Naomi E. Chayen, John R. Helliwell, and Edward H. Snell
- Published in print:
- 2010
- Published Online:
- May 2010
- ISBN:
- 9780199213252
- eISBN:
- 9780191707575
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199213252.003.0019
- Subject:
- Physics, Crystallography: Physics
Major increases in brightness are anticipated with the upcoming coherent X‐ray lasers. Extrapolation suggests that a single macromolecule ‘sample’ may be sufficient to generate a measurable X‐ray ...
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Major increases in brightness are anticipated with the upcoming coherent X‐ray lasers. Extrapolation suggests that a single macromolecule ‘sample’ may be sufficient to generate a measurable X‐ray diffraction pattern, a continuous Fourier transform of the molecule giving easier phase determination. The practical difficulties are enormous in the recording of such diffraction patterns, not least the so‐called ‘molecule blow‐up problem’ due to the thermal and radiation blast that a single molecule must take. By taking the exposure at a sufficiently small time‐flash, a few femtoseconds, this may be practical. For 3D structure determination multiple sample orientations are needed. A risk is too few photons in the femtosecond pulse that must be used to take data before sample damage occurs. A nanocluster of molecules would be a way of compensating for that and a ‘jet stream’ of these would lead to powder diffraction patterns rather than single‐molecule patterns.Less
Major increases in brightness are anticipated with the upcoming coherent X‐ray lasers. Extrapolation suggests that a single macromolecule ‘sample’ may be sufficient to generate a measurable X‐ray diffraction pattern, a continuous Fourier transform of the molecule giving easier phase determination. The practical difficulties are enormous in the recording of such diffraction patterns, not least the so‐called ‘molecule blow‐up problem’ due to the thermal and radiation blast that a single molecule must take. By taking the exposure at a sufficiently small time‐flash, a few femtoseconds, this may be practical. For 3D structure determination multiple sample orientations are needed. A risk is too few photons in the femtosecond pulse that must be used to take data before sample damage occurs. A nanocluster of molecules would be a way of compensating for that and a ‘jet stream’ of these would lead to powder diffraction patterns rather than single‐molecule patterns.
Dennis Sherwood and Jon Cooper
- Published in print:
- 2010
- Published Online:
- January 2011
- ISBN:
- 9780199559046
- eISBN:
- 9780191595028
- Item type:
- book
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199559046.001.0001
- Subject:
- Physics, Crystallography: Physics
This book presents a complete account of the theory of the diffraction of X-rays by crystals with particular reference to the processes of determining the structures of protein molecules. The book ...
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This book presents a complete account of the theory of the diffraction of X-rays by crystals with particular reference to the processes of determining the structures of protein molecules. The book develops from first principles all relevant mathematics, diffraction, and wave theory. The practical aspects of sample preparation and X-ray data collection using both laboratory and synchrotron sources are covered along with data analysis at both the theoretical and practical levels. The important role played by the Patterson function in structure analysis by both molecular replacement and experimental phasing approaches is covered, as are methods for improving the resulting electron density map. The theoretical basis of methods used in refinement of protein crystal structures are then covered in depth along with the crucial task of defining the binding sites of ligands and drug molecules. The complementary roles of other diffraction methods which reveal further detail of great functional importance in a crystal structure are outlined.Less
This book presents a complete account of the theory of the diffraction of X-rays by crystals with particular reference to the processes of determining the structures of protein molecules. The book develops from first principles all relevant mathematics, diffraction, and wave theory. The practical aspects of sample preparation and X-ray data collection using both laboratory and synchrotron sources are covered along with data analysis at both the theoretical and practical levels. The important role played by the Patterson function in structure analysis by both molecular replacement and experimental phasing approaches is covered, as are methods for improving the resulting electron density map. The theoretical basis of methods used in refinement of protein crystal structures are then covered in depth along with the crucial task of defining the binding sites of ligands and drug molecules. The complementary roles of other diffraction methods which reveal further detail of great functional importance in a crystal structure are outlined.
Gautam Desiraju and Thomas Steiner
- Published in print:
- 2001
- Published Online:
- January 2010
- ISBN:
- 9780198509707
- eISBN:
- 9780191708206
- Item type:
- book
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198509707.001.0001
- Subject:
- Physics, Crystallography: Physics
The weak hydrogen bond, also known as non-conventional hydrogen bond, has been the subject of intense scrutiny over recent years in several fields, in particular structural chemistry, structural ...
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The weak hydrogen bond, also known as non-conventional hydrogen bond, has been the subject of intense scrutiny over recent years in several fields, in particular structural chemistry, structural biology, and the pharmaceutical sciences. Today, there is a large body of experimental and theoretical evidence confirming that hydrogen bonds like C-H···O, N-H···π, C-H···π and even bonds like O-H··· metal play distinctive roles in molecular recognition, guiding molecular association, and in determining molecular and supramolecular architectures. The relevant compound classes include organometallic complexes, organic and bio-organic systems, as well as DNA and proteins.Less
The weak hydrogen bond, also known as non-conventional hydrogen bond, has been the subject of intense scrutiny over recent years in several fields, in particular structural chemistry, structural biology, and the pharmaceutical sciences. Today, there is a large body of experimental and theoretical evidence confirming that hydrogen bonds like C-H···O, N-H···π, C-H···π and even bonds like O-H··· metal play distinctive roles in molecular recognition, guiding molecular association, and in determining molecular and supramolecular architectures. The relevant compound classes include organometallic complexes, organic and bio-organic systems, as well as DNA and proteins.
Daniel L. Stein and Charles M. Newman
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691147338
- eISBN:
- 9781400845637
- Item type:
- book
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691147338.001.0001
- Subject:
- Sociology, Science, Technology and Environment
Spin glasses are disordered magnetic systems that have led to the development of mathematical tools with an array of real-world applications, from airline scheduling to neural networks. This book ...
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Spin glasses are disordered magnetic systems that have led to the development of mathematical tools with an array of real-world applications, from airline scheduling to neural networks. This book offers the most concise, engaging, and accessible introduction to the subject, fully explaining what spin glasses are, why they are important, and how they are opening up new ways of thinking about complexity. This one-of-a-kind guide to spin glasses begins by explaining the fundamentals of order and symmetry in condensed matter physics and how spin glasses fit into and modify this framework. The book then explores how spin-glass concepts and ideas have found applications in areas as diverse as computational complexity, biological and artificial neural networks, protein folding, immune response maturation, combinatorial optimization, and social network modeling. Providing an essential overview of the history, science, and growing significance of this exciting field, the book also features a forward-looking discussion of what spin glasses may teach us in the future about complex systems. This is a useful book for students and practitioners in the natural and social sciences, with new material even for the experts.Less
Spin glasses are disordered magnetic systems that have led to the development of mathematical tools with an array of real-world applications, from airline scheduling to neural networks. This book offers the most concise, engaging, and accessible introduction to the subject, fully explaining what spin glasses are, why they are important, and how they are opening up new ways of thinking about complexity. This one-of-a-kind guide to spin glasses begins by explaining the fundamentals of order and symmetry in condensed matter physics and how spin glasses fit into and modify this framework. The book then explores how spin-glass concepts and ideas have found applications in areas as diverse as computational complexity, biological and artificial neural networks, protein folding, immune response maturation, combinatorial optimization, and social network modeling. Providing an essential overview of the history, science, and growing significance of this exciting field, the book also features a forward-looking discussion of what spin glasses may teach us in the future about complex systems. This is a useful book for students and practitioners in the natural and social sciences, with new material even for the experts.
Janos T. Kodra, Marie Skovgaard, Dennis Madsen, and David A. Liberles
- Published in print:
- 2007
- Published Online:
- September 2008
- ISBN:
- 9780199299188
- eISBN:
- 9780191714979
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199299188.003.0003
- Subject:
- Biology, Evolutionary Biology / Genetics
Many bioactive peptides and proteins of pharmaceutical interest are found in animal venoms. Nature often reuses scaffolds within protein frameworks to develop new properties. The binding core of the ...
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Many bioactive peptides and proteins of pharmaceutical interest are found in animal venoms. Nature often reuses scaffolds within protein frameworks to develop new properties. The binding core of the peptide from venomous animals is conserved through species (built on a small number of permissive scaffolds). The same scaffolds are often found in nature in protein, performing other non-toxic functions, and it is likely that such conserved motifs are the result of divergent evolution from a common ancestor protein framework via gene duplication. This chapter describes the use of ancestral sequence reconstruction to identify and reconstruct the evolutionary history of important physiological protein and peptide and to connect their common ancestor to certain venom peptides and proteins. This process helps with identifying which amino acids are important for functioning and which ultimately can be used to engineer new bioactive peptide with tailor made properties.Less
Many bioactive peptides and proteins of pharmaceutical interest are found in animal venoms. Nature often reuses scaffolds within protein frameworks to develop new properties. The binding core of the peptide from venomous animals is conserved through species (built on a small number of permissive scaffolds). The same scaffolds are often found in nature in protein, performing other non-toxic functions, and it is likely that such conserved motifs are the result of divergent evolution from a common ancestor protein framework via gene duplication. This chapter describes the use of ancestral sequence reconstruction to identify and reconstruct the evolutionary history of important physiological protein and peptide and to connect their common ancestor to certain venom peptides and proteins. This process helps with identifying which amino acids are important for functioning and which ultimately can be used to engineer new bioactive peptide with tailor made properties.
Jane Skelly, Maninder K. Sohi, and Thil Batuwangala
- Published in print:
- 2007
- Published Online:
- September 2007
- ISBN:
- 9780198520979
- eISBN:
- 9780191706295
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198520979.003.0001
- Subject:
- Biology, Biochemistry / Molecular Biology
The ideal protein-expression strategy for X-ray structural analysis should provide correctly folded, soluble, and active protein in sufficient quantities for successful crystallization. Subsequent ...
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The ideal protein-expression strategy for X-ray structural analysis should provide correctly folded, soluble, and active protein in sufficient quantities for successful crystallization. Subsequent isolation and purification must be designed to achieve a polished product as rapidly as possible, involving a minimum number of steps. The simplest and least expensive methods employ bacterial hosts such as Escherichia coli, Bacillus, and Staphylococcus but if the target protein is from an eukaryotic source requiring post-translational processing for full functionality, an eukaryotic vector-host system would be appropriate. This chapter discusses the processes of cloning and expression, and protein extraction and isolation.Less
The ideal protein-expression strategy for X-ray structural analysis should provide correctly folded, soluble, and active protein in sufficient quantities for successful crystallization. Subsequent isolation and purification must be designed to achieve a polished product as rapidly as possible, involving a minimum number of steps. The simplest and least expensive methods employ bacterial hosts such as Escherichia coli, Bacillus, and Staphylococcus but if the target protein is from an eukaryotic source requiring post-translational processing for full functionality, an eukaryotic vector-host system would be appropriate. This chapter discusses the processes of cloning and expression, and protein extraction and isolation.
Maninder K. Sohi and Ivan Laponogov
- Published in print:
- 2007
- Published Online:
- September 2007
- ISBN:
- 9780198520979
- eISBN:
- 9780191706295
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198520979.003.0015
- Subject:
- Biology, Biochemistry / Molecular Biology
In the living cell, protein-DNA interactions take place during genetic processes such as chromatin organization, recombination, replication, transcription, and DNA repair. In order to fully ...
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In the living cell, protein-DNA interactions take place during genetic processes such as chromatin organization, recombination, replication, transcription, and DNA repair. In order to fully understand the mechanism of these processes, study of protein-DNA interactions at atomic level is required. Despite the wealth of knowledge and attempts of several investigators to classify protein-DNA complexes on the basis of structural analysis of well over 200 protein-DNA complexes, the prediction and modelling based on three-dimensional structure or amino acid sequence of a protein and nucleotide sequence of DNA is challenging. X-ray crystallography is the most powerful technique used for structural studies and the development of technology for the production and purification of large quantities of proteins and DNA is vital to its success. Advances in oligonucleotide synthesis have not only provided ease of synthesis of large quantities of pure DNA but also of any required DNA sequence. This has resulted in the crystallization and structure determination of a vast number of DNA oligonucleotides and protein-DNA complexes. Since 1994 there has been a dramatic increase in the number of the protein-DNA complex structures solved annually. The first and most difficult step in the X-ray crystallographic study is the growth of well-diffracting crystals of the protein-DNA complex under investigation. This chapter describes methods employed to purify proteins and DNA for cocrystallization, procedures for crystallization of protein-DNA, and characterization of cocrystals.Less
In the living cell, protein-DNA interactions take place during genetic processes such as chromatin organization, recombination, replication, transcription, and DNA repair. In order to fully understand the mechanism of these processes, study of protein-DNA interactions at atomic level is required. Despite the wealth of knowledge and attempts of several investigators to classify protein-DNA complexes on the basis of structural analysis of well over 200 protein-DNA complexes, the prediction and modelling based on three-dimensional structure or amino acid sequence of a protein and nucleotide sequence of DNA is challenging. X-ray crystallography is the most powerful technique used for structural studies and the development of technology for the production and purification of large quantities of proteins and DNA is vital to its success. Advances in oligonucleotide synthesis have not only provided ease of synthesis of large quantities of pure DNA but also of any required DNA sequence. This has resulted in the crystallization and structure determination of a vast number of DNA oligonucleotides and protein-DNA complexes. Since 1994 there has been a dramatic increase in the number of the protein-DNA complex structures solved annually. The first and most difficult step in the X-ray crystallographic study is the growth of well-diffracting crystals of the protein-DNA complex under investigation. This chapter describes methods employed to purify proteins and DNA for cocrystallization, procedures for crystallization of protein-DNA, and characterization of cocrystals.
Stephen J. Moss and Jeremy Henley (eds)
- Published in print:
- 2002
- Published Online:
- March 2012
- ISBN:
- 9780192632241
- eISBN:
- 9780191724763
- Item type:
- book
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780192632241.001.0001
- Subject:
- Neuroscience, Molecular and Cellular Systems
This book reviews the recent advances in understanding of the molecular and cellular mechanisms that control the assembly, transport, targeting, and anchoring of the protein complexes making up the ...
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This book reviews the recent advances in understanding of the molecular and cellular mechanisms that control the assembly, transport, targeting, and anchoring of the protein complexes making up the most important ion channels and receptor families, fundamental to synaptic function. Improved understanding of these processes is expected to reveal novel therapeutic targets relevant to a range of disease states. The first section of the book contains three chapters dealing with cation channels and provides an account of what is known about the structures and the assembly and targeting of these multimeric proteins. The focus of the book then moves on to cover ligand-gated ion channels with two chapters on acetylcholine receptors. The final section of the book contains four chapters covering the excitatory and inhibitory amino acid receptors. The book provides an integrated overview of advances in the field of molecular neurobiology.Less
This book reviews the recent advances in understanding of the molecular and cellular mechanisms that control the assembly, transport, targeting, and anchoring of the protein complexes making up the most important ion channels and receptor families, fundamental to synaptic function. Improved understanding of these processes is expected to reveal novel therapeutic targets relevant to a range of disease states. The first section of the book contains three chapters dealing with cation channels and provides an account of what is known about the structures and the assembly and targeting of these multimeric proteins. The focus of the book then moves on to cover ligand-gated ion channels with two chapters on acetylcholine receptors. The final section of the book contains four chapters covering the excitatory and inhibitory amino acid receptors. The book provides an integrated overview of advances in the field of molecular neurobiology.
Daniel L. Stein and Charles M. Newman
- Published in print:
- 2013
- Published Online:
- October 2017
- ISBN:
- 9780691147338
- eISBN:
- 9781400845637
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691147338.003.0007
- Subject:
- Sociology, Science, Technology and Environment
This chapter explores how spin glass concepts have found use in and, in some cases, further advanced areas such as computational complexity, combinatorial optimization, neural networks, protein ...
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This chapter explores how spin glass concepts have found use in and, in some cases, further advanced areas such as computational complexity, combinatorial optimization, neural networks, protein conformational dynamics and folding, and computer science (through the introduction of new heuristic algorithms such as simulated annealing and neural-based computation, and through new approaches to analyzing hard combinatorial optimization problems). It also introduces some “short takes” on topics that space constraints prevent covering in detail, but should be at least mentioned: prebiotic evolution, Kauffman's NK model, and the maturation of the immune response. The chapter summarizes the heart of what most people mean when they refer to spin glasses as relevant to complexity. It focuses on the early, classic papers in each subject, giving the reader a flavor of each.Less
This chapter explores how spin glass concepts have found use in and, in some cases, further advanced areas such as computational complexity, combinatorial optimization, neural networks, protein conformational dynamics and folding, and computer science (through the introduction of new heuristic algorithms such as simulated annealing and neural-based computation, and through new approaches to analyzing hard combinatorial optimization problems). It also introduces some “short takes” on topics that space constraints prevent covering in detail, but should be at least mentioned: prebiotic evolution, Kauffman's NK model, and the maturation of the immune response. The chapter summarizes the heart of what most people mean when they refer to spin glasses as relevant to complexity. It focuses on the early, classic papers in each subject, giving the reader a flavor of each.
Gary F. Marcus
- Published in print:
- 2005
- Published Online:
- January 2007
- ISBN:
- 9780195179675
- eISBN:
- 9780199869794
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195179675.003.0002
- Subject:
- Philosophy, Metaphysics/Epistemology
This chapter examines an apparent tension created by recent research on neurological development and genetics on the one hand and cognitive development on the other. It considers what it might mean ...
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This chapter examines an apparent tension created by recent research on neurological development and genetics on the one hand and cognitive development on the other. It considers what it might mean for intrinsic signals to guide the initial establishment of functional architecture. It argues that an understanding of the mechanisms by which the body develops can inform our understanding of the mechanisms by which the brain develops. It cites the view of developmental neurobiologists Fukuchi-Shimogori and Grove, that the patterning of the part of the brain responsible for our higher functions is coordinated by the same basic mechanisms and signaling protein families used to generate patterning in other embryonic organs. Thus, what's good enough for the body, is good enough for the brain.Less
This chapter examines an apparent tension created by recent research on neurological development and genetics on the one hand and cognitive development on the other. It considers what it might mean for intrinsic signals to guide the initial establishment of functional architecture. It argues that an understanding of the mechanisms by which the body develops can inform our understanding of the mechanisms by which the brain develops. It cites the view of developmental neurobiologists Fukuchi-Shimogori and Grove, that the patterning of the part of the brain responsible for our higher functions is coordinated by the same basic mechanisms and signaling protein families used to generate patterning in other embryonic organs. Thus, what's good enough for the body, is good enough for the brain.
Xun Gu
- Published in print:
- 2010
- Published Online:
- January 2011
- ISBN:
- 9780199213269
- eISBN:
- 9780191594762
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199213269.003.0008
- Subject:
- Biology, Biomathematics / Statistics and Data Analysis / Complexity Studies
The concept of gene pleiotropy may play a key role in developing an integrated view of protein evolution. Although the capacity of a gene that may affect multiple phenotypic characters has been used ...
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The concept of gene pleiotropy may play a key role in developing an integrated view of protein evolution. Although the capacity of a gene that may affect multiple phenotypic characters has been used to explain many biological phenomena, little has been known about the extent of pleiotropy at the genome level. Based on the premise that links between gene pleiotropy and the dimensionality of organismal fitness, the author of this book has provided a feasible statistical framework to estimate the degree of gene pleiotropy. This chapter discusses this issue.Less
The concept of gene pleiotropy may play a key role in developing an integrated view of protein evolution. Although the capacity of a gene that may affect multiple phenotypic characters has been used to explain many biological phenomena, little has been known about the extent of pleiotropy at the genome level. Based on the premise that links between gene pleiotropy and the dimensionality of organismal fitness, the author of this book has provided a feasible statistical framework to estimate the degree of gene pleiotropy. This chapter discusses this issue.
Jane L. Hurst and Robert J. Beynon
- Published in print:
- 2008
- Published Online:
- September 2008
- ISBN:
- 9780199216840
- eISBN:
- 9780191712043
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199216840.003.0006
- Subject:
- Biology, Animal Biology, Evolutionary Biology / Genetics
Scents play a central role in rodent societies, communicating information about identity (species, sex, individual, kinship) and status (social, reproductive, health, age). This requires the ...
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Scents play a central role in rodent societies, communicating information about identity (species, sex, individual, kinship) and status (social, reproductive, health, age). This requires the interaction between volatile and involatile molecular components of scents, the spatial deposition pattern of scent marks, and time of deposition. The major histocompatibility complex (MHC) and major urinary proteins (MUPs) are both highly polymorphic systems that contribute to scents. Most studies have focused on MHC in inbred laboratory rodents. However, studies of wild rodents are revealing that MUPs provide a species and sex-specific genetic identity signature that also underlies individual and kin recognition in house mice. MUPs are mediators of both identity and current status information. Although MHC contributes to the recognition of familiar scents, there is little evidence that it provides direct information about genetic identity.Less
Scents play a central role in rodent societies, communicating information about identity (species, sex, individual, kinship) and status (social, reproductive, health, age). This requires the interaction between volatile and involatile molecular components of scents, the spatial deposition pattern of scent marks, and time of deposition. The major histocompatibility complex (MHC) and major urinary proteins (MUPs) are both highly polymorphic systems that contribute to scents. Most studies have focused on MHC in inbred laboratory rodents. However, studies of wild rodents are revealing that MUPs provide a species and sex-specific genetic identity signature that also underlies individual and kin recognition in house mice. MUPs are mediators of both identity and current status information. Although MHC contributes to the recognition of familiar scents, there is little evidence that it provides direct information about genetic identity.
Michael L. Arnold
- Published in print:
- 2008
- Published Online:
- January 2009
- ISBN:
- 9780199539581
- eISBN:
- 9780191716225
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199539581.003.0006
- Subject:
- Biology, Animal Biology, Evolutionary Biology / Genetics
This chapter argues that many of the human foodstuffs generated from animals have evolved at least in part as a result of reticulation. Specifically, introgressive hybridization and hybrid speciation ...
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This chapter argues that many of the human foodstuffs generated from animals have evolved at least in part as a result of reticulation. Specifically, introgressive hybridization and hybrid speciation have affected our most widely used animal protein sources such as cattle, pigs, tuna, sheep, goats, and trout as well as some of the lesser-utilized species such as peacock bass, chamois, mammoths, and partridges.Less
This chapter argues that many of the human foodstuffs generated from animals have evolved at least in part as a result of reticulation. Specifically, introgressive hybridization and hybrid speciation have affected our most widely used animal protein sources such as cattle, pigs, tuna, sheep, goats, and trout as well as some of the lesser-utilized species such as peacock bass, chamois, mammoths, and partridges.
Georgina Ferry
- Published in print:
- 2011
- Published Online:
- January 2013
- ISBN:
- 9780197264812
- eISBN:
- 9780191754029
- Item type:
- chapter
- Publisher:
- British Academy
- DOI:
- 10.5871/bacad/9780197264812.003.0006
- Subject:
- Sociology, Migration Studies (including Refugee Studies)
This chapter focuses on Austrian-born molecular biologist Max Perutz (1914–2002). Perutz was one of twenty scientific refugees from continental Europe who went on to win Nobel Prizes. A chemist and ...
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This chapter focuses on Austrian-born molecular biologist Max Perutz (1914–2002). Perutz was one of twenty scientific refugees from continental Europe who went on to win Nobel Prizes. A chemist and molecular biologist, he led the first successful attempt to discover the three-dimensional structure of protein molecules using X-ray crystallography, for which he shared the 1962 Nobel Prize. He was the founding chairman of the Laboratory of Molecular Biology in Cambridge, an institution that continues to thrive and counts thirteen Nobel Prize-winners among those who have spent time in its laboratories. Although Perutz applied to the Society for the Protection of Science and Learning (SPSL) for funding, in the event he did not need their money. His case, however, offers an excellent example of the emotional and practical support SPSL's officers extended to all academics who found themselves in precarious situations in the years following the rise to power of the Nazis in Germany and their subsequent conquest or annexation of neighbouring countries.Less
This chapter focuses on Austrian-born molecular biologist Max Perutz (1914–2002). Perutz was one of twenty scientific refugees from continental Europe who went on to win Nobel Prizes. A chemist and molecular biologist, he led the first successful attempt to discover the three-dimensional structure of protein molecules using X-ray crystallography, for which he shared the 1962 Nobel Prize. He was the founding chairman of the Laboratory of Molecular Biology in Cambridge, an institution that continues to thrive and counts thirteen Nobel Prize-winners among those who have spent time in its laboratories. Although Perutz applied to the Society for the Protection of Science and Learning (SPSL) for funding, in the event he did not need their money. His case, however, offers an excellent example of the emotional and practical support SPSL's officers extended to all academics who found themselves in precarious situations in the years following the rise to power of the Nazis in Germany and their subsequent conquest or annexation of neighbouring countries.
David A. Pearce
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780198508786
- eISBN:
- 9780191723803
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198508786.003.0010
- Subject:
- Neuroscience, Disorders of the Nervous System
This chapter begins with a discussion of proteins associated with lysosomal storage diseases and their orthologues in model organisms. It then discusses studies of orthologous proteins associated ...
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This chapter begins with a discussion of proteins associated with lysosomal storage diseases and their orthologues in model organisms. It then discusses studies of orthologous proteins associated with lysosomal storage diseases; biogenesis and trafficking to the lysosome; proteins associated with disease and with lysosome biogenesis and their orthologues in model organisms; and studies of orthologous proteins implicated in disease that are involved in lysosome biogenesis.Less
This chapter begins with a discussion of proteins associated with lysosomal storage diseases and their orthologues in model organisms. It then discusses studies of orthologous proteins associated with lysosomal storage diseases; biogenesis and trafficking to the lysosome; proteins associated with disease and with lysosome biogenesis and their orthologues in model organisms; and studies of orthologous proteins implicated in disease that are involved in lysosome biogenesis.
Mark R. Sanderson and Jane V. Skelly (eds)
- Published in print:
- 2007
- Published Online:
- September 2007
- ISBN:
- 9780198520979
- eISBN:
- 9780191706295
- Item type:
- book
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198520979.001.0001
- Subject:
- Biology, Biochemistry / Molecular Biology
Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of ...
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Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of accurate molecular structures is a pre-requisite for rational drug design, and for structure-based function studies to aid the development of effective therapeutic agents and drugs. The successful determination of the complete genome (genetic sequence) of several species (including humans) has recently directed scientific attention towards identifying the structure and function of the complete complement of proteins that make up that species; a new and rapidly growing field of study called ‘structural genomics’. There are now several important and well-funded global initiatives in operation to identify all of the proteins of key model species. One of the main requirements for these initiatives is a high-throughput crystallization facility to speed-up the protein identification process. The extent to which these technologies have advanced calls for an updated review of current crystallographic theory and practice. This book features the latest conventional and high-throughput methods, and includes contributions from a team of internationally recognized leaders and experts.Less
Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of accurate molecular structures is a pre-requisite for rational drug design, and for structure-based function studies to aid the development of effective therapeutic agents and drugs. The successful determination of the complete genome (genetic sequence) of several species (including humans) has recently directed scientific attention towards identifying the structure and function of the complete complement of proteins that make up that species; a new and rapidly growing field of study called ‘structural genomics’. There are now several important and well-funded global initiatives in operation to identify all of the proteins of key model species. One of the main requirements for these initiatives is a high-throughput crystallization facility to speed-up the protein identification process. The extent to which these technologies have advanced calls for an updated review of current crystallographic theory and practice. This book features the latest conventional and high-throughput methods, and includes contributions from a team of internationally recognized leaders and experts.
Anthony T. Campagnoni
- Published in print:
- 2004
- Published Online:
- May 2009
- ISBN:
- 9780195152227
- eISBN:
- 9780199865024
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195152227.003.0019
- Subject:
- Neuroscience, Development, Disorders of the Nervous System
This chapter presents a brief overview of the molecular biology of the myelin protein genes and their expression into mRNA and protein. Topics discussed include classic myelin basic proteins and ...
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This chapter presents a brief overview of the molecular biology of the myelin protein genes and their expression into mRNA and protein. Topics discussed include classic myelin basic proteins and golli proteins, myelin proteolipid proteins, myelin-associated/oligodendrocyte basic protein, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein, and peripheral myelin protein zero.Less
This chapter presents a brief overview of the molecular biology of the myelin protein genes and their expression into mRNA and protein. Topics discussed include classic myelin basic proteins and golli proteins, myelin proteolipid proteins, myelin-associated/oligodendrocyte basic protein, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein, and peripheral myelin protein zero.
Robin L. Garrell and Heather D. Maynard
- Published in print:
- 2010
- Published Online:
- September 2010
- ISBN:
- 9780199219698
- eISBN:
- 9780191594229
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199219698.003.0011
- Subject:
- Mathematics, Mathematical Biology
Current technologies to modify surfaces and control the surface properties are reviewed, with particular emphasis on alterations for biomedical and bioanalytical applications. A brief tutorial on the ...
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Current technologies to modify surfaces and control the surface properties are reviewed, with particular emphasis on alterations for biomedical and bioanalytical applications. A brief tutorial on the mechanisms of biomolecular adsorption provides background for understanding the relationship between surface wettability and biomolecular (particularly protein) adsorption. Methods for modifying surface wettability, materials that minimize or prevent fouling, and techniques for assessing protein fouling and the effectiveness of surface modifications are reviewed. Examples of “designer surfaces” are given, ranging from dynamic coatings in which small molecules or polymers are adsorbed on device surfaces, to covalent modifications such as PEGylation, hydrogel assembly, and the use of functionalized alkyl silanes. New device materials, including hydrogels made from PEGylated monomers, biodegradable polyesters, and photocurable perfluoropolyethers, are also discussed. The chapter closes with approaches that lead to the direct and indirect capture of proteins and peptides and the integration of live cells with microfluidic devices.Less
Current technologies to modify surfaces and control the surface properties are reviewed, with particular emphasis on alterations for biomedical and bioanalytical applications. A brief tutorial on the mechanisms of biomolecular adsorption provides background for understanding the relationship between surface wettability and biomolecular (particularly protein) adsorption. Methods for modifying surface wettability, materials that minimize or prevent fouling, and techniques for assessing protein fouling and the effectiveness of surface modifications are reviewed. Examples of “designer surfaces” are given, ranging from dynamic coatings in which small molecules or polymers are adsorbed on device surfaces, to covalent modifications such as PEGylation, hydrogel assembly, and the use of functionalized alkyl silanes. New device materials, including hydrogels made from PEGylated monomers, biodegradable polyesters, and photocurable perfluoropolyethers, are also discussed. The chapter closes with approaches that lead to the direct and indirect capture of proteins and peptides and the integration of live cells with microfluidic devices.
Eric A. Gaucher
- Published in print:
- 2007
- Published Online:
- September 2008
- ISBN:
- 9780199299188
- eISBN:
- 9780191714979
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199299188.003.0002
- Subject:
- Biology, Evolutionary Biology / Genetics
The perspective on natural history and medicine by Emile Zuckerkandl combined with the chemical expertise of Linus Pauling generated many novel ideas concerning molecular evolution. These included ...
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The perspective on natural history and medicine by Emile Zuckerkandl combined with the chemical expertise of Linus Pauling generated many novel ideas concerning molecular evolution. These included generating multiple sequence alignments, determining phylogenetic relationships based on sequence data, formulating the molecular clock hypothesis, and the proposal to resurrect ancestral sequences based on information contained within extant sequences, inter alia. Although the field of ancestral sequence reconstruction is still burgeoning, the concepts guiding the field are embraced by today's community more so than when originally proposed by Zuckerkandl and Pauling. This chapter presents a view of the field of ancestral sequence reconstruction, including recognition that genes are dynamic fossils in that they record ancient events while still adapting to new environments. It concludes with a discussion of the potential of combining ancestral sequence space and synthetic biology to expand protein functionality for directed evolution studies.Less
The perspective on natural history and medicine by Emile Zuckerkandl combined with the chemical expertise of Linus Pauling generated many novel ideas concerning molecular evolution. These included generating multiple sequence alignments, determining phylogenetic relationships based on sequence data, formulating the molecular clock hypothesis, and the proposal to resurrect ancestral sequences based on information contained within extant sequences, inter alia. Although the field of ancestral sequence reconstruction is still burgeoning, the concepts guiding the field are embraced by today's community more so than when originally proposed by Zuckerkandl and Pauling. This chapter presents a view of the field of ancestral sequence reconstruction, including recognition that genes are dynamic fossils in that they record ancient events while still adapting to new environments. It concludes with a discussion of the potential of combining ancestral sequence space and synthetic biology to expand protein functionality for directed evolution studies.
Tal Pupko, Adi Doron-Faigenboim, David A. Liberles, and Gina M. Cannarozzi
- Published in print:
- 2007
- Published Online:
- September 2008
- ISBN:
- 9780199299188
- eISBN:
- 9780191714979
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199299188.003.0004
- Subject:
- Biology, Evolutionary Biology / Genetics
Modeling of sequence evolution is fundamental to ancestral sequence reconstruction. Care must be taken in choosing a model, however, as the use of unrealistic models can lead to erroneous ...
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Modeling of sequence evolution is fundamental to ancestral sequence reconstruction. Care must be taken in choosing a model, however, as the use of unrealistic models can lead to erroneous conclusions. The choice of model and the effects of assumptions inherent within are discussed in this chapter in terms of their effects on probabilistic ancestral sequence reconstruction. This chapter discusses standard probabilistic models, site rate variation to these models, and deviations from the standard (homogeneous, stationary, reversible) models. Model selection, selecting one model from many, given data, and the comparison of different models are included as well as covarion models, the use of outside information when modeling, and the treatment of gaps.Less
Modeling of sequence evolution is fundamental to ancestral sequence reconstruction. Care must be taken in choosing a model, however, as the use of unrealistic models can lead to erroneous conclusions. The choice of model and the effects of assumptions inherent within are discussed in this chapter in terms of their effects on probabilistic ancestral sequence reconstruction. This chapter discusses standard probabilistic models, site rate variation to these models, and deviations from the standard (homogeneous, stationary, reversible) models. Model selection, selecting one model from many, given data, and the comparison of different models are included as well as covarion models, the use of outside information when modeling, and the treatment of gaps.
