Glycosylation is a common and extremely important modification in biological molecules, particularly of proteins. "HIV Glycans in Infection and Immunity"provides an overview of the roles of glycans in the transmission/infection, antigenicity, and immunogenicity of HIV and the HIV envelope glycoprotein. It explores recent advances in the understanding of the impact of HIV glycans in infection and their promise for immunological and therapeutic intervention.

Novel collaborations between glycobiologists and immunologists in recent years have led to key advances in the understanding of HIV glycans. These cross-disciplinary endeavors, their achievements and their impact on the field are all addressed, herein."

Master Medicine: Microbiology and Infection is brief and accessible, approached from the point of view of what you will need to know in order to understand the clinical work you will eventually be doing. It includes a wide range of self-assessment material, ideal for testing your understanding, and helping you to prepare for your exams. Concise synoptic (not telegraphic text). Appropriate self-assessment material. Only covers core, so student knows the whole book is essential. Includes key objectives. Contains simple and memorable diagrams for reproduction in exams. Ideal for learning as well as examination review, specifically trying to stimulate the student into assessing his/her own knowledge. The books in the series both complement other available major texts, but also contain enough material to stand in the own right. Provides examination practice. Part of co-ordinated series. Contents refined to reflect 'core knowledge' Major revision of self-assessment material to match change in exam styles (more Extended Matching Questions and OSC-style questions)

Microbiological matters continue to exercise considerable influence on product quality. In both the pharmaceutical and medical device industries, products of greater sophistication, along with evolving regulatory requirements, are elevating the challenges related to maintaining microbiological integrity.
Updated to reflect technological and regulatory changes, the Guide to Microbiological Control in Pharmaceuticals and Medical Devices, Second Edition covers thoseprincipal aspects of microbiology that arerelevant to the preformulation, formulation, manufacturing, and license application stages involved with the production of pharmaceuticals and medical devices.
In recognition of the diverse disciplines involved in pharmaceutical and medical device production, this work provides a brief introduction to microbiology geared towards the nonmicrobiologist. Covering good manufacturing practice in the control of contamination, the text explores quality control, the preservation of formulations, and principles of sterilization, including microbiological-specific considerations for biotechnological products and other medical devices. It also provides additional materials on package integrity and contamination risks in clean rooms.
The editors have produced a companion text, the Handbook of Microbiological Quality Control in Pharmaceuticals and Medical Devices ("see reverse"), which when paired with the Guide offers a complete theoretical and practical treatment of microbiological control.
This book provides a comprehensive distillation of information concerning methodology and regulations that would otherwise remain scattered throughout the literature. It allows scientists frommany fields to address potential problems in advance and implement suitable strategies at the earliest stages of development.

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death in the United States. Annually approximately 30,000 Americans are diagnosed with the disease and most will die from it within five years. P- creatic ductal adenocarcinoma is unique because of its late onset in age, high mortality, small tumor samples infiltrated with normal cells, and a lack of both early detection and effective therapies. Some of these characteristics have made studying this disease a challenge. Pancreatic cancer develops as a result of the accumulation of genetic alterations in cancer-causing genes, such as the oncogenes and the tumor-s- pressor genes. In the last decade, major progress has been made in identifying important oncogenes and tumor-suppressor genes for the disease. In Panc- atic Cancer: Methods and Protocols, we review the classical techniques that have contributed to the advances in pancreatic research and introduce new strategies that we hope will add to future breakthroughs in the field of cancer biology. Pancreatic Cancer: Methods and Protocols provides a broad range of protocols for molecular, cellular, pathological, and statistical analyses of s- radic and familial pancreatic cancer. It covers topics from in vitro cell c- tures to in vivo mouse models, DNA to protein manipulation, and mutation analyses to treatment development. We believe that our book will prove an invaluable source of proven protocols for those who are interested in either basic or translational research in pancreatic cancer.

Since the publication of the first edition of Pharmaceutical Biotechnology over a decade ago, a not-so-subtle shift in the meaning of the term "biotechnology" has occurred. It has come to mean something very specific, namely the development of drug substances with large protein and polypeptide molecules. These substances can be used as drugs in their own right but may also be used to manipulate cellular DNA in order to produce a required molecule that is believed to have desirable properties in the treatment of a disease. Accordingly, the second edition of this popular text reflects that change of definition by including new material that explores the development of these protein-based therapeutic substances. See what's new in the Second Edition: -Expanded coverage of the formulation of proteins -Additional information on proteins used as drug delivery systems -Detailed discussion of interactions between proteins and phospholipids -Increased information on proteomics and gene therapy -Exploration of pulmonary administration and oral delivery of proteins -A broad review of vaccines -Discussion of genetic engineering and genomics -Challenges and issues involved in the development and the production of a drug

Type IV secretion systems (T4SSs) are highly versatile membrane-associated transporter machines used by Gram-negative and Gram-positive bacteria to deliver substrate molecules to a large variety of target cells. This volume summarizes our current knowledge of the large variety and structural diversity of T4SSs in pathogenic Escherichia, Agrobacterium, Legionella, Coxiella, Bartonella, Helicobacter, Enterococcus and other species. Divided into 13 chapters contributed by leading experts, it presents findings that significantly enhance our understanding of how various pathogens manipulate host cell functions to trigger bacterial uptake, promote intracellular growth, suppress defense mechanisms and of how bacteria spread antibiotic resistances, thus facilitating bacterial colonization and disease development. The book is an invaluable source of information for researchers and clinicians.

In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences. Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to "remember" their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of human diseases.

Apoptosis is a regulated, energy-dependent process by which a cell se- destructs. This mechanism of programmed cell death plays an important role in normal development and control of cell numbers in mature a- mals. Apoptosis was initially defined by morphological criteria to describe the distinctive appearance of dying cells that developed nuclear conden- tion, cell shrinkage, and cytoplasmic blebbing. Initiation of the apoptotic process can come from external or internal stimuli and is highly regulated both by molecules that facilitate and by molecules that inhibit the process. Common features of apoptosis include activation of proteases and - cleases, mitochondrial membrane permeabilization, chromatin disruption, and translocation of phosphatidylserine from the inner to the outer s- face of the plasma membrane. Apoptotic cells attract phagocytes that - gulf the apoptotic bodies and prevent tissue damage in the region. Intense investigation of the cell death process has defined many molecular features of the pathway by which regulation and execution can be exploited by pathogens.

Filled with highly instructional visual images, this atlas covers typical and atypical presentations of microorganisms covering the breadth of clinical microbiology and offers insightful comments aiding their identification and clinical significance. It presents more than 425 colored photomicrographs harvested over the author's 40-year career augmented by an up to date text describing each microbial entity included. While not a text book, the photomicrographic accompaniment of microorganisms and their clinical presentation, should make the atlas of immense value for clinical microbiologists, medical, nursing, and laboratory students, and infectious diseases practitioners.

Prominent experts in biodefense research-many from the US Army Medical Research Institute of Infectious Diseases-authoritatively delineate the universe of scientific, medical, and legal issues facing the biodefense research community. Regarding medical countermeasures and decontamination, the authors describe the treatment and pathogenesis of a variety of established pathogens (anthrax, plague, smallpox, Brucellosis, Glanders, and Coxiella burnettii) and review what is known about the aerosol route of infection and decontamination processes. They also examine how to discover the presence of these agents, or other previously unknown biological weapons, and detail the ongoing efforts to counter these agents, including proteomic and genomic analysis as a gateway to better diagnostics, therapeutics, vaccinations, genotyping, and forensics. Additional chapters discuss the development and use technology to identify and characterize these infectious organisms, emerging threats, and the development of countermeasures.

Book covers course with topics in infectious diseases in children and is intended for Pediatric Infectious disease clinical researchers, trainees, trainers, and all those who manage the research of children with infections and the children themselves. The conference is being supported by several societies and is sponsored by several pharmaceutical companies, such as Aventis, Baxter, Chiron Vaccines, Wyeth, etc. ToC reflects the scientific program found here: http: //www.oxfordiic.org/#course

This is a review text on medical microbiology and immunology containing approximately 625 board-type review questions on left-hand pages with answers and explanations on facing right-hand pages. It is designed for medical students taking microbiology as well as for those studying for Step 1 of the National Board Exams and is also useful for Step 3 National Boards on infectious diseases or allergy and immunology. The book's main sections cover general and medical microbiology, bacteriology, virology, immunology, and parasitology. The answers summarize relevant information and point out the fault in incorrect answers. Line drawings and figures are used for questions concerning structure of both molecules and organisms and for interpreting graphical results. Authors Reese, Brownell, and Nair, all with the Medical College of Georgia, bring a combined total of some 85 years of medical school teaching experience to their development of the questions and annotated answers for this book.

This innovative reference explores a wide selection of topics associated with aging, providing a solid understanding of the significance and molecular basis of the aging process and charting the course of future research in the area. Stresses the interplay of mitochondria, mitochondrial DNA, oxidants, and antioxidants! Featuring the research of over 55 experts in the area, Understanding the Process of Aging -covers the functions of nitric oxide and peroxynitrite in mitochondria -integrates several views on the role of mitochondria in the development of apoptosis -gives a quantitative analysis of mutations of mitochondrial DNA during human aging -highlights mitochondrial free radical production -introduces new roles of ubiquinone in mitochondrial functions -offers new antioxidant-based complementary therapeutic strategies -details aspects of intact cells and whole organisms in health and disease -and more! Featuring over 1800 references, tables, drawings, and photographs, Understanding the Process of Aging benefits nutritionists and dieticians, geriatricians, cell and molecular biologists, chemists and biochemists, pharmacologists, biotechnologists, neurologists, cardiologists, oncologists, dermatologists, and graduate and medical school students in these disciplines.

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.

Filling a gap in the literature, this guide analyzes EBV infection and all of its associated disorders including infectious mononucleosis, Burkitt lymphoma, and Hodgkin's disease. Opening with a historical introduction, the reference progresses from molecular virology, epidemiology, immunology, and pathology to clinical presentation, diagnosis, disease detection, patient management, and vaccine development.

The genus Chlamydia encompasses a number of species of obligate intracellular bacteria, including important human pathogens like the most common bacterial agent of sexually transmitted disease. This volume reviews current knowledge of chlamydial biology, covering the unusual structure of the bacteria - which alternate between metabolically almost inactive and fast-dividing forms. It also discusses the ways in which Chlamydia manipulates the host cytoskeleton and subverts the host cell's defence, and illustrates how genomics have begun to uncover the diversity and complexity of chlamydial strains that look very similar but may cause distinct forms of disease. Further, it describes how techniques are now finally being established that can genetically modify Chlamydia, and discusses why such modification is still very difficult and what progress we can expect. Lastly, it presents our current understanding of chlamydial disease: what do we know about chronic infections, what are the mechanisms of inflammatory damage, and what are the prospects of a vaccine? Written be specialists in these various areas, the book is a valuable work of reference for students and scientists with an interest in the molecular, cellular and immunobiology of these fascinating bacteria.

Human Vaccines: Emerging Technologies in Design and Development discusses the advances in molecular biology, biophysics, and informatics-among other disciplines-that have provided scientists with the tools to create new vaccines against emerging and re-emerging pathogens. For example, the virus-like particle technologies that led to licensing of highly efficacious HPV vaccines have only come into full realization in the last 10 years. Their success has, in turn, accelerated the pace with which nanoparticle vaccines are being developed Given the rapidity with which the field is changing and the absence of any text documenting this change, there is a need for a resource that surveys these new vaccine technologies, assesses their potential, and describes their applications. This book provides that resource and complements traditional vaccinology books, but also serves as an excellent standalone for researchers and students with basic knowledge in immunology.

Metabolomics and Microbiomics: Personalized Medicine from the Fetus to the Adult encompasses the most recent advances on the usage of metabolomics and microbiome research to improve disease diagnosis and healthcare. Medicine is changing from epidemiologic, descriptive, reductionist, and reactive approaches to individualized, predictive, and holistic ones by applying microbiomics to understand the functionality of the human body. The book discusses topics such as systems biology approaches, omics technologies, perinatal programming, and personalized medicine. It also discusses the ethical implications of microbiomics research and new pathways of research, such as renal regenerative medicine, gender medicine in perinatology, and animals and the science of healing. The book is a valuable resource for medical professionals and researchers in metabolomics, nutrition, microbiology, and personalized-predictive medicine. The book also will appeal to non-specialized professionals who may take advantage of its captivating and simple language.

Macrophages are a key component of the innate immune system and play an integral role in host defense and homeostasis. On one hand, these cells contribute to host defence by triggering inflammation, displaying microbicidal/tumoricidal properties, regulating the activation of adaptive immunity and promoting resolution of inflammation. On the other hand, they contribute to essential trophic functions such as neural patterning, bone morphogenesis and ductal branching in mammary glands. Thus, macrophages are extremely versatile cells that can respond efficiently to tissue micro environmental cues by polarizing to distinct phenotypes, depending on the functions they need to perform. Indeed, functional diversity and plasticity are hallmarks of these cells.

Macrophages may also play a detrimental role. An overwhelming body of literature has indicated their crucial role in pathogenesis. The list includes sepsis, cancer, metabolic syndrome, immunodeficiency, auto-immune disease-virtually impacting every major pathology that we know. These observations have suggested macrophages and their related molecules as potential targets in therapeutic applications. Available evidence proclaims macrophages as a key player in homeostasis, host defense and disease. Crucial developments in the past few years call for a re-evaluation and update of our understanding of macrophages. The present book is an endeavour that attempts provide state-of-the art knowledge of these cells in health and disease.