in that branch of science now known as molecular biology.
Concepts and Terminology on Plant/Pest Relationships: Toward Consensus in Plant Pathology and Crop Protection
Authors: Bos L , Parlevliet J E 
Published: July 2003

In plant pathology, terminological confusion still reigns despite national attempts at standardization. Terminological agreements reached within the crop protection community in The Netherlands are elaborated here and presented as an endeavor toward international consensus. Much of the on-going terminological disconcert derives from differences in outlook between academically oriented biologists (including biologically trained pathologists) and pathologists working in and for agricultural institutions where disease and harm have anthropocentric connotations. The name crop protection science more realistically covers and marks the field dealt with by most plant pathologists, and adoption of the FAO-defined term pest to encompass all biotic factors that are harmful to plants and their products is advocated. The effect of pests on plants and the interrelationships between pests and plants in dependence upon the environment, topical in resistance breeding, are especially dealt with. A diagrammatic model is used to better describe these relationships and to define the terms that denote the phenomena and mechanisms involved.
The Petite Bourgeoisie in Late Capitalism
Authors: Bechhofer F. , Elliott B. 
Published: July 2003

Over the past decade or so social scientists and policy makers have grown increasingly interested in the role of the petite bourgeoisie in capitalist societies. The paper begins by sketching the major sociological approaches to the study of this stratum and the diverse characteristics of and propositions put forth about the fortunes of the petite bourgeoisie. The second section draws together evidence from several western societies in an attempt to appraise arguments about the alleged archaism, the long run decline, or the possible regeneration of the small business sector of western economies. The economic significance of the petite bourgeoisie is assessed with respect to information about the capacity of the stratum to provide employment, to generate new jobs, and to stimulate innovation. The small business sector also has considerable political significance. Though its role in the political life of particular societies shows considerable variation it is everywhere an important repository of ideas and sentiments supportive of capitalism and the institutions of liberal democracy. This is a fact which contemporary right wing governments have been quick to recognize. The petite bourgeoisie is a socially distinctive and persistent element in capitalist societies. Factors that do much to account for its reproduction include the effects of recession, processes of technical change, and government policies that support and encourage smallseale entrepreneurial activity. The paper concludes by arguing that even in economies dominated by large corporations, petits bourgeois businesses continue to provide jobs for a substantial proportion of the population and the most personal and direct experience of capitalism for many citizens.
Urban Policy Analysis
Authors: Clark Terry Nichols 
Published: July 2003

Four overlapping subfields of urban policy analysis are reviewed. The political leadership analyses include elite theories, group theory, neo-Marxist work, and network analyses. Consideration of citizen preferences involves populist spatial theories, budget pies, and policy responsiveness. Bureaucratic theories include incrementalism, the dynamic bureau head, and professionalism. Population and economic location analyses increasingly stress small firms, simultaneity of job and residential choice, and impacts of public policy. These alternative approaches were often advanced as one-factor interpretations. But a contextual relativism approach seeks to reconcile their ostensibly conflicting results. Results differ by context. Current work specifies how rules of the game, identified by distinct political cultures, shift processes across contexts.
Female Labor Force Behavior and Fertility in the United States
Authors: Lehrer Evelyn , Nerlove Marc 
Published: July 2003

This article critically reviews the literature on fertility and female labor force behavior in the United States, with particular emphasis on recent quantitative research by economists, demographers, and sociologists. We first examine the empirical evidence regarding the influence on fertility and female employment of certain key variables: the value of female time, husband's income, and relative economic status. Then the issue of whether there is direct causality between fertility and female labor supply is addressed. We review simultaneous equations models and a new approach to the study of causality. Sequential decision-making models are also discussed. Factors that may mediate the fertility-labor supply nexus are examined. These include childcare arrangements, husband's income, wife's education, and the convenience of employment. Differentials in the relationship between fertility and labor supply among racial and religious groups are noted. The article concludes with a discussion of changes over time in the association between fertility and female employment.
New Developments in the Sampling of Special Populations
Authors: Sudman Seymour , Kalton Graham 
Published: July 2003

This paper describes alternative methods for careful sampling of special populations. It discusses the use of single or multiple lists, even when incomplete, along with supplementary measures using telephone and mail techniques. If the special populations are clustered there are several alternatives for reducing costs substantially. These involve telephone or mail screenings to eliminate zero segments with a single contact, use of two or three contacts to eliminate zero segments if face-to-face screening is required, use of lists to identify nonzero segments, use of combined screening, and reducing the sampling rate in nonzero areas that have low densities. For some populations the use of network sampling can be very effective. Some populations can be defined by their activities and sampled at locations where they participate. These careful methods should be used if one is trying to generalize to a total special population.