This book introduces some key problems in bioinformatics, discusses the models used to formally describe these problems, and analyzes the algorithmic approaches used to solve them. After introducing the basics of molecular biology and algorithmics, Part I explains string algorithms and alignments; Part II details the field of physical mapping and DNA sequencing; and Part III examines the application of algorithmics to the analysis of biological data. Exciting application examples include predicting the spatial structure of proteins, and computing haplotypes from genotype data. Figures, chapter summaries, detailed derivations, and examples, are provided.

Cardiac Gene Expression: Methods and Protocols presents both cutting-edge and established methods for studying cardiac gene expression. The protocols provide a template for solid research, and cover the process through screening, analysis, characterization, and functional confirmation of novel genes or known genes with a new function.
Section I, Cardiac Gene Expression Profiling: The Global Perspective, discusses several different approaches to examining, identifying, and analyzing changes in transcriptome gene expression. Section II, Cardiac Gene Regulation: Gene-Specific mRNA Measurement in the Myocardium, outlines more sensitive and gene-targeted expression methods. Section III, Cardiac Gene Regulation: Promoter Characterization in the Myocardium, provides protocols for the study of underlying gene regulation mechanisms by focusing on the interaction of transcription factors with their cognate cis binding elements. Section IV, In Silico Assessment of Regulatory cis-Elements and Gene Regulation, and Section V, Cardiac Single Network Polymorphisms, emphasize new analytical approaches for deciphering the functional elements buried in the 3 billion nucleotides of the human genome and other model genomes. The concluding section, Gene Overexpression and Targeting in the Myocardium, highlights methods that facilitate overexpression or cardiac-specific targeted gene deletion.

Charge migration through DNA has been the focus of considerable interest in recent years. This book presents contributions from an international team of researchers active in this field. It contains a wide range of topics that includes the mathematical background of the quantum processes involved, the role of charge transfer in DNA radiation damage, a new approach to DNA sequencing, DNA photonics, and many others.

There is much more to heredity than genes For much of the twentieth century it was assumed that genes alone mediate the transmission of biological information across generations and provide the raw material for natural selection. Yet, it's now clear that genes are not the only basis of heredity. In Extended Heredity, evolutionary biologists Russell Bonduriansky and Troy Day explore the latest research showing that what happens during our lifetimes-and even our parents' and grandparents' lifetimes-can influence the features of our descendants. Based on this evidence, Bonduriansky and Day develop an extended concept of heredity that upends ideas about how traits can and cannot be transmitted across generations, opening the door to a new understanding of inheritance, evolution, and even human health.

Protocols for Nucleic Acid Analysis by Non-radioactive Probes, Second Edition provides a firm background on the basic preparative protocols required for the analysis of nucleic acids by nonradioactive methods. Presenting the methodologies using amazing new applications, this volume offers guide chapters on nucleic acid extractions, preparation of nucleic acid blots, and labeling of nucleic acids with nonradioactive haptens. New fluorescent techniques such as Real Time PCR and microarrays are also included, allowing users to get a nonradioactive protocol implemented in the laboratory with minimum adaptation required and fastest time to results.
The protocols follow the successful Methods in Molecular Biology series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

This second part in the two-volume work Microarrays details applications and data analysis. It includes insight into non-mammalian vertebrate systems, processes and protocols for high quality glass-based microarrays. Coverage includes applications in DNA, peptide, antibody and carbohydrate microarraying, oligonucleotide microarrays generated from hydrolysis PCR probe sequences, microarray platforms in clinical practice, and screening of cDNA libraries on glass slide microarrays. Authors in this volume also discuss protocols for predicting DNA duplex stability on oligonucleotide arrays and integrated analysis of microarray results.

The onset of cancer presents one of the most fundamental problems in modern biology. In "Dynamics of Cancer," Steven Frank produces the first comprehensive analysis of how particular genetic and environmental causes influence the age of onset.

The book provides a unique conceptual and historical framework for understanding the causes of cancer and other diseases that increase with age. Using a novel quantitative framework of reliability and multistage breakdown, Frank unifies molecular, demographic, and evolutionary levels of analysis. He interprets a wide variety of observations on the age of cancer onset, the genetic and environmental causes of disease, and the organization of tissues with regard to stem cell biology and somatic mutation. Frank uses new quantitative methods to tackle some of the classic problems in cancer biology and aging: how the rate of increase in the incidence of lung cancer declines after individuals quit smoking, the distinction between the dosage of a chemical carcinogen and the time of exposure, and the role of inherited genetic variation in familial patterns of cancer.

This is the only book that presents a full analysis of the age of cancer onset. It is a superb teaching tool and a rich source of ideas for new and experienced researchers. For cancer biologists, population geneticists, evolutionary biologists, and demographers interested in aging, this book provides new insight into disease progression, the inheritance of predisposition to disease, and the evolutionary processes that have shaped organismal design.

The contents of this book focus on the recent investigations in molecular bi- ogywhereapplicationsoftopologyseemtobeverystimulating. Thevolumeis based on the talks and lectures given by participants of the three-month p- gram"TopologyinCondensedMatter,"whichwasheldintheMaxPlanck- stitut fur Physik komplexer Systeme, Dresden, Germany, 8May-31July 2002, under the scienti?c direction of Professors M. Kl eman, S. Novikov and - self. The aim of this program was to discuss recent applications of topology to several areas in condensed matter physics and molecular biology. The ?rst volume "Topology in Condensed Matter" is concerned with m- ern applications of geometrical and topological techniques to such new and classic ?elds of physics like electron theory of metals, theory of nano-crystals, aperiodic and liquid crystals, quantum computation and so on. This volume is published simultaneously in "Springer Series in Solid-State Physics." The present volume gives an exposition of the role of topology in the theory of proteins and DNA. The last thirty years a?rmed very e?cient - plications of modern mathematics, especially topology, in physics. The union of mathematics and physics was very stimulating for both sides. On the other hand, the impact of mathematics in biology has been rather limited. H- ever here also some interesting results were obtained. In particular, there are applications of knot theory in the theory of circular closed DNA. The - cent discoveries in molecular biology indicate future successful applications of topology."

This book constitutes the refereed proceedings of the 4th RECOMB Comparative Genomics Satellite Workshop, RECOMB-CG 2006. The 17 revised full papers presented were carefully reviewed and selected from 34 initial submissions. The papers address a broad variety of aspects and components of the field of comparative genomics, ranging from new quantitative discoveries about genome structure and process to theorems on the complexity of computational problems inspired by genome comparison.

This volume includes, in an integrated way, modern computational studies of nucleic acids, ranging from advanced electronic structure quantum chemical calculations through explicit solvent molecular dynamics (MD) simulations up to mesoscopic modelling, with the main focus given to the MD field.It gives an equal emphasis to the leading methods and applications while successes as well as pitfalls of the computational techniques are discussed. The systems and problems studied include: Accurate calculations of base pairing energies; Electronic properties of nucleic acids and electron transfer, through various types of nucleic acid; and, Calculating DNA elasticity. This book is ideally suited to academics and researchers in organic and computational chemistry as well as biochemistry and particularly those interested in the molecular modelling of nucleic acids.Besides the state-of-the art science, the book also provides introductory information to non-specialists to enter this field.

Plant Genes, Genomes and Genetics provides a comprehensive treatment of all aspects of plant gene expression. Unique in explaining the subject from a plant perspective, it highlights the importance of key processes, many first discovered in plants, that impact how plants develop and interact with the environment. This text covers topics ranging from plant genome structure and the key control points in how genes are expressed, to the mechanisms by which proteins are generated and how their activities are controlled and altered by posttranslational modifications. Written by a highly respected team of specialists in plant biology with extensive experience in teaching at undergraduate and graduate level, this textbook will be invaluable for students and instructors alike. Plant Genes, Genomes and Genetics also includes: specific examples that highlight when and how plants operate differently from other organisms; special sections that provide in-depth discussions of particular issues; end-of-chapter problems to help students recapitulate the main concepts; rich, full-colour illustrations and diagrams clearly showing important processes in plant gene expression; a companion website with PowerPoint slides, downloadable figures, and answers to the questions posed in the book. Aimed at upper level undergraduates and graduate students in plant biology, this text is equally suited for advanced agronomy and crop science students inclined to understand molecular aspects of organismal phenomena. It is also an invaluable starting point for professionals entering the field of plant biology.

DNA Repair and Human Disease highlights the molecular complexities of a few well-known human hereditary disorders that arise due to perturbations in the fidelity of diverse DNA repair machineries.

Mitochondrial DNA is one of the most closely explored genetic systems, because it can tell us so much about the human past. This book takes a unique perspective, presenting the disparate strands that must be tied together to exploit this system. From molecular biology to anthropology, statistics to ancient DNA, this first volume of three presents a comprehensive global picture and a critical appraisal of human mitochondrial DNA variation.

Fungal comparative genomics started in 2000 by the genome sequencing of several yeast species. Since then, over 30 fungal genome sequences have become available. This set represents a huge evolutionary divergence, but also contains closely related genomes. This volume describes how to use this set of genomes to trace events in genome evolution, to extract information about highly conserved and less conserved sequence elements, and to develop novel methods in genomics.

2 On the Early History of 5-mC In the fall of 1966, Norton D. Zinder of Rockefeller University in New York City presented the Harvey Lecture on "Phage RNA as Genetic Material" (Zinder 1966). Frankly,I do not remember manydetailsofhis talk. However, one ofhis concluding remarks, in which he thanked his teacher Rollin Hotchkiss, stuck in my mind andbecame an important leitmotiffor much of my own scienti?c career. Norton's relevant passages went somethinglikethis (approximate quotation): When we hope to have made a scienti?c discovery, we better spend much of our time immediately after this fortunate event in trying to counter our own beliefsand interpretations. Onlyafter a lot of painstaking scrutiny involving many control experiments when our discoveryhas stood the test of careful consideration, can one hope that our colleagues will beabletocon?rm the new ?ndings. Of course, it is a major task of the scienti?c community to respectfully meet supposedly novel announ- ments withdisbelief and skepticism and in turn commence the process of disproving these concepts. Consistent con?rmations, with plenty of modi?cations to be sure, will providethe encouragement necessary to continue and to improve the initial observations and conclusions. Apparently, the scienti?c tradition re?ected in this overall cautious attitude had emanatedfrom the laboratory of Oswald Avery that Rollin Hotchkiss had been trained in. This certainly most important of scienti?ccredos seems tocontradict intuitively held notions and might bethought to run counter to general practice.

Genome Exploitation: Data Mining the Genome is developed from the 23rd Stadler Genetic Symposium. This volume discusses and illustrates how scientists are going to characterize and make use of the massive amount of information being accumulated about the plant and animal genomes. Genome Exploitation: Data Mining the Genome is a state-of-the-art picture on mining the Genome databases. This is one of the few times that researchers in both plants and animals will be working together to create a seminal data resource.

A unique PCR troubleshooting guide that is an essential companion for anyone who uses the polymerase chain reaction technique. Aimed at a reader with some experience in PCR the book discusses the many and varied problems encountered with PCR together with tips, advice and procedures to obviate rather than overcome the PCR problems. Written in the language of the laboratory with a little humour and a down-to-earth approach, the book is easy to read and understand. If you fail at PCR, consult this book The advice in these pages is invaluable and is the sort of advice that is not usually found elsewhere.

Since the first edition of this book dedicated to differential display (DD) technology was published in 1997, we have witnessed an explosive interest in studying differential gene expression. The gene-hunting euphoria was initially powered by the invention of DD, which was gradually overtaken by DNA microarray technology in recent years. Then why is there still the need for second edition of this DD book? First of all, DD still enjoys a substantial lead over DNA microarrays in the ISI citation data (see Table 1), despite the h- dreds of millions of dollars spent each year on arrays. This may come as a surprise to many, but to us it implies that many of the DNA microarray studies went unpublished owing to their unfulfilled promises (1). Second, unlike DNA microarrays, DD is an "open"-ended gene discovery method that does not depend on prior genome sequence information of the organism being studied. As such, DD is applicable to the study of all living organisms-from bacteria, fungi, insects, fish, plants, to mammals-even when their genomes are not sequenced. Second, DD is more accessible technically and financially to most cost-conscious "cottage-industry" academic laboratories. So clearly DD still has its unique place in the modern molecular biological toolbox for gene expression analysis.

The first edition of this book, published in 1999 and called DNA Repair Protocols: Eukaryotic Systems, brought together laboratory-based methods for studying DNA damage and repair in diverse eukaryotes: namely, two kinds of yeast, a nematode, a fruit fly, a toad, three different plants, and human and murine cells. This second edition of DNA Repair Protocols covers mammalian cells only and hence its new subtitle, Mammalian Systems. There are two reasons for this fresh emphasis, both of them pragmatic: to cater to the interests of what is now a largely mammalocentric DNA repair field, and to expedite editing and prod- tion of this volume. Although DNA Repair Protocols: Mammalian Systems is a smaller book than its predecessor, it actually contains a greater variety of methods. Fourteen of the book's thirty-two chapters are entirely new and areas of redundancy present in the first edition have been eliminated here (for example, now just two chapters describe assays for nucleotide excision repair [NER], rather than seven). All eighteen returning chapters have been revised, many of them ext- sively. In order to maintain a coherent arrangement of topics, the four-part p- titioning seen in the first edition was dispensed with and chapters concerned with ionizing radiation damage and DNA strand breakage and repair were re- cated to near the front of the book. Finally, an abstract now heads each chapter.

The complexity of genome evolution poses many exciting challenges to devel- ers of mathematical models and algorithms, who have recourse to a spectrum of algorithmic, statisticalandmathematicaltechniques, rangingfromexact, heur- tic, ?xed-parameter and approximation algorithms for problems based on par- mony models to Monte Carlo Markov Chain algorithms for Bayesian analysis of problems based on probabilistic models. The annual RECOMB Satellite Workshop on Comparative Genomics (RECOMB ComparativeGenomics)is aforumonallaspects andcomponents of this ?eld, rangingfromnew quantitativediscoveriesabout genomestructureand process to theorems on the complexity of computational problems inspired by genome comparison. The informal steering committee for this meeting consists of David Sanko?, Jens Lagergren and Aoife McLysaght. Thisvolumecontainsthepaperspresentedatthe3rdRECOMBComparative Genomicsmeeting, whichwasheldinDublin, Ireland, onSeptember18-20,2005. The ?rst two meetings of this series were held in Minneapolis, USA (2003) and Bertinoro, Italy (2004). This year, 21 papers were submitted, of which the Program Committee - lected 14 for presentation at the meeting and inclusion in this proceedings.Each submission was refereed by at least three members of the Program Committee. Aftercompletionofthereferees'reports, anextensiveWeb-baseddiscussiontook placeformakingdecisions.TheRECOMBComparativeGenomics2005Program Committee consisted of the following 27 members: Vineet Bafna, Anne Be- eron, Mathieu Blanchette, Avril Coghlan, Dannie Durand, Nadia El-Mabrouk, Niklas Eriksen, Aaron Halpern, Rose Hoberman, Daniel Huson, Jens Lagergren, Giuseppe Lancia, Emmanuelle Lerat, Aoife McLysaght, Istvan Miklos, Bernard Moret, PavelPevzner, Ben Raphael, Marie-FranceSagot, David Sanko?, Cathal Seoighe, Beth Shapiro, Igor Sharakhov, Mike Steel, Jens Stoye, Glenn Tesler and Louxin Zhan. We would like to thank the ProgramCommittee members for their dedication and hard wo

Understanding of the molecular basis of DNA damage and its repair has increased dramatically in recent years and there is now a substantial knowledge concerning the products that arise from free-radical attack on DNA. Free-radical DNA damage may lead to mutations, cancer and cell death. There are various free radical sources, notably ionizing radiation or oxidative stress. In the radiotherapy of cancer and in the case of some anticancer drugs, use is made of cell killing by excessive DNA damage.nbsp; The mechanisms that lead to these products have been studied on the model level and with small double-stranded DNA fragments and are discussed in some detail. The basics of the underlying free-radical chemistry are dealt with in separate chapters. Understanding of the molecular basis of DNA damage and its repair has increased dramatically in recent years, and substantial knowledge now exists concerning the products arising from free-radical attack on DNA. Free-radical DNA damage may lead to mutations, cancer, and cell death. Free radicals have various sources, notably ionizing radiation and oxidative stress. In radiotherapy for cancer and with some anticancer drugs, use is made of cell death by excessive DNA damage. The mechanisms leading to products of free-radical attack which have been studied in models and with small double-stranded DNA fragments are discussed in detail, and the basics of the underlying free-radical chemistry are dealt with in separate chapters.

The field of DNA computation has flourished since the publication of Adleman's seminal article, in which he demonstrated for the first time how a computation may be performed at a molecular level by performing standard operations on a tube of DNA strands. Since Adleman's original experiment, interest in DNA computing has increased dramatically. This book provides a broad overview of the entire field of DNA computation, tracing its history and development. It contains detailed descripions of all major theoretical models and experimental results to date, which are lacking in existing texts. Potential future developments are also discussed. The book is a useful reference source for researchers and students, as well as an accessible introduction for people new to the field.

A collection of readily reproducible methods for the design, preparation, and use of RNAs for silencing gene expression in cells and organisms. The techniques range widely and include methods addressing the biochemical aspects of the silencing machinery, RNA silencing in non-mammalian organisms, and the in vivo delivery of siRNAs and silencing vectors. There are also techniques for designing, preparing, and using RNAs to silence gene expression, for fine-tuning regulation by targeting specific isoforms of a given gene, and for the study and use of microRNAs. The protocols follow the successful Methods in Molecular Biology (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

Introduction The goal of this book is to introduce XML to a bioinformatics audience. It does so by introducing the fundamentals of XML, Document Type De?nitions (DTDs), XML Namespaces, XML Schema, and XML parsing, and illustrating these concepts with speci?c bioinformatics case studies. The book does not assume any previous knowledge of XML and is geared toward those who want a solid introduction to fundamental XML concepts. The book is divided into nine chapters: Chapter 1: Introduction to XML for Bioinformatics. This chapter provides an introduction to XML and describes the use of XML in biological data exchange. A bird's-eye view of our ?rst case study, the Distributed Annotation System (DAS), is provided and we examine a sample DAS XML document. The chapter concludes with a discussion of the pros and cons of using XML in bioinformatic applications. Chapter 2: Fundamentals of XML and BSML. This chapter introduces the fundamental concepts of XML and the Bioinformatic Sequence Markup Language (BSML). We explore the origins of XML, de?ne basic rules for XML document structure, and introduce XML Na- spaces. We also explore several sample BSML documents and visualize these documents in the TM Rescentris Genomic Workspace Viewer.

In the past half century, filamentous fungi have grown in commercial importance not only in the food industry but also as sources of pharmaceutical agents for the treatment of infectious and metabolic diseases and of specialty proteins and enzymes used to process foods, fortify detergents, and perform biotransformations. The commercial impact of molds is also measured on a negative scale since some of these organisms are significant as pathogens of crop plants, agents of food spoilage, and sources of toxic and carcinogenic compounds. Recent advances in the molecular genetics of filamentous fungi are finding increased application in the pharmaceutical, agricultural, and enzyme industries, and this trend promises to continue as the genomics of fungi is explored and new techniques to speed genetic manipulation become available.

This volume focuses on the filamentous fungi and highlights the advances of the past decade, both in methodology and in the understanding of genomic organization and regulation of gene and pathway expression.