bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective and sensitive measurement of vitamin C, ubiquinol-10, and other low-molecular-weight antioxidants
Authors: Mohr Detlef , Stocker Roland 
Published: November 2023

Abstract
Inadvertent modification of biological macromolecules by free radical-mediated oxidation is implicated in the pathogenesis of a number of human diseases, such as cancer and atherosclerosis. The latter in particular has received much attention recently. Since oxidation of lipids carried in the circulation by lipoproteins can precede that of the apoprotein, considerable interest has focused on the oxidation of lipoprotein lipids and its inhibition by endogenous antioxidants. In particular, the antioxidative action of ascorbate, a-tocopherol, ubiquinol-10, carotenoids, and bile pigments have been investigated in more or less detail. The selective and sensitive detection of endogeneous antioxidants in human plasma and lipoproteins has, therefore, become increasingly important. Although numerous, simple and mostly colorimetric assays are often employed for the measurement of many of the antioxidants, their suitability for the selective detection of antioxidants in complex biological mixtures such as human plasma, is limited. Also, many of the extremely labile (i.e. autoxidizable) antioxidants are present in small concentrations which renders colorimetric assays particularly problematic. Lengthy derivatization procedures required to increase sensitivity can lead to artificial underestimation or even complete loss of the compounds of interest. In this situation, high performance liquid chromatographic (HPLC) methods are useful alternatives and can guarantee a high degree of selectivity and sensitivity. In particular, with the availability of simpler and more reliable electrochemical cells, HPLC with electrochemical detection (HPLC-EC) has become a frequently used detection method. This detection method provides high sensitivity and additional selectivity, due to the different and characteristic redox activity of different antioxidants.
Targeting and import of peroxisomal proteins
Authors: pure Christopher j. Dan 
Published: November 2023

Abstract
Progress in our understanding of the mechanisms by which proteins are targeted to and imported into peroxisomes has been slow compared with the rate at which the processes involved in mitochondrial and endoplasmic reticulum (ER) protein translocation have been elucidated (see Chapters 1 and 4, respectively). This has been due partly to the greater technical difficulty of studying peroxisomes (especially in vitro) and partly to a general ignorance of the importance of peroxisomes to cellular and organismal viability. However, in recent years there has been a considerable increase in interest in, and a parallel increase in understanding of, the way peroxisomes and related organelles (i.e. glyoxysomes and glycosomes) are formed. This has been spurred on largely by the desire to explain the molecular basis of the human genetic disorders of peroxisome biogenesis, such as Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease CIRO), and rhizomelic chondrodysplasia punctata (RCDP) (Table 1) (1), and the mechanism by which certain hypolipidaemic drugs and xenobiotics cause phenomenal expansion of the peroxisomal compartmental volume (2-5). This increased interest is well reflected in the numerous reviews written in recent years on various aspects of peroxisomal, glyoxysomal, and glycosomal biogenesis in general and protein targeting in particular (6-27).
Enzyme-labelled tests with colorimetric, fluorimetric and chemiluminescent detection systerns
Authors: Howes Iain , Blincko Stuart , Little John , Edwards Raymond 
Published: November 2023

Abstract
Enzymes are widely used as labels in immunoassay procedures. They demonstrate great versatility and have been applied to all types of immunoassay. Originally employed in immunostaining and gel-precipitin techniques, enzymes subsequently demonstrated particular utility when used with solid-phase separation systems such as antibody coated plastics (e.g. ELISA) and reagent linked particles (e.g. magnetic cellulose). Enzymes are also used in non separation assays in which enzyme activity is altered by antibody binding. See Chapter 1 for details of nomenclature and classification.
Light scattering techniques
Authors: Newman David j. , Thakkar Hansa , Price christopher P 
Published: November 2023

Abstract
Quantitative immunoaggregation assays are very widely used due to their inherent simplicity and, in the liquid phase anyway, their ready automation, excellent precision and very fast reaction times. Gel-based immunoaggre gation assays are certainly simple and robust but this chapter will focus on the various liquid phase techniques. Amongst the various homogeneous immunoassay technologies available, immunoaggregation assays are one of the few that are available to research scientists who wish to develop their own assays, as they can be carried out not only in sophisticated automated instruments but also in virtually any good quality spectrophotometer. They can be used for both haptens and proteins in most biological matrices and for analytes across the pM to mM concentration range; furthermore, they can use monoclonal and polyclonal antibodies both intact and fragment. Thus, using the appropriate detection system, immunoaggregation assays can compete very effectively, in terms of detection limits and convenience, with many enzyme and radioisotopically labelled immunoassays, and perform significantly better in terms of precision and ease of automation. The commonest techniques are immunoturbidimetry and immunonephelometry with and without the use of particle enhancement. These involve different aspects of light scattering; however, as turbidity can be measured on any spectrophotometer and nephelometry requires specialized equipment that may not be available in every laboratory, the main focus will be on the use of turbidimetric light scattering.
Tumour suppressor genes and inheritance of cancer
Authors: Black Donald M 
Published: November 2023

Abstract
Several genes have been identified which confer an inherited predisposition to cancer. Although the susceptibility is usually inherited as a dominant trait, at the cellular level the susceptibility mutations are almost always recessive. Therefore, for the cancer to develop, the dominant wild-type copy of the gene must be mutated or deleted. Such genes are called tumour suppressors. They encode proteins of diverse function which need to be inactivated for the initiation and progression of malignancy. The existence of families with susceptibility to cancer are important in two ways. First, they give us additional insights into the molecular events which underlie the transformation from normal to tumour cells; and secondly, they allow the possibility of genetic testing for cancer risk.
Trypanosoinatid genetics
Authors: Swindle John , Tait Andrew 
Published: November 2023

Abstract
The genetics of the trypanosomatid group of protozoa have been the subject of considerable research over the last 15 years. The trypanosomatids include a number of highly pathogenic parasitic species which infect a very wide range of hosts including man and domestic livestock. In terms of molecular genetics, the most intensively studied are Leishmania and trypanosomes. This chapter will primarily focus on Trypanosoma brucei, Trypanosoma cruzi, and a few Leishmania species. Two fundamental aspects of the genetics of these parasites will be considered: first, a basic description of their genomes and genome organization together with a review of our current state of knowledge on classical genetics; and second, a review of modern transfection-based molecular genetics. The lack of readily available classical genetic systems, which have been used so effectively in yeast, Drosophila, and Caenorhabditis elegans, has been a major restraint, although the availability of reverse genetics has circumvented some of these limitations.
The three genomes of Plasmodium
Authors: Feagin Jean E , Lanzer Michael 
Published: November 2023

Abstract
The Greek physician Hippocrates, who lived in the fifth century BC, was the first to describe the characteristic symptoms of a malaria infection: intermittent and often relapsing fever attacks that are accompanied by drenching sweats and followed by shaking chills. Centuries later, the medical almanac of 1888 referred to malaria as one of the great scourges of humanity, wreaking havoc in human civilizations throughout history and claiming more lives than any other infectious disease. Today, malaria is still a major health problem, causing an estimated 300 million cases of illness and killing 1-2 million people-mostly infants-every year. About 2.2 billion people (41% of the world’s population) are now in danger of contracting malaria. The prospect for the future is bleak. The number of malaria cases is expected to rise due to the emergence and spread of drug-resistant malaria parasites and pesticide-resistant malaria-transmitting mosquitoes. Furthermore, a widely effective anti-malarial vaccine is not expected in the near future although several candidate vaccines are now in clinical trials.
Integration of control devices: A global regulatory network in Escherichia coli
Authors: Hengge-Aronis Regine 
Published: November 2023

Abstract
Until the present day, the fundamental concepts developed by F. Jacob and J. Monod in the 1960s during their studies of the lac operon (1), have mainly shaped our view of the regulation of gene expression. What is the structure and function of regulatory proteins, how do they bind to DNA, and how do they influence the rate of transcription of this DNA? Especially with Escherichia coli, these questions can be at least partially answered for many regulatory proteins. Based on this knowledge, we can now start to determine the roles of these single regulatory systems within the physiology of a cell. As single-cell organisms, bacteria process a multitude of environmental signals and use this information to optimally balance their metabolism, growth rate, DNA replication, and cell division. This requires the coordination and interaction of a large number of single regulatory systems in regulatory networks.
Chemically engineered antibodies
Authors: Stevenson G T , Kan K S 
Published: November 2023

Abstract
The chemical engineering described in this chapter will utilize just two immunoglobulin (lg) modules: mouse monoclonal Fab’’Y from individual antibodies, and human Fc-y from normal lgG1. These can be combined in various ways to provide antibody derivatives exhibiting combinations of bi-specificity, chimerism, and multiple Fe regions. Our derivatives have been designed to kill neoplastic cells, in vitro or in vivo, usually by the recruitment of natural effectors such as complement and cells bearing Fc-y receptors. After describing the preparation of the lg modules we shall give three examples of derivatives which may be prepared from them. Once the principles of construction are understood the range of accessible derivatives will encompass far more than these examples, and may be extended to other purposes such as immunohistology. The technology offers a rapid and economic prediction of the performance of some constructs, such as chimeric antibodies, which could then be engineered genetically to avoid the need for repeated chemical preparation. But it is capable also of yielding derivatives with geometries virtually impossible to obtain by genetic means.
Generation and selection of human monoclonal antibodies against melanoma-associated antigens: a model for production of anti-tumour antibodies
Authors: Thomas M D , Melamed, M D , Newton J 
Published: November 2023

Abstract
Melanomas are generally resistant to chemotherapy and radiotherapy, and often give rise to metastases (1). However, the neoplastic transformation of melanocytes induces qualitative and quantitative modulation of cell mem brane antigens (2,3). These tumour-associated immunogenic markers suggest the possibility of a strategy for selective diagnosis and even therapy for melanoma (4—8), e.g. by the production of tumour-specific human monoclonal antibodies. The melanoma tumour can thus be used as a favourable case for the establishment of techniques for the production of anti-tumour Mabs.
Synthetic Peptides in Epitope Mapping
Authors: Rodda Stuart J , Tribbick, Gordon , Maeji N Joe 
Published: November 2023

Abstract
Synthetic peptides can be used as a tool for probing the nature of antibodydefined (B cell) epitopes or T cell receptor (TCR)-defined (T cell) epitopes. Linear synthetic peptides homologous with the sequence of a protein antigen are suitable for mapping the ‘linear’ (continuous) type of B cell epitope, and all T cell epitopes. The power of the synthetic peptide approach to epitope mapping has been greatly expanded by the development of techniques for the parallel synthesis of hundreds to thousands of peptides, and by improvements in the chemistry of peptide synthesis which make the synthesis of peptides beyond 20mers in length feasible on a mass scale.
Liposomes
Authors: Claassen Eric , Iwaarden Freek Van 
Published: November 2023

Abstract
Liposomes can be used in a number of different ways to influence the homeostasis of a given organism. Typical examples include their use as vaccine, adjuvant, drug delivery system, immunomodulator, imaging agent, or as a cosmetic. Liposomes in their most basic form consist of spontaneously formed phospholipid bilayers enveloping an aqueous phase. When preparing liposomes from naturally occurring (phospho)lipids, in the correct concentrations and without adding foreign substances to the preparation, one can assume that the ensuing vesicles are non-immunogenic (i.e. not a target for antibodies or specific T cells) and biodegradable. However, this type of vesicle can still be a target for immune attack by the innate branch of the immune system embodied in most cases by macrophages which will take up almost any particulate matter not bearing the proper MHC molecules. As reviewed recently (1) the innate immune response which is very swift and efficient in removing non-self does not receive enough attention in the design of liposomes. Consequently, ‘natural’ liposomes can be used to influence macrophages in several ways. First, by the inclusion of a toxic substance the macrophages can be killed or temporarily suppressed. The latter can also be achieved by overloading the macrophages with large doses of ‘empty natural’ liposomes. Secondly, by the inclusion of immunomodulators, both in the aqueous or lipid phase, one can stimulate the macrophages. The efficiency of elimination, stimulation, or suppression is critically dependent on factors such as: liposome size, charge, stability, content, and membrane composition. Minor variations in these factors may have major consequences for the eventual outcome.
Immunochemical assays for complement components
Authors: Wurzner R , Mollnes, T E , Morgan B P 
Published: November 2023

Abstract
The complement system consists of more than 25 different plasma proteins. Most components are circulating in the blood in an inactive form. Classical or alternative pathway activation of the complement system results in the generation of multiple complement proteolytic cleavage products, recruited from these inactive precursor molecules in a sequentially proceeding cascade (1). This leads to an alteration of their antigenic pattern and thus to the consumption of the native molecule. Concomitantly, complement activation initiates formation of multimolecular complexes which function as convertases within the cascade or express other functions such as the membranolytic effects of the membrane attack complex, the terminal complement complex (TCC) generated on biological membranes. Such activation-dependent changes can be revealed by the appearance of neoepitopes, and by the disappearance of native-restricted epitopes (2), and are usually assessed by means of monoclonal antibodies in enzyme immunoassays (abbreviated as EIAs or ELISAs). The present chapter focuses on sensitive and specific quantitation of complement proteins, fragments, and complexes to reliably assess complement activation in vivo. Figure 1 gives an overview of the complement system and indicates the proteins on which neoepitopes have been found upon activation.
Expressing cloned genes in the yeasts Saccharomyces cerevisiae and Pichia pastoris
Authors: Tuite Mick F , Clare, Jeff J , Romanos Mike A 
Published: November 2023

Abstract
When considering whether or not to express a heterologous gene in yeast, one has not only to decide which strategy should be used—vector, strain, promoter, etc.—but also which yeast. The term ‘yeast’, although widely regarded to be synonymous with the yeast Saccharomyces cerevisiae, is in fact an umbrella term covering approximately 500 different yeast species. The reason for this laxity in terminology is perhaps simple laziness, but there are ever increasing numbers of researchers turning to S. cerevisiae as a model organism for their studies on gene structure, function, and regulation. The completion and release of the entire genome sequence of S. cerevisiae will ensure that such interest is maintained.
Role of DNA methylation in mammalian development
Authors: LI E 
Published: November 2023

Abstract
Methylation of genomic DNA at the CS position of cytosine residues is the predominant form of DNA modification in plants and vertebrates. DNA methylation is a developmentally regulated process that acts in concert with other regulatory mechanisms to control gene expression. Evidence suggests that DNA methylation is involved in a diverse range of biological processes which include regulation of tissue specific gene expression, cell differentiation, genomic imprinting, X chromosome inactivation, regulation of chromatin structure, DNA replication, viral latency, carcinogenesis, and ageing. The importance of DNA methylation has been increasingly recognized as many recent studies have provided direct evidence for its role in cancer (1, 2). While numerous studies have focused on the role of DNA methylation in gene regulation, little is known about how DNA methylation itself is regulated during development. One major obstacle in studying the function of DNA methylation in eukaryotic organisms in the past had been the lack of a genetic model system. Recently, DNA methylation-deficient mutants have been successfully generated in several model organisms including mice, Arabidopsis thaliana, and Neurospora crassa (3-5).
Function and epigenetic modification of the imprinted H19 gene
Authors: Bartolomei Marisa S 
Published: November 2023

Abstract
The H19 gene encodes one of the most abundant RNA polymerase II transcripts in the mouse embryo. This gene was originally identified as a fetal liver-specific cDNA whose postnatal repression paralleled that of the u-fetoprotein gene (1). H19 has been identified in other screens including those for genes that are activated during the differentiation of C3H10T1 / 2 cells (referred to as myoH) (2), as well as during the differentiation of embryonic stem cells (3). The H19 gene was also isolated as a developmentally regulated gene in rabbit vascular smooth muscle cells (4) and as a gene associated with tumour suppression in syrian hamster embryo cells (5). While these studies have led to a more detailed understanding of the expression and nature of the gene product, it was not until H19 was found to be imprinted, or expressed exclusively from the maternally-inherited allele, that the function of the gene could be elucidated (6, 7). It is the purpose of this review to summarize what is known about the function and imprinting of the H19 gene as well as to assess the merits of using H19 as a general model to study imprinting.
The imprinted insulin-like growth factor 2 gene
Authors: Feil Robert , Moore Thomas F , Oswald Joachim , Walter Jorn , Sun Fanglin , Reik Wolf 
Published: November 2023

Abstract
The insulin-like growth factors IGFl and IGF2 are mitogenic polypeptides which are structurally and functionally homologous to the hormone insulin. Both single chain peptides play important roles in pathways regulating growth and development (1, 2). Their action is mediated by specific interactions with cell surface receptors and is further modified by at least six different IGF-binding proteins. Two IGF receptors have been identified. The type-1 receptor has a higher affinity for IGFl than for IGF2 and is related to the insulin receptor. The type-2 receptor, which is also a receptor for mannose-6-phosphate, binds IGF2 with high affinity, but is structurally distinct from the type-1 and insulin receptors. IGFl and IGF2 mediate their effects on growth and development through the type-1 receptor (3).
Genomic imprinting as a developmental process disturbed in cancer
Authors: Feinberg Andrew P 
Published: November 2023

Abstract
One of the most exciting recent discoveries in the study of genomic imprinting is direct evidence of its role in human cancer. Several indirect lines of evidence had suggested such a role. First was the observation that hydatidiform moles and ovarian teratomas arise from androgenetic (46 chromosomes, all of paternal origin) and parthogenetic embryos (46 chromosomes, all of maternal origin), respectively (1, 2). Thus, even if a normal number of chromosomes is present, neoplasia results from an imbalance between maternal and paternal chromosomes. Furthermore, an excess of the paternal genome leads to a more malignant growth than an excess of the maternal genome, suggesting that maternal and paternal chromosomes have differential effects on growth homeostasis.
Heterokaryons reveal that differentiation requires continuous regulation
Authors: Blau Helen M 
Published: November 2023

Abstract
As vertebrates develop, totipotent cells in the early embryo give rise to cell types specialized for function in tissues. In Waddington’s epigenetic landscape, differentiated cells enter grooves, or valleys (Waddington 1940), a depiction which suggests that their fate is not easily changed. Although this appears to be the case, the mechanism by which this stability is maintained and propagated to differentiated cell progeny remains unknown. In this review I present evidence which suggests that the differentiated state requires continuous regulation. The implication of this type of control mechanism is that at any given time the balance of positive and negative regulators present in a cell is critical. To sustain threshold concentrations of key regulators and ensure stability, feedback mechanisms seem essential. Yet, to date, relatively few feedback loops with a role in differentiation have been elucidated. A genetic complementation approach appears to hold promise of identifying novel regulators capable of tipping the balance, acting in a feedback loop, and reinforcing the decision either to grow or to differentiate.