bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphokine responses to HIV infection
Authors: Matear P M , Naraghi A , Deakin S , Meager A , Vyakarnam A , Vyakarnam A 
Published: November 2023

Abstract
Studies of cytokine production in HIV infections are important because cytokines have been implicated in viral pathogenesis leading to AIDS. One of the characteristic features of HIV infection, as in many chronic disease states, is the dysregulated production of several cytokines (see refs 1-5). These cytokines include TNFot, TNFfJ, IFN gamma, IL-6, IL-1, and IL-4. In addition to their effects on HIV replication, TNFot and IFN gamma have been shown to induce HIV replication in macrophages and CD4-positive T cells (1-4, 6, 7). The pattern of cytokines produced by HIV-positive individuals and AIDS patients could also be important in regulating their immune response to the virus, e.g. by selectively activating Thl or Th2 cells (8-10). Additionally, the pattern of cytokines may serve as a disease marker, distinguishing infected individuals who are healthy from those with disease. Recent studies have shown, for example, that asymptomatic HIV-positive individuals produced a predominantly Thl cytokine pattern (high IL-2, high IFN gamma, low IL-4 production) whereas those with disease symptoms produce a predominantly Th2 cytokine pattern (high IL-4, low IFN gamma, and low IL-2) (11).
The use of flow cytometry to study platelet activation
Authors: Michelson Alan D , Shattil Sanford J 
Published: November 2023

Abstract
Many common clinical conditions have been reported to be associated with platelet hyperreactivity and/or circulating activated platelets: coronary artery disease (angina pectoris, acute myocardial infarction) diabetes mellitus stroke exercise emotional stress cigarette smoking pregnancy and pre-eclampsia blood bank storage of platelets for transfusion cardiopulmonary bypass angioplasty deep vein thrombosis hyperlipoproteinaemia essential thrombocythemia adult respiratory distress syndrome However, the role of platelet activation in clinical settings is controversial, in part because the methods used to detect platelet activation (e.g. platelet aggregation and radioimmunoassays of plasma P-thromboglobulin (pTG) and/or platelet factor 4 (PF4) have major methodologic problems (1-6)).
Measurement of protein phosphorylation, kinase activity, and G protein function in intact platelets and membrane preparations
Authors: Wadman Isobel A , Virdee Kanwar , Fernandez Denise S , Wasunna Christine L , Farndale Richard W 
Published: November 2023

Abstract
We have collated in this chapter methods for locating or determining the activity of platelet signalling proteins. SDS-PAGE provides a means of separating the proteins, their labelling is achieved either by covalent or affinity methods, and they are usually detected on film, either by autoradiography or Western blotting. The preparation of platelets and platelet membranes from Blood Transfusion Service concentrates, together with basic electrophoretic methods, are described in Section 1. Methods for protein phosphorylation and the determination of kinase activity are described in Section 2, and for GTP binding proteins in Section 3. We expect that the reader will modify the precise conditions of the methods to suit their particular need; the protocols below will provide a starting point from which these and other assays may be developed.
The use of pulsed-field gel electrophoresis to map the human MHC
Authors: Sanséau Philippe , Trowsdale John 
Published: November 2023

Abstract
The major histocompatibility complex (MHC) is located on the short arm of chromosome 6 in the distal portion of the 6p21.3 band. It consists of three linked gene clusters covering 4 Mb of DNA. The class I and class II regions encode highly polymorphic families of cell surface glycoproteins involved in immune regulation. The class I region which covers -1500 kb, contains at least 40 genes including the classical transplantation antigens (HLA-A, -B, and -C). This region is located at the telomeric side of the MHC. The class II region encodes the classical antigens (HLA-DP, -DQ, -DR) but also novel class II genes like HLA-DM, and the TAPs and LMPs involved in antigen processing. The class I and class II regions are separated by the class III region which spans - 1100 kb. This part of the MHC contains a large number of genes unrelated to the classical transplantation antigens, although some are involved in the immune system, such as the complement genes C2, C4, and Bf, the tumour necrosis factor (TNF) A and B genes, and the heat shock protein HSP70 genes.
Sequence analysis of major histocompatibility molecules
Authors: Lawlor Da Yid A , Laud Purnima 
Published: November 2023

Abstract
The GenBank database for nucleotide sequences contains over 1500 000 entries and 1.5% are derived from loci of the major histocompatibility complex (MHC). Parham noted that in 1986 approximately 12000 amino acid residues had been determined for human class I molecules by protein and DNA sequencing methods. He attributed the exponential growth of sequence information (fivefold increase in database size in less than three years) to the replacement of protein sequencing with the more efficient DNA sequencing procedures (1). At today’s rate, the derived amino acid information for all MHC molecules increases by that amount every two weeks. Table I lists the MHC sequence entries in GenBank for the various classes and species.
Peroxides and other products
Authors: Brown R K , Kelly F J 
Published: November 2023

Abstract
The only definitive way to demonstrate excessive free radical activity in vivo is by electron spin resonance as already discussed in Chapter 2, but clearly this is currently inapplicable in clinical practice due to the nature of the spin traps that must be used. Instead investigators must rely upon the measurement of established markers of free radical activity in biological fluids and tissues. Traditionally, most markers of oxidative injury utilized reflect free radical attack on polyunsaturated fatty acids, with the classical route of attack involving lipid peroxidation, generating hydroperoxides, endoperoxides, long-lived aldehydes and the end-products malondialdehyde, ethane, and pentane.
Mechanisms of oncogene perturbation
Authors: Imreh Stephan , Szekely Laszlo , Wiman Klas G , Klein George 
Published: November 2023

Abstract
Viruses have been implicated for a long time as possible aetiologic agents in the genesis of human and animal tumours. Isolation of various DNA and RNA viruses that induced tumours in experimental animals led to the belief that all of them carry genetic elements, oncogenes, that are responsible for tumour induction. However, it became apparent that the oncogenes of the RNA tumour viruses have been acquired from the host cell genome, were not necessary for viral replication, and were maintained in the virus stocks under sustained selection for tumorigenicity. In contrast the oncogenic DNA viruses were found to encode proteins that are essential for viral replication and are also responsible for tumour induction. Viruses of different types are believed to contribute to the aetiology of approximately 15% of all human tumours (1).
Oncogenic cytoplasmic protein tyrosine kinases
Authors: Roche Serge , Courtneidge Sara A 
Published: November 2023

Abstract
Phosphorylation on tyrosine residues accounts for only 0.05% of total protein phosphorylation in mammalian cells, yet protein tyrosine kinases play important roles in the intracellular transduction of extracellular signals. They are involved in various biological responses including cell growth and differentiation, cell motility, and cell secretion. Protein tyrosine kinases can be divided into two groups: receptor and non-receptor tyrosine kinases. The receptor class comprises a family of cell surface proteins, which act as receptors for a variety of ligands. They are composed of an extracellular domain which contains the ligand binding site, a transmembrane domain, and a cytoplasmic domain that contains catalytic activity. This class of kinase is detailed in Chapter 3. Members of the second class of tyrosine kinases do not have extracellular sequences and do not span the plasma membrane. They can be located in the cytoplasm, on the inner part of the plasma membrane, or in the nucleus. The cytoplasmic tyrosine kinases have been sub classified into a number of families based upon their structural homology.
The tumour suppressor gene p53
Authors: Gangopadhyay Suman B , Abraham Jacinth , Lin Yun Ping , Benchimol Sam 
Published: November 2023

Abstract
The p53 tumour suppressor gene is frequently a target for recessive mutations in a wide range of human and rodent malignancies. The loss of wild-type p53 expression in tumour cells appears to provide these cells with a selective growth advantage in vivo. The existence of mice that are devoid of p53 expression indicates that p53 is not required for normal cell growth or development. However, the increased incidence of tumours in p53 null mice as well as in mutant p53 transgenic mice compared with their normal littermates demonstrates the critical role of p53 in suppressing tumour growth. Two models have been proposed to explain the role of p53 as a tumour suppressor. In one model, p53 participates in the cellular response to DNA damage by delaying cell cycle progression at a Gl checkpoint (see Chapter 7).
Clinical relevance of oncogenes
Authors: Sikora Karol , Pandha Hardey 
Published: November 2023

Abstract
In most developed countries, one person in three will develop cancer during their lifetime. This will increase to one in two by the year 2010, reflecting shifts in the age characteristics of the population. The disease represents a considerable public health problem. The term ‘cancer ‘ comprises over 200 disorders which differ in their genetic basis, aetiology, clinical characteristics, patterns of progression, and final outcome to sufficient degrees to be classified as separate entities. Genetic alterations are at the very centre of tumorigenesis so that, at a cellular level, cancer can be designated a genetic disorder.
Kinetoplast DNA: structure and replication
Authors: Englund Paul T , Guilbride D Lys , hwa kuo-yuan , Johnson catharine e. , Li Congjun , Rocco laura J , Torri AL F 
Published: November 2023

Abstract
Trypanosomatid protozoa are parasites which are responsible for important human diseases in tropical areas of the world. Examples are Trypanosoma brucei, an African trypanosome, T. cruzi, a South American trypanosome, and Leishmania. These parasites are among the most primitive of the eukaryotes and, because of their ancient lineage, it is not surprising that they have unusual biological properties. They are among the first eukaryotes to have mitochondria and one of their most remarkable features is their mitochondrial DNA, known as kinetoplast DNA (kDNA). Unlike any other DNA in nature, kDNA is organized into a network containing several thousand topologically interlocked DNA circles. The circles are of two types. There are several thousand small minicircles and a few dozen larger maxicircles. Figure 1 shows an electron micrograph of part of a kDNA network from the trypanosomatid Crithidia fasciculata. Each cell contains a single network within the matrix of its single mitochondrion (for reviews, see Refs. 1-5).
Developtnental regulation of gene expression in African trypanosotnes
Authors: Pays Etienne , Vanhamme Luc 
Published: November 2023

Abstract
The parasitic way of life of many trypanosomatids requires frequent, drastic, and rapid adaptations to the different environments encountered during their development. In particular, Trypanosoma and Leishmania are cyclically transmitted from different insects to mammals, where some species proliferate intracellularly and others extracellularly. In their mammalian hosts, the parasites live at 37°C and have to protect themselves against lytic factors and cells. They are able not only to recognize and use specific components of the host, such as growth factors, cytokines and surface receptors, but also to produce molecules that influence the activity of mammalian cells, for instance to modify the phenotype of macrophages and lymphocytes. When taken up by insect vectors, they undergo a cold shock as well as a complete change of the extracellular milieu, and must interact with totally different cells. The adaptations of the parasite are achieved through extensive re-programming of gene expression, comparable to that occurring during cell differentiation in metazoans. In this chapter, we review the information available on the genetic mechanisms involved in these differentiation processes.
Trans-splicing in trypanosotnatid protozoa
Authors: Ullu Elisabetta , Tschudi Christian , Gunzl Arthur 
Published: November 2023

Abstract
Trans-splicing is an intermolecular RNA processing reaction in which exons from two separate RNA molecules are joined together to form a mature species (Fig. 1). In one form of trans-splicing, the partners of this reaction are the pre-mRNA and a small RNA, the spliced leader (SL) RNA. The SL sequence, which represents the 5’ end of the SL RNA, is joined to the 3’ splice site located just at the boundary of the mature mRNA within the polycistronic pre-mRNA. The first evidence for this type of trans-splicing (or SL addition) was obtained in trypanosomatid protozoa in 1982 (1), when it was noted that an identical 39-nucleotide sequence is present at the very 5’ end of transcripts coding for different variant surface glycoproteins in Trypanosoma brucei. This sequence, the SL or mini-exon, was subsequently found at the 5’ terminus of every mRNA of trypanosomatids. Critical evidence in support of the trans-splicing model was the detection of various predicted splicing intermediates in T. brucei cells (2--4). It is now clear that trans-splicing and cis-splicing (removal of intervening sequences from pre-mRNA) are fundamentally similar processes. More recently, the list of organisms endowed with trans-splicing has grown to include nematodes (5) as well as trematodes (6, 7) and euglenoids (8).
Mechanisins of drug resistance in protozoan parasites
Authors: Wirth Dyann F , Cowman Alan 
Published: November 2023

Abstract
Drug resistance in microorganisms is an increasing problem in world health today. Commonly used antimicrobial agents are no longer effective and the rate at which resistance develops, often to multiple drugs, has increased the urgency for a solution to this problem. Drug-resistant strains have been found among almost all infectious organisms from viruses to multicellular parasitic nematodes. The impact of drug-resistant infectious diseases on world health is just beginning to be assessed. Certain antimicrobial agents are no longer usable as resistance is so widespread. An example of this trend is the antimalarial drug chloroquine; in many malariaendemic areas, chloroquine resistance is so prevalent that the drug is no longer recommended. Yet, antimalarials are the most commonly purchased drugs in the world. Resistance to other antimalarials is emerging faster than new drugs are being developed. Similar trends are apparent in other infectious diseases and the problem of drug resistance promises to be a major challenge facing the world in the later part of this decade and into the 21st century.
Prokaryotic DNA topology and gene expression
Authors: Drlica Karl , Wu Erden-Dalai , Chen Chang-Rung , Wang Jian-Ying , Zhao Xilin , Xu Chen , Qiu Lin , Malik Muhammad , Kayman, Samuel , Friedman S Marvin 
Published: November 2023

Abstract
Systems that regulate initiation of transcription are built on the binding of specific proteins to their cognate DNA sites. Complexity is generated by interactions of the primary DNA recognition proteins with themselves and with other proteins, sometimes through formation of distinct structures that either block or facilitate transcription. All of these interactions occur on a chromosome that undergoes structural changes mediated by other proteins (topoisomerases and DNA bending proteins) that alter the interactions between specific regulatory proteins and DNA. The aim of this chapter is to provide a framework for understanding how the dynamics of chromosome topology influences gene expression.
Two-component systems
Authors: Atkinson Mariette R , Ninfa Alexander J 
Published: November 2023

Abstract
In this chapter, we will discuss the signal transduction systems known as the two-component systems. This review covers the literature in this area through July 1995. Signal transduction by these systems requires at least one each of two different types of conserved protein domains, known as the histidine protein kinase domain (HPK) and response regulator domain (RR). Signal transduction by the HPK and RR domains involves the reversible phosphorylation of each of these domains and the transfer of phosphoryl groups between HPK and RR domains. Phosphorylation of the response regulator domain results in an altered conformation that permits a regulatory target to be engaged, either by the RR domain itself or, more frequently, by additional protein domains linked to the RR domain that are controlled by the conformational state of the RR domain. Various regulatory mechanisms, some of which act through the HPK domain and others acting directly on the RR domain, regulate the intracellular concentration of the phosphorylated form of the RR domain in response to stimuli. When the intracellular concentration of the phosphorlated form of the RR domain reaches a critical level, the regulatory target is engaged, triggering a physiological adaptation. Thus, the overall logic employed by the two-component systems is that a targeted physiological adaptation is regulated via the control of the concentration of the phosphorylated form of the RR domain. Different mechanisms of regulation of these phosphorylation and phosphotransfer reactions, in as much as these are currently known, will be discussed in this review.
Purification of sequence-specific DNA-binding proteins by affinity chromatography
Authors: Kaplan Ken B , Sorger Peter K 
Published: November 2023

Abstract
This chapter describes methods for the purification of sequence-specific DNA-binding proteins by DNA affinity chromatography. Although it deals exclusively with yeast proteins. the majority of techniques presented should also be useful in the analysis of a broad range of sequence-specific DNA binding proteins from a variety of sources. including animal cells.
Chemical modification
Authors: Imoto Taiji , Yamada Hidenori 
Published: November 2023

Abstract
Chemical modification is one of the most useful methods of identifying the functional groups of a protein. Whether or not the various types of amino acid side chains are involved in a protein’s function can be determined readily by whether or not chemical modification of that type of amino acid affects the function. This requires only chemical reactions that are reasonably specific for each type of amino acid side chain. Suitably specific reactions are available for aspartic acid, glutamic acid, histidine, lysine, arginine, methionine, tryptophan, tyrosine. and cysteine residues. A few, less satisfactory reactions are available for serine, threonine, asparagine. and glutamine residues. hut none arc available for glycine, alanine, valine, leucine, isoleucine, phenylalanine, and proline, which have no reactive groups on their side chains. Fortunately, reactive groups are usually required for important functional roles, so chemical modification is able to test all the likely functional amino acids.
Consequences of genomic imprinting for fetal development
Authors: Fundele Reinald H , Suran M Azim , Allen Nicholas D 
Published: November 2023

Abstract
Mouse embryos with only paternal (androgenetic; ag) or maternal (gynogenetic; gg and parthenogenetic; pg) genomes both suffer embryonic lethality but with opposite phenotypes (1-5). This is because of the presence of imprinted genes in the mammalian genome whose expression or repression state is dependent on their parental origin. In addition, the analysis of uniparental isodisomies where specific chromosomes are derived from one parent only has led to the identification of specific chromosome regions that harbour imprinted genes (6-9). In these genetic experiments, there is again the appearance of embryonic and postnatal mice with opposite phenotypes (6, 8).
The cloning of tumour suppressor genes
Authors: Housman David E 
Published: November 2023

Abstract
The identification of a class of genes whose action is required to regulate cell growth and whose absence leads to unregulated cell proliferation can be attributed to two lines of experimental investigation. The term tumour suppressor gene is most clearly associated with the pioneering somatic cell genetic work of Dr Harris and his collaborators and contemporaries in the late 1970s. Terms such as anti-oncogene were first associated with the work of Knudson (1971) and his collaborators who carried out a statistical analysis of the age of onset of childhood cancers and suggested that a specific small number of rate-limiting events was involved in the aetiology of childhood cancers and that hereditary predisposition could reduce the number of such steps to a single rate-limiting event. These two intellectual pathways in fact crossed and merged in the late 1980s and early 1990s.
The road to monoclonal antibodies
Authors: Cotton R G H 
Published: November 2023

Abstract
This article aims to highlight the contribution of cell fusion to the monoclonal antibody technique, and to describe the scientific background to this technique and the early days of its application. The scientific background will be approached both from the broader context of immunogenetics as well as from the local aspect in Cambridge from 1970 to 1974. This summary illustrates the natural progression of scientific findings and techniques towards the development of the monoclonal antibody technique.
Genes that suppress the action of mutated ras genes
Authors: Makoto Noda 
Published: November 2023

Abstract
Three major types of approach have been taken to address the question of how activated ras oncogenes induce malignant cell transformation: enzymology, genetics, and cell biology. Ras proteins have intrinsic guanine nucleotide-binding activity as well as GTP-hydrolysing (GTPase) activity (for review see Barbacid (1987)). Therefore, cellular factors which affect these activities in the test tube can be sought. The GTPase activating protein (GAP) and the guanine nucleotide-exchange factors (GNEFs) have been identified in this fashion (McCormick 1989; Downward et al. 1990; Huang et al. 1990; Wolfman and Macara 1990). Oncogenically mutated (‘activated’) Ras proteins show either decreased intrinsic GTPase activity or poor susceptibility to GAP (reviewed in Barbacid (1987) and Krengel et al. (1990)) and, therefore, GAP probably serves as a negative regulator and GNEFs as positive regulators of Ras. Although enzymology can yield precise results, it has its limitations. For instance, interaction between purified proteins does not necessarily reflect the physiological functions of the proteins in vivo. Also, the applicability of this technique is confined to the molecules directly interacting with Ras proteins.
Unfinished business
Authors: Harris Henry 
Published: November 2023

Abstract
The original experiments that revealed the existence of normal cellular genes that had the ability to suppress malignancy also revealed that this suppression was not achieved by mechanisms that inhibited the multiplication of cells in vitro (Harris et al. 1969). For the fusion of tumour cells with normal fibroblasts generated hybrids that multiplied vigorously in culture but that were unable to produce tumours; and when chromosome segregation permitted the re-emergence of the malignant phenotype, there was often little or no difference in growth rate between the non-malignant hybrids and the malignant segregants derived from them (Harris 1971). It was therefore clear that something happened when the cells were injected into the animal that did not happen when the cells were grown in vitro.