bluuebunny/crossref_metadata_2025 huggingface dataset:
Second-order differential equations in the phase plane
Authors: Jordan D W , Smith P
Published: November 2023

Very few ordinary differential equations have exact solutions. This is not simply because ingenuity fails, but because the repertory of standard functions (polynomials, exp, sin, and so on) in terms of which solutions may be expressed is too limited to accommodate the variety of differential equations encountered in practice. Even if a solution can be found, the ‘formula’ is often too complicated to display clearly the principal features of the solution; this is particularly true of implicit solutions and of solutions which are in the form of integrals or infinite series. The qualitative study of differential equations is concerned with how to deduce important characteristics of the solutions of differential equations without actually solving them. In this Chapter we introduce a geometrical device, the phase plane, which is used extensively for obtaining directly from the differential equation such properties as equilibrium, periodicity, unlimited growth, stability, and so on. The classical pendulum problem shows how the phase plane may be used to reveal all the main features of the solutions of a particular differential equation.
Plane autonomous systems and linearization
Authors: Jordan D W , Smith P
Published: November 2023

This approach permits a useful line of argument based on a mechanical interpretation of the original equation. Frequently, however, the appropriate formulation of mechanical, biological, and geometrical problems is not through a second-order equation at all, but directly as a more general type of first-order system of the Near the equilibrium points we may make a linear approximation to X(x,y), Y(x,y), solve the simpler equations obtained, and so determine the local character of the paths. This enables the stability of the equilibrium states to be settled and is a starting point for global investigations of the solutions. Assume that the functions X(x, y) and Y(x,y) are smooth enough to make the system regular (see Appendix A) in the region of interest. As in Section 1.2, the system is called autonomous because the time variable t does not appear in the right-hand side of (2.1). We shall give examples later of how such systems arise.
Periodic solutions; averaging methods
Authors: Jordan D W , Smith P
Published: November 2023

It should be possible to take advantage of this fact to construct approximate solutions: the phase paths will be nearly circular for c small enough. However, the original equation will not, in general, have a center at the origin. The approximate and the exact solutions may differ only by a little over a single cycle, but the differance may prevent the paths from closing; apart from exceptional paths, which are limit cycles. The phase diagram will generally consist of slowly changing spirals and, possibly, limit cycles, all being close to circular. We show several methods for estimating the radii of limit cycles and for detecting a center. Extensions of the methods permit determination of the stability and the period of limit cycles, the shape of the spiral path around limit cycles and amplitude-frequency relations in the case of a center. Similar estimates are successful even in very unpromising cases where E is not small and the supporting arguments are no longer plausible (see Example 4.12 and Section 4.5). In such cases we can say that we are guided to the appropriate sense of how best to fit a circle to a non-circular path by arguments which are valid when E is small.
The evolution of music: Theories, definitions and the nature of the evidence
Authors: Cross Ian , Morley Iain
Published: November 2023

It is nowadays uncontroversial among scientists that there is biological continuity between humans and other species. However, much of what humans do is not shared with other animals. Human behaviour seems to be as much motivated by inherited biology as by acquired culture, yet most musical scholarship and research has treated music solely from a cultural perspective. Over the past 50 years, cognitive research has approached the perception of music as a capacity of the individual mind, and perhaps as a fundamentally biological phenomenon.
The human nature of dance: Towards a theory of aesthetic community
Authors: Bond Karen
Published: November 2023

My first theoretical musings about whether dance might be part of our human biological endowment date to my daughter’s infancy, a time of sensory–emotional delights, full of breathy duets of dipping and twirling, finger dancing and shared rhythms. I had a distinct sense that she was initiating these dances, and I remember thinking, ‘I wonder if we’re wired for this.’ I forged a deeper connection between dance and biology two decades later during an extended inquiry into the meanings and effects of dance for six non-verbal children with deaf-blindness (Bond 1991, 1994a).
Inbreeding In Egypt And In This Book: A Childish Perspective
Authors: Hamilton William d.
Published: November 2023

The amount of inbreeding in the living world is great if we count species that inbreed1 much less great if we estimate total inbred biomass. This is because most of the world ’s species are small-bodied and these are the ones most apt to inbreed. Most of the world ’s biomass is in big organisms like trees and grass. The relation of inbreeding to size (and concomitant longevity) is little discussed in other chapters of this book. I will later devote part of mine to saying why I think such a relation exists but first will illustrate my claim about size and numbers with some examples chosen from among my own earliest experiences of entomology. Although the examples are anecdotes and as such perhaps inappropriate to a serious book about inbreeding, they nevertheless give entry to an ever-surprising world that is strongly linked to our theme.
Tomato Attractors On The Wall Of An Abandoned Church
Authors: Sasaki Akira
Published: November 2023

It was early July of 1999 when I arrived at Oxford to resume the collaborative research on the desynchronization in host-parasite metapopulation dynamics with Bill Hamilton, which we had started in the previous summer. He had just returned from a journey to Congo. The journey was not to test the Red Queen hypothesis for the evolution of sex or the Hamilton-Zuk hypothesis about sexual selection. He went to collect chimpanzee feces. And the feces must have been collected from chimpanzee troops living around the former Stanleyville in the Belgian Congo.
Statistical Evidence in Medical Trials
Authors: Simon Stephen D
Published: November 2023

Statistical Evidence in Medical Trials is a lucid, well-written and entertaining text that addresses common pitfalls in evaluating medical research. Including extensive use of publications from the medical literature and a non-technical account of how to appraise the quality of evidence presented in these publications, this book is ideal for health care professionals, students in medical or nursing schools, researchers and students in statistics, and anyone needing to assess the evidence published in medical journals. Stephen D. Simon earned a Ph.D. in statistics from the University of Iowa in 1982. He currently works as a research biostatistician at Children's Mercy Hospitals and Clinics in Kansas City, MO. He has authored or co-authored over 60 publications in a variety of medical and statistical journals, four of which have won awards. He has given a wide range of lectures and classes on statistics, evidence based medicine, research ethics, and quality control.
One of the most basic natural systems: the pendulum
Authors: Bertuglia Cristoforo Sergio , Vaio Franco
Published: November 2023

Let us start by illustrating the model of an oscillating pendulum, basing ourselves on the simplest assumption: a pendulum that makes small oscillations in obviously completely theoretical conditions, in which there is no form of friction. Let us imagine that we strike the pendulum, initially still in a position of stable equilibrium, with a small force: it distances itself from equilibrium, but, as it does so, it starts to undergo the action of a restoring force, which increases with the size of the open angle with respect to the vertical (Figure 5.1 ). The speed of the pendulum decreases until it cancels itself out, when the restoring force becomes equal to the force applied initially that moved the pendulum from equilibrium.
Extension of the concepts and models used in physics to economics
Authors: Bertuglia Cristoforo Sergio , Vaio Franco
Published: November 2023

Models such as the osci11ators, in particular the harmonic oscillator illustrated in chapter 8, constitute a set of mathematical models of physical systems that have been studied for some time and that represent some of the first and most important accomplishments of classical-era mathematical physics. In principle, models of this kind can be used to describe any oscillating system, with a few simple adaptations that don’t affect their substance. In particular., the linear model of the harmonic oscillator is particularly suited to describing all cases of oscil1ating systems for which linear approximation is considered acceptable: these range from systems in physics, e.g. when we describe the movement of electrons in an oscillating electric circuit, or of the electrical or magnetic fields of an electromagnetic wave, to systems in other disciplines in which we believe that we can observe periodic oscillations over time, such as an economic system, a population, etc.
‘Axiomatics, Empiricism, and Anschauung in Hilbert’s Conception of Geometry: Between Arithmetic and General Relativity’
Authors: Corry Leo
Published: November 2023

To what extent the philosophy of mathematics of any individual mathematician is relevant to historically understanding his mathematical work, and to what extent his mathematical work has any bearing in understanding philosophical issues related with mathematics, are questions that have different meanings and have to be approached differently when they refer to different mathematicians. Take, for example, Descartes and Frege. These two thinkers can be considered philosophers in the strict sense of the word, with philosophical interests going well beyond the strict scope of mathematics, each of them in his own way. They devoted much of their time and efforts to develop coherent, well-elaborated philosophical systems, and their writings turned them into philosophers in the eyes of the philosophical community. Their philosophical systems are directly relevant to addressing central questions pertaining to the nature of mathematical knowledge, but they were not intended exclusively as answers to specific problems in the philosophy of mathematics. And besides their intense involvement with philosophical questions, both Descartes and Frege contributed positive mathematical results of various kinds, albeit of different overall impact on mathematics at large, and while working under quite different professional circumstances. A natural question that the historian may be easily led to ask in relation to these two thinkers concerns the mutual relationship between the philosophical systems they developed and the mathematics that each of them produced. One way to answer this question is by investigating, separately, the philosophy and the mathematics of each of them, and then trying to articulate the said relationship.
Emmy Noether’s ‘Set Theoretic’ Topology: From Dedekind to the Rise of Functors
Authors: McLarty Colin
Published: November 2023

‘In these days the angel of topology and the devil of abstract algebra fight for the soul of each individual mathematical domain.’ (Weyl 1939, 500) If Hermann Weyl ever put faces on these spirits they were his good friends, the angel Luitzen Brouwer, and the devil Emmy Noether. Weyl well describes the scope of their ambition. But topology and algebra were not fighting each other. They would come to share the soul of most of mathematics. And the angel and devil had worked together. In 1926 and 1927 Emmy Noether induced young topologists gathered around Brouwer to use her algebra to organize the kind of work on topological maps that Brouwer taught. This created the still current basis for ‘algebraic topology.’ It was a huge advance for the structuralist conception of mathematics. And it turned Noether from a great algebraist to a decisive figure for twentieth-century mathematics.
Epigenetic events in cancer
Authors: Cheng Jonathan C , Jones Peter A
Published: November 2023

The diverse cell types in multicellular organisms have identical genotypes but are functionally and morphologically different. This is due to differences in gene expression patterns which are established during development and are subsequently retained through mitosis. Stable alterations of this kind are known as epigenetic modifications, which are defined as heritable, but potentially reversible changes in gene expression that occur without alterations in the DNA sequence. In this chapter, we will focus on two key epigenetic phenomena that seemingly impact each other: DNA methylation and chromatin inheritance.
The spread of tumours
Authors: Hart Ian
Published: November 2023

Metastasis is ‘the transfer of disease from one organ or part to another not directly connected with it. It may be due to the transfer of pathogenic organisms or to the transfer of cells, as in malignant tumours’. This transfer of cancer cells, which underlies the metastasis of malignant tumours, is perhaps the fundamental problem in oncology. Surgical removal, often combined with irradiation and chemotherapy, frequently is successful in the treatment of primary tumours (particularly when initiated early in tumour development) but wide- spread dissemination of the cancer cells often defeats this approach to treatment. Neoplastic cell spread is responsible for the major portion of can- cer deaths, while the relentless and seemingly intractable movement of a cancer from a primary site to distant organs is a major factor in people’s fear of neoplastic disease.
Animal models of cancer
Authors: Jonkers Jos , Berns Anton
Published: November 2023

Animal models have been invaluable in the study of human cancer, and they will undoubtedly continue to be so. Spontaneous as well as carcinogen-induced malignancies have been studied in baboons, dogs, birds, rabbits, hamsters, rats, mice, and zebrafish; even fruit flies have been instrumental in the identification of Drosophila tumour suppressor genes (TSGs) with orthologues involved in human cancer. Nevertheless, the mouse remains the animal of choice for several reasons. First, mice and humans have roughly the same complement of genes, and most signalling pathways are highly conserved between the two species.
Constraints on the acquisition of specialization for face processing
Authors: Gauthier Isabel
Published: November 2023

The domain-specificity of the mechanisms supporting face perception is debated both for early preferences observed in the newborn and later skills found in adults. However, an even more complex question is that of the relationship between newborns’ face preference and adult face expertise. Here, I review the evidence addressing the question of the necessity of early constraints for the development of expertise with objects or faces. These results suggest little reason to postulate that newborn’s face preferences constrain the acquisition of face recognition in adults, beyond conjectures of an evolutionary benefit.
Atypical representational change: Conditions for the emergence of atypical modularity
Authors: Thomas Michael S C , Richardson Fiona M
Published: November 2023

Where do functional modules come from? This question is particularly pertinent for developmental disorders, where some researchers have argued that apparently domain-specific behavioural deficits (e.g., in language) correspond to the failure of an isolated module to develop normally. Such a view requires that modules are pre-specified and develop independently. By contrast, other researchers argue that functional modules are emergent, the product of development rather than a precursor to it. If this is true, the emergence of specialized structures (as exhibited, for example, in patterns of lateralization) might be disrupted in developmental disorders, where the process of development is itself atypical.
Modeling integration and dissociation in brain and cognitive development
Authors: O’Reilly Randall C
Published: November 2023

Over the course of development, brain areas can become increasingly dissociated in their functions, or increasingly integrated. Computational models can provide insights into how and why these opposing effects happen. This paper presents a computational framework for understanding the specialization of brain functions across the hippocampus, neocortex, and basal ganglia. This framework is based on computational tradeoffs that arise in neural network models, where achieving one type of learning function requires very different parameters from those necessary to achieve another form of learning.
The infant as synesthete?
Authors: Maurer Daphne , Mondloch Catherine J
Published: November 2023

The hypothesis that newborns’ perception is synesthetic holds up well in light of recent evidence on the neural basis of synesthesia, on developmental plasticity, and on cross-modal interactions in non-synesthetic adults and children. The starting point for this paper is our previous proposal that newborns’ perception is synesthetic: that their undifferentiated sensory pathways lead to cross-modal influences on their perception resulting in perceptual experiences that resemble, in some respects, the perception of adults with synesthesia (Maurer 1993; Maurer and Maurer 1988; Maurer and Mondloch 1996, 2004; see Johnson and Vecera 1996, for a similar argument they called the parcellation conjecture).
Learning about learning and development with modern imaging technology
Authors: Casey B J , Amso Dima , Davidson Matthew C
Published: November 2023

Predictive learning is a cornerstone of cognitive development. Knowing what events to expect when, and in which contexts, is critical for the individual in planning and maintaining appropriate thoughts and actions in different contexts over time. Adjusting behavior when these predictions are violated is an essential element of cognitive control. In this chapter we describe three different neural systems involved in predictive learning and cognitive control: a frontostriatal system that learns about the frequency of events, a frontocerebellar system that learns about their timing, and a hippocampal system that learns about the contexts in which they occur.
To See Feelingly: Emotion, Motivation And Hypnosis
Authors: Woody Erik , Szechtman Henry
Published: November 2023

In the late 1950s and early 1960s, Weitzenhoffer and Hilgard laid the foundation for modern hypnosis research by devising standardized hypnosis scales. They modified the earlier hypnosis scale of Friedlander and Sarbin (1938) by adding additional comparatively easy test suggestions, particularly direct motor suggestions, resulting in two alternate forms, the Stanford Hypnotic Susceptibility Scales, Forms A and B (SHSS: A and SHSS: B; Weitzenhoffer and Hilgard 1959). They then devised another hypnosis scale with a better representation of relatively difficult suggestions, such as hallucinations and age regression, resulting in the Stanford Hypnotic Susceptibility Scale, Form C (SHSS: C; Weitzenhoffer and Hilgard 1962). The SHSS: C is now widely regarded as the gold standard of hypnosis research (Woody and Barnier 1996).
Universal Circles
Authors: Calegari Danny
Published: November 2023

In this chapter we begin a systematic study of the macroscopic geometry and topology of taut foliations. The leafwise geometry can be understood via Candel’s uniformization Theorem (to be proved below), which implies that for a taut foliation ℱ of an atoroidal 3-manifold M, one can find a metric on M for which every leaf of F is hyperbolic, with respect to the induced path metric.
Neuroeconomics
Authors: Zak Paul J
Published: November 2023

Neuroeconomics is an emerging transdisciplinary field that uses neuroscientific measurement techniques to identify the neural substrates associated with economic decisions. ‘Economics’ here should be interpreted in the broadest possible sense as any (human or non-human) decision process that is made by evaluating alternatives. A classic nonhuman example is ‘optimal foraging’ where, for example, an ungulate must decide when to expend energy to move from the patch of grass it is currently eating to a different location with an uncertain quantity and quality of grass. A human example would be whether to accept a job as a stock analyst at Goldman Sachs for $100 000 per year but with few future pay increases or advancement versus a job as a stockbroker for a small company starting at $40 000 per year but with the potential for much greater income if successful (and the risk of being fired if not). Both of these examples can be expressed mathematically as constrained optimization problems that generate empirically testable predictions. A prediction in the human example is that a person who is more risk averse (in a precisely defined and agreed upon mathematical sense) is more likely to take the ‘safe’ $100 000 per year job, whereas someone who is less risk averse will gravitate towards the job as a stockbroker.
Convergence of random variables
Authors: Grimmett Geoffrey R , Stirzaker David R
Published: November 2023

The many modes of convergence of a sequence of random variables are discussed and placed in context, and criteria are developed for proving convergence. These include standard inequalities, Skorokhod’s theorem, the Borel–Cantelli lemmas, and the zero–one law. Laws of large numbers, including the strong law, are proved using elementary arguments. Martingales are defined, and the martingale convergence theorem proved, with applications. The relationship between prediction and conditional expectation is explored, and the condition of uniform integrability described.
Behavioural adaptive strategies
Authors: Nevo Eviatar
Published: November 2023

Endogenous rhythmicity appears to be synchronized with, and selected by, the environment as an adaptive strategy increasing fitness. Subterranean mammals, both herbivores and insectivores, are active day and night, and their activity is linked with feeding periods. This is true for Geomys (Vaughan and Hansen, 1961; Elliott, 1976; De Coursey, 1989; Benedix, 1991, 1994), Talpa, Parascalopus (Godfrey and Crowcroft, 1960), and Scalopus (Harvey, 1976). In some species daytime activity is either greater, (Spalax; Savic’ and Mikes, 1967), preferable (Eremitalpa, Ellobius; Dubost, 1968), distinct, (Tachyoryctes, but little less so in Heliophobius; Jarvis, 1973b), or absolute, (Ctenomys; Pearson, 1959 and Heterocephalus; Jarvis, 1978).
Peripheral Arterial Chemoreceptors and Respiratory-Cardiovascular Integration
Authors: Daly M de Burgh
Published: November 2023

The book describes how changes in respiration can affect the heart and circulation, with particular reference to the control of the two systems by small organs, known as chemoreceptors, which are situated in the neck and chest. These are stimulated when the body is partly deprived of an oxygen supply. Apart from a detailed description of the mechanisms by which the respiratory and circulatory systems are integrated the book also contains chapters which would appeal to those interested in the historical, morphological, medico-legal and clinical aspects of the subject.
Early radiation of the Mollusca
Authors: Morris N J
Published: November 2023

During the last three decades more and more Cambrian Mollusca have been discovered, particularly among the small shelly faunas of the Lower and Middle Cambrian. Many of these have led to considerable discussion about their classification and the course of molluscan phylogeny. These early molluscs show an important radiation at the beginning of the Phanerozoic which led to the diversification into the recognized classes living today. This radiation seems to have been dependent on the origin of a dorsal exoskeleton and its subsequent calcification, and possibly its interference with the ancestral pattern of simple metamery. The apparent synchronous development of a skeleton in several independent phyla suggests there may be a link with changing composition of the atmosphere and sea.
Adaptive divergence and taxonomic radiation in post-Palaeozoic bivalves
Authors: Skelton P W , Crame J A , Morris N J , Harper E M
Published: November 2023

Post-Palaeozoic marine bivalve families diversified with significant persistence. None of seven distinct clades dominated the expansion; most were involved. Only the pteriomorphs showed a decline, connected with the prolonged demise of exposed byssate taxa. Nine other autecological categories recognized by us recruited families more or less proportionately, although siphonate burrowers proliferated disproportionately at the expense of non-siphonate burrowers. Increasing predation pressure on bivalves from early in the Mesozoic, associated with the ‘Mesozoic marine revolution’, is identified as the main cause of these changes. The various adaptive pathways followed by different clades were highly conditioned by the constructional attributes of their body plans, a major role being played by the form of the ligament. Siphons evolved in several burrowing clades as a secondary adaptation.
Interpretations of early land plant radiations: ‘facile adaptationist guesswork’ or reasoned speculation?
Authors: Edwards D , Davies M S
Published: November 2023

The diversification of higher plants following initial colonization of the land is analysed at the species level both qualitatively and quantitatively based on data from Laurussia. The overall pattern of diversification broadly parallels that described for marine invertebrates in that, following the appearance of pteridophyte-like plants (Cooksonia: rhyniophytoid) in the late Wenlock, numbers remained low until the end of the Silurian-early Devonian, when a proliferation of rhyniophytoids occurred. This was followed by a diversification of Zosterophyllophytina in the late Gedinnian-early Siegenian, and Trimerophytina and taxa of less certain affinity later in the Lower Devonian.
The biology of the cyanogenic glycosides: new developments
Authors: Nahrstedt Adolf
Published: November 2023

Several reviews of the cyanogenic compounds have been presented during the past years, particularly of the cyanogenic glycosides. Among them are reviews on their occurrence (Hegnauer 1986; Nahrstedt 1987), their function (Nahrstedt 1985; Hegnauer 1986), toxicity (Poulton 1983), biosynthesis (Conn 1988), and their occurrence and physiology in insects (Nahrstedt 1988). A comprehensive volume, Cyanide compounds in biology, was published in 1988 by the Ciba Foundation. All these activities indicate that the cyanogenic compounds are an important subject for biological research. This chapter aims to summarize recent progress in this area.
A perspective on plant-animal interactions in seagrasses: physical and biological determinants influencing plant and animal abundance
Authors: Orth ROBERT J
Published: November 2023

Quantitative studies on benthic faunal commumtes associated with seagrass beds have shown these ecosystems to contain a significantly higher diversity and density of fauna when compared with adjacent, unvegetated areas. Hypotheses suggested for this abundance and diversity include habitat complexity, refuge from predation, increased food supplies, hydrodynamic effects on larval supply, and stable substrates. Manipulative laboratory and field experiments have shown that this high diversity may result from complex, and highly interrelated plant-plant, plant-animal, plant-physical environment, and animal-animal interactions. In particular, predator-prey studies have shown that foraging success is reduced by macrophyte complexity, and that the relationship between habitat complexity and predation success is non-linear. Important components of predator-prey interactions are the relative sizes as well as the behavioural repertoire of both predator and prey. Current debate centres around the role of structural complexity, initial settlement densities of recruiting individuals, the physical location of a seagrass meadow in relation to larval supply or source of adults or juveniles, and the ability of individuals to move within and between seagrass areas once settled, in determining population abundances in a given seagrass area. Since seagrasses modify hydrodynamic processes, they may play an important role in determining larval supply rates and larval settlement.
Role of algae in the recruitment of marine invertebrate larvae
Authors: Morse Aileen N C
Published: November 2023

Recruitment of marine invertebrate larvae is a dynamic feature of the structuring of shallow-water marine communities. It has recently been recognized that a clear understanding of early settlement events is essential for a more complete assessment and prediction of the effect of recruitment on the structure of these communities. The availability and nature of suitable settlement and recruitment substrata must be considered as important factors in this process. Both direct and indirect evidence suggest that algae provide critical substrata for the recruitment of a number of invertebrate larvae in the form of essential settlement cues, space, shelter from predators, and a reliable food supply for further development and growth. The wide distributions (and in many instances extensive stands) of a variety of algal species apparently involved in these recruitment processes serve to emphasize the important contribution of algae to overall structuring of shallow-water benthic communities. Where possible, the roles of algae as suitable settlement substrata are discussed in relation to other factors perceived as important to the recruitment processes of marine invertebrate larvae.
Plant-herbivore coevolution: a reappraisal from the marine realm and its fossil record
Authors: Steneck Roberts.
Published: November 2023

Stable coexistence and interdependencies between herbivores and their food plants are often interpreted as resulting from coevolution. An untested assumption is that such intimate associations reflect an ‘evolutionary arms-race’ over geological time. An examination of the fossil record of apparently ‘coevolved’ species of marine limpets and their algal hosts indicated that these mutualistic associations evolved recently and the timing of specific adaptations and coadaptations does not support the arms-race model. Alternatively, several recent ecological studies support the hypothesis that trophic specialization and stable coexistence will be most prevalent among herbivores that are small, have low metabolic demands, reduced mobility and are predator-susceptible. They will commonly be associated with algae that are relatively large, welldefended, of poor food quality, and have great thallus longevity and regenerative ability. Among the pool of herbivores capable of stable coexistence, it is possible that unilateral adaptations to generalized anti-herbivore defences occasionally evolve and in rare instances species-specific algal coadaptations result in mutualisms. The significance of mutualisms may be exaggerated if they are interpreted as being ‘coevolved’ when they may represent only an end point along an adaptive continuum which has been channelled by phyletic constraints.
Synthesis of non-peptide CCK antagonists
Authors: Freidinger Roger M
Published: November 2023

The current list of peptide hormones and neurotransmitters presents many potential opportunities for the development of new therapeutic agents. Useful drugs might be obtained from compounds which either mimic or block the effects of the native peptides. To date, however, few peptide-based drugs have been obtained, primarily because of limitations inherent in the peptide structure itself. These deficiencies include rapid degradation by proteases leading to short duration, poor oral absorption, and lack of specificity.
Detection of CCK receptor subtypes in mammalian brain using highly selective non-peptide antagonists
Authors: Hill D R , Singh L , Boden P , Pinnock R , Woodruff, G N , Hughes J .
Published: November 2023

The neuropeptide CCK occurs in the mammalian CNS in a variety of molecular forms, but it is the sulphated octapeptide (CCK-8S) that predominates (Vanderhaeghen et al. 1975; Dockray 1976; Rehfeld 1978; Larsson and Rehfeld 1979). Since its discovery in brain, the effects of CCK-8S and of related peptide fragments such as CCK-4 and pentagastrin have been studied extensively in a wide variety of systems. These studies have led to the implication of CCK in a variety of physiological systems. For instance, CCK has been suggested as an endogenous satiety factor and as such may play an important role in the regulation of feeding (Gibbs et al. 1973; Morley et al. 1982; Crawley and Kiss 1985; Dourish et al. 1989a, b; Chapter 17 of this volume). Other studies have indicated that the peptide may be intimately involved in mediating the transmission of painful stimuli or modulating the endogenous opioid system (Jurna and Zetler 1981; Faris et al. 1983; Watkins et al. 1984; see also Pittaway and Hill 1987; Baber et al. 1989; Chapters 43-45 of this volume). This suggestion is sup ported by the presence of CCK immunoreactivity and also by the presence of mRNA in brain regions such as the periaqueductal grey, the thalamus, and the spinal cord which are known to be of importance in the central processing of sensory information (Skirboll et al. 1983; Innis and Aghajanian 1986; Savasta et al. 1988; Chapter 4 of this volume).
Agonist and antagonist pharmacology of CCK-receptor-mediated responses of rat ventromedial hypothalamic neurons
Authors: Kemp, J A , Marshall G R , Kew J N C
Published: November 2023

The ventromedial hypothalamic (VMH) nucleus of the rat contains high levels of CCK immunoreactivity which is thought to arise from an afferent input from the parabrachial nucleus (Inagaki et al. 1984; Zaborsky et al. 1984). It also contains high levels of CCK8 receptor binding sites (Day et al. 1986), and CCK-8S is a potent excitant of VMH neurons (Kow and Pfaff 1986; Bowden and Hill 1988; Kemp et al. 1989). Thus the VMH slice has become a useful preparation with which to study the pharmacology of brain CCK8 receptors and has enabled comparisons to be made with results from receptor binding studies. Recently, several selective agonists and antagonists for CCK receptors have become available, and we have used these to examine in greater detail the pharmacology of the CCK-receptor-mediated excitatory responses of VMH neurons. Extracellular recordings of single-cell action potential firing rates were made using conventional techniques on 350 µm thick slices containing the VMH nucleus. These were placed in a small recording chamber (volume approximately 0.3 ml) where they were continuously perfused, at a rate of 2 ml/min, with warmed (33°C) oxygenated artificial cerebrospinal fluid (aCSF). Agonists were dissolved in the aCSF, from concentrated stock solutions, and were applied for periods of 1 min.
Plasma and cerebrospinal fluid concentrations of CCK and satiety
Authors: ödersten P S , Lindén A
Published: November 2023

The inhibitory effect on food intake of exogenously administered CCK octapeptide CCK-8, initially noted as a side-effect (Sjödin 1972), was first demonstrated experimentally by Gibbs et al. (1973) (see Chapter 17 of this volume). This observation drew attention to peripheral mechanisms in the control of feeding behaviour, a field which had previously been dominated by studies of the brain, notable hypothalamic regulatory mechanisms of hunger. A drawback in the classical experiments on hunger mechanisms had been that the stimuli which initiate a meal in a food-deprived animal are unknown. The study of the peripheral mechanisms which suppress feeding or induce satiety during a meal offered a new perspective because the stimulus which controls the behaviour (satiety) is known (food) and its site of action is also known: the gastro-intestinal tract, a major endocrine organ in the body (Smith 1982). The secretions of this organ may be involved in satiety because administration of food into stomach transplants devoid of nervous supply elicits satiety in animals (Koopmans 1981) and food intake in hungry rats is reduced after their blood is mixed with that of satiated rats (Davis et al. 1967). Thus it is necessary to study the secretions of the gastro-intestinal tract during ingestion of food, particularly as CCK-8, which is secreted from the duodenum during feeding, has been suggested to be a primary satiety-inducing hormone (see Chapter 17 of this volume). However, the study of CCK-8 in satiety has been hampered by the absence of sensitive assay methods. With the development of such methods (Linden 1989), the role of CCK-8 in food intake and satiety has become accessible to direct study and our recent series of such investigations is discussed below.
Introduction
Authors: Crawley Jacqueline N
Published: November 2023

Current information on the coexistence of CCK and dopamine in mid-brain neurons of several species is presented in this part. The mesocorticolimbic dopamine system mediates a variety of spontaneous behaviour, including exploration, feeding, stress responses, drug self-administration, and electrical self-stimulation (Stellar and Stellar 1985; Kalivas and Nemeroff 1988). The nigrostriatal dopamine pathway mediates motor functions including coordinated locomotor activities and extrapyramidal stereotypies (DeLong 1990). The tubero-infundibular dopamine tract regulates the release of many pituitary hormones (Meltzer et al. 1978). Dopamine receptor antagonists are the primary treatment for schizophrenia (Carlsson 1988), while dopamine precursors are the primary treatment for Parkinson’s disease (Caine 1977).The discovery by Hokfelt and co-workers that two neuropeptides, CCK and neurotensin, coexist with dopamine in mid-brain neurons of the ventral tegmentum and substantia nigra (Hokfelt et al. 1986) was an exciting revelation for both basic researchers and clinicians studying dopaminergic mechanisms in neuropsychiatric syndromes. The anatomical distribution of these peptide neuromodulators in discrete subdivisions of the mesocorticolimbic and nigrostriatal pathways is described in detail in Chapter 32.
CCK: its role in dopamine-related disorders
Authors: Kuiper M A , van Kamp G J , Wolters E Ch.
Published: November 2023

The peptide now recognized as CCK was originally identified as the compound responsible for causing contraction of the gall bladder and stimulation of pancreatic enzyme secretion (Jorpes and Mutt 1966). However, CCK is also synthesized in the CNS (Dockray et al. 1977). The brain peptide differs from the gastric peptide and consists primarily of the biologically active sulphated carboxyl-terminal octapeptide (CCK-8S). It is distributed throughout the whole brain with the exception of the cerebellum. In the cerebral cortex and hippocampus CCK exceeds the level of any other neuropeptide (Crawley 1985a), and there is abundant evidence that CCK and related peptides exert neurotransmitter/neuromodulator roles in the CNS (see Chapters 1 and 4 of this volume).Hökfelt et al. (1980) demonstrated colocalization of dopamine (DA) and CCK in mesolimbic neurons projecting from the ventral tegmental area of the mid-brain and innervating the posteriomedian nucleus accumbens. This initiated research on CCK in relation to DA-related disorders, e.g. Parkinson’s disease, schizophrenia, and tardive dyskinesia. In Parkinson’s disease, progressive loss of nigrostriatal DA neurons leads to striatal DA deficiency and this correlates (after a threshold of about 80 per cent loss) with the severity of parkinsonian disability. Schizophrenia is a disorder believed to be related to hyperactivity of the dopaminergic system, which is treated with DA receptor antagonists. Tardive dyskinesia is one of the (often irreversible) complications of prolonged treatment with dopamine antagonists.
Variation of flower colours by genetic manipulation of the biosynthesis of anthocyanins
Authors: Mol Joseph N M
Published: November 2023

Flavonoids constitute the main class of flower pigments. Carotenoids on the other hand are responsible for many of the bright yellows and oranges, especially in composites such as gerberas and chrysanthemums. The third class of flower pigments, the betalains are mainly found in cacti, ice plants, and beets.
Gall midges (Cecidomyiidae): classification and biology
Authors: Harris Keith M
Published: November 2023

The Cccidomyiidae probably originated in the Mesozoic age from a group of Diptera with mycophagous larvae. The family is almost certainly monophyletic and of the three extant subfamilies, the Lestremiinae and Porricondylinae are still essentially mycophagous, with larvae feeding on macrofungi and on fungal mycelium in soil, in decaying wood, and in other dead organic matter. The third subfamily, the Cecidomyiinae, contains the greatest number of species and exhibits the greatest biological diversity. It must have evolved rapidly with flowering plants in the Cenozoic. Most of the included species are phytophagous and many induce galls, especially on the aerial parts of flowering plants. Gall induction seems to have evolved on a number of separate occasions within the main phytophagous tribes (Asphondylini, Cecidomyiini, Clinodiplosini, Lasiopterini, and Oligotrophini).
Life cycle strategies in a guild of dipteran gall farmers on the common reed
Authors: De Bruyn Luc
Published: November 2023

The flies of the genus Lipara are strict monophagous parasites of the common reed, Phragmites australis (Poaceae). Due to feeding activities and/or metabolic products, the newly formed internodes of the shoot are significantly shortened and a typical cigar-or spike-like gall is formed at the top of the shoot. Reed is a perennial rhizomatous grass that produces fresh shoots every year during spring. Because the shoots dry up and die at the end of the summer, they can only serve as a source of food for the herbivore during a short time of the year. Previous studies have revealed a high between-plant and between-year variation in plant quality caused by several interacting factors, such as the genetic differences between reed clones, the water and nutrient content of the soil, and interspecific competition with other plants. In addition, the annual germination and growth of the reed is strongly influenced by climatic factors. In the course of evolution, two main solutions have evolved to overcome the above mentioned problems within the genus Lipara.
Pursuit of new leads to antitumour and anti-HIV agents from plants
Authors: Cardellina II J H , Boyd M R
Published: November 2023

During the mid-to-late 1980s the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI) dramatically revamped its approach to the discovery of new leads for antitumour agents (Boyd 1986, 1989, 1993; Boyd et al. 1992). The essential starting point of this new strategy was the primary screen. In vivo testing with murine leukaemia models gave way to in vitro screening against human solid tumour cell lines. Concurrently, the mounting AIDS crisis and the urgent need for AIDS-antiviral chemotherapeutic agents led to an extension of this programme to include a search for novel anti-HIV compounds (Boyd 1988). The screening protocols for these tandem efforts had to be amenable to high throughput and had to accommodate both pure compounds and complex crude extracts (Boyd 1986, 1988, 1989, 1993; Boyd eta/. 1992). These screens are now operated on a large scale by the DTP/NCI extramural service screening programme for the annual testing of tens of thousands of synthetic and natural compounds submitted annually to the NCI by academic and industrial investigators from all over the globe.
Pharmacochemical investigation of Indonesian medicinal plants
Authors: Kitagawa I , Shibuya H
Published: November 2023

Indonesia is perhaps one of the richest countries in the world in natural resources, and the diversity of its botanical resources is particularly important. Indonesian people have a long tradition of using medicinal plants and about 80 per cent of the population are still using them. The number of plant species in the Indonesian archipelago is estimated to be about 40 000, among which about 1000 species have been used as medicinal plants. However, most of them have not yet been verified on the basis of modern science (Riswan and Sangat-Roemantyo 199la,b). In the other words, Indonesia is a very important and attractive country in view of the discovery of novel, naturally occurring lead compounds for the development of new medicines.
The structure and function of the protein kinases: a survey
Authors: Hardie D G
Published: November 2023

In eukaryotic cells, the protein phosphorylation-dephosphorylation cycles catalysed by protein kinases and phosphatases represent perhaps the major mechanism for switching cellular pathways in response to changing circumstances. The only other general mechanism which rivals the ubiquity of protein phosphorylation-dephosphorylation in cellular control is the interconversion of G proteins between their GDP- and OTP-bound forms, catalysed by GDP dissociation factors and GTPase activating proteins. Protein phosphorylation regulates proteins involved in the whole gamut of cellular processes, from metabolic enzymes, through membrane channels and pumps, cytoskeletal proteins and transcription factors, to the protein kinases and phosphatases themselves. It can currently be said to have three broad functions:
Biochemical evidence for an Snfl homologue in higher plants
Authors: Ball K L
Published: November 2023

HMG-CoA reductase kinase (HRK) from higher plants has recently been purified and characterized, and appears to be a functional homologue of the mammalian AMP-activated protein kinase (AMPK). The AMPK has itself recently been shown to be a putative homologue of a yeast protein from Saccharomyces cerevisiae named Snfl, and a protein kinase family from higher plants (the Rkinl family). Similarities between AMPK and HRK implicate the latter as a possible regulator of isoprenoid and sterol metabolism in plants, as well as raising the possibility that it may in some way be involved in cellular stress responses. New immunochemical data linking HRK to Rkinl and Snfl now also open up a whole area of possible roles for HRK in the regulation of plant carbohydrate metabolism.
Protein phosphorylation in germinating seeds
Authors: Georgatsos J G
Published: November 2023

Seed germination is a process whereby the metabolic rate of a quiescent or dormant seed rises sharply due to an increase in water uptake. The term ‘metabolic rate’ covers our ignorance of the sequence, in time and place, of the specific chemical events triggered by the entrance of water inside the seed. Changes in a number of components in various parts of the germinating seed, as a function of time, indicate the sequential activation of metabolic processes, apparently due to the activation of a large number of genes. According to Thomas (1993) more than 3 x 10 different genes are expressed in embryos and seedlings of dicotyledonous plants. However, not all enzymes and other functional proteins increase at the onset of germination. A number of enzymes are stored within the dry seed, whose activity may fall as germination proceeds, remain constant, or increase, although at different rates (Figs 11.1 and 11.2). The increases in enzyme activities are in most cases due to de novo synthesis of enzyme protein, resulting from earlier expression of the corresponding genes. The time following seed imbibition that a gene is expressed may vary from a few minutes to several days. In such situations one would expect extensive signal transduction, stimulated by the inter- and intracellular traffic of physical and/or chemical messages.