bluuebunny/crossref_metadata_2025 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

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

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

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

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

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.
Angular Momentum Evolution of Young Stars and Disks
Authors: Bodenheimer Peter
Published: July 2003

The effects of angular momentum play an important role in star formation. However, when a young star emerges on the Hertzsprung-Russell diagram it is generally rotating slowly. This article reviews the observations regarding the angular momentum of molecular cloud cores, of proto stars, and of the disks, binary orbits, and spin of young stars. Various physical processes for transfer of angular momentum during the star formation process are discussed, including magnetic braking during the molecular cloud stage; fragmentation during the protostar collapse; viscosity, magnetic torques, and gravitational torques in disks; and magnetically driven mass loss in a star-disk system. Important problems for future study are highlighted.
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.
Adaptation
Authors: Alland Alexander
Published: July 2003

The subject of this paper is adaptation. I shall frame my discussion in terms of three topics which have nagged anthropology since its beginning. These topics are: 1. the role of biogenetic factors in cultural behavior; 2. the relation between behavioral systems and the external or natural environment; 3. the relation between mind, behavior, and ecological adaptation. I hope to show that these three topics reduce to a single theme when they are considered in terms of the central problem, adaptation. In addition, I hope to show that two of the major lines of development within anthropology, ecology and structuralism, can be reconciled and combined in a unified approach to human adaptation.
Refugees and Exile: From "Refugee Studies" to the National Order of Things
Authors: Malkki Liisa H.
Published: July 2003

This review offers a critical mappingo f the construction-in-progress of refugees and displacement as an anthropological domain of knowledge. It situates the emergence of “the refugee” and of “refugee studies” in two ways: first, historically, by looking at the management of displacement in Europe in the wake of World War II; and second, by tracing an array of different discursive and institutional domains within which “the refugee” and/or “being in exile” have been constituted. These domains include international law, international studies, documentary production by the United Nations and other international refugee agencies, development studies, and literary studies. The last part of the review briefly discusses recent work on displacement, diaspora, and deterritorialization in the context of studies of cultural identity, nationalism, transnational cultural forms—work that helps to conceptualize the anthropological study of displacement in new ways.
Language and Borders
Authors: Urciuoli Bonnie
Published: July 2003

Linguistic elements such as phonemes, lexemes, and syntactic or morphological rules cannot be taken for granted as the shape in which border-making elements come. From the actor’s viewpoint, border-making elements take on their social reality as “languages,” “accents,” “mixing,” or “words.” These terms emerge among the people to whom language identities matter, in relations shaped by the politics of ethnicity, race, and class within the nation and by the politics of ethnic nationalism.
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.
A LONG LIFE IN TIMES OF GREAT UPHEAVAL
Authors: Lipmann Fritz
Published: July 2003

I was born in the middle of the last year of the last century, in the city of Königsberg, the capital of East Prussia. It is now Russian and its name is Kaliningrad. I lived through the two world wars and was lucky to leave Germany in 1931 to live in Denmark, where I worked for seven years. In 1939, shortly before the outbreak of the second world war, I got the opportunity to come and settle in the United States when I was already 40 years old. My work was not unknown, but also not well known.
DNA EXCISION REPAIR
Authors: Sancar Aziz
Published: July 2003

In nucleotide excision repair DNA damage is removed through incision of the damaged strand on both sides of the lesion, followed by repair synthesis, which fills the gap using the intact strand as a template, and finally ligation. In prokaryotes the damaged base is removed in a 12-13 nucleotide (nt)-long oligomer; in eukaryotes including humans the damage is excised in a 24-32 nt-long fragment. Excision in Escherichia coli is accomplished by three proteins designated UvrA, UvrB, and UvrC. In humans, by contrast, 16 polypeptides including seven xeroderma pigmentosum (XP) proteins, the trimric replication protein A [RPA, human single-stranded DNA binding protein (HSSB)], and the multisubunit (7-10) general transcription factor TFIIH are required for the dual incisions. Transcribed strands are specifically targeted for excision repair by a transcription-repair coupling factor both in E. coli and in humans. In humans, excision repair is an important defense mechanism against the two major carcinogens, sunlight and cigarette smoke. Individuals defective in excision repair exhibit a high incidence of cancer while individuals with a defect in coupling transcription to repair suffer from neurological and skeletal abnormalities.
DNA REPAIR IN EUKARYOTES
Authors: Wood Richard D.
Published: July 2003

Eukaryotic cells have multiple mechanisms for repairing damaged DNA. 06-methylguanine-DNA methyltransferase directly reverses some simple alkylation adducts. However, most repair strategies excise lesions from DNA. Two major pathways are base excision repair (BER), which eliminates single damaged-base residues, and nucleotide excision repair (NER), which excises damage within oligomers that are 25-32 nucleotides long. The specialized DNA glycosylases and AP endonucleases of BER act on spontaneous and induced DNA alterations caused by hydrolysis, oxygen free radicals, and simple alkylating agents. NER utilizes many proteins (including the XP proteins in humans) to remove the major UV-induced photoproducts from DNA, as well as other types of modified nucleotides. Different DNA polymerases and ligases are used to complete the separate pathways. Some organisms have alternative schemes, which include the use of photolyases and a specific UV-endonuclease for repairing UV damage to DNA. Finally, double-strand breaks in DNA are repaired by mechanisms that involve recombination proteins and, in mammalian cells, a DNA protein kinase.
MECHANISMS OF HELICASE-CATALYZED DNA UNWINDING
Authors: Lohman Timothy M. , Bjornson Keith P.
Published: July 2003

DNA helicases are essential motor proteins that function to unwind duplex DNA to yield the transient single-stranded DNA intermediates required for replication, recombination, and repair. These enzymes unwind duplex DNA and translocate along DNA in reactions that are coupled to the binding and hydrolysis of 5′-nucleoside triphosphates (NTP). Although these enzymes are essential for DNA metabolism, the molecular details of their mechanisms are only beginning to emerge. This review discusses mechanistic aspects of helicasecatalyzed DNA unwinding and translocation with a focus on energetic (thermodynamic), kinetic, and structural studies of the few DNA helicases for which such information is available. Recent studies of DNA and NTP binding and DNA unwinding by the Escherichia coli (E. coli) Rep helicase suggest that the Rep helicase dimer unwinds DNA by an active, rolling mechanism. In fact, DNA helicases appear to be generally oligomeric (usually dimers or hexamers), which provides the helicase with multiple DNA binding sites. The apparent mechanistic similarities and differences among these DNA helicases are discussed.
RHIZOBIUM LIPO-CHITOOLIGOSACCHARIDE NODULATION FACTORS: Signaling Molecules Mediating Recognition and Morphogenesis
Authors: Dénarié Jean , Debellé Frédéric , Promé Jean-Claude
Published: July 2003

Rhizobia elicit on their specific leguminous hosts the formation of new organs, called nodules, in which they fix nitrogen. The rhizobia] nodulation genes specify the synthesis of lipo-chitooligosaccharide signals, the Nod factors (NFs). Each rhizobial species has a characteristic set of nodulation genes that specifies the length of the chitooligosaccharide backbone and the type of substitutions at both ends of the molecule, thus making the NFs specific for a given plant host. At extremely low concentrations, purified NFs are capable of eliciting on homologous legume hosts many of the plant developmental responses characteristic of the bacteria themselves, including cell divisions, and the triggering of a plant organogenic program. This review summarizes our current knowledge on the biosynthesis, structure, and function of this new class of signaling molecules. Finally we discuss the possibility that these signals could be part of a new family of plant lipochitooligosaccharide growth regulators.
The Structural Basis of Large Ribosomal Subunit Function
Authors: Moore Peter B. , Steitz Thomas A.
Published: July 2003

▪ Abstract  The ribosome crystal structures published in the past two years have revolutionized our understanding of ribonucleoprotein structure, and more specifically, the structural basis of the peptide bonding forming activity of the ribosome. This review concentrates on the crystallographic developments that made it possible to solve these structures. It also discusses the information obtained from these structures about the three-dimensional architecture of the large ribosomal subunit, the mechanism by which it facilitates peptide bond formation, and the way antibiotics inhibit large subunit function. The work reviewed, taken as a whole, proves beyond doubt that the ribosome is an RNA enzyme, as had long been surmised on the basis of less conclusive evidence.
Volumetric Properties of Proteins
Authors: Chalikian Tigran V.
Published: July 2003

▪ Abstract  Structural and thermodynamic characterizations of a variety of intra- and intermolecular interactions stabilizing/destabilizing protein systems represent a major part of multidisciplinary efforts aimed at solving the problems of protein folding and binding. To this end, volumetric techniques have been successfully used to gain insights into protein hydration and intraglobular packing. Despite the fact that the use of volumetric measurements in protein-related studies dates back to the 1950s, such measurements still represent a relatively untapped yet potentially informative means for tackling the problems of protein folding and binding. This notion has been further emphasized by recent advances in the development of highly sensitive volumetric instrumentation that has led to intensifying volumetric investigations of protein systems. This paper reviews the volumetric properties of proteins and their low-molecular-weight analogs, in particular, discussing the recent progress in the use of volumetric data for studying conformational transitions of proteins as well as protein-ligand, protein-protein, and protein–nucleic acid interactions.
The Binding of Cofactors to Photosystem I Analyzed by Spectroscopic and Mutagenic Methods
Authors: Golbeck John H.
Published: July 2003

▪ Abstract  This review focuses on cofactor-ligand and protein-protein interactions within the photosystem I reaction center. The topics include a description of the electron transfer cofactors, the mode of binding of the cofactors to protein-bound ligands, and a description of intraprotein contacts that ultimately allow photosystem I to be assembled (in cyanobacteria) from 96 chlorophylls, 22 carotenoids, 2 phylloquinones, 3 [4Fe-4S] clusters, and 12 polypeptides. During the 15 years that have elapsed from the first report of crystals to the atomic-resolution X-ray crystal structure, cofactor-ligand interactions and protein-protein interactions were systematically being explored by spectroscopic and genetic methods. This article charts the interplay between these disciplines and assesses how good the early insights were in light of the current structure of photosystem I.
Heat Shock Transcription Factors: Structure and Regulation
Authors: Wu Carl
Published: July 2003

Organisms respond to elevated temperatures and to chemical and physiological stresses by an increase in the synthesis of heat shock proteins. The regulation of heat shock gene expression in eukaryotes is mediated by the conserved heat shock transcription factor (HSF). HSF is present in a latent state under normal conditions; it is activated upon heat stress by induction of trimerization and high-affinity binding to DNA and by exposure of domains for transcriptional activity. Analysis of HSF cDNA clones from many species has defined structural and regulatory regions responsible for the inducible activities. The heat stress signal is thought to be transduced to HSF by changes in the physical environment, in the activity of HSF-modifying enzymes. or by changes in the intracellular level of heat shock proteins.
Production, Isotopic Composition, and Atmospheric Fate of Biologically Produced Nitrous Oxide
Authors: Stein Lisa Y. , Yung Yuk L.
Published: July 2003

▪ Abstract  The anthropogenic production of greenhouse gases and their consequent effects on global climate have garnered international attention for years. A remaining challenge facing scientists is to unambiguously quantify both sources and sinks of targeted gases. Microbiological metabolism accounts for the largest source of nitrous oxide (N2O), mostly due to global conversion of land for agriculture and massive usage of nitrogen-based fertilizers. A most powerful method for characterizing the sources of N2O lies in its multi-isotope signature. This review summarizes mechanisms that lead to biological N2O production and how discriminate placement of15N into molecules of N2O occurs. Through direct measurements and atmospheric modeling, we can now place a constraint on the isotopic composition of biological sources of N2O and trace its fate in the atmosphere. This powerful interdisciplinary combination of biology and atmospheric chemistry is rapidly advancing the closure of the global N2O budget.
Environmental Industries with Substantial Start-Up Costs as Contributors to Trade Competitiveness
Authors: Baumol William J.
Published: July 2003

This article describes a second reason beside externalities that can justify government support of new environmental-protection techniques. A new analysis of industries with high start-up costs and scale economies shows that the country in which such an industry is located is not dictated by comparative advantage. Hence, gain of a scale-economies activity need not entail loss of another and can increase income in the acquiring country. High start-up costs also impede entry by a prospective rival country, making it easier for the current producer country to retain it. Private enterprise may not find it attracti ve to undertake such socially-beneficial fields because of the substantial private risks that result from their high start-up costs. So, new environmental-protection techniques with high start-up costs or scale economies can contribute to a nation's prosperity even when unattractive to private enterprise in the absence of government support.
Privatization and Reform in the Global Electricity Supply Industry
Authors: Bacon R. W.
Published: July 2003

This paper reviews the origins of the current global interest in the privatization and reform of the electricity supply industry. Particular emphasis is placed on the issues of restructuring the industry into separate firms and the difficulties of attracting private capital into an industry in which some state ownership remains. The targets to be met, the means of achieving them. and potential difficulties in implementing such changes are analyzed. An overview of actual experience is provided, along with a discussion of the problems of assessing whether these changes have been successful. Finally, some lessons are drawn for the future development of the process.
International Environmental Labeling
Authors: Modl Albert , Hermann Ferdinand
Published: July 2003

Environmentally acceptable products are continuing to gain importance on the market. This review covers programs that are targeted to mark products or services that are less environmentally harmful than others that serve the same purpose. Several environmental-labeling programs were created in the late 1980s and early 1990s. To illustrate the principles of such labeling systems, various programs are presented in detail. The programs were chosen to represent a wide spectrum o f characteristics: stringent and less demanding, wellestablished and recently created, national and multinational, and from various parts of the world. Similarities and differences, as well as advantages and disadvantages, are discussed.
Host Immunity to Ticks
Authors: Wikel Stephen K.
Published: July 2003

The tick-host-pathogen interface is characterized by complex immunological interactions. Tick feeding induces host immune regulatory and effector pathways involving antibodies, complement, antigen-presenting cells, T lymphocytes, and other bioactive molecules. Acquired resistance impairs tick engorgement, ova production, and viability. Tick countermeasures to host defenses reduce T-lymphocyte proliferation, elaboration of the TH1 cytokines interleukin-2 and interferon-γ, production of macrophage cytokines interleukin-1 and tumor necrosis factor, and antibody responses. The dynamic balance between acquired resistance and tick modulation of host immunity affects engorgement and pathogen transmission. A thorough understanding of acquired immunity to ticks is essential for rational development of antitick vaccines.
Insect Pests of Beans in Africa: Their Ecology and Management
Authors: Abate T. , Ampofo J. K. O.
Published: July 2003

Damage by insect pests, inter alia, is considered the liming factor of bean praduction in Africa. This paper reviews the current status of insect pests of beans, focusing on their ecology and management, as well as the potential for integrated pest management (IPM) approaches in subsistence farming conditions, under which most beans are grown in Africa. Although numerous insect pests attacked parts of beans, bean stem maggots and bruchids are the most important field and storage pests, respectively. Foliage beetles, flower thrips, pollen beetles, pod borers, pod bugs, and sap suckers such as aphids also inflict signifcant damage. Control of bean pests in Africa is achieved through the use of a traditional IPM approach that consists of appropriate sowing dates, optimum plant density, varietal mixtures, intercropping, good crop husbandry, and locally available materials. Research should focus on low-input IPM approaches that encompass farmers’ current practices, host-plant resistance, and natural biological control.
Ion Channels as Targets for Insecticides
Authors: Bloomquist Jeffrey R.
Published: July 2003

Ion channels are the primary target sites for several classes of natural and synthetic insecticidal compounds. The voltage-sensitive sodium channel is the major target site for DDT and pyrethroids, the veratrum alkaloids, andN-alkylamides. Recently, neurotoxic proteins from arthropod venoms, some of which specifically attack insect sodium channels, have been engineered into baculoviruses to act as biopesticides. The synthetic pyrazolines also primarily affect the sodium channel, although some members of this group target neuronal calcium channels as well. The ryanoids have also found use as insecticides, and these materials induce muscle contracture by irreversible activation of the calcium-release channel of the sarcoplasmic reticulum. The arylheterocycles (e.g. endosulfan and fipronil) are potent convulsants and insecticides that block the GABA-gated chloride channel. In contrast, the avermectins activate both ligand and voltage-gated chloride channels, which leads to paralysis. At field-use rates, a neurotoxic effect of the ecdysteroid agonist RH-5849 is observed that involves blockage of both muscle and neuronal potassium channels. The future use of ion channels as targets for chemical and genetically engineered insecticides is also discussed.
Ecology and Behavior of Ground Beetles (Coleoptera: Carabidae)
Authors: Lövei Gábor L. , Sunderland Keith D.
Published: July 2003

The ground beetles form the speciose beetle family Carabidae and, since their emergence in the Tertiary, have populated all habitats except deserts. Our knowledge about carabids is biased toward species living in north-temperate regions. Most carabids are predatory, consume a wide range of food types, and experience food shortages in the field. Feeding on both plant and animal material and scavenging are probably more significant than currently acknowledged. The most important mortality sources are abiotic factors and predators; pathogens and parasites can be important for some developmental stages. Although competition among larvae and adults does occur, the importance of competition as a community organization is not proven. Carabids are abundant in agricultural fields all over the world and may be important natural enemies of agricultural pests.
Tympanal Hearing in Insects
Authors: Hoy R. R. , Robert D.
Published: July 2003

Specialized hearing organs, known as tympanal organs, have evolved in at least seven different orders of insects. Tympanal organs are usually defined by the presence of a tympanal membrane (or eardrum). They are backed by an air-filled space or cavity and are innervated by a chordotonal sensory organ. In some insects, however, a recognizable tympanal membrane may not be easily identified by visual inspection, yet may possess tympanal hearing organs. In insects that possess them, tympanal hearing organs may mediate the detection of predators, prey, and potential mates and rivals. Unlike the ears of vertebrates, which are localized to cranial segments, the ears of insects may be found in a bewildering variety of locations on their bodies, depending on the species. The embryological and evolutionary origins of tympanal organs are related to ancestral states as proprioceptive chordotonal organs.
CHROMOSOME PARTITIONING IN BACTERIA
Authors: Wake R. G. , Errington J.
Published: July 2003

This review addresses chromosome partitioning in Escherichia coli and Bacillus subtilis. The first part deals with events associated with completion of a round of replication to an extent that yields separable chromosomes. Events more directly involved in chromosome movement are covered in the second part. In the final section, a model for chromosome partitioning based on the information presented in the first two parts is presented.
THE PLANT RESPONSE IN PATHOGENESIS, SYMBIOSIS, AND WOUNDING: Variations on a Common Theme?
Authors: Baron C. , Zambryski P. C.
Published: July 2003

Upon interaction with pathogenic Pseudomonads or symbiotic Rhizobia, or after wounding by abrasion or insects, the plant reacts in superficially different ways, leading to either a close association or defense against the intruder. However, a closer examination reveals that similar genes and metabolic pathways are induced. This raises the possibility that signal perception and transduction proceed via similar pathways, leading to overlaps in the response reaction. This review compares current knowledge of the plant reaction to apparently different biotic and abiotic stimuli, and highlights that within the course of evolution similar response mechanisms were adapted to specific needs.
MOLECULAR GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS
Authors: Larsson Nils-Göran , Clayton David A.
Published: July 2003

This review focuses on mutations of mitochondrial DNA (mtDNA) which are an important cause of mitochondrial disorders in humans and are also associated with common neurodegenerative disorders and aging. The high copy number of mtDNA and its maternal transmission make the inheritance of mtDNA mutations fundamentally different from the Mendelian inheritance of nuclear DNA mutations. There is often a mixture of wild-type and mutated mtDNAs (heteroplasmy), and heterogeneity in the distribution of mutated mtDNAs is one plausible explanation for the widely varying phenotypes in patients with mitochondrial disorders. The application of molecular genetics has led to significant progress in the studies of human mitochondrial disorders in the past decade. Future studies including the development of animal models are needed to advance our understanding of the pathogenesis of mitochondrial disorders to enable, in tum, the development of novel therapies and genetic rescue strategies for the treatment of human disease.
GENETICS OF USTILAGO MAYDIS, A FUNGAL PATHOGEN THAT INDUCES TUMORS IN MAIZE
Authors: Banuett F.
Published: July 2003

Ustilago maydis induces tumors in maize. It is dimorphic, with a unicellular, nonpathogenic form, and a dikaryotic, filamentous, pathogenic form that requires the plant for its growth. The life cycle is regulated by two mating type loci,a and b: a has two alleles, which encode a pheromone and a receptor; b is multiallelic and encodes a combinatorial homeodomain protein. Cell fusion occurs between haploid cells with different a alleles. The dikaryon formed exhibits filamentous growth if the cells also carry any two different b alleles. The b locus is the major pathogenicity determinant, fuz7, which encodes a MAP kinase activator, is also necessary for tumor induction and may respond to plant signals. Several other genes have been identified (fuz1, fuz2, rtf1, uac, ubc) that affect different aspects of the life cycle transitions. Some of them may identify targets of the b locus. Signaling between pathogen and plant is of key importance in tumor induction and fungal growth and differentiation within the plant. The role of siderophores is also discussed.
Positive and Negative Selection of T Cells
Authors: Starr Timothy K. , Jameson Stephen C. , Hogquist Kristin A.
Published: July 2003

A functional immune system requires the selection of T lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens. This selection occurs predominantly in the thymus, where lymphocyte precursors first assemble a surface receptor. In this review we summarize the current state of the field regarding the natural ligands and molecular factors required for positive and negative selection and discuss a model for how these disparate outcomes can be signaled via the same receptor. We also discuss emerging data on the selection of regulatory T cells. Such cells require a high-affinity interaction with self-antigens, yet differentiate into regulatory cells instead of being eliminated.
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.
MHC Class-I Transgenic Mice
Authors: Arnold Bernd , Hämmerling Günter J.
Published: July 2003

The introduction of cloned genes into the germline of mice has been proven to be a powerful tool to investigate the role of the respective gene products within the immune system. Here we summarize the transgenic mouse models that have been established with major histocompatibility complex (MHC) class-I genes. Foreign class-I alleles can be expressed in transgenic mice according to their normal expression patterns as authentic self molecules and can function in T-cell responses in the same way as endogenous class-I molecules. Since this is also true for most of the introduced human HLA class-I alleles, there is great interest in establishing mouse models for HLA-linked diseases. A new field of experimental approaches concerning self-tolerance has been opened by tissue specific expression of MHC antigens under specific promoters. Besides negative selection in the thymus, peripheral mechanisms could be identified that induce and maintain self-tolerance.
Cytokine Receptors and Signal Transduction
Authors: Miyajima Atsushi , Kitamura Toshio , Harada Nobuyuki , Yokota Takashi , Arai Ken-ichi
Published: July 2003

Cytokinesp lay a vital role in coordinating immune and inflammatory responses. Unlike growth factor receptors with a tyrosine kinase, cytokine receptors have no intrinsic tyrosine kinase activity. Based on their structure, cytokinere ceptors are classified into several groups. High affinity receptors for IL-2, IL-3, IL-5, IL-6, and GM-CSF are composed of at least two distinct subunits, α and β. The α subunits are primary cytokine binding proteins, and the β subunits are required for formation of high affinity binding sites as well as for signal transduction. The GM-CSF, IL-3, and IL-5 receptors appear to share the same β subunit in human, and therefore cross-talk among these cytokines may occur at the receptor level. High affinity receptors presumably are linked to various signal transduction pathways that lead to different cytokine functions. Differential expression of the cytokine receptors as well as reorganization of intracellular signalling pathways are critical for development of hemopoietic cells.
Transepithelial Transport of Immunoglobulins
Authors: Mostov Keith E.
Published: July 2003

Immunoglobulins are transported across a variety of epithelial tissues. The best studied example of this is the transport of polymeric IgA and IgM by the polymeric immunoglobulin receptor (pIgR) across many types of epithelial cells. The pIgR binds its ligand at the basolateral surface and is internalized into endosomes. Here it is sorted into vesicles that transcytose it to the apical surface. At the apical surface the pIgR is proteolytically cleaved, and the large extracellular fragment (known as secretory component) is released together with the ligand. The pIgR contains a cytoplasmic domain of 103 amino acids that contains several sorting signals. Targeting from the trans-Golgi network to the basolateral surface is determined by the membrane-proximal 17 residues of this domain. There are two endocytosis signals that contain crucial tyrosine residues. Transcytosis of the pIgR is stimulated by binding of polymeric IgA. Phosphorylation of a cytoplasmic serine promotes transcytosis of the pIgR without ligand bound. Transcytosis may be regulated by the heterotrimeric Gs protein, protein kinase C and calmodulin. IgG is transcytosed from the apical to basolateral surface in several epithelial tissues such as the placenta and the small intestine of newborn rats. The receptor for intestinal transport of IgG is structurally similar to class I MHC molecules.
Making Antibodies by Phage Display Technology
Authors: Winter Greg , Griffiths Andrew D. , Hawkins Robert E. , Hoogenboom Hennie R.
Published: July 2003

Antibody fragments of predetermined binding specificity have recently been constructed from repertoires of antibody V genes, bypassing hybridoma technology and even immunization. The V gene repertoires are harvested from populations of lymphocytes, or assembled in vitro, and cloned for display of associated heavy and light chain variable domains on the surface of filamentous bacteriophage. Rare phage are selected from the repertoire by binding to antigen; soluble antibody fragments are expressed from infected bacteria; and the affinity of binding of selected antibodies is improved by mutation. The process mimics immune selection, and antibodies with many different binding specificities have been isolated from the same phage repertoire. Thus human antibody fragments have been isolated with specificities against both foreign and self antigens, including haptens, carbohydrates, secreted and cell surface proteins, viral coat proteins, and intracellular antigens from the lumen of the endoplasmic reticulum and the nucleus. Such antibodies have potential as reagents for research and in therapy.
Materials Design for the Next Generation Thermal Barrier Coatings
Authors: Clarke D.R. , Levi C.G.
Published: July 2003

▪ Abstract  The emphasis in this short review is to describe the materials issues involved in the development of present thermal barrier coatings and the advances necessary for the next generation, higher temperature capability coatings.
Non-Fluorinated Polymer Materials for Proton Exchange Membrane Fuel Cells
Authors: Rozière Jacques , Jones Deborah J.
Published: July 2003

▪ Abstract  The past 10 years have witnessed a tremendous acceleration in research devoted to non-fluorinated polymer membranes, both as competitive alternatives to commercial perfluorosulfonic acid membranes operating in the same temperature range and with the objective of extending the range of operation of polymer fuel cells toward those more generally occupied by phosphoric acid fuel cells. Important requirements are adequate membrane mechanical strength at levels of functionalization (generally sulfonation) and hydration allowing high proton conductivity, and stability in the aggressive environment of a working fuel cell, in particular thermohydrolytic and chemical stability. This review provides an overview of progress made in the development of proton-conducting hydrocarbon and heterocyclic-based polymers for proton exchange and direct methanol fuel cells and describes the various approaches made to polymer modification/synthesis and salient properties of the materials formed, including those relating to proton transport and proton conductivity, e.g., water diffusion and electro-osmotic drag. The microstructure, deduced from small angle X-ray and neutron diffraction measurements of representative non-fluorinated polymers is compared with that of perfluorosulfonic acid membranes. Different degradation mechanisms and aging processes that can result in chemical and morphological alteration are considered, and recent characterization of membrane-electrode assemblies (MEAs) in direct methanol and hydrogen-air (oxygen) fuel cells completes this review of the state of the art. While several types of non-fluorinated polymer membrane have demonstrated lifetimes of 500–4000 h, only a limited number of systems exist that hold promise for long-term operation above 100°C. 1
Composite Membranes for Medium-Temperature PEM Fuel Cells
Authors: Alberti G. , Casciola M.
Published: July 2003

▪ Abstract  The main obstacles to greater commercialization of polymer electrolyte fuel cells are mostly related to the low-proton conductivity at low-relative humidity of the known ionomeric membranes, to their high methanol permeability and poor mechanical properties above ∼130°C. A possible solution for these problems has been found in the development of composite membranes, where particles of suitable fillers are dispersed in the ionomer matrix. The preparation methods for obtaining composite membranes are described, and recent work dealing with composite ionomeric membranes containing silica, heteropolyacids, layered metal phosphates, and phosphonates is reviewed. Finally, new strategies for the preparation of nano-composite membranes and for the filling of porous polymeric membranes with highly conductive zirconium phosphonates are described. The expected influence of size and orientation of these particles on membrane properties, such as conductivity and permeability to methanol, is also discussed.