Search

The most relevant aspects related to flowering, fruit set, and fruit development are reviewed in this chapter. In relation to flowering, special attention has been paid to the genetic, environmental aspects, particularly temperature and water stress, and to the endogenous factors, such as the nutritional status of the plant and the influence of the fruit as a decisive factor in alternate bearing. The main cultural practices to both reduce and increase flowering intensity are also reviewed. Fertilization and parthenocarpy are studied from an environmental, hormonal, and nutritional point of view, paying special attention to the competition phenomena between developing fruits, as a decisive factor in fruit setting and final fruit size. We also review the endogenous factors related to these processes and the most effective cultural practices to increase fruit set (the application of GA3 and girdling branches) and the final fruit size (the application of synthetic auxins). This chapter ends with the study of seed development.

Senescence, or biological aging, is the steady deterioration of functional features of an organism, which ultimately leads to its death. Leaf senescence is an intricate and tightly synchronized developmental process that involves a coordinated sequence of molecular events that eventually leads to the death of the leaf. The critical factors that contribute to the commencement of leaf senescence are environmental stresses like darkness, drought, pathogen attack, and extreme temperatures, as well as endogenous factors, including age, plant hormones, and growth regulators. Every biological process has its own importance, and so leaf senescence also makes a significant contribution to the strength of plants by controlling the translocation of major nutrients to the reproductive and growing organs. Over the past decade, numerous attempts have been made to decipher the mechanistic view of leaf senescence via transcriptomic, proteomic, and metabolomic studies. It has been found that within plants, after the perception of stress signals, there occurs a prominent senescence syndrome that results in the ultimate upregulation of thousands of senescence-associated genes (SAGs), which is characterized by degradation of macromolecules, decrease in photosynthetic activity, remobilization of nutrients, and ultimately cell death. Currently, genomic and transcriptomic analyses have identified many SAGs that are induced during the onset of leaf senescence, which eventually may play an important role in deciphering the molecular mechanism responsible for signal perception, execution, and regulation of leaf senescence.

Fleshy fruit experiences profound physiological, biochemical, and structural modifications during ripening to facilitate seed dispersal and to become attractive and nutritious for human consumption. The metabolic networks regulating fruit ripening are very complex, and ethylene appears to be a key factor acting in concert with other environmental signals and endogenous factors. The classical distinction between climacteric and nonclimacteric ripening is now questionable, as different patterns of synthesis and sensitivity to ethylene may operate in the ripening of different fruits. In recent years, much progress has been done in the characterization of the main biochemical pathways implicated in the different ripening-associated processes and in the identification of key genes controlling these events. This chapter highlights current understanding and advances in the regulation of fruit ripening and key metabolic pathways associated with the different ripening-related processes, with emphasis on their impact on fruit quality.

Dietary and lifestyle factors play an important role in human health, as nutritional imbalances are major determinants of various diseases including cancer. Emerging literature suggests that diet and lifestyle factors have a major impact on gene expression through epigenetic mechanisms. Epigenetic modifications are heritable and cause potentially reversible changes in gene expression without altering the DNA sequence. Epigenetic inscriptions include changes in DNA methylation, histone modifications, and small noncoding microRNAs. Atypical epigenetic alterations possibly occur at an early stage during neoplastic development and are widely recognized as essential players in cancer progression. Additionally, environmental cues might lead to epigenetic modifications, thus providing a link between susceptible genes and environmental factors in the etiology of cancer. This chapter primarily highlights the role of various epigenetic mechanisms in the regulation and maintenance of the mammalian genome. This chapter also discusses the impact of endogenous factors including diet, lifestyle, environment, and socioeconomic status on the process of carcinogenesis through various epigenetic modifications. Elucidating the impact of dietary and lifestyle factors on epigenetic mechanisms may serve as a personalized prognostic tool for gauging cancer susceptibility and providing recommendations and guidance for the prevention of cancer.

In this review, we highlight critical unresolved questions in the etiology and mechanisms causing preterm brain injury. Involvement of neurons, glia, endogenous factors and exogenous exposures is considered. The structural and functional correlates of interrupted development and injury in the premature brain are under active investigation, with the hope that the cellular and molecular mechanisms underlying developmental abnormalities in the human preterm brain can be understood, prevented or repaired.

The natural aging process is associated with changes in structure and function of the human lung that becomes pronounced with advanced age. Age-related changes in immune function and immune regulation likely play an important role in age-associated lung remodeling and respiratory infection risk and environmental exposures plus a variety of endogenous factors may accelerate the pace of changes affecting the aging lung. The integrity of barriers that protect against respiratory pathogens decline with aging, which, combined with less robust immune responses in the elderly, increase susceptibility to respiratory infections.

Despite numerous attempts to develop an accurate and reliable postmortem interval (PMI) estimation tool, this still remains one of the major challenges that face forensic scientists. This is mainly because decomposition is affected by a sequence of several factors including edaphic and environmental parameters concomitant with the activity of exogenous organisms such as microorganisms, insects, and scavengers. Also the phenomenon depends on the cadaver's endogenous factors such as health condition and cause of death. This chapter gives an overview of the highly variable cadaver decomposition processes and their major influencing factors; discusses established and emerging biochemical, physicochemical, histological, physiological, and molecular techniques developed by researchers on their quest to find the “ultimate PMI estimation tool”; considers current classification methods; and proposes an alternative categorization approach. Also novel techniques and/or areas of ongoing research in other forensic subdisciplines are explored succinctly as appropriate.

Several theoretical developmental models, such as Bronfenbrenner ecological approach and Super and Harkness concept of “developmental niche” highlight the influence of caretakers on children’s social, emotional, and cognitive development. Direct influence occurs through shared genetics, parenting style, and behaviors, while cultural and social values have an indirect impact. To fully understand the child’s psychological adjustment, one should take into account significant contexts, such as the family and the interactions between exogenous and endogenous factors.

Development involves several maturation stages and is a critical period for the integrity of the brain, mainly because of sensitivity to the effects of endogenous factors and environmental stimuli. Tobacco smoking is most common among licit and illicit drug use in pregnant women worldwide. Prenatal and postnatal exposure to tobacco smoke has been associated with neurobiological deficits, such as changes in neuronal differentiation, synaptic proteins, neurogenesis, apoptosis, myelination, oxidative stress, and vascularization. Tobacco smoking during pregnancy has been associated with neurobehavioral disorders (e.g., learning and memory impairments and attention deficit/hyperactivity disorder) and a higher incidence of sudden infant death syndrome. This chapter focuses on the development of the nervous system and the ways in which this plastic process can be affected by nicotine and tobacco smoke, leading to pathological consequences that can be expressed throughout the lifespan.

In the exploration of the role of dietary factors in carcinogenesis, both essential nutrients and other compounds in foods with biological activity may be important. Further, endogenous factors including genetic one may interact with the nutritional compounds to impact the development of cancer. These interactions may operate in two directions. Genes can affect the action of the compounds of dietary origin (e.g., increasing or decreasing the amount needed for good nutritional status), and these compounds can affect the action of genes (e.g., increasing or decreasing expression). Genetic factors may affect the metabolism of carcinogens and procarcinogens found in food, and food components can interact with genetic factors to play a role in prevention of carcinogenesis. Methodologic issues regarding the study of diet, genetic variation, and cancer are reviewed and examples are provided of mechanisms for potential nutrition–gene interactions in cancer.

The loss of self-tolerance leads to pathological immune reactions against host antigens and autoimmunity. Most autoimmune diseases have an unclear pathology, with genetic, environmental, and endogenous factors playing a role. Epigenetic factors have been shown to substantially contribute to the etiology of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, and systemic sclerosis. Recent research efforts tried to integrate cell type specific epigenetic changes into genetic susceptibility loci as causes of disease. This is a promising attempt to understand disease relevant pathways leading to new drug development or to the identification of disease specific biomarkers.

The process of aging is determined by a complex interaction of endogenous factors such as genes combined with influencing exogenous factors such as nutrition and lifestyle. The progressive accumulation of damage caused by reactive species is often called oxidative stress and is associated with age-related diseases and aging. Defense mechanisms against oxidative stress involve the antioxidative network in which nutritional factors could intervene in a regulatory manner. An ideal nutritional biomarker of aging should be a biological parameter that can predict functional capability at some age better than chronological age including the consequences of nutritional status with regard to age. Due to high regulation of the antioxidative network and the complexity of human aging the determination of individual biomarkers is challenging and the prediction of biological age by a single marker is implausible. Most often a combination of different biomarkers might be the preferable approach.

When compared to animal and insect organisms, plants have a small number of hormones. This is attributed to the complexity of hormone crosstalks among them. Recent studies obtained from model plants, Arabidopsis and rice, have shown the interaction of variety of signalling molecules with phytohormone metabolism and signalling. We review recent and exciting studies in the field of cytokinin, a major classic of phytohormones, by focusing upon the regulation of metabolisms – biosynthesis and degradation of cytokinins. Endogenous factors as well as environmental cues having an impact on the regulation of cytokinin metabolisms are summarized. Practical applications by altering cytokinin metabolisms in crop species are discussed.

Dying and death are continuous biological processes. In the great majority of cases, individual death is attributed to irreversible cessation of respiratory and circulatory functions. Circulatory and respiratory arrest are followed by early postmortem changes such as postmortem lividity and rigor mortis. However, metabolism of tissues continues for some hours after death. In this supravital period, reactions of tissues on excitation are much like those in life. Supravital reactions as well as the time-dependent criteria of postmortem lividity and rigor mortis are used for estimating the time since death. Different exogenous and endogenous factors contribute to destruction and decomposition. Endogenous factors are autolysis, putrefaction, and decay, while exogenous factors include animal predation, exposure to the elements, and mechanical injury. While these natural processes lead to dissolution and disintegration of the cadaver down to bones and tendons, special environmental conditions may preserve a body. Preservation processes include mummification or adipocere formation. It can also be found in bog bodies and permafrost corpses.

Publisher Summary This chapter discusses the factors influencing irritant potential, delineates general clinical presentations of irritant dermatitis, and addresses workup and treatment. In addition, it addresses methods of evaluating a chemical's irritant potential and discusses the irritation potential of some agricultural chemicals and plants. Irritant contact dermatitis (ICD) is defined as nonimmunologic skin inflammation after contact to a substance or physical factor. Although epidemiologic data are scarce, ICD appears to be an important cause of occupational and nonoccupational skin disease. Various factors influence a chemical's irritant potential. Intrinsic molecular properties such as molecular structure, size, ionization state, lipid solubility, and pKa determine the chemical's interaction with the skin barrier and epidermal cells. Irritant potential is also dependent on the molar concentration and volume and duration of the exposure. Physical factors such as extremes of temperature and humidity, as well as mechanical factors such as occlusion and friction, can enhance irritation of chemicals or act as irritants. Endogenous factors such as age, anatomical site, preexisting dermatologic conditions, and genetic background may influence an individual's predisposition to irritant dermatitis. There is a decreased susceptibility of irritation with increasing age, with children younger than 8 years being most susceptible to skin irritation. Few human studies exist, and new studies are currently inhibited by the U.S. Environmental Protection Agency's ethics system. Lastly, epidemiologic data that are so helpful for many contact allergens remain scarce for agricultural irritants. The techniques and assays are efficient; however, a regulatory system that promotes developing and registering relevant data in this arena is lacking.

Research into the molecular and cellular mechanisms underlying angiogenesis has led to the identification of numerous endogenous factors that act as promoters and inhibitors of pathological retinal neovascularization. The most potent of the promoters, vascular endothelial growth factor (VEGF), already has been validated as a therapeutic target, with two clinically approved agents currently in use. This article reviews the modes of action of VEGF, as well as the other endogenous regulatory molecules whose roles in ocular neovascularization are best characterized with a view to outlining possible new therapeutic options, whether to be employed singly or in combinatorial approaches.

Neurodegenerative diseases are characterized by progressive dysfunction and death of cells that frequently affect specific neural systems, thereby implying some form of selective vulnerability. Recent studies have provided insight into the basic processes common to neurodegeneration and into cell-death programs and their roles in the complex group of disorders that are briefly reviewed in this chapter. The major basic processes inducing neurodegeneration are considered multifactorial ones caused by genetic, environmental, and endogenous factors related to aging. Converging lines of investigation have revealed potential common pathogenic mechanisms underlying many diverse neurodegenerative disorders, including abnormal protein dynamics; oxidative stress (OS) and formation of free radicals/reactive oxygen species (ROS); impaired bioenergetics and mitochondrial dysfunctions; fragmentation of neuronal Golgi apparatus (GAs); disruption of cellular/axonal transport; neuroinflammatory/neuro-immune processes; dysfunction of neurotrophins; and actions and mutations of molecular chaperones. These processes and their role in neurodegenerative diseases are briefly discussed in the chapter.

Publisher Summary This chapter discusses the putative chemical messengers and their potential regulatory mechanisms in the control of sea-urchin reproduction. Sea-urchin reproduction is characterized by specific cycles of gametogenesis and nutritive phagocyte growth and depletion. Seasonal changes in environmental factors—such as photoperiod, temperature, and salinity—influence reproduction within a population. The nutritional condition also affects gametogenesis. The environmental and nutritional effects on the physiology and morphology of the gonads suggest that these exogenous cues are transduced to endogenous factors that regulate reproduction in the adult sea urchin. Diet plays a vital role in the stimulation and maintenance of gonad production and is one parameter that is easily manipulated in aquaculture. The formulated feeds supplemented with steroids affect gametogenesis and nutrient allocation to nutritive phagocytes. Sex steroids, proteins, catecholaminergic, and cholingeric factors all play roles in regulating various aspects of gonad function. Examination of these chemical messengers in the context of gonad production, gametogenesis, and nutrient translocation allows the generation of new hypotheses for research into the manipulation of gonad production and regulation of gametogenesis.

Publisher Summary The chapter presents a discussion on the potential benefits and risks of metabolic modifiers in animal nutrition. Somatotropin enhances the growth of animals through effects on maintenance, intake, digestibility and the efficiency of nutrient utilization, and affects these processes through direct and indirect (via IGF-1) actions. Optimal use of somatotropin requires more knowledge of nutrient requirements and details of its mechanisms of action. Ghrelin and leptin are important components of the integrated pathway regulating physiological energy balance with potential to enhance animal production. Chromium picolinate supplements may enhance growth and body composition in pigs and in poultry, but in cattle, may only be beneficial during periods of stress, as in calves following transport to the feedlot. The chapter focuses on the recent developments in knowledge concerning metabolic modifiers. The chapter presents a discussion on feed additives, implants and pharmaceuticals, endogenous factors that may modulate how feed additives, pharmaceuticals or nutrients influence biological responsiveness. Some of these factors may have an environmental or genetic basis. Some of the substances considered are endogenous compounds involved in modulation of aspects of growth or cell biology in response to variations in hormone activity or nutrition. Although many of the compounds that fall into the category of metabolic modifiers show merit for improvement of growth, productivity or body composition of livestock, there are also substantial concerns regarding the health and safety aspects of using some of these products in food-producing animals. Activation of α-adrenergic receptors can have important physiological and metabolic effects, especially concerning heat and energy conservation.

Growth from birth to adulthood is a complex biological process, part of overall morphological development. Linear height growth, as well as morphology, depends on skeletal development as a result of a variety of interactions, including endogenous factors, such as genetics, hormones, and growth factors, and exogenous factors, such as nutrition, physical activity, and psychosocial environment. This article essentially deals with the endocrine control of growth and describes the role of circulating hormones and growth factors. It is noteworthy that a number of genetic, developmental, or acquired diseases have contributed to the understanding of the mode of action of these substances.

Publisher Summary This chapter discusses that microglia have been viewed as the quiescent though potentially active arm of the innate immune response in the central nervous system (CNS). After injury, they become activated and migrate to the lesion site. The participation of activated CNS-resident microglia in the inflammatory response that follows traumatic injuries or chronic neurodegenerative diseases in the CNS has been viewed as detrimental. Attempts have been made to treat these conditions by anti-inflammatory therapy. The chapter suggests that microglia act as stand-by cells in the service of both the immune and the nervous systems. Yet, their ability to fully benefit damaged tissue rather than to be inactive or even destructive reflects their activation. They exercise their neural function by buffering harmful self-compounds, and clearing debris from the damaged site and their immune function by providing immune-related requirements for recovery. It also suggests that regulation is achieved by the operation of a T-cell mediated response directed against abundant self-antigens residing in the damaged site. Since this regulatory mechanism was found to be protective against harmful endogenous factors released as a result of the injury, boosting of an autoimmune response, while avoiding autoimmune disease induction, might constitute the basis for the development of a therapeutic vaccination against neurodegenerative or other brain-related diseases.

Diseases in fish are serious problems for the development of aquaculture. The outbreak of fish disease is largely dependent on environmental and endogenous factors resulting in opportunistic infection. Recent studies, particularly on stress response, have revealed that bidirectional communication between the endocrine and immune systems via hormones and cytokines exists at the level of teleost fish. Recently information on such messengers and receptors has accumulated in fish research particularly at the molecular level. Furthermore, it has become apparent in fish that cells of the immune system produce or express hormones and their receptors and vice versa to exchange information between the two systems. This review summarizes and updates the knowledge on endocrine-immune interactions in fish with special emphasis on the roles of such mediators or receptors for their interactions.

Publisher Summary This chapter provides an overview on targeting aggression in mice. The chapter illustrates that gene targeting has the potential to yield new insights into the study of aggression, there are some shortcomings of this technique that must be recognized when interpreting behavioral data of knockout animals. One conceptual problem with behavioral studies of mice with targeted genetic deletions, which is shared with all ablation studies, is that behavioral tests study the effects of the missing gene not the effects of the gene directly. Disadvantage of using gene-targeting techniques in the study of aggression is that the products of many genes are essential to normal function, and inactivating the gene may prove lethal or induce gross morphological or physiological abnormalities that can complicate interpretation of discrete behavioral effects. Against those disadvantages are several important advantages to using knockout mice in behavioral research: (1) disabling a gene is often a very precise and “clean” ablation, (2) the effects of the gene product can be abolished without the side-effects of drugs, and (3) genetic manipulations may be the only way to determine the precise role of many endogenous factors on behavior.

Publisher Summary The evidence that inhibiting angiogenesis have a positive effect on controlling solid tumors has increased dramatically. However, as the various biological factors that promote or inhibit this process are identified, It is evident that angiogenesis may be difficult to control and no single target is fundamental over the rest. Angiogenesis is required for the development of many proliferative diseases, including rheumatoid arthritis, psoriasis, solid tumor growth, metastasis, as well as diabetic retinopathy and age related macular degeneration. At least, 20 endogenous factors have been identified so far that either promote or inhibit angiogenesis. This chapter discusses those factors that may be useful as targets for therapy. The chapter discusses the oncology aspects of anti-angiogenesis research because most of the effort in recent times has been spent there, even though several models for assessing anti-angiogenic effects for oncology involve testing in eye models. For cancer, the inhibition of angiogenesis is a departure from the traditional therapy. In that, it attempts to inhibit the process, whereby a tumor recruits its own microvasculature to gain nutrients and rid itself of cellular by-products rather than attempting to kill the tumor itself. Thus, anti-angiogenic therapy should be viewed as cytostatic rather than cytotoxic and drugs that inhibit angiogenesis may need to be administered in conjunction with traditional anti-cancer agents.

This chapter examines the different aspects of immunomodulation in the fish. The general health of fish is a function of their environment, the nature of pathogens, and factors intrinsic to the fish themselves. Circulating levels of leukocytes change through time when fish are stressed. Changes following physical types of stressors include depression in the number of lymphocytes in the circulation, or the number of these cells relative to the number of erythrocytes. Negative effects of stress on disease resistance appear to be because of the depression of antibody-synthesizing capability through effects on lymphocytes. Stress effects on the immune system of fish may be mediated by the endocrine system. Catecholamines and corticosteroids are the major stress hormones of vertebrates. Some species of teleosts do not fit the general paradigm for the endocrine stress response, the extremely rapid secretion of catecholamines and rapid secretion of cortisol following the onset of stress. The mechanism of buffering in rainbow trout can be attributed to the elevation in the concentration of corticosteroid-binding globulin as spawning approaches. The globulin reduces the amount of free cortisol that could pass into the ovarian fluid and, subsequently, the egg.

Publisher Summary This chapter examines the physiological processes in conifers during winter dormancy including tolerance to frost and desiccation, water relations, and carbon metabolism and the regulatory influences of environmental and endogenous factors. Conifers attain full dormancy before the onset of full winter. Full-winter dormancy is characterized by the formation of resting buds, the suspension of growth processes—elongation and divisional growth—reduction of metabolic activity, the enhancement of frost and desiccation resistance, and changes in cellular and cytoplasmic structures. Frost can inhibit photosynthesis completely, both through stomatal closure and at the chloroplast level. Photo-inhibition is considered to be a mechanism to protect chloroplasts from photo-oxidative damage. Dormancy is attained through a multitude of physiological and structural changes at the cellular level, which require induction by endogenous and photoperiodic control in early autumn. Winter respiration may not impose a major quantitative stress on carbon balance, the long winter periods of 58 months may result in significant cumulative effects.

This chapter describes the urinary–excretory rhythms. As the kidneys deal with so many substances, a study of urinary rhythms enables the comparison of the effectiveness of exogenous and endogenous factors in these different substances. In accord with the kidneys' homeostatic and excretory functions, the average rate of excretion of a substance on different days will change and the effect of this upon rhythmicity can be assessed. As the process of urine formation has so many stages, each of which might manifest circadian rhythmicity, a study of the rhythmicity shown by these different stages gives some idea of the causal nexus that exists within the system. Different urinary constituents show differences in the relative importance of endogenous and exogenous components in determining their rhythmicity. As with other variables, comparisons between rhythms and subjects are more easily made if account of varying exogenous influences is taken. One part of this exogenous influence is the pattern of sleep and wakefulness and associated changes such as posture and food intake. Another part of the exogenous influence is eating habits. To the extent that eating habits are normally closely related to the pattern of sleep–wakefulness, the use of midsleep as a reference point will take them into account also. Hormones influence renal rhythms, and it is through these humoral factors that some of the homeostatic functions of the kidney operate.

Publisher Summary This chapter presents the approaches to normal language acquisition. The language is unique to man; it is believed that language must be part of the essential nature of man, an inborn or innate capacity. Therefore, the chapter presents the innateness hypothesis, which was given by Noam Chomsky. The hypothesis states when the child reaches a critical stage of maturation, language acquisition begins de novo, without essential reference to other cognitive factors. Under innate constraints that are specific to the language faculty of the mind, the child constructs a grammar that best fits the data, using a process of hypothesis formation and testing. However, this hypothesis does not present the answers related to language acquisition in children. The acquisition of language involves both endogenous and exogenous factors, and it is taken as axiomatic that the endogenous factors must include an ultimately genetic basis that is properly described as innate, in the sense that it is given at conception and is species specific.

The combination of passive immunoneutralization of an endogenous factor with frequent sampling techniques to delineate the pattern of secretion represents a powerful tool for dissecting the contribution of that factor to normal and/or abnormal pituitary function. Passive immunoneutralization offers all of the advantages of other known means of abolishing endogenous factors. It has the specificity and the selectivity of antagonists while retaining the potential for replacement of biological activity that is possible with organ removal or selective brain cuts or lesions. The only major drawback to this approach is the potential difficulty in obtaining the appropriate reagents. The inherent flexibility of the model, however, increases the probability of obtaining useful data with those reagents that are available. At present, the number of studies using immunoneutralization is relatively small, but the knowledge gained from these studies has been substantial. As the number of immunoneutralization and replacement studies increases in the future, the usefulness of this powerful approach will be extended to its full potential.

The rhythm of deep body temperature possesses a large endogenous component. This chapter discusses cardiovascular, respiratory, metabolic, and gastrointestinal rhythms. These rhythms possess a large exogenous component and show clearly the direct effect of the environment and activity of the individual; it has sometimes been difficult to demonstrate that a particular rhythm has any endogenous component. By attributing the endogenous components of the cardiovascular and respiratory systems to a combination of rhythms—in deep body temperature, the autonomic nervous system and arousal mediated by the reticular formation—there is no reason to site the internal clock in one or more of these areas. These areas are important components in the nexus between the timing mechanism and the observed rhythms. Metabolic and gastrointestinal rhythms, like those of the cardiovascular and respiratory systems, are much affected by external events such as, in this case, the rhythmic intake of food. Experiments in which food intake is modified in an attempt to investigate the endogenous components of the rhythms lead to two difficulties in interpretation. There is evidence that the metabolic rhythms are influenced by the nature of the diet. As a result of all these complicating factors, it is rarely possible to infer much about endogenous factors from the present body of knowledge.

Publisher Summary This chapter discusses the regulation of the sleep–waking rhythm by environmental and endogenous factors. According to the serotonin (5-HT) hypothesis of sleep, slow wave sleep (SWS) should be abolished in the chronic cerveau isole preparation, as the 5-HT nerve terminals would be degenerated. Cortical slow waves can be generated by various nonspecific factors—for example, drugs and change in CSF pressure—and that EEG synchronization does not indicate, therefore, necessarily the presence of SWS. Factor S produces a behaviorally natural sleep in the cat that exhibits a strong urge to return to sleep when it is awakened whereas in the rabbit, factor S has been shown to increase the duration of the long SWS episodes. In an experiment described in the chapter, capsaicin applied via a single cannula had an immediate desynchronizing action caused by the mechanical stimulation of the preoptic region, an effect that was not seen when the drug was administered via a double cannula.

Publisher Summary This chapter discusses some new findings on possible biological correlates of extremely high mathematical and verbal abilities and proposes that a combination of exogenous and endogenous factors also determines the sex difference in mathematical reasoning ability. Large sex differences in mathematical reasoning ability are found prior to puberty among intellectually advanced students. This difference could predict subsequent sex differences in achievement in mathematics and science. Because few differences are found in the backgrounds and attitudes of the boys and girls tested, it is unlikely that simple environmental hypotheses can entirely explain the data presented in the chapter. Some of the findings on physiological correlates of extreme precocity are difficult to reconcile with most of the biologically oriented hypotheses that have been proposed to account for sex differences in cognitive functioning. The chapter proposes a single unifying hypothesis to account for sex differences observed. Because there are well-documented differences in the environment as well as in the biology of boys and girls, it is a combination of both of these factors that cause the sex difference in mathematical reasoning ability.

Publisher Summary This chapter discusses the regulation of the sleep-waking rhythm by environmental and endogenous factors. The daily pattern of sleep and waking corresponds closely to the circadian rest–activity rhythm characterized by highly regular endogenous cycles. Light and other environmental factors may influence the phase of the rhythm by nonlinear mechanisms. In addition to its rhythmic aspect, sleep may also be regarded as a homeostatic process as a total or selective deprivation gives rise to compensatory changes. Neurotransmitters, and in particular the monoamines, are known to be critically involved in sleep regulation although their precise role remains to be established. Dynamic evidence indicates that an as yet unidentified sleep-inducing factor derived from the brain of sleep-deprived animals may play a crucial role in sleep-homeostasis. These developments may be important for the search of a physiological sleep remedy in medicine.

Publisher Summary This chapter describes the positive inotropic action of digitalis and endogenous factors: Na,K-ATPase and positive inotropy and endogenous glycoside. It is suggested that progress have been made in understanding how cardiac glycosides produce their powerful stimulating action on cardiac contraction. The evidence to date suggests strongly that the Na,K-ATPase is the pharmacological receptor, or if there are multiple mechanisms, one of the pharmacological receptors. It appears that inhibition of Na,K-ATPase enzyme activity and subsequent increase in the activity of Na ion at the inside of the sarcolemmal membrane that in turn activates a Na/Ca exchange “carrier,” represents the sequence of changes that lead from a binding of digitalis to the Na,K-ATPase, to the positive inotropic action. The critical experiments that are now needed to solidify this hypothesis must involve simultaneous measurements of aNai and aCai, contraction, and digitalis binding to Na,K-ATPase and to other suggested sites. These experiments are certainly not easy. They require a relatively simple type of cardiac preparation, such as viable single cells devoid of fibroblasts, in which contraction can be quantitatively measured. The possibility that endogenous substances exist that regulate the pump by an action on the outside of the sarcolemma is very exciting.

Publisher Summary This chapter presents the epidemiology of ganglionic eminence hemorrhage. The etiologic studies of intraventricular hemorrhage in the newborn appear to reflect several recent technologic advances: (1) the availability of computerized tomography and of ultrasonography, allowing the diagnosis to be made accurately and with minimal risk; (2) the linear-array real-time ultrasound scanner that allows the diagnosis to be made at the incubator; (3) small transducers now allowing arterial blood pressure to be monitored in the critically ill newborn. The findings emphasize that gestational age-related factors may be of considerable importance in the etiology of ganglionic eminence hemorrhage. In the endogenous risk factor hypotheses, biological characteristics of the germinal matrix make infants of low gestational age more vulnerable than older infants. Modern epidemiology suggests that invariably both exogenous and endogenous factors exist for every disease. The discriminant functions in which the maternal characteristics are the dependent variables provide support for the interpretation that these maternal characteristics are correlates of low gestational age. As many of the identified risk factors are correlates of low gestational age, it is plausible that these risk factors are not causes of ganglionic eminence hemorrhage but rather indicators of the most important causal risk factor, that is, low gestational age.

Publisher Summary This chapter discusses the factors regulating the metabolism of steroids. There are two aspects to metabolic research—the search for the intermediate and final products of metabolism, and the study of the regulating mechanisms that control the formation and breakdown of these products. The hypothalamus, hypophysis, and steroid hormone-producing organs form a functional unit for the homeostatic regulation of the plasma level of hormones. This functional unit operates by the principle of automatic control. The control loop is divided into two parts: the controller and the controlled system. The steroid metabolic activity is not constant however can be affected by various exogenous and endogenous factors. Within the control loop, these factors function as disturbance variables, which can cause qualitative and quantitative changes in the controlled variable of the system, the plasma hormone level and hence in the input signal for the error-sensing device. The metabolism of steroid hormones of the ∆ 4 -3-ketone type is qualitatively and quantitatively dependent on sex in a large series of reactions.

Summary It is well known that hypothalamus, hypophysis, and steroid hormone-producing organs form a functional unit for the homeostatic regulation of the plasma level of hormones. This functional unit operates by the principle of automatic control; i. e., it is a closed control loop, which can be divided into two parts: the controller and the controlled system. Trie most important organ of the controlled system is the liver. It is the center of steroid metabolism and may be regarded as the antagonist to the endocrine glands. Since steroid metabolic activity of the liver is not constant, but can be affected by various exogenous and endogenous factors, these factors function as disturbance variables, which can cause qualitative and quantitative changes in the controlled variable of the system, the plasma hormone level. The present paper is concerned with these disturbing factors, i. e., the factors that control steroid hormone metabolism. The following factors are known to act directly on steroid metabolism in the liver: sexual state, stage of development, treatment with hormones (sex hormones, anabolic steroids, corticosteroids, thyroid hormone), certain drugs, state of nourishment, conditions of stress and the rate of blood flow through the liver. An attempt will be made to establish a classification of the disturbance variables, to obtain an insight into the mechanism of their effects on steroid metabolism in the liver, and to discuss the possible reactions on the components of the control loop. To ensure that the discussion will be as consistent as possible, we shall concentrate on demonstrably direct effects of disturbing factors on the intermediary metabolism of ⧍ 4 -3-ketosteroids.