bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolutionary Answer to the Problem of Faith and Reason
Authors: Schellenberg J L 
Published: November 2023

Abstract
The problem of faith and reason, as I shall understand it here, is the problem of showing how the religious impulse of humanity can be reconciled with the rational one. Some, for example those held in thrall by postmodernism or scientism, may think they are solving the problem of faith and reason when they denounce one or other of these human proclivities. But, on my understanding of the problem, they are simply refusing to admit it. Fortunately, more relevant approaches can also be found in philosophy of religion. The deductive theistic proofs of thinkers like Anselm and Leibniz exemplify one; Swinburne’s cautious inductive and cumulative case for the existence of God another; Plantinga’s more experientially grounded “Reformed Epistemology”, which regards theistic belief as properly basic, a third; John Hick’s neo-Kantian religious pluralism, more irenic than the- ism though still experientially grounded, a fourth. But no existing answer to the problem of how to reconcile reason and religion seems to me whol- ly satisfactory; certainly none has won wide acceptance. Here I wish to outline a response that has not thus far been attempted, except implicitly in my recent books. It will, I hope, prove worthwhile to set it out more explicitly and crisply and under a single guiding concept, so that it can be captured, as it were, at a glance, and thus more easily compared with other answers.
Subcellular Localization of Biological Molecules
Authors: Cumming Riciiard , Fallon Rachel 
Published: November 2023

Abstract
The complexity of higher organisms is due in part to the wide variety of tissues and cells which have become specialized for different functions. Cells can often be differentiated from each other on the basis of size, shape, fine structural differences and on the basis of phenotypic molecular markers. Techniques such as tissue culture can help to elucidate the function of individual cell types by growing them and manipulating them under controlled conditions. A further degree of complexity comes from the organization of structures within the cell; at the simplest level we can divide the cell into nucleus and cytoplasm, while sophisticated techniques allow distinction be tween many different structures such as mitochondria, lyzosomes, ribosomes, etc. It is now widely appreciated that these structures perform varied cellular functions and that different molecules are localized within different subcellular compartments (e.g. neuronal compartmentation of cytoskeletal proteins) (1). In addition to the well-known movement of nucleic acids between the nucleus and the cytoplasm, it is now known, for example, that trans\ocation of specific molecules from one region of the cell to another appears to represent the mechanism of action of molecules including steroids, cyclic nucleotides and receptors.
Selection and Synthesis of Receptor-Specific Radioligands
Authors: Mcfarthing Kevin G 
Published: November 2023

Abstract
The vast majority of biological phenomena involve molecular communication between cells. The molecules which mediate this communication require the presence of a target molecule, or receptor, on the target cell which recognizes the signal and translates this, usually by a complex series of intracellular events, into a biological effect or response. The study of the distribution, concentration, structure, and function of these receptors is thus fundamental to the understanding of the biological response.
Polypeptide Neurotoxins as Probes for Certain Voltage-Dependent K+ Channels
Authors: Dolly J Oliver 
Published: November 2023

Abstract
A paucity of specific probes for membrane-bound, neuronal proteins has restricted their molecular characterization, particularly where functional assays applicable to broken cell preparations are not available. Thus, the discovery of toxins acting electively on nicotinic acetylcholine receptor or Na+ channel proteins, for example, has resulted in the elucidation of their detailed structural and functional properties.
Gel-Filtration Assays for Solubilized Receptors
Authors: Hulme E C 
Published: November 2023

Abstract
There are two basic strategies which can be applied to the assay of soluble receptor-ligand complexes. The first is to render the complex insoluble, and then to apply the filtration or centrifugation techniques which are described elsewhere in this book to separate bound from free ligand (Chapters 6, 7); a variant on this approach is to absorb the free ligand, and then to assay the residual binding (Chapter 8). The second is to use solution technology, namely equilibrium dialysis, or gel-filtration, to assay the levels of bound and free ligand.
Receptor-Binding Kinetics
Authors: Prinz Heino 
Published: November 2023

Abstract
The first steps involved in receptor-ligand interactions are always second order binding reactions. They may, or may not, involve conformational changes of the receptor protein. The velocity of binding may be extremely rapid for neuroreceptors but can be much slower for hormone receptors. This diversity leads to a variety of experimental methods employing mostly fluorescent or radioactive ligands. Likewise, the analysis of kinetic experi ments is performed on very different levels lepending on the type and quality of the data. Usually, and as a first app oximation, simple second order association reactions are assumed, which are sufficient for the analysis of most receptor-binding kinetics (1). Possible deviations from these schemes may lead to new insights into the binding mechanism and are, therefore, the focus of this chapter. It should be remembered that disproving a given mechanism is much simpler than proving another one.
Opioid Receptors
Authors: Demoliou-mason Catherine D , Barnard Eric A 
Published: November 2023

Abstract
Evidence for the heterogeneity of opioid receptor sites in the CNS has been provided by a variety of studies. At least three classes of binding sites have been identified and designated as μ (morphine), δ (enkephalin) and x (dynorphin). The assignment of these sites as distinct receptor subtypes has been supported by a variety of studies (reviewed in reference 1): specific ligand competition, selective protection from irreversible inactivation, differential anatomical distributions, the differing pharmacological profiles of various opiate and opioid peptide ligands, and differential affinity cross-linking studies (2).
α2-Adrenergic Receptor Purification
Authors: Regan John W , Matsui Hiroaki 
Published: November 2023

Abstract
Despite recent progress in the purification and cloning of α2 -radrenergic receptors (1,2), the purification of sufficient quantities of receptor for structural characterization remains a formidable challenge. This is due to the low natural abundance of α2 -adrenergic receptors which necessitates a substantial purification (100 000-fold) to obtain a pure preparation of the receptor. With the advent of the molecular cloning of the gene for the human platelet α2 -adrenergic receptor and the possibility of designing high-yield expression systems, this purification problem will be reduced but probably not eliminated. A useful and presently essential tool for the purification of α2 -adrenergic receptors is affinity chromatography.
Structural deductions from receptor sequences
Authors: Green N M 
Published: November 2023

Abstract
Receptors are a class of proteins, expressed mainly on the extracellular surface of the plasma membrane, which transmit effects of chemical stimuli to the cytoplasm. This may involve gating of ions by the receptor, modulation of systems coupled to GTP-binding proteins, direct activation of a protein kinase domain of the receptor, or internalization of the stimulating ligand (virus receptors). A few receptors for lipid-soluble molecules (steroids, retinoic acid) exist as soluble cytoplasmic proteins, but neither these nor the virus receptors will receive explicit consideration here. The methods discussed are nevertheless generally applicable to all types of protein.
Preparation of G-proteins and their subunits
Authors: Sternweis Paul C , Pang Iok-Hou 
Published: November 2023

Abstract
The actions of many hormones that interact with receptors on the cell surface are mediated by a family of GTP-dependent regulatory proteins (G-proteins). The G-proteins are stimulated by a host of receptors and regulate a variety of intracellular activities (adenylyl cyclase, phospholipases, ion channels, and a cGMP-dependent phosphodiesterase). Membership in this family is still growing through the use of molecular genetics and more sophisticated techniques for detection and purification of the proteins from diverse sources. The details of the structural complexity and mechanisms of action of the identified G-proteins have been reviewed (1, 2). A brief discussion follows.
Reconstitution of hormone-sensitive adenylate cyclase and tyrosine kinases
Authors: Cerione Richard A 
Published: November 2023

Abstract
A prerequisite for structure-function studies of purified cell surface receptor proteins is the development of methods for functionally inserting these proteins into well-defined phospholipid vesicle systems. A great deal of progress has been made over the past several years in achieving the reconstitution of the components of the P-adrenergic receptor-coupled adenylate cyclase system (1-4). The development of these reconstituted systems has served two important purposes:
(a) it has enabled a direct assessment of whether the different macromolecular components (i.e. the P-adrenergic receptor, the guanine nucleotide regula tory protein, and adenylate cyclase itself) were purified in a completely functional form; and
(b) it has opened the way to mechanistic studies aimed at probing the detailed pathways responsible for both the stimulatory and inhibitory regulation of this signal-transduction system.
Polyphosphoinositide turnover
Authors: Oldham Kenneth G 
Published: November 2023

Abstract
Receptor-stimulated phospholipase C-mediated hydrolysis of phosphatidyl inositol 4,5-bisphosphate (Ptdlns 4,5-P2) results in the formation of two second messengers: diacylglycerol, which exerts its effect by activating protein kinase C; and myo-inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), which acts by mobilizing calcium from cellular stores. In the original simple picture of calcium mobilization by Ins 1,4,5-P3, Ins 1,4,5-P3 is sequentially degraded, by a series of phosphatases, to inositol which is then reincorporated into phosphatidylinositol (Ptdlns) by the enzyme Ptdlns synthase-the so-called inositol phosphate cycle.
Molecular pharmacology of ion channels using the patch clamp
Authors: Gurney Alison M 
Published: November 2023

Abstract
Many receptors are coupled to membrane ionic channels. Indeed, direct activation of channels by neurotransmitters is the most rapid kind of receptor mediated response known. In other instances, ion-channel activity is modulated by intracellular messengers, liberated when transmitters, hormones, or drugs bind to receptors on the extracellular surface of the plasma membrane.
Much of our understanding of how ion channels function in cell membranes, and how they are influenced by receptor activation, has been provided by voltage clamp experiments. These simply involve setting the voltage across the membrane at a known level while measuring ionic flux as an electric current. Introduction of the patch clamp has refined the technique to the extent that the current flowing through an individual channel in a small patch of cell membrane can be resolved.
Interleukin-2 and the interleukin-2 receptor complex
Authors: Diamantstein T 
Published: November 2023

Abstract
Interleukin 2 (IL-2), originally designated as a T cell growth factor, is a glycoprotein with a molecular weight of 15.4 kD. The genes encoding the human, murine, and bovine IL-2 were cloned, their nucleotide sequences determined, and corresponding amino acid sequences deduced.-3 Human IL-2 consists of 133 amino acids and possesses an intramolecular disulfide bridge (between position 58 and 105) essential for the biological activity of the molecule. The position of the cysteine residues, 58 and 105, are also preserved in other species. These results demonstrate the importance of the folding of the molecule for its biological activity. IL-2 is an α-helical protein consisting of antiparallel smaller helical segments (designated A, B, C, D, E, and F), with helix B being interrupted by proline and divided into two sections, B and B′. The specific mutagenesis of human IL-2 genes and the use of antibodies directed against specific sites of IL-2 make it possible to define the sections important for IL-2 receptor binding. The regions responsible for binding IL-2 to the α-chain of the IL-2 receptor (IL-2R) are situated in specific areas of the helices B, B′, E, and F. Specific sections of helices A and F were defined as the areas responsible for IL-2 binding to the β chain of the IL-2R. The 0- and N-bound sugars give IL-2 microheterogenicity with regard to size and loading, but do not influence its biological activity.
The development of regimens for combination immunotherapy
Authors: Creekmore S P , Longo, D L , Urba W J 
Published: November 2023

Abstract
Immunotherapy regimens based on interleukin-2 (IL-2) are a central feature of many current investigations of biological therapy for cancer. Originally described as a factor necessary to support T cell proliferation,1 IL-2 is now known to potentiate several cell types that may have antitumour activity: large granular lymphocytes (LGLs) such as natural killer (NK) and lymphokine-activated killer (LAK) cells, cytotoxic T cells,5 and monocyte/ macrophages. In addition, antitumour activity may result from secondary effects through cytokine regulatory interactions, either directly from the administered T cell, or indirectly through cytokine production by IL-2 stimulated LGLs or other IL-2-responsive cells. Clinical trials of IL-2 in combination with adoptively transferred LAK cells have shown antitumour responses in 20-40 per cent of patients with melanoma and renal cell cancer. As a single agent, without the adoptive transfer of exogenously generated cells, IL-2 has also been shown to induce responses in such patients. However, antitumour responses are usually partial, and require levels of IL-2 dose intensity that are accompanied by substantial toxicity and expense, although improvements in these areas have been achieved with greater experience. Attention is being addressed, therefore, to making immunotherapy more effective and less toxic.
VII collagen, entactin, and laminin) found in basement membranes
Authors: Hudson Billy G , Gunwar Sripad , Chung Albert E , Burgeson Droberte 
Published: November 2023

Abstract
Basement membranes are specialized extracellular matrices that play key roles in diverse biological processes. The processes include: orchestration of embryonic development, maintenance of tissue architecture during remodelling and development, and ultrafiltration of blood. They appear as an amorphous sheet-like structure that is positioned between a cell layer and a thick collagenous stroma, as exemplified by the dermal—epidermal junction of human skin (Figure IA) or between two layers of cells, as exemplified by the renal glomerular basement membrane (Figure I B). In general, basement membranes are composed of several macromolecular constituents, including type IV collagen, laminin, entactin, and heparan sulfate proteoglycan (perlecan) which interact to form a supramolecular structure ( Figure IC). In the case of skin, this suprastructure is connected to the underlying stroma by anchoring fibrils that are composed of type VII collagen.
Structure and function of the steroid receptor zinc finger region
Authors: Freedman Leonard P 
Published: November 2023

Abstract
Steroid hormone receptors are ligand-inducible transcriptional regulatory proteins. Like many eukaryotic transcription factors, nuclear hormone receptors appear to be organized into relatively discrete functional domains (1), and it is this common domain organization that groups these receptors into a superfamily of functionally and most likely structurally related proteins (reviewed in Chapter 1). Because of this modularity, domains for ligand binding (located in the carboxy-terminal region), DNA binding (located toward the central or amino terminus), nuclear localization (within both the DNA and ligand-binding domains), and transcriptional modulation (localized to more variable regions of the receptors, including the N-terminus) (Fig. 1), can all confer their specific functions when linked to unrelated, nonreceptor proteins (2-7). This has led to the efficacy of examining in detail the properties of a particular receptor functional domain, such as the DNA-binding domain, and of avoiding, at least initially, the potential physical/chemical complexities of studying a full-length native receptor.
The Use Of Cell-Free Extracts Of Xenopus Eggs For Studying Dna Replication In Vitro
Authors: Hutchison C J 
Published: November 2023

Abstract
Cell-free extracts of Xenopus eggs provide the only available systems that support the initiation, elongation, and completion of eukaryolic chromosomal replication in vitro (1, 2). These extracts have been used extensively to study the control of entry into S phase (3, 4), the dependency upon completion of S phase as a requirement for entry into mitosis (5, 6), and the role or the nuclear envelope in the initiation and cell-cycle control of S phase (7-10). Although the exploitation of these extracts reflects the current interest in cell cycle control mechanisms, it also reflects their limitations. The extracts lend themselves to analysis of periodic enzyme activities and to immunochemical dissection. However, they are difficult to fractionate. This has restricted those of us who are interested in the enzymology of DNA synthesis to testing for the involvemenl of previously identified proteins at replication forks (11, 12). Nevertheless, these extracts still represent powerful experimental tools, whose preparation and manipulation will be reviewed.
Xenopus Egg Extracts As A System For Studying Mitosis
Authors: Felix Marie-Anne , Clarke Paul R , Coleman Julia , Verde, Fulvia , Karsenti Eric 
Published: November 2023

Abstract
The ultimate goal (or dream) for a biochemist is to isolate the individual components of a complex system, for example all the enzymes involved in cell-cycle control, to mix them back together, and finally show that the system functions again as it did in the context of the whole cell. This is a very difficult task, however, and no highly complex process has been brought to this point yet. A simpler way to analyse complex systems is to use functional complementation assays. In organisms like Drosophila or yeast, this is feasible using a genetic approach. A single function is eliminated by mutation of a gene and then restored by complementation with the corresponding, fully functional gene. This approach has limitations however, as it is not always possible to locate exactly where and when, in a cascade of events, a gene product function is required. Complex in vitro systems that closely mimic the in vivo situation are required to fill in the gaps between genetic approaches and the reconstitution of functional processes from purified components in vitro. Frog egg extracts belong to this category of systems.
Maturation-Promoting Factor And Cyclin-Dependent Protein Kinases
Authors: Doree Marcel , Lorca. Thierry , Picard Andre 
Published: November 2023

Abstract
The cell cycle has two main phases: interphase and mitosis. In interphasc the cell nucleus remains intact and chromosomes are replicated. In mitosis the cytoplasmic network of microtubules breaks down and is reassembled into the mitotic spindle, whilst the chromosomes condense and attach to it (metaphase). Then the spindle segregates the chromosomes (anaphase), ensuring that each daughter nucleus will have one copy of every chromosome. At the end of mitosis the cell divides to form two complete daughter cells that are genetically identical to the parcnl.
Telomerase
Authors: Kipling David 
Published: November 2023

Abstract
In three ciliates and two mammals it has been shown that terminal repeat sequences are synthesized by a specialized DNA polymerase called telomerase (reviewed by Greider 1990; Blackburn 1992). This chapter investigates to what extent the known properties of telomerase are consistent with various features of the terminal repeat sequences of many species, including the majority for which telomerase has yet to be biochemically identified. These structural features have been described in detail in Chapter 3.
Genome rearrangements and telomeres
Authors: Kipling David 
Published: November 2023

Abstract
What is the substrate for telomere addition in vivo? Much of what we know of this comes from analysis of the process of programmed genome fragmentation and de novo telomere addition in ciliates such as Oxytricha and Tetrahymena and the nematode Ascaris. The unusual life cycle of these organisms will be reviewed. The analysis of de nova telomere addition suggests that telomere sequence addition occurs onto A+ T-rich sequences which would not be predicted to be telomerase substrates in vitro.
Human telomere loss, ageing, and cancer
Authors: Kipling David 
Published: November 2023

Abstract
The telomere is a specialized structure which causes the natural ends of a linear chromosome to behave differently from simple double-strand breaks. This concept was first elaborated by Muller (Chapter 2) on the basis of the inability to recover terminal deletions in Drosophila. In what way does such a double-strand break behave differently from a telomere? Such breaks in maize, resulting from the action of dicentric chromosomes, cause repeated rounds of breakage-fusion-bridge cycles (McClintock 1941, 1942). Thus the idea developed that without a telomere a chromosome end was prone to fusion and recombination. Another consequence is that a break will activate a cell cycle checkpoint and arrest cell division. In yeast the action of components of the RAD9 pathway cause cell cycle arrest in response to DNA damage (Hartwell and Weinert 1989), so that a cell with a damaged genome does not exacerbate the problem by going through division and instead is allowed time to repair the break. A single break in the yeast genome, for example caused by the HO endonuclease, is sufficient to cause cell cycle arrest (Brown et al. 1991; Benneti et al. 1993). If a cell with linear chromosomes is to continue division then telomeres must somehow not activate such checkpoints.
Structure and maintenance of Drosophila telomeres
Authors: Kipling David 
Published: November 2023

Abstract
Drosophila melanogaster has a telomeric sequence organization and mechanism of sequence addition dramatically different from other species which have been analysed. From what has been reviewed up to this point one might think that all eukaryotic chromosomal telomeres consist of a tandem repeat array based on a short sequence, probably synthesized by telomerase. Candida albicans is unusual, as its terminal repeats are 23 bp in length, but it is still possible that they are synthesized by telomerase. However, Drosophila provides the most clear exception to this type of telomere structure and synthesis (reviewed by Biessmann and Mason 1992; Mason and Biessmann 1993).