Some historical perspectives on thermoregulation.

In this paper, selected historical aspects of thermoregulation and fever are presented as background to the application of molecular biology to thermoregulation. Temperature-sensing mechanisms, coordination of thermal information, thermoregulatory circuitry, efferent responses to thermal stimuli, set point mechanisms, and some of the mechanisms and consequences of fever and hyperthermia are highlighted. Neurotransmitters used in thermoregulatory circuits are also discussed. An attempt is made to include information from comparative physiological sources. Possible future avenues of research in the light of recent new technologies are also presented.     

Some perspectives on the viscosity of actin filaments

Measurements of the dynamic viscosity of various actin filament preparations under conditions of low and controlled shear: (a) confirm the shear rate dependence of F-actin viscosities and show that this dependence obeys the power law relationship observed for entangled synthetic polymers; (b) permit estimation of the extent to which shear artifact amplifies changes in the apparent viscosity of F-actin measured in a falling ball viscometer; (c) show that gel-filtration chromatography of actin and the addition of cytochalasin B to F-actin bring about small (20-40%) changes in the viscosity of the F-actin solutions. These variations are consistent with alterations in the actin-binding protein concentrations required for incipient gelation, a parameter inversely related to average filament length. Therefore: (a) changes in the viscosity of F-actin can be magnified by use of the falling ball viscometer, and may exaggerate their biological importance; (b) chromatography of actin may not be required to obtain meaningful information about the rheology of actin filaments; (c) changes in actin filament length can satisfactorily explain alterations in F-actin viscosity exerted by cytochalasin B and by chromatography, obviating the need to postulate specific interfilament interactions.     

Quantitative modeling perspectives on the ErbB system of cell regulatory processes

The complexities of the processes involved in ErbB-mediated regulation of cellular phenotype are broadly appreciated, so much so that it might be reasonably argued that this highly studied system provided significant impetus for the systems perspective on cell signaling processes in general. Recent years have seen major advances in the level of characterization of the ErbB system as well as our ability to make measurements of the system. This new data provides significant new insight, while at the same time creating new challenges for making quantitative statements and predictions with certainty. Here, we discuss recent advances in each of these directions and the interplay between them, with a particular focus on quantitative modeling approaches to interpret data and provide predictive power. Our discussion follows the sequential order of ErbB pathway activation, beginning with considerations of receptor/ligand interactions and dynamics, proceeding to the generation of intracellular signals, and ending with determination of cellular phenotype. As discussed herein, these processes become increasingly difficult to describe or interpret in terms of traditional models, and we review emerging methodologies to address this complexity.     

Some perspectives on the transfer of cell-mediated immunity by immune-RNA

Summary Ribonucleic acid extracts of lymphoid cells from immune hosts were used to transfer in vivo and in vitro cell-mediated immune reactivity to a variety of antigens. The in vivo immune responses transferred by RNA included the delayed cutaneous hypersensitivity reaction to fungal and chemically-defined antigens and the tumor-rejection reaction to guinea pig hepatoma antigens. The in vitro immune responses transferred by RNA included macrophage migration inhibition by fungal, chemically-defined, and tumor antigens. The transfer activity of RNA preparations was contained in the 8 s to 18 s species of RNA and was sensitive to RNAse but not to DNase or trypsin. Antigen was not detectable in the RNA preparations and appeared to have no role in the transfer activity. Syngeneic, allogeneic, or xenogeneic sources of RNA could transfer immune reactivity. In each system tested, the transfer of cell-mediated reactivity by RNA was specific for the antigen used to sensitize the RNA donor. The potential use of RNA-mediated transfer of immunity is discussed.     

Some perspectives on preservation and disinfection in the present day

The present day objectives for the use of disinfectants and preservatives are unchanged from those of the immediate and distant past. Major developments in this field reflect a general diversification and broadening of regulatory tests of biocide performance, rather than the introduction of novel chemical entities or new applications. This has increased the reliance put upon in-vitro tests of biocide performance conducted to predict safety and efficacy in the field. The ability of microorganisms to adapt their physiology to that of the growth environment has made them an outstanding success in nature. Equally, it is the failure of many in-vitro experiments to correctly mimic these phenotypes that often makes the results irrelevant. Whilst the tests themselves are designed with reproducibility and predictive efficiency in mind, the procedures deployed often decrease the relevance of the test result. Failure to control factors such as growth rate, nutrient limitation, biofilm development and dormancy within the inocula contribute to this anomaly.     

Mathematical modeling in metal metabolism: Overview and perspectives

A review of mathematical modeling in metal metabolism is presented. Both endogenous and exogenous metals are considered. Four classes of methods are considered: Petri nets, multi-agent systems, determinist models based on differential equations and stochastic models. For each, a basic theoretical background is given, then examples of applications are given, detailed and commented. Advantages and disadvantages of each class of model are presented. A special attention is given to determinist differential equation models, since almost all models belong to this class.     

Some considerations of and perspectives in coastal ecology

Ecophysiological studies of plant species in wet saline habitats have been one-sided in the past, emphasizing sodium chloride only. More emphasis should be given to anaerobiosis, to mechanical factors, to the effects of a surplus of other nutrients in seawater and coastal ecosystems and their metabolic impact as well as to aspects of nutrient (re)allocation. Research should incorporate theoretical models on plant strategies maximizing yield, minimizing risk. At the population level, a new operational parameter for ecological optima and ecological stress is presented considering normal and skewed distributions of plant parameters in relation to growth and the concentration of mineral nutrients.Some considerations on the ecological effects of phenotypic plasticity and genetic variability are given by emphasizing the aspects of diaspores.Future investigations of coastal vegetation should consider the interaction of populations within plant communities, including the regulating effects of animals.Nomenclature of vascular plants follows H. Heukels & R. van der Meijden, 1983. Flora van Nederland, 20th ed. Wolters-Noordhoff, Groningen; that of plant communities V. Westhoff & A. J. den Held, 1969. Plantengemeenschappen in Nederland. Thieme & Cie, Zutphen.     

Childhood acute lymphocytic leukemia and perspectives on risk assessment of early-life stage exposures

Recognition that children are a potentially susceptible subpopulation has led to the development of child-specific sensitivity factors. Establishing reliable sensitivity factors in support of risk assessment of early-life stage exposures can be aided by evaluating studies that enhance our understanding both of the biological basis of disease processes and the potential role of environmental exposures in disease etiology. For these reasons, we evaluated childhood acute lymphocytic leukemia (ALL) studies from the point of view of mechanism and etiology. ALL is the most common form of childhood cancer proposed to result from a prenatal primary event and a postnatal second event. This multi-stage model is supported by the observation that chromosomal translocations/fusion genes (e.g., TEL-AML1) involved in producing ALL are detected at birth (prenatal event), and a postnatal event (e.g., TEL deletion) is required for disease manifestation. It appears that a proportion of ALL cases are the result of environmental exposures, in which case preconceptional, prenatal, and postnatal stages are likely to be critical exposure windows. To this end, we recognized postnatal infection-related risk factors as potential candidates associated with the ALL second event. Additionally, we discuss use of ALL-associated fusion genes and genetic polymorphisms, together or separately, as indicators of ALL susceptibility and increased risk. The possibility of using fusion genes alone as biomarkers of response is also discussed because they can serve as predictors of key events in the development of a mode of action (a sequence of key events, starting with interaction of an agent with a cell, ultimately resulting in cancer formation) for particular environmental exposures. Furthermore, we discuss use of an initiated animal model for ALL, namely transgenic mice with TEL-AML1 expression, for exploring mechanisms by which different classes of environmental exposures could be involved in inducing the postnatal step in ALL formation.     

Persistent activity in limbic system neurons: neurophysiological and modeling perspectives

Neural activity persisting for one to hundreds of seconds has been postulated to be a substrate of memory. This review article illustrates examples of such activity in limbic system structures including the hippocampus, postsubiculum, and the anterodorsal thalamus. These neuronal responses include better known correlates with the spatial position as well as with head direction of the animal relative to its environment as well as other lesser known examples. Since head direction responses are greater when the animal is actively moving than when passively rotated, it has been proposed that there might be a general mechanism where the behavioral state of the animal can provide modulatory gating of such persistent signals. This would regulate the relative influence of these signals on downstream structures. Neural network attractor models of the head direction cell system are presented to demonstrate how these responses might originate, as well as the dynamics by which they are updated during movements.     

Some nonstandard modeling techniques in theoretical biology

Three topics are surveyed. (1) The quasisteady-state assumption is a fundamental example of frequent instances in theoretical biology where advantage can be taken of the simultaneous existence of widely separated time scales. It is shown that appropriate scaling can provide a markedly sharper estimate of the range of validity of this approximation. (2) A new methodology for modelling dynamically changing networks is applied to simple morphogenesis in fungal colonies. A brief discussion is given of possible application to the complex polymerization and cross-linking that characterize cytoplasmic fibers. (3) It is shown that problems in ecology and immunology can be illuminated by considering nonlocal interactions (and hence integrodifferential equations) that generate patterns in “aspect space” or “shape space.”     

Some properties of cryopreserved acute leukemia cells

We have described a method of cryopreservation of large quantities of human leukemia cells. After storage for long periods the cells retain specific membrane antigens measured using in vitro lymphocyte cultures, and they also functioned suitably as target cells in an immunological assay system. These findings solve some of the logistic problems involved in conducting a large-scale active immunotherapy program for acute leukemia in man.     

Some problems and solutions for modeling overall cardiovascular regulation

A brief history of the development of mathematical models of the cardiovascular system is presented. Until the advent of computers, very little modeling of transient physiological phenomena was done, but this is now commonplace. The problem of stability in complex physiological models fortunately is averted by the fact that the physiological controls are themselves highly stable. The reason for this is that evolution has eliminated unstable feedback loops because they are lethal. Indeed, enough safety factor has been provided in the design of the body so that even poor mathematical models are often quite stable. An especially important use of complex cardiovascular models has been to derive new concepts of cardiovascular function. One such concept is the “principle of infinite gain” for long-term control of arterial pressure, which states that the long-term level of arterial pressure is controlled by a balance between the fluid intake and the output of fluid by the kidneys, not by the level of total peripheral resistance as has been a long-standing misconception based on acute rather than chronic animal experiments.     

Codigestion of solid wastes: a review of its uses and perspectives including modeling

The last two years have witnessed a dramatic increase in the number of papers published on the subject of codigestion, highlighting the relevance of this topic within anaerobic digestion research. Consequently, it seems appropriate to undertake a review of codigestion practices starting from the late 1970s, when the first papers related to this concept were published, and continuing to the present day, demonstrating the exponential growth in the interest shown in this approach in recent years. Following a general analysis of the situation, state-of-the-art codigestion is described, focusing on the two most important areas as regards publication: codigestion involving sewage sludge and the organic fraction of municipal solid waste (including a review of the secondary advantages for wastewater treatment plant related to biological nutrient removal), and codigestion in the agricultural sector, that is, including agricultural - farm wastes, and energy crops. Within these areas, a large number of oversized digesters appear which can be used to codigest other substrates, resulting in economic and environmental advantages. Although the situation may be changing, there is still a need for good examples on an industrial scale, particularly with regard to wastewater treatment plants, in order to extend this beneficial practice. In the last section, a detailed analysis of papers addressing the important aspect of modelisation is included. This analysis includes the first codigestion models to be developed as well as recent applications of the standardised anaerobic digestion model ADM1 to codigestion. (This review includes studies ranging from laboratory to industrial scale.).