The Annexins is focused on a specific family of calcium and membrane-binding proteins, annexins, ubiquitously spread within living organisms, including animals, plants and fungi. The volume covers important areas of annexinology. The characterization of structural-functional relationship within the annexin family of proteins, together with emerging transgenic animal models, provides an up-to-date overview of potential physiological roles of annexins. Growing evidence of participation of annexins in human diseases, called annexinopathies, related to disturbances in signal transduction, vesicular traffic, ion homeostasis and energy metabolism within the cell. The book will attract a broad scientific audience, not only scientists interested in annexins, but also others involved in multidisciplinary studies, as well as undergraduate and postgraduate students. It can be used in courses relating to special topics such as calcium homeostasis, calcium-binding proteins, membrane structure and transport properties, various signal transduction pathways, and membrane trafficking.

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

In this volume, a distinguished international group of contributors present the latest molecular, organismal, and epidemiological research on arenaviruses. Their work will broaden both the clinician's and the researcher's knowledge of basic mechanisms of immunological tolerance, viral immunosuppression, the nature of protective immune responses to vaccination, and viral effects on cell functions.

The genus Aspergillus has a worldwide distribution and is one of the most common of all groups of fungi. They are possibly the greatest contami nants of natural and man-made organic products, and a few species can cause infections in man and animals. The aspergilli are also one of the most important mycotoxin-producing groups of fungi when growing as contaminants of cereals, oil seeds, and other foods. Not all aspergilli are viewed as troublesome contaminants, however, as several species have had their metabolic capabilities harnessed for commercial use. The aspergilli have long been associated in the Far East with the koji stage of several food fermentations, particularly soy sauce and miso, and subsequently as a source of useful enzymes. The ability of these fungi to produce several organic acids, especially citric acid, has created major industrial complexes worldwide. Traditional methods of strain develop ment have been extensively studied with the industrial strains, while more recently, recombinant DNA technology has been applied to the aspergilli with emphasis on heterologous protein production. In compiling this book, I have been fortunate to have the full enthu siastic involvement of the authors, and to them I extend my very grateful thanks for mostly being on time and for producing such readable and authoritative chapters. Collectively, we hope that our efforts will strengthen the scientific understanding of this intriguing group of filamentous fungi and further their use in the field of biotechnology.

The NATO Advanced Research Workshop entitled "The Photosynthetic Bacterial Reaction Center: Structure, Spectroscopy, and Dynamics" was held May 10-15, 1992, in the Maison d'H6tes of the Centre d'Etudes Nuc1eaires de Cadarache near Aix-en-Provence in the south of France. This workshop is the most recent of a string of meetings which started in Feldafing (Germany) in March 1985, soon after the three-dimensional structure of the bacterial reaction center had been elucidated by X-ray crystallography. This was followed, in September 1987, by a workshop in Cadarache and, in March 1990, by a second meeting in Feldafing. Although one of the most important processes on Earth, photosynthesis is still poorly understood. Stimulated by the breakthrough of solving the bacterial reaction center structure at atomic resolution, the field of relating this structure to the function of the reaction center, i. e. the remarkably efficient conversion and storage of solar energy, has been developing vigorously. Once the general organization of the cofactors and some details of the protein-cofactor interactions were known, it became possible to combine a variety of spectroscopic techniques with the powerful tool of site-directed mutagenesis in order to address increasingly incisive questions about the specific role of some amino acid residues in the electron transfer process. Still another promising tool is being developed, namely the exchange of a number of the native bacteriochlorophyll and bacteriopheophytin cofactors by chemically modified pigments.

Varicella-zostervirus(VZV)isamedicallyimportanthumanherpesvirus,belo- ingtothesubfamilyAlphaherpesviridae. Thecapacitytopersistinsensoryneurons isade?ningcharacteristicoftheAlphaherpesviridaesubgroupwhichalsoincludes herpessimplexvirus1and2;likeVZV,simianvaricellavirus(SVV),pseudorabies virus-1(PRV-1),andequineherpesvirus-1(EHV-1)belongtotheVaricellovirus genus. ThebasicelementsoftheinfectiouscycleofVZVinthehumanhostarethat infectionofthena?vehostresultsinvaricella,commonlyknownaschickenpox, latencyisestablishedinsensoryganglia,andreactivationcauseszosteror"sh- gles. "Therelationshipbetweenthecausative agentofvaricellaandzoster was demonstratedmorethan100yearsagowhenchildreninoculatedwithmaterialfrom zosterlesionswereshowntodevelopvaricella. Thelocalizeddistributionofthe zosterrashwasalsorecognizedasdemarcatingthedematomeinnervatedbyaxons fromneuronsineachofthesensoryganglia. Earlyelectronmicroscopystudies showedthatvirusparticleswerepresentinhighconcentrationsinthevesicular ?uidfrombothvaricellaandzosterlesions,andVZVwasamongthe?rstviruses propagatedinvitrobyJohnEndersandThomasWeller. Theintroductionofim- nosuppressivetherapiesformalignancyledtoobservationssuggestingtheneed forcell-mediatedimmunityinthehostresponsetovaricellaanditsroleinma- tainingVZVlatency. Fortunately,earlystudiesofthemolecularvirologyofVZV revealedthatitwasinhibitedbyinterferencewiththethymidinekinasegene,and thelife-threateningandoftenfatalVZVinfectionsexperiencedbythesepatients becametreatablewithantiviraldrugs. Subsequently,thecapacitytogrowVZVin tissueculturewasexploitedtocreatealiveattenuatedVZVvaccinebyMichiaki Tashihaki. Whilenowtakenforgranted,theseearlyinsightsaboutVZVandits characteristicsasahumanpathogenaswellasthedevelopmentofeffectivean- viral drugs and vaccines occurred over many decades. Importantly, these early observationssetthestagefortheremarkableprogressthathasbeenmadeinour understandingofthemolecularbiologyofVZV,thesubtletiesofitstropismfor differentiatedhumancells,includinglymphocytesaswellasskinandneurons,and themechanismsbywhichthevirusachievesanequilibriumwiththehostsothatit persistsnotjustintheindividualbutinthehumanpopulation. v vi Preface Thepurposeofthisvolumeistoreviewkeyareasofprogressinthe?eldofVZV research,aswellasworkontherelatedSVV,writtenbythosewhohavecontributed manyofthenew? ndingsthathaveenrichedourknowledgeoftheuniquech- acteristicsofthisubiquitoushumanpathogen. AlthoughtheVZVgenomeisthe smallestamongthehumanherpesviruses,therapidlyacceleratingpaceofdiscovery about VZV and VZV-host interactions re?ected in these reviews promises to continueasnewtoolsareavailableandnewhypothesesaregeneratedtoexplain howVZVhascreatedandmaintaineditsnicheinthehuman"virome"Therelationshipbetweenthecausative agentofvaricellaandzoster was demonstratedmorethan100yearsagowhenchildreninoculatedwithmaterialfrom zosterlesionswereshowntodevelopvaricella. Thelocalizeddistributionofthe zosterrashwasalsorecognizedasdemarcatingthedematomeinnervatedbyaxons fromneuronsineachofthesensoryganglia. Earlyelectronmicroscopystudies showedthatvirusparticleswerepresentinhighconcentrationsinthevesicular ?uidfrombothvaricellaandzosterlesions,andVZVwasamongthe?rstviruses propagatedinvitrobyJohnEndersandThomasWeller. Theintroductionofim- nosuppressivetherapiesformalignancyledtoobservationssuggestingtheneed forcell-mediatedimmunityinthehostresponsetovaricellaanditsroleinma- tainingVZVlatency. Fortunately,earlystudiesofthemolecularvirologyofVZV revealedthatitwasinhibitedbyinterferencewiththethymidinekinasegene,and thelife-threateningandoftenfatalVZVinfectionsexperiencedbythesepatients becametreatablewithantiviraldrugs. Subsequently,thecapacitytogrowVZVin tissueculturewasexploitedtocreatealiveattenuatedVZVvaccinebyMichiaki Tashihaki. Whilenowtakenforgranted,theseearlyinsightsaboutVZVandits characteristicsasahumanpathogenaswellasthedevelopmentofeffectivean- viral drugs and vaccines occurred over many decades. Importantly, these early observationssetthestagefortheremarkableprogressthathasbeenmadeinour understandingofthemolecularbiologyofVZV,thesubtletiesofitstropismfor differentiatedhumancells,includinglymphocytesaswellasskinandneurons,and themechanismsbywhichthevirusachievesanequilibriumwiththehostsothatit persistsnotjustintheindividualbutinthehumanpopulation. v vi Preface Thepurposeofthisvolumeistoreviewkeyareasofprogressinthe?eldofVZV research,aswellasworkontherelatedSVV,writtenbythosewhohavecontributed manyofthenew?ndingsthathaveenrichedourknowledgeoftheuniquech- acteristicsofthisubiquitoushumanpathogen. AlthoughtheVZVgenomeisthe smallestamongthehumanherpesviruses,therapidlyacceleratingpaceofdiscovery about VZV and VZV-host interactions re?ected in these reviews promises to continueasnewtoolsareavailableandnewhypothesesaregeneratedtoexplain howVZVhascreatedandmaintaineditsnicheinthehuman"virome"sos- cessfully. Further improvements in the clinical management of VZV infection shouldemergeinparallelwithbetterinsightsintoVZVmolecularvirologyand pathogenesis. Stanford,CA,June,2010 AllisonAbendroth AnnM. Arvin JenniferF. Moffat Contents TheVaricella-ZosterVirusGenome ...1 JeffreyI. Cohen VZVMolecularEpidemiology ...15 JudithBreuer RolesofCellularTranscriptionFactorsinVZVReplication ...43 WilliamT. Ruyechan EffectsofVaricella-ZosterVirusonCellCycleRegulatoryPathways ...67 JenniferF. MoffatandRebeccaJ. Greenblatt Varicella-ZosterVirusOpenReadingFrame66ProteinKinase andItsRelationshiptoAlphaherpesvirusUS3Kinases ...79 AngelaErazoandPaulR. Kinchington VZVORF47SerineProteinKinaseandItsViralSubstrates ...99 TeriK. KenyonandCharlesGrose OverviewofVaricella-ZosterVirusGlycoproteinsgC,gHandgL ...113 CharlesGrose,JohnE. Carpenter,WallenJackson,andKarenM. Duus AnalysisoftheFunctionsofGlycoproteinsEandIandTheirPromoters DuringVZVReplicationInVitroandinSkinandT-CellXenografts intheSCIDMouseModelofVZVPathogenesis ...129 AnnM. Arvin,StefanOliver,MikeReichelt,JenniferF. Moffat, MarvinSommer,LeighZerboni,andBarbaraBerarducci Varicella-ZosterVirusGlycoproteinM ...147 YasukoMoriandTomohikoSadaoka vii viii Contents VaricellaZosterVirusImmuneEvasionStrategies ...155 AllisonAbendroth,PaulR. Kinchington,andBarrySlobedman VZVInfectionofKeratinocytes:ProductionofCell-FreeInfectious VirionsInVivo ...173 MichaelD. GershonandAnneA. Gershon Varicella-ZosterVirusTCellTropismandthePathogenesis ofSkinInfection ...189 AnnM. Arvin,JenniferF. Moffat,MarvinSommer,StefanOliver, XibingChe,SusanVleck,LeighZerboni,andChia-ChiKu ExperimentalModelstoStudyVaricella-ZosterVirusInfection ofNeurons ...211 MeganSteain,BarrySlobedman,andAllisonAbendroth MolecularCharacterizationofVaricellaZosterVirusinLatently InfectedHumanGanglia:PhysicalStateandAbundanceofVZV DNA,QuantitationofViralTranscriptsandDetection ofVZV-Speci?cProteins ...229 YevgeniyAzarkh,DonGilden,andRandallJ. Cohrs NeurologicalDiseaseProducedbyVaricellaZosterVirusReactivation WithoutRash ...2 43 DonGilden,RandallJ. Cohrs,RaviMahalingam,andMariaA. Nagel Varicella-ZosterVirusNeurotropisminSCIDMouse-Human DorsalRootGangliaXenografts ...255 L. Zerboni,M. Reichelt,andA. Arvin RodentModelsofVaricella-ZosterVirusNeurotropism ...277 JeffreyI. Cohen SimianVaricellaVirus:MolecularVirology ...291 WayneL. Gray SimianVaricellaVirusPathogenesis ...309 RaviMahalingam,IlhemMessaoudi,andDonGilden Varicella-ZosterVirusVaccine:MolecularGenetics ...323 D. ScottSchmid VZVTCell-MediatedImmunity ...341 AdrianaWeinbergandMyronJ. Levin Contents ix PerspectivesonVaccinesAgainstVaricella-ZosterVirusInfections ...359 AnneA. GershonandMichaelD. Gershon Index ...373 . Contributors Allison Abendroth Department of Infectious Diseases and Immunology, UniversityofSydney,BlackburnBuilding,Room601,Camperdown,NSW 2006, Australia and Centre for Virus Research, Westmead Millennium Institute,Westmead,NSW2145,Australia,allison. abendroth@sydney. edu. au AnnM. Arvin StanfordUniversitySchoolofMedicine,G311,Stanford,CA 94305,USA,aarvin@stanford.

These Proceedings of the Fourth International Congress on the Cornea continue a tradition of summarizing the state-of-the art basic and clinical research in cornea and ex- ternal diseases since the first Congress was held in 1964. Reflecting the emerging impor- tance of refractive surgery, two of the twelve sessions of the Congress were devoted to refractive surgery; this is reflected in an emphasis in these Proceedings. In addition, an en- tire session was devoted to the molecular and cellular biology of the cornea with impor- tant new information on the role of growth factors and cytokine modulation of corneal wound healing. Within these Proceedings an international group of expert researchers and practitioners provide the latest insights into the tear film and ocular surface, corneal trans- plantation and eyebanking, the corneal stroma and endothelium, contact lenses, microbial and nonmicrobial keratitis, keratoconus, and world corneal health. Notable subjects covered include the latest understanding of the barrier function of the ocular surface epithelium, corneal hydration control, the molecular mechanisms con- trolling gene expression in corneal wound healing, stromal~pithelial interactions in the cornea, the immunology of blepharitis, the effect of contact lenses on the conjunctiva, morphologic and functional evaluation of the human corneal endothelium, long-term fol- low-up of penetrating keratoplasty in keratoconus, the Tampa trephine penetrating kerato- plasty, and the refractive results of the Nidek EC-5000 excimer laser.

Fluorescence is a very powerful tool for work at the frontier of cell biology, photobiology and bioinstrumentation. The stated aim of the workshop was to highlight the significance of fluorescence work for the understanding of cell and tissue physiology, physiopathology and pharmacology, particulary in terms of the analytical use of fluorescent probes in oncology. In the organization of the workshop a multidisciplinary approach was selected. The purpose of the Advanced Research Workshop (ARW) was to bring together researchers in the various disciplines of tissue optics, imaging, microspectrofluorometry and state of the art probes, in order to explore the full benefits that can be derived in biomedicine through the convergence of these approaches. When applied to in vivo and in situ studies, fluorescence and related optical methods enable us to explore within tissues, cells and organelles photon effects previously understood only in solution photochemistry. Processes which can be studied at the molecular level by photophysics, photochemistry and physical chemistry can be evaluated in living tissue by fluorescence spectroscopy and imaging at the intracellular level in terms of structure and function. Thus, fluorescence adds a new dimension to cell biology and physiology. This approach is now supported by a full and versatile, rapidly growing armamentarium of new selective probes for organelles, enzymes, cations, cytoskeleton and metabolic control.

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

This book, Mechanisms in the Pathogenesis of Enteric Diseases 2, is an out come of the Second International Rushmore Conference on Mechanisms in the Pathogenesis of Enteric Diseases, held September 3D-October 3, 1998 in Rapid City, South Dakota, USA. Its chapters represent many of the reviews and papers presented at the conference. The meeting was organized by members of the North-Central Regional Research Committee "NC-62", a consortium of researchers of bovine and swine enteric diseases from land-grant institutions supported by the United States Department of Agriculture. The Rushmore Conferences were conceived as a forum for an interdiscipli nary discussion of mechanisms of infectious enteric diseases. It was intended that such a discussion would stimulate cross-pollination of ideas, and nurture synergistic collabora tions among scientists who might otherwise not interact. Enteric diseases are caused by widely divergent pathogens and parasites in broadly different settings, and affect multi ple organ systems. Some enteric diseases affect a single species, while others may affect multiple species, perhaps including human beings. Some enteric diseases were present in antiquity, while others have recently emerged. Knowledge regarding a particular disease or pathogen has frequently proven useful in understanding another disease or pathogen, because common themes in pathogenesis exist. As this knowledge base grows,strategies in the prevention and control of various enteric diseases often converge. Cross-discipli nary discussions and collaborations facilitate growth of this knowledge base, as well as development of tools for disease interdiction.

Hot Topics in Infection and Immunity in Children brings together leading experts in the field to provide a current and authoritative view concerning the hottest topics of concern to clinicians caring for children with infections and research scientists working in the areas of infectious disease, immunology, microbiology and public health. The book is based on a collection of manuscripts from a faculty of authors of international standing who contributed to a course in Paediatric Infection and Immunity in Oxford, UK in June 2003.

It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

This concise yet comprehensive text surveys the field of bacterial metabolism in terms useful to students and researchers. Emphasis is on those metabolic reactions occurring only in bacteria. Thus, the book describes in detail the energy metabolism of the various groups of bacteria. In addition it examines pathways used by bacteria for the degradation of organic compounds, the synthesis of cellular consituents, the regulation of bacterial metabolism and the fixation of molecular nitrogen. The general arrangement of the first edition has been retained. However, it has been thoroughly revised and updated in recognition of the rapid progress of research in this field. Readers will also appreciate the increased emphasis on membrane-associated processes. From the review of the second edition: If there is a better textbook in its fields, I'm not aware of it, and I feel the book deserves a place on the shelf of any serious student of microbiology. -ASM News

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both."

This book details recent findings in the field of cave microbiology and builds on fast-paced efforts to exploit an unconventional and underexplored environment for new microorganisms which may provide an untapped source of drugs: microorganisms from caves.

For years, toxoplasmosis has been known as disease mostly affecting newborns. Since immunocompromised patients (AIDS) present a high risk of reactivation of chronic toxoplasmosis this parasitic disease has gained increasing interest. Besides presenting clinical and therapeutical concepts, this volume provides current knowledge about genetics and immunology of T. gondii and the interaction with its 'host'. Since in vivo and in vitro models of toxoplasmosis exist, and genetic manipulation has become possible, this protozoan parasite has recently been accepted as a model for understanding the pathogenesis and persistance of other intracellular parasites. The articles of the book compromise both reviewing current concepts and reporting on yet unpublished results of leading scientists in this field.

Dr. Hilary Koprowski is the pioneer of live polio vaccine, the first researcher to advance the diagnostic and therapeutic use of monoclonal antibodies, and the developer of the "gold standard" rabies vaccine. A world-reknowned maverick in biomedical research, Koprowski's research methods were often considered controversial and even radical. Nonetheless, he acquired key positions in many research organizations, such as the Rockefeller Foundation, Lederle Labs, and Wistar Institute, initiating landmark studies from cancer research to multiple sclerosis. One of his crowning achievements, the successful crusade for monoclonal antibodies, resulted in his founding of Centocor, a forerunner in the corporate world of biomedicine. This account of Koprowski's life history is a mixture of personal interviews, anecdotes, and legends of the art and science behind the man.

In this book, outstanding researchers from the US and Japan review recent progress in Epstein-Barr virus research. Most people carry EBV in memory B-cells in a latent stage. Many malignancies such as T/NK cell lymphoma, AIDS-associated B-cell lymphoma, gastric carcinoma and Hodgkin's disease have been causally linked to EBV. The development of molecular biology technique has allowed us to study the roles of individual EBV genes that act in the maintenance and disruption of EBV latency.

In 1898 Camillo Golgi reported his newly observed intracellular structure, the apparato reticolare interno, now universally known as the Golgi Apparatus. The method he used was an ingenious histological technique (La reazione nera) which brought him fame for the discovery of neuronal networks and culminated in the award of the Nobel Prize for Physiology and Medicine in 1906. This technique, however, was not easily reproducible and led to a long-lasting controversy about the reality of the Golgi apparatus. Its identification as a ubiquitous organelle by electron microscopy turned out to be the breakthrough and incited an enormous wave of interest in this organelle at the end of the sixties. In recent years immunochemical techniques and molecular cloning approaches opened up new avenues and led to an ongoing resurgence of interest. The role of the Golgi apparatus in modifying, broadening and refining the structural information conferred by transcription/translation is now generally accepted but still incompletely understood. During the coming years, this topic certainly will remain center stage in the field of cell biology. The centennial of the discovery of this fascinating organelle prompted us to edit a new comprehensive book on the Golgi apparatus whose complexity necessitated the contributions of leading specialists in this field. This book is aimed at a broad readership of glycobiologists as well as cell and molecular biologists and may also be interesting for advanced students of biology and life sciences.

Part I The Nano-Scale Biological Systems in Nature; Molecular bio-motors in living cells - by T. Nishizaka; The form designed by viral genome - by K. Onodera; Part II Detection and Characterization Technology; Atomic force microscopy applied to nano-mechanics of the cell - by A. Ikai; Design, synthesis and biological application of fluorescent sensor molecules for cellular imaging - by K. Kikuchi; Dynamic visualization of cellular signaling - by Q. Ni and J. Zhang; Part III Fabrication Technology; Surface acoustic wave atomizer and electrostatic deposition - by Y. Yamagata; Electrospray deposition of biomolecules by V.N. Morozov; Part IV Processing Technology; Droplet handling - by T.Torii; Integrated microfluidic systems - by S. Kaneda and T. Fujii; Part V Applications; A novel non-viral gene delivery system: Multifunctional envelope-type nano device - by H. Hatakeyama, H. Akita, K. Kogure, and H. Harashima; Biosensors - by M. Saito, H.M. Hiep, N. Nagatani, and E.Tamiya; Micro bioreactors - by Sato and T. Kitamori

Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

The First International Symposium on the Interface between Analytical Chemistry and Microbiology: Applications of Chromatography and Mass Spectrometry was held June 1987 at the University of South Carolina, Columbia, SC, U.S.A. The purpose of the "Interface" meeting was to forge connections between analytical chemists and microbiologists that are using chromatography and mass spectrometry to solve common problems. The goals were admirably fulfilled. Nearly a hundred participants from seven European countries, Japan, and the United States participated in hearing twenty-three plenary talks and thirty-six submitted papers and posters. The papers and discussions displayed the breadth and depth of current research applications and revealed future directions. This book "Analytical Microbiology Methods: Chromatography and Mass Spectrometry" is loosely based on some of the presentations and discussions at the meeting. Each chapter describes specific methodology and applications in the context of the relevant scientific background. The present book continues the theme of an earlier book, "Gas Chromatography/Mass Spectrometry Applications in Microbiology", edited by G. Odham, L. Larsson, and P-A. Mardh, published by Plenum Press in 1984.

The complement system is a group of proteins which plays a major role in the processing and removal of microorganisms and tissue breakdown products from the circulation and extracellular spaces. The system is activated by a wide range of targets, and activation leads to the production of opsonins, chemotaxis of granulocytes, cell lysis and other biological activities. Inappropriate overactivation of the system contributes to inflammatory tissue damage in the host, while inadequate activation leads to accumulation of immune complexes and other debris in the circulation, and susceptibility to infection. The biology and biochemistry of the system is now adequately understood, and attempts can be made to manipulate the activation and activities of the system for potential therapeutic purposes. The reviews in this volume summarise what is known of the ways in which the complement system can be activated, by interaction with antibodies, microorganisms, cell debris, and complex carbohydrates and how the activities and activation of the system have been modified, accidentally or by design, in vitro or in vivo by drugs, venoms, particulate carbohydrates, specific antibodies, synthetic peptides and other reagents.

In the last few decades there has been an ever-increasing component in most BSc Zoology degree courses of cell biology, physiology and genetics, for spectacular developments have taken place in these fields. Some aspects of biotechnology are now also being included. In order to accommodate the new material, the old zoology courses were altered and the traditional two-year basis of systematics of the animal kingdom, comparative anatomy (and physiology) and evolution, was either severely trimmed or reduced and presented in an abridged form under another title. Soon after these course alterations came the swing to modular teaching in the form of a series of shorter, separate courses, some of which were optional. The entire BSc degree course took on a different appearance and several different basic themes became possible. One major result was that in the great majority of cases taxonomy and systematics were no longer taught and biology students graduated without this basic training. We field biologists did appreciate the rising interest in ecology and environ mental studies, but at the same time lamented the shortage of taxonomic skills, so that often field work was based on incorrect identifications. For years many of us with taxonomic inclinations have been bedevilled by the problem of teaching systematics to undergraduates. At a guess, maybe only 5% of students find systematics interesting. It is, however, the very basis of all studies in biology - the correct identification of the organism concerned and its relationships to others in the community."